[Title 21 CFR ]
[Code of Federal Regulations (annual edition) - April 1, 2022 Edition]
[From the U.S. Government Publishing Office]
[[Page i]]
Title 21
Food and Drugs
________________________
Parts 500 to 599
Revised as of April 1, 2022
Containing a codification of documents of general
applicability and future effect
As of April 1, 2022
Published by the Office of the Federal Register
National Archives and Records Administration as a
Special Edition of the Federal Register
[[Page ii]]
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[[Page iii]]
Table of Contents
Page
Explanation................................................. v
Title 21:
Chapter I--Food and Drug Administration, Department
of Health and Human Services (Continued) 3
Finding Aids:
Table of CFR Titles and Chapters........................ 629
Alphabetical List of Agencies Appearing in the CFR...... 649
List of CFR Sections Affected........................... 659
[[Page iv]]
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Cite this Code: CFR
To cite the regulations in
this volume use title,
part and section number.
Thus, 21 CFR 500.23 refers
to title 21, part 500,
section 23.
----------------------------
[[Page v]]
EXPLANATION
The Code of Federal Regulations is a codification of the general and
permanent rules published in the Federal Register by the Executive
departments and agencies of the Federal Government. The Code is divided
into 50 titles which represent broad areas subject to Federal
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parts covering specific regulatory areas.
Each volume of the Code is revised at least once each calendar year
and issued on a quarterly basis approximately as follows:
Title 1 through Title 16.................................as of January 1
Title 17 through Title 27..................................as of April 1
Title 28 through Title 41...................................as of July 1
Title 42 through Title 50................................as of October 1
The appropriate revision date is printed on the cover of each
volume.
LEGAL STATUS
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HOW TO USE THE CODE OF FEDERAL REGULATIONS
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collection request.
[[Page vi]]
Many agencies have begun publishing numerous OMB control numbers as
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``[RESERVED]'' TERMINOLOGY
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(a) The incorporation will substantially reduce the volume of
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(b) The matter incorporated is in fact available to the extent
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(c) The incorporating document is drafted and submitted for
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that volume.
[[Page vii]]
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Oliver A. Potts,
Director,
Office of the Federal Register
April 1, 2022
[[Page ix]]
THIS TITLE
Title 21--Food and Drugs is composed of nine volumes. The parts in
these volumes are arranged in the following order: Parts 1-99, 100-169,
170-199, 200-299, 300-499, 500-599, 600-799, 800-1299 and 1300 to end.
The first eight volumes, containing parts 1-1299, comprise Chapter I--
Food and Drug Administration, Department of Health and Human Services.
The ninth volume, containing part 1300 to end, includes Chapter II--Drug
Enforcement Administration, Department of Justice, and Chapter III--
Office of National Drug Control Policy. The contents of these volumes
represent all current regulations codified under this title of the CFR
as of April 1, 2022.
For this volume, Ann Worley was Chief Editor. The Code of Federal
Regulations publication program is under the direction of John Hyrum
Martinez, assisted by Stephen J. Frattini.
[[Page 1]]
TITLE 21--FOOD AND DRUGS
(This book contains parts 500 to 599)
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Part
chapter i--Food and Drug Administration, Department of
Health and Human Services (Continued)..................... 500
[[Page 3]]
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES (CONTINUED)
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Editorial Note: Nomenclature changes to chapter I appear at 69 FR
13717, Mar. 24, 2004, and 69 FR 18803, Apr. 9, 2004.
SUBCHAPTER E--ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS
Part Page
500 General..................................... 5
501 Animal food labeling........................ 15
502 Common or usual names for nonstandardized
animal foods............................ 33
507 Current good manufacturing practice, hazard
analysis, and risk-based preventive
controls for food for animals........... 34
509 Unavoidable contaminants in animal food and
food-packaging material................. 68
510 New animal drugs............................ 72
511 New animal drugs for investigational use.... 86
514 New animal drug applications................ 91
515 Medicated feed mill license................. 128
516 New animal drugs for minor use and minor
species................................. 132
520 Oral dosage form new animal drugs........... 158
522 Implantation or injectable dosage form new
animal drugs............................ 272
524 Ophthalmic and topical dosage form new
animal drugs............................ 357
526 Intramammary dosage form new animal drugs... 384
528 New animal drugs in genetically engineered
animals................................. 390
529 Certain other dosage form new animal drugs.. 391
530 Extralabel drug use in animals.............. 398
556 Tolerances for residues of new animal drugs
in food................................. 405
558 New animal drugs for use in animal feeds.... 420
564
[Reserved]
570 Food additives.............................. 550
571 Food additive petitions..................... 562
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573 Food additives permitted in feed and
drinking water of animals............... 567
579 Irradiation in the production, processing,
and handling of animal feed and pet food 593
582 Substances generally recognized as safe..... 594
584 Food substances affirmed as generally
recognized as safe in feed and drinking
water of animals........................ 618
589 Substances prohibited from use in animal
food or feed............................ 619
590-599
[Reserved]
[[Page 5]]
SUBCHAPTER E_ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS
PART 500_GENERAL--Table of Contents
Subpart A [Reserved]
Subpart B_Specific Administrative Rulings and Decisions
Sec.
500.23 Thermally processed low-acid foods packaged in hermetically
sealed containers.
500.24 Emergency permit control.
500.25 Anthelmintic drugs for use in animals.
500.26 Timed-release dosage form drugs.
500.27 Methylene blue-containing drugs for use in animals.
500.29 Gentian violet for use in animal feed.
500.30 Gentian violet for animal drug use.
500.45 Use of polychlorinated biphenyls (PCB's) in the production,
handling, and storage of animal feed.
500.46 Hexachlorophene in animal drugs.
500.50 Propylene glycol in or on cat food.
Subpart C_Animal Drug Labeling Requirements
500.51 Labeling of animal drugs; misbranding.
500.52 Use of terms such as ``tonic'', ``tone'', ``toner'', or
``conditioner'' in the labeling of preparations intended for
use in or on animals.
500.55 Exemption from certain drug-labeling requirements.
Subpart D_Requirements for Specific Animal Drugs
500.65 Epinephrine injection 1:1,000 in 10-milliliter containers for
emergency treatment of anaphylactoid shock in cattle, horses,
sheep, and swine.
Subpart E_Regulation of Carcinogenic Compounds Used in Food-Producing
Animals
500.80 Scope of this subpart.
500.82 Definitions.
500.84 Conditions for approval of the sponsored compound.
500.86 Marker residue and target tissue.
500.88 Regulatory method.
500.90 Waiver of requirements.
500.92 Implementation.
Subpart F_Methods for Detection of Residues of Carcinogenic Compounds
Used in Food-Producing Animals
500.1410 N-methyl-2-pyrrolidone.
Authority: 21 U.S.C. 321, 331, 342, 343, 348, 351, 352, 353, 360b,
371, 379e.
Source: 40 FR 13802, Mar. 27, 1975, unless otherwise noted.
Subpart A [Reserved]
Subpart B_Specific Administrative Rulings and Decisions
Sec. 500.23 Thermally processed low-acid foods packaged
in hermetically sealed containers.
Except as provided in Sec. 507.5(b) of this chapter, the provisions
of parts 507 and 113 of this chapter apply to the manufacturing,
processing, or packing of low-acid foods in hermetically sealed
containers, and intended for use as food for animals.
[80 FR 56337, Sept. 17, 2015]
Sec. 500.24 Emergency permit control.
The provisions of part 108 of this chapter shall apply to the
issuance of emergency control permits for the manufacturer or packer of
thermally processed low-acid foods packaged in hermetically sealed
containers, and intended for use as food for animals.
[61 FR 37681, July 19, 1996]
Sec. 500.25 Anthelmintic drugs for use in animals.
(a) The Commissioner of Food and Drugs has determined that, in order
to assure that anthelmintic drugs, including animal feeds bearing or
containing such drugs, which do not carry the prescription statement are
labeled to provide adequate directions for their effective use, labeling
of these anthelmintic drugs shall bear, in addition to other required
information, a statement that a veterinarian should be consulted for
[[Page 6]]
assistance in the diagnosis, treatment, and control of parasitism.
(b) The label and any labeling furnishing or purporting to furnish
directions for use, shall bear conspicuously the following statement:
``Consult your veterinarian for assistance in the diagnosis, treatment,
and control of parasitism.''
(c) For drugs covered by approved new animal drug applications, the
labeling revisions required for compliance with this section may be
placed into effect without prior approval, as provided for in Sec.
514.8(c)(3) of this chapter. For drugs listed in the index, the labeling
revisions required for compliance with this section may be placed into
effect without prior granting of a request for a modification, as
provided for in Sec. 516.161(b)(1) of this chapter.
(d) Labeling revisions required for compliance with this section
shall be placed into effect by February 25, 1975, following which, any
such drugs that are introduced into interstate commerce and not in
compliance with this section will be subject to regulatory proceedings.
[40 FR 13802, Mar. 27, 1975, as amended at 71 FR 74782, Dec. 13, 2006;
72 FR 69120, Dec. 6, 2007]
Sec. 500.26 Timed-release dosage form drugs.
(a) Drugs are being offered in dosage forms that are designed to
release the active ingredients over a prolonged period of time. There is
a possibility of unsafe overdosage or ineffective dosage if such
products are improperly made and the active ingredients are released at
one time, over too short or too long a period of time, or not released
at all. Drugs marketed in this form, which are referred to by such terms
as timed-release, controlled-release, prolonged-release, sustained-
release, or delayed-release drugs, are regarded as new animal drugs
within the meaning of section 201(v) of the Federal Food, Drug, and
Cosmetic Act.
(b) Timed-release dosage form animal drugs that are introduced into
interstate commerce are deemed to be adulterated within the meaning of
section 501(a)(5) of the act and subject to regulatory action, unless
such animal drug is the subject of an approved new animal drug
application, or listed in the index, as required by paragraph (a) of
this section.
(c) The fact that the labeling of this kind of drug may claim
delayed, prolonged, controlled, or sustained-release of all or only some
of the active ingredients does not affect the new animal drug status of
such articles. A new animal drug application or index listing is
required in any such case.
(d) New animal drug applications for timed-release dosage form
animal drugs must contain, among other things, data to demonstrate
safety and effectiveness by establishing that the article is
manufactured using procedures and controls to ensure release of the
total dosage at a safe and effective rate. Data submitted in the new
animal drug application must demonstrate that the formulation of the
drug and the procedures used in its manufacture will ensure release of
the active ingredient(s) of the drug at a safe and effective rate and
that these release characteristics will be maintained until the
expiration date of the drug. When the drug is intended for use in food-
producing animals, data submitted must also demonstrate that, with
respect to possible residues of the drug, food derived from treated
animals is safe for consumption.
[42 FR 8635, Feb. 11, 1977, as amended at 60 FR 38480, July 27, 1995; 72
FR 69120, Dec. 6, 2007]
Sec. 500.27 Methylene blue-containing drugs for use in animals.
(a) New information requires a re- evaluation of the status of drugs
containing methylene blue (tetramethylthionine chloride) for oral use in
cats or dogs.
(1)(i) It has been demonstrated that two orally administered urinary
antiseptic-antispasmodic preparations that contained methylene blue
cause Heinz body hemolytic anemia in cats when used according to label
directions. The specific cause of the reaction was determined to be the
methylene blue contained in the preparations. The reaction can be severe
enough to cause death of treated animals.
(ii) The Heinz body hemolytic anemia reaction to methylene blue has
also
[[Page 7]]
been demonstrated in dogs under laboratory conditions. The precise
mechanism by which methylene blue produces the characteristic
erythrocytic inclusion bodies (Heinz bodies) and associated hemolytic
anemia is unclear.
(2) The effectiveness of orally administered methylene blue as a
urinary antiseptic is open to question. It appears that following oral
administration, methylene blue is poorly and erratically absorbed and
also slowly and erratically excreted in the urine. Studies in the dog
indicate it is excreted in the urine essentially as leukomethylene blue
stabilized in some manner. Methylene blue itself is stepwise
demethylated in alkaline solutions (alkaline urine being a frequent
consequence of urinary infection) to Azure B, Azure A, and Azure C. The
antiseptic efficacy of all of these excretion products is
unsubstantiated.
(3) In view of the foregoing, the Commissioner has concluded that
animal drugs containing methylene blue for oral use in cats or dogs are
neither safe nor generally recognized as effective within the meaning of
section 201(v) of the act and are therefore considered new animal drugs.
Accordingly, all prior formal and informal opinions expressed by the
Food and Drug Administration that such drugs are ``not new drugs'' or
``no longer new drugs'' are hereby revoked.
(b) Animal drugs that contain methylene blue for oral use in cats or
dogs and not the subject of an approved new animal drug application
(NADA) are deemed to be adulterated under the provisions of section
501(a) (5) and/or (6) and/or misbranded under section 502(a) of the act
and subject to regulatory action as of April 10, 1978.
(c) Sponsors of animal drugs that contain methylene blue for oral
use in cats or dogs and not the subject of an approved new animal drug
application (NADA) may submit an application in conformity with Sec.
514.1 of this chapter. Such applications will be processed in accordance
with section 512 of the act. Submission of an NADA will not constitute
grounds for continued marketing of this drug substance until such
application is approved.
(d) New animal drug applications required by this regulation
pursuant to section 512 of the act shall be submitted to the Food and
Drug Administration. Center for Veterinary Medicine, Office of New
Animal Drug Evaluation (HFV-100), 7500 Standish Pl., Rockville, MD
20855.
[43 FR 9803, Mar. 10, 1978; 43 FR 12310, Mar. 24, 1978, as amended at 54
FR 18279, Apr. 28, 1989; 57 FR 6475, Feb. 25, 1992; 60 FR 38480, July
27, 1995]
Sec. 500.29 Gentian violet for use in animal feed.
The Food and Drug Administration has determined that gentian violet
is not generally recognized as safe for use in animal feed and is a food
additive subject to section 409 of the Federal Food, Drug, and Cosmetic
Act (the act), unless it is intended for use as a new animal drug, in
which case it is subject to section 512 of the act. The Food and Drug
Administration has determined that gentian violet is not prior
sanctioned for any use in animal feed.
[56 FR 40506, Aug. 15, 1991]
Sec. 500.30 Gentian violet for animal drug use.
The Food and Drug Administration (FDA) has determined that gentian
violet is not generally recognized as safe and effective for any
veterinary drug use in food animals and is a new animal drug subject to
section 512 of the Federal Food, Drug, and Cosmetic Act. FDA has
determined that gentian violet is not exempted from new animal drug
status under the ``grandfather'' provisions of the Drug Amendments of
1962 (21 U.S.C. 342).
[56 FR 40507, Aug. 15, 1991]
Sec. 500.45 Use of polychlorinated biphenyls (PCB's) in the production,
handling, and storage of animal feed.
(a) Polychlorinated biphenyls (PCB's) represent a class of toxic
industrial chemicals manufactured and sold under a variety of trade
names, including: Aroclor (United States); Phenoclor (France); Colphen
(Germany); and Kanaclor (Japan). PCB's are highly stable, heat
resistant, and nonflammable chemicals. Industrial uses of PCB's include,
or did include in the past, their
[[Page 8]]
use as electrical transformer and capacitor fluids, heat transfer
fluids, hydraulic fluids, plasticizers, and in formulations of
lubricants, coatings, and inks. Their unique physical and chemical
properties and widespread, uncontrolled industrial applications have
caused PCB's to be a persistent and ubiquitous contaminant in the
environment, causing the contamination of certain foods. In addition,
incidents have occurred in which PCB's have directly contaminated animal
feeds as a result of industrial accidents (leakage or spillage of PCB
fluids from plant equipment). These accidents in turn cause the
contamination of food intended for human consumption (meat, milk, and
eggs). Investigations by the Food and Drug Administration have revealed
that heat exchange fluids for certain pasteurization equipment used in
processing animal feed contain PCB's. Although heat exchange fluids in
such equipment are considered to be in closed systems, leakage has
occurred that resulted in direct contamination of animal feed with PCB's
and subsequently resulted in the transfer of PCB's to human food
produced by animals consuming the contaminated feed. The use of PCB-
containing coatings on the inner walls of silos has resulted in the
contamination of silage which has in turn caused PCB residues in the
milk of dairy cows consuming the contaminated silage. Since PCB's are
toxic chemicals, the PCB contamination of food as a result of these and
other incidents represent a hazard to public health. It is therefore
necessary to place certain restrictions on the industrial uses of PCB's
in the production, handling, and storage of animal feed.
(b) The following special provisions are necessary to preclude
accidental PCB contamination of animal feed:
(1) Coatings or paints for use on the contact surfaces of feed
storage areas may not contain PCB's or any other harmful or deleterious
substances likely to contaminate feed.
(2) New equipment or machinery for handling or processing feed in or
around an establishment producing animal feed shall not contain PCB's.
(3) On or before Sept. 4, 1973, the management of establishments
producing animal feed shall:
(i) Have the heat exchange fluid used in existing equipment or
machinery for handling and processing feed sampled and tested to
determine whether it contains PCB's, or verify the absence of PCB's in
such formulations by other appropriate means. On or before Sept. 4,
1973, any such fluid formulated with PCB's must to the fullest extent
possible commensurate with current good manufacturing practices, be
replaced with a heat exchange fluid that does not contain PCB's.
(ii) Eliminate to the fullest extent possible commensurate with
current good manufacturing practices from the animal feed producing
establishment any PCB-containing lubricants for equipment or machinery
used for handling or processing animal feed.
(iii) Eliminate to the fullest extent possible commensurate with
current good manufacturing practices from the animal feed producing
establishment any other PCB-containing materials, whenever there is a
reasonable expectation that such materials could cause animal feed to
become contaminated with PCB's either as a result of normal use or as a
result of accident, breakage, or other mishap.
(iv) The toxicity and other characteristics of fluids selected as
PCB replacements must be adequately determined so that the least
potentially hazardous replacement should be used. In making this
determination with respect to a given fluid, consideration should be
given to (a) its toxicity; (b) the maximum quantity that could be
spilled onto a given quantity of food before it would be noticed, taking
into account its color and odor; (c) possible signaling devices in the
equipment to indicate a loss of fluid, etc.; (d) and its environmental
stability and tendency to survive and be concentrated through the food
chain. The judgment as to whether a replacement fluid is sufficiently
non-hazardous is to be made on an individual installation and operation
basis.
(c) For the purpose of this section, the provisions do not apply to
electrical transformers and condensers containing PCB's in sealed
containers.
[[Page 9]]
(d) For the purpose of this section, the term animal feed includes
all articles used for food or drink for animals other than man.
Sec. 500.46 Hexachlorophene in animal drugs.
(a) The Commissioner of Food and Drugs has determined that there are
no adequate data to establish that animal drugs containing
hexachlorophene are safe and effective for any animal use other than in
topical products for use on non-food-producing animals as part of a
product preservative system at a level not to exceed 0.1 percent; that
there is no information on the potential risk to humans from exposure to
hexachlorophene by persons who apply animal products containing the drug
at levels higher than 0.1 percent; and that there is likewise no
information on human exposure to animals on which these animal drugs
have been used and no information on possible residues of
hexachlorophene in edible products of food-producing animals treated
with new animal drugs that contain any quantity of hexachlorophene.
(b) Animal drugs containing hexachlorophene for other than
preservative use on non-food-producing animals at levels not exceeding
0.1 percent are considered new animal drugs and shall be the subject of
new animal drug applications (NADA's).
(c) Any person currently marketing animal drugs that contain
hexachlorophene other than as part of a product preservative system for
products used on non-food-producing animals at a level not exceeding 0.1
percent shall submit a new animal drug application, supplement an
existing application, or reformulate the product by September 29, 1977.
Each application or supplemental application shall include adequate data
to establish that the animal drug is safe and effective. If the animal
drug is currently subject to an approved new animal drug application,
each reformulation shall require an approved supplemental application.
The interim marketing of these animal drugs may continue until the
application has been approved, until it has been determined that the
application is not approvable under the provisions of Sec. 514.111 of
this chapter, or until an existing approved application has been
withdrawn.
(d) After September 29, 1977, animal drugs that contain
hexachlorophene other than for preservative use on non-food-producing
animals at a level not exceeding 0.1 percent that are introduced into
interstate commerce shall be deemed to be adulterated within the meaning
of section 501(a)(5) of the act (21 U.S.C. 351(a)(5)) unless such animal
drug is the subject of a new animal drug application submitted pursuant
to paragraph (c) of this section. Action to withdraw approval of new
animal drug applications will be initiated if supplemental new animal
drug applications have not been submitted in accordance with this
section.
(e) New animal drug applications submitted for animal drugs
containing hexachlorophene for use in or on food-producing animals shall
include adequate data to assure that edible products from treated
animals are safe for human consumption under the labeled conditions of
use.
[42 FR 33725, July 1, 1977; 42 FR 37975, July 26, 1977]
Sec. 500.50 Propylene glycol in or on cat food.
The Food and Drug Administration has determined that propylene
glycol in or on cat food is not generally recognized as safe and is a
food additive subject to section 409 of the Federal Food, Drug, and
Cosmetic Act (the act). The Food and Drug Administration also has
determined that this use of propylene glycol is not prior sanctioned.
[61 FR 19544, May 2, 1996]
Subpart C_Animal Drug Labeling Requirements
Sec. 500.51 Labeling of animal drugs; misbranding.
(a) Among the representations on the label or labeling of an animal
drug which will render the drug misbranded are any broad statements
suggesting or implying that the drug is not safe and effective for use
when used in accordance with labeling direction, or suggesting or
implying that the labeling does not contain adequate warnings or
[[Page 10]]
adequate directions for use. Such statements include, but are not
limited to:
(1) Any statement that disclaims liability when the drug is used in
accordance with directions for use contained on the label or labeling.
(2) Any statement that disclaims liability when the drug is used
under ``abnormal'' or ``unforeseeable'' conditions.
(3) Any statement limiting the warranty for the products to a
warranty that the drug in the package contains the ingredients listed on
the label.
(b) This regulation is not intended to prohibit any liability
disclaimer that purports to limit the amount of damages or that sets
forth the legal theory under which damages are to be recovered.
(c) Any person wishing to obtain an evaluation of an animal drug
liability disclaimer under this regulation may submit it to Division of
Compliance, (HFV-230), Center for Veterinary Medicine, Food and Drug
Administration, 7500 Standish Pl., Rockville, MD 20855. A supplemental
NADA providing appropriately revised labeling shall be submitted for any
approved new animal drug the labeling of which is not in compliance with
this regulation.
[41 FR 8473, Feb. 27, 1976, as amended at 54 FR 18279, Apr. 28, 1989; 57
FR 6475, Feb. 25, 1992]
Sec. 500.52 Use of terms such as ``tonic'', ``tone'', ``toner'',
or ``conditioner'' in the labeling of preparations intended for use
in or on animals.
(a) The use of terms such as tonic, tone, toner, and similar terms
in the labeling of a product intended for use in or on animals implies
that such product is capable of a therapeutic effect(s) and causes such
a product to be a drug within the meaning of section 201(g) of the
Federal Food, Drug, and Cosmetic Act. The unqualified use of such terms
in a product's labeling fails to provide adequate directions and
indications for use of such product and causes it to be misbranded
within the meaning of section 502(a) and (f)(1) of the act. The terms
tonic, tone, toner, and similar terms may be used in labeling only when
appropriately qualified so as to fully inform the user regarding the
intended use(s) of the product.
(b) The unqualified use of the term conditioner and similar terms in
the labeling of a product intended for use in or on animals implies that
such product is capable of a therapeutic effect(s) and causes such a
product to be a drug within the meaning of section 201(g) of the act.
The unqualified use of such terms in a product's labeling fails to
provide adequate directions and indications for use of such product and
causes it to be misbranded within the meaning of section 502(a) and
(f)(1) of the act. The term conditioner and similar terms may be used in
labeling only when appropriately qualified so as to fully inform the
user regarding the intended use(s) of the product. A product labeled as
a ``conditioner'' or with a similar term can be either a food or drug
depending upon the manner in which the term is qualified in the labeling
to reflect the product's intended use.
(c) An article so qualified as to be represented as a drug must be
the subject of an approved new animal drug application unless the use of
the article under the conditions set forth in its labeling is generally
recognized as safe and effective among experts qualified by scientific
training and experience to evaluate the safety and effectiveness of
animal drugs.
Sec. 500.55 Exemption from certain drug-labeling requirements.
(a) Section 201.105(c) of this chapter provides that in the case of
certain drugs for which directions, hazards, warnings, and use
information are commonly known to practitioners licensed by law, such
information may be omitted from the dispensing package. Under this
proviso, the Commissioner of Food and Drugs will offer an opinion, upon
written request, stating reasonable grounds therefore on a proposal to
omit such information from the dispensing package.
(b) The Commissioner of Food and Drugs has considered submitted
material covering a number of drug products and has offered the opinion
that the following drugs when intended for those veterinary uses for
which they are now generally employed by the veterinary medical
profession, should be exempt from the requirements of
[[Page 11]]
Sec. 201.105(c) of this chapter, provided that they meet the conditions
prescribed in this paragraph. Preparations that are not in dosage unit
form (for example, solutions) will be regarded as meeting the conditions
with respect to the maximum quantity of drug per dosage unit if they are
prepared in a manner that enables accurate and ready administration of a
quantity of drug not in excess of the stated maximum per dosage unit:
Atropine sulfate. As an injectable for cattle, goats, horses, pigs, and
sheep, not in excess of 15 milligrams per dosage unit; as an injectable
for cats and dogs, not in excess of 0.6 milligram per dosage unit.
Barbital sodium. For oral use in cats and dogs, not in excess of 300
milligrams per dosage unit.
Epinephrine injection. 1:1,000. For cats, dogs, cattle, goats, horses,
pigs, and sheep (except as provided in Sec. 500.65).
Morphine sulfate. As an injectable for dogs, not in excess of 15
milligrams per dosage unit.
Pentobarbital sodium. For oral use in cats and dogs, not in excess of
100 milligrams per dosage unit.
Phenobarbital sodium. For oral use in cats and dogs, not in excess of
100 milligrams per dosage unit.
Procaine hydrochloride injection. Containing not in excess of 2 percent
procaine hydrochloride, with or without epinephrine up to a
concentration of 1:50,000. For use in cats, dogs, cattle, goats, horses,
pigs, and sheep.
Thyroid. For oral use in dogs, not in excess of 60 milligrams per dosage
unit.
Subpart D_Requirements for Specific Animal Drugs
Sec. 500.65 Epinephrine injection 1:1,000 in 10-milliliter containers
for emergency treatment of anaphylactoid shock in cattle, horses, sheep,
and swine.
(a) Anaphylactoid reactions in cattle, horses, sheep, and swine
occur occasionally from the injection of antibiotics, bacterins, and
vaccines. Adequate directions for use of these antibiotics, bacterins,
and vaccines can generally be written for use by the laity and thus are
available to livestock producers. Epinephrine injection is effective for
the treatment of anaphylactoid reactions in animals and would be of
value in saving lives of animals if it were readily available at the
time of administration of the causative agents. In connection with this
problem the Food and Drug Administration has obtained the views of the
Advisory Committee on Veterinary Medicine, and other experts, and has
concluded that adequate directions for over-the-counter sale of
epinephrine injection 1:1,000 can be prepared.
(b) In view of the above, the Commissioner of Food and Drugs has
concluded that it is in the public interest to make epinephrine
injection 1:1,000 available for sale without a prescription provided
that it is packaged in vials not exceeding 10 milliliters and its label
bears, in addition to other required information, the following
statements in a prominent and conspicuous manner: ``For emergency use
only in treating anaphylactoid shock. Usual Dosage: Cattle, horses,
sheep, and swine--1 cubic centimeter per 100 pounds of body weight.
Inject subcutaneously''.
(c) The labeling must also bear a description of the symptoms of
anaphylactoid shock including glassy eyes, increased salivation,
grinding of the teeth, rapid breathing, muscular tremors, staggering
gait, and collapse with death following. These symptoms may appear
shortly after injection of a bacterin, vaccine, or antibiotic.
Subpart E_Regulation of Carcinogenic Compounds Used in Food-Producing
Animals
Source: 52 FR 49586, Dec. 31, 1987, unless otherwise noted.
Sec. 500.80 Scope of this subpart.
(a) The Federal Food, Drug, and Cosmetic Act requires that sponsored
compounds intended for use in food-producing animals be shown to be safe
and that food produced from animals exposed to these compounds be shown
to be safe for consumption by people. The statute prohibits the use in
food-producing animals of any compound found to induce cancer when
ingested by people or animals unless it can be determined by methods of
examination prescribed or approved by the Secretary (a function
delegated to the Commissioner of Food and Drugs) that no residue of that
compound will be found in the food produced from those animals
[[Page 12]]
under conditions of use reasonably certain to be followed in practice.
This subpart identifies the steps a sponsor of a compound shall follow
to secure the approval of the compound. The requirements of this subpart
shall also apply to a request for an import tolerance under Sec.
510.205 of this chapter. FDA guidance documents contain the procedures
and protocols FDA recommends for the implementation of this subpart.
These guidance documents are available from the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852. Requests for these guidance documents
should be identified with Docket No. 1983D-0288.
(b) If FDA concludes on the basis of the threshold assessment that a
sponsor shall conduct carcinogenicity testing on the sponsored compound,
FDA will also determine whether and to what extent the sponsor shall
conduct carcinogenicity testing on metabolites of the sponsored
compound. The bioassays that a sponsor conducts must be designed to
assess carcinogenicity and to determine the quantitative aspects of any
carcinogenic response.
(c) If FDA concludes on the basis of the threshold assessment or at
a later time during the approval process or during the review of a
request for an import tolerance that the data show that the sponsored
compound and its metabolites should not be subject to this subpart, FDA
will continue to consider the compound for approval under the general
safety provisions of the Federal Food, Drug, and Cosmetic Act for risks
other than cancer or continue its review of the import tolerance request
under the provisions of Sec. Sec. 510.201 through 510.213 of this
chapter (Subpart C--Import Tolerances for Residues of Unapproved New
Animal Drugs in Food).
(d) This subpart does not apply to essential nutrients.
[52 FR 49586, Dec. 31, 1987, as amended at 59 FR 14365, Mar. 28, 1994;
62 FR 66983, Dec. 23, 1997; 65 FR 56480, Sept. 19, 2000; 67 FR 78174,
Dec. 23, 2002; 68 FR 24879, May 9, 2003; 69 FR 17292, Apr. 2, 2004; 86
FR 52410, Sept. 21, 2021]
Sec. 500.82 Definitions.
(a) The definitions and interpretations contained in section 201 of
the act apply to those terms when used in this subpart.
(b) The following definitions apply to this subpart:
Act means the Federal Food, Drug, and Cosmetic Act (sections 201-
901, 52 Stat. 1040 et seq. as amended (21 U.S.C. 301-392)).
Essential nutrients means compounds that are found in the tissues of
untreated, healthy target animals and not produced in sufficient
quantity to support the animal's growth, development, function, or
reproduction, e.g., vitamins, essential minerals, essential amino acids,
and essential fatty acids. These compounds must be supplied from
external sources.
FDA means the Food and Drug Administration.
Limit of detection (LOD) means the lowest concentration of analyte
that can be confirmed by the approved regulatory method.
Marker residue means the residue selected for assay whose
concentration is in a known relationship to the concentration of the
residue of carcinogenic concern in the last tissue to deplete to its
Sm.
No residue means the marker residue is below the limit of detection
using the approved regulatory method. The ``no residue'' designation
applies only to compounds of carcinogenic concern.
Preslaughter withdrawal period or milk discard time means the time
after cessation of administration of the sponsored compound at which no
residue is detectable in the edible product using the approved
regulatory method (i.e., the marker residue is below the LOD).
Regulatory method means the aggregate of all experimental procedures
for measuring and confirming the presence of the marker residue of the
sponsored compound in the target tissue of the target animal.
Rm means the concentration of the marker residue in the
target tissue when the residue of carcinogenic concern is equal to
Sm.
Residue means any compound present in edible tissues of the target
animal
[[Page 13]]
which results from the use of the sponsored compound, including the
sponsored compound, its metabolites, and any other substances formed in
or on food because of the sponsored compound's use.
Residue of carcinogenic concern means all compounds in the total
residue of a demonstrated carcinogen excluding any compounds judged by
FDA not to present a carcinogenic risk.
Sm means the concentration of a residue of carcinogenic concern in a
specific edible tissue corresponding to no significant increase in the
risk of cancer to the human consumer. For the purpose of Sec.
500.84(c)(1), FDA will assume that this Sm will correspond to
the concentration of residue in a specific edible tissue that
corresponds to a maximum lifetime risk of cancer in the test animals of
1 in 1 million.
So means the concentration of a residue of carcinogenic concern in
the total human diet that represents no significant increase in the risk
of cancer to the human consumer. For the purpose of Sec. 500.84(c)(1),
FDA will assume that this So will correspond to the
concentration of test compound in the total diet of test animals that
corresponds to a maximum lifetime risk of cancer in the test animals of
1 in 1 million.
Sponsor means the person or organization proposing or holding an
approval by FDA for the use of a sponsored compound or the person
initiating a request for an import tolerance under Sec. 510.205 of this
chapter.
Sponsored compound means any drug or food additive or color additive
proposed for use, or used, in food-producing animals or in their feed.
Target animals means the production class of animals in which a
sponsored compound is proposed or intended for use.
Target tissue means the edible tissue selected to monitor for
residues in the target animals, including, where appropriate, milk or
eggs.
Test animals means the species selected for use in the toxicity
tests.
Threshold assessment means FDA's review of data and information
about a sponsored compound to determine whether chronic bioassays in
test animals are necessary to resolve questions concerning the
carcinogenicity of the compound.
[52 FR 49586, Dec. 31, 1987, as amended at 67 FR 78174, Dec. 23, 2002;
77 FR 50593, Aug. 22, 2012; 84 FR 32992, July 11, 2019; 86 FR 52410,
Sept. 21, 2021]
Sec. 500.84 Conditions for approval of the sponsored compound.
(a) On the basis of the results of the chronic bioassays and other
information, FDA will determine whether any of the substances tested are
carcinogenic.
(b) If FDA concludes that the results of the bioassays do not
establish carcinogenicity, then FDA will not subject the sponsored
compound to the remainder of the requirements of this subpart.
(c) For each sponsored compound that FDA decides should be regulated
as a carcinogen, FDA will either analyze the data from the bioassays
using a statistical extrapolation procedure as outlined in paragraph
(c)(1) of this section or evaluate an alternate procedure proposed by
the sponsor as provided in Sec. 500.90. In either case, paragraphs
(c)(2) and (3) of this section apply.
(1) For each substance tested in separate bioassays, FDA will
calculate the concentration of the residue of carcinogenic concern that
corresponds to a maximum lifetime risk to the test animal of 1 in 1
million. FDA will designate the lowest value obtained as So.
Because the total diet is not derived from food-producing animals, FDA
will make corrections for food intake. FDA will designate as
Sm the concentration of residue in a specific edible tissue
corresponding to a maximum lifetime risk of cancer in test animals of 1
in 1 million.
(2) From the appropriate residue chemistry data FDA will calculate
the Rm as described in Sec. 500.86(c). The sponsor must
provide a regulatory method in accordance with Sec. 500.88(b). FDA will
calculate the LOD of the method from data submitted by the sponsor under
Sec. 500.88. The LOD must be less than or equal to Rm.
(3) FDA will conclude that the provisions of this subpart are
satisfied when no residue of the compound is detectable (that is, the
marker residue is
[[Page 14]]
below the LOD) using the approved regulatory method under the conditions
of use of the sponsored compound, including any required preslaughter
withdrawal period or milk discard time.
[52 FR 49586, Dec. 31, 1987, as amended at 67 FR 78174, Dec. 23, 2002;
77 FR 50593, Aug. 22, 2012]
Sec. 500.86 Marker residue and target tissue.
(a) For each edible tissue, the sponsor shall measure the depletion
of the residue of carcinogenic concern until its concentration is at or
below Sm.
(b) In one or more edible tissues, the sponsor shall also measure
the depletion of one or more potential marker residues until the
concentration of the residue of carcinogenic concern is at or below
Sm.
(c) From these data, FDA will select a target tissue and a marker
residue and designate the concentration of marker residue
(Rm) that the regulatory method must be capable of measuring
in the target tissue. FDA will select Rm such that the
absence of the marker residue in the target tissue above Rm
can be taken as confirmation that the residue of carcinogenic concern
does not exceed Sm in each of the edible tissues and,
therefore, that the residue of carcinogenic concern in the diet of
people does not exceed So.
(d) When a compound is to be used in milk- or egg-producing animals,
milk or eggs must be the target tissue in addition to the tissue
selected to monitor for residues in the edible carcass.
(Approved by the Office of Management and Budget under control number
0910-0228)
Sec. 500.88 Regulatory method.
(a) The sponsor shall submit for evaluation and validation a
regulatory method developed to monitor compliance with FDA's operational
definition of no residue.
(b) The regulatory method must be able to confirm the identity of
the marker residue in the target tissue at a minimum concentration
corresponding to the Rm. FDA will determine the LOD from the
submitted analytical method validation data.
(c) FDA will publish in the Federal Register the complete regulatory
method for ascertaining the marker residue in the target tissue in
accordance with the provisions of sections 409(c)(3)(A), 512(d)(1)(I),
and 721(b)(5)(B) of the act.
(d) If the sponsor initially submitted a request for an import
tolerance under Sec. 510.205 of this chapter, FDA will make the
complete regulatory method for ascertaining the marker residue in the
target tissue publicly available pursuant to Sec. 510.207(b) of this
chapter.
(Approved by the Office of Management and Budget under control number
0910-0228)
[52 FR 49586, Dec. 31, 1987, as amended at 67 FR 78174, Dec. 23, 2002;
86 FR 52410, Sept. 21, 2021]
Sec. 500.90 Waiver of requirements.
In response to a petition or on the Commissioner's own initiative,
the Commissioner may waive, in whole or in part, the requirements of
this subpart except those provided under Sec. 500.88. A petition for
this waiver may be filed by any person who would be adversely affected
by the application of the requirements to a particular compound. The
petition shall explain and document why the requirements from which a
waiver is requested are not reasonably applicable to the compound, and
set forth clearly the reasons why the alternative procedures will
provide the basis for concluding that approval of the compound satisfies
the requirements of the anticancer provisions of the act. If the
Commissioner determines that waiver of any of the requirements of this
subpart is appropriate, the Commissioner will state the basis for that
determination in the regulation approving marketing of the sponsored
compound.
(Approved by the Office of Management and Budget under control number
0910-0228)
Sec. 500.92 Implementation.
(a) This subpart E applies to all new animal drug applications, food
additive petitions, color additive petitions, and requests for import
tolerances concerning any compound intended for use in food-producing
animals (including supplemental applications and amendments to
petitions).
(b) This subpart E also applies in the following manner to compounds
already approved:
[[Page 15]]
(1) For those compounds that FDA determines may induce cancer when
ingested by man or animals, i.e., suspect carcinogens, Sec. Sec.
500.80(b), 500.82, and 500.90 apply.
(2) For those compounds that FDA determines have been shown to
induce cancer when ingested by man or animals, Sec. Sec. 500.82 through
500.90 apply.
[52 FR 49586, Dec. 31, 1987, as amended at 86 FR 52410, Sept. 21, 2021]
Subpart F_Methods for Detection of Residues of Carcinogenic Compounds
Used in Food-Producing Animals
Source: 76 FR 72618, Nov. 25, 2011, unless otherwise noted.
Sec. 500.1410 N-methyl-2-pyrrolidone.
(a) Standard for residues. No residues of n-methyl-2-pyrrolidone may
be found in the uncooked edible tissues of cattle and swine as
determined by methods in paragraph (b) of this section.
(b) Incorporation by reference. The standards required in this
section are incorporated by reference into this section with the
approval of the Director of the Federal Register under 5 U.S.C. 552(a)
and 1 CFR part 51. All approved material is available for inspection at
the Food and Drug Administration's Dockets Management Staff (HFA-305),
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500, between
9 a.m. and 4 p.m., Monday through Friday. It may be obtained from the
sources indicated elsewhere in paragraph (b) of this section and at:
https://www.fda.gov/about-fda/center-veterinary-medicine/cvm-foia-
electronic-reading-room. It is also available for inspection at the
National Archives and Records Administration (NARA). For information on
the availability of this material at NARA, email [email protected],
or go to: www.archives.gov/federal-register /cfr/ibr-locations.html.
(1) Food and Drug Administration, Center for Veterinary Medicine,
7500 Standish Pl., Rockville, MD 20855, 240-402-7002.
(i) ``Method of Analysis: N-methyl-2-pyrrolidone,'' September 26,
2011; the method of analysis for uncooked edible tissues of cattle.
(ii) [Reserved]
(2) Merck Animal Health, 29160 Intervet Lane, Millsboro, DE 19966,
1-800-211-3573.
(i) ``Determinative and Confirmatory Procedures for the Analysis of
N-Methyl-2-pyrrolidone (NMP) in Swine Liver Tissue using LC-MS/MS,''
July 20, 2017; the method of analysis for uncooked edible tissues of
swine.
(ii) [Reserved]
(c) Related conditions of use. See Sec. Sec. 522.814 and 522.955 of
this chapter.
[87 FR 10966, Feb. 28, 2022]
PART 501_ANIMAL FOOD LABELING--Table of Contents
Subpart A_General Provisions
Sec.
501.1 Principal display panel of package form animal food.
501.2 Information panel of package for animal food.
501.3 Identity labeling of animal food in package form.
501.4 Animal food; designation of ingredients.
501.5 Animal food; name and place of business of manufacturer, packer,
or distributor.
501.8 Labeling of animal food with number of servings.
501.15 Animal food; prominence of required statements.
501.17 Animal food labeling warning statements.
501.18 Misbranding of animal food.
Subpart B_Specific Animal Food Labeling Requirements
501.22 Animal foods; labeling of spices, flavorings, colorings, and
chemical preservatives.
Subparts C-E [Reserved]
Subpart F_Exemptions From Animal Food Labeling Requirements
501.100 Animal food; exemptions from labeling.
501.103 Petitions requesting exemptions from or special requirements for
label declaration of ingredients.
501.105 Declaration of net quantity of contents when exempt.
501.110 Animal feed labeling; collective names for feed ingredients.
[[Page 16]]
Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342, 343,
348, 371.
Source: 41 FR 38619, Sept. 10, 1976, unless otherwise noted.
Subpart A_General Provisions
Sec. 501.1 Principal display panel of package form animal food.
The term principal display panel as it applies to food in package
form and as used in this part, means the part of a label that is most
likely to be displayed, presented, shown, or examined under customary
conditions of display for retail sale. The principal display panel shall
be large enough to accommodate all the mandatory label information
required to be placed thereon by this part with clarity and
conspicuousness and without obscuring design, vignettes, or crowding.
Where packages bear alternate principal display panels, information
required to be placed on the principal display panel shall be duplicated
on each principal display panel. For the purpose of obtaining uniform
type size in declaring the quantity of contents for all packages of
substantially the same size, the term area of the principal display
panel means the area of the side or surface that bears the principal
display panel, which area shall be:
(a) In the case of a rectangular package where one entire side
properly can be considered to be the principal display panel side, the
product of the height times the width of that side;
(b) In the case of a cylindrical or nearly cylindrical container, 40
percent of the product of the height of the container times the
circumference;
(c) In the case of any otherwise shaped container, 40 percent of the
total surface of the container: Provided, however, That where such
container presents an obvious principal display panel such as the top of
a triangular or circular package, the area shall consist of the entire
top surface. In determining the area of the principal display panel,
exclude tops, bottoms, flanges at tops and bottoms of cans, and
shoulders and necks of bottles or jars. In the case of cylindrical or
nearly cylindrical containers, information required by this part to
appear on the principal display panel shall appear within that 40
percent of the circumference which is most likely to be displayed,
presented, shown, or examined under customary conditions of display for
retail sale.
Sec. 501.2 Information panel of package for animal food.
(a) The term information panel as it applies to packaged food means
that part of the label immediately contiguous and to the right of the
principal display panel as observed by an individual facing the
principal display panel with the following exceptions:
(1) If the part of the label immediately contiguous and to the right
of the principal display panel is too small to accommodate the necessary
information or is otherwise unusable label space, e.g., folded flaps or
can ends, the panel immediately contiguous and to the right of this part
of the label may be used.
(2) If the package has one or more alternate principal display
panels, the information panel is immediately contiguous and to the right
of any principal display panel.
(3) If the top of the container is the principal display panel and
the package has no alternate principal display panel, the information
panel is any panel adjacent to the principal display panel.
(b) All information required to appear on the label of any package
of food pursuant to Sec. Sec. 501.4, 501.5, 501.8 and 501.17 shall
appear either on the principal display panel or on the information
panel, unless otherwise specified by regulations in this chapter.
(c) All information appearing on the principal display panel or the
information panel pursuant to this section shall appear prominently and
conspicuously, but in no case may the letters and/or numbers be less
than \1/16\ inch in height unless an exemption pursuant to paragraph (f)
of this section is established. The requirements for conspicuousness and
legibility shall include the specifications of Sec. Sec. 501.15 and
501.105(h) (1) and (2).
(1) Packaged foods are exempt from the type size requirements of
this paragraph: Provided, That:
(i) The package is designed such that it has a surface area that can
bear an
[[Page 17]]
information panel and/or an alternate principal display panel.
(ii) The area of surface available for labeling on the principal
display panel of the package as this term is defined in Sec. 501.1 is
less than 10 square inches.
(iii) The label information includes a full list of ingredients in
accordance with regulations in this part.
(iv) The information required by paragraph (b) of this section
appears on the principal display panel or information panel label in
accordance with the provisions of this paragraph (c) except that the
type size is not less than \3/64\ inch in height.
(2) Packaged foods are exempt from the type size requirements of
this paragraph: Provided, That:
(i) The package is designed such that it has a single obvious
principal display panel as this term is defined in Sec. 501.1 and has
no other available surface area for an information panel or alternate
principal display panel.
(ii) The area of surface available for labeling on the principal
display panel of the package as this term is defined in Sec. 501.1 is
less than 12 square inches and bears all labeling appearing on the
package.
(iii) The label information includes a full list of ingredients in
accordance with regulations in this part.
(iv) The information required by paragraph (b) of this section
appears on the single, obvious principal display panel in accordance
with the provisions of this paragraph (c) except that the type size is
not less than \1/32\ inch in height.
(3) Packaged foods are exempt from the type size requirements of
this paragraph: Provided, That:
(i) The package is designed such that it has a total surface area
available to bear labeling of less than 12 square inches.
(ii) The label information includes a full list of ingredients in
accordance with regulations in this part.
(iii) The information required by paragraph (b) of this section
appears on the principal display panel or information panel label in
accordance with the provisions of this paragraph (c) except that the
type size is not less than \1/32\ inch in height.
(d) All information required to appear on the principal display
panel or on the information panel pursuant to this section shall appear
on the same panel unless there is insufficient space. In determining the
sufficiency of the available space, any vignettes, design, and other
nonmandatory label information shall not be considered. If there is
insufficient space for all of this information to appear on a single
panel, it may be divided between these two panels except that the
information required pursuant to any given section or part shall all
appear on the same panel. A food whose label is required to bear the
ingredient statement on the principal display panel may bear all other
information specified in paragraph (b) of this section on the
information panel.
(e) All information appearing on the information panel pursuant to
this section shall appear in one place without other intervening
material.
(f) If the label of any package of food is too small to accommodate
all of the information required by Sec. Sec. 501.4, 501.5, 501.8, and
501.17, the Commissioner may establish by regulation an acceptable
alternative method of disseminating such information to the public,
e.g., a type size smaller than one-sixteenth inch in height, or labeling
attached to or inserted in the package or available at the point of
purchase. A petition requesting such a regulation, as an amendment to
this paragraph shall be submitted pursuant to part 10 of this chapter.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 4716, Jan. 25, 1977;
42 FR 15675, Mar. 22, 1977]
Sec. 501.3 Identity labeling of animal food in package form.
(a) The principal display panel of a food in package form shall bear
as one of its principal features a statement of the identity of the
commodity.
(b) Such statement of identity shall be in terms of:
(1) The name now or hereafter specified in or required by any
applicable Federal law or regulation; or, in the absence thereof,
(2) The common or usual name of the food; or, in the absence
thereof,
[[Page 18]]
(3) An appropriately descriptive term, or when the nature of the
food is obvious, a fanciful name commonly used by the public for such
food.
(c) Where a food is marketed in various optional forms (whole,
slices, diced, etc.), the particular form shall be considered to be a
necessary part of the statement of identity and shall be declared in
letters of a type size bearing a reasonable relation to the size of the
letters forming the other components of the statement of identity;
except that if the optional form is visible through the container or is
depicted by an appropriate vignette, the particular form need not be
included in the statement. This specification does not affect the
required declarations of identity under definitions and standards for
foods promulgated pursuant to section 401 of the act.
(d) This statement of identity shall be presented in bold type on
the principal display panel, shall be in a size reasonably related to
the most prominent printed matter on such panel, and shall be in lines
generally parallel to the base on which the package rests as it is
designed to be displayed.
(e) Under the provisions of section 403(c) of the Federal Food,
Drug, and Cosmetic Act, a food shall be deemed to be misbranded if it is
an imitation of another food unless its label bears, in type of uniform
size and prominence, the word imitation and, immediately thereafter, the
name of the food imitated.
(1) A food shall be deemed to be an imitation and thus subject to
the requirements of section 403(c) of the act if it is a substitute for
and resembles another food but is nutritionally inferior to that food.
(2) A food that is a substitute for and resembles another food shall
not be deemed to be an imitation provided it meets each of the following
requirements:
(i) It is not nutritionally inferior to the food for which it
substitutes and which it resembles.
(ii) Its label bears a common or usual name that complies with the
provisions of Sec. 502.5 of this chapter and that is not false or
misleading, or in the absence of an existing common or usual name, an
appropriately descriptive term that is not false or misleading. The
label may, in addition, bear a fanciful name which is not false or
misleading.
(3) A food for which a common or usual name is established by
regulation (e.g., in a standard of identity pursuant to section 401 of
the act, in a common or usual name regulation and may, in addition, bear
a fanciful name which is not false or misleading, and established
pursuant to part 502 of this chapter), and which complies with all of
the applicable requirements of such regulation(s), shall not be deemed
to be an imitation.
(4) Nutritional inferiority includes:
(i) Any reduction in the content of an essential nutrient that is
present in a measurable amount.
(ii) If the Commissioner concludes that a food is a substitute for
and resembles another food but is inferior to the food imitated for
reasons other than those set forth in this paragraph, he may propose
appropriate revisions to this regulation or he may propose a separate
regulation governing the particular food.
(f) A label may be required to bear the percentage(s) of a
characterizing ingredient(s) or information concerning the presence or
absence of an ingredient(s) or the need to add an ingredient(s) as part
of the common or usual name of the food pursuant to part 502 of this
chapter.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 14091, Mar. 15, 1977;
54 FR 18279, Apr. 28, 1989]
Sec. 501.4 Animal food; designation of ingredients.
(a) Ingredients required to be declared on the label of a food,
including foods that comply with standards of identity that require
labeling in compliance with this part 501, except those exempted by
Sec. 501.100, shall be listed by common or usual name in descending
order of predominance by weight on either the principal display panel or
the information panel in accordance with the provisions of Sec. 501.2.
(b) The name of an ingredient shall be a specific name and not a
collective (generic) name, except that:
[[Page 19]]
(1) Spices, flavorings, colorings and chemical preservatives shall
be declared according to the provisions of Sec. 501.22.
(2) An ingredient which itself contains two or more ingredients and
which has an established common or usual name, conforms to a standard
established pursuant to the Meat Inspection or Poultry Products
Inspection Acts by the U.S. Department of Agriculture, or conforms to a
definition and standard of identity established pursuant to section 401
of the Federal Food, Drug, and Cosmetic Act, shall be designated in the
statement of ingredients on the label of such food by either of the
following alternatives:
(i) By declaring the established common or usual name of the
ingredient followed by a parenthetical listing of all ingredients
contained therein in descending order of predominance except that, if
the ingredient is a food subject to a definition and standard of
identity established in this subchapter E, only the ingredients required
to be declared by the definition and standard of identity need be
listed; or
(ii) By incorporating into the statement of ingredients in
descending order of predominance in the finished food, the common or
usual name of every component of the ingredient without listing the
ingredient itself.
(3) Skim milk, concentrated skim milk, reconstituted skim milk, and
nonfat dry milk may be declared as skim milk or nonfat milk.
(4) Milk, concentrated milk, reconstituted milk, and dry whole milk
may be declared as milk.
(5) Bacterial cultures may be declared by the word cultured followed
by the name of the substrate, e.g., made from cultured skim milk or
cultured buttermilk.
(6) Sweetcream buttermilk, concentrated sweetcream buttermilk,
reconstituted sweetcream buttermilk, and dried sweetcream buttermilk may
be declared as buttermilk.
(7) Whey, concentrated whey, reconstituted whey, and dried whey may
be declared as whey.
(8) Cream, reconstituted cream, dried cream, and plastic cream
(sometimes known as concentrated milkfat) may be declared as cream.
(9) Butteroil and anhydrous butterfat may be declared as butterfat.
(10) Dried whole eggs, frozen whole eggs, and liquid whole eggs may
be declared as eggs.
(11) Dried egg whites, frozen egg whites, and liquid egg whites may
be declared as egg whites.
(12) Dried egg yolks, frozen egg yolks, and liquid egg yolks may be
declared as egg yolks.
(13) A livestock or poultry feed may be declared by a collective
name listed in Sec. 501.110 if it is an animal feed within the meaning
of section 201(w) of the act and meets the requirements for the use of a
collective name as prescribed in Sec. 501.110 for certain feed
ingredients.
(14) [Reserved]
(15) When all the ingredients of a wheat flour are declared in an
ingredient statement, the principal ingredient of the flour shall be
declared by the name(s) specified in Sec. Sec. 137.105, 137.200,
137.220, 137.225 of this chapter, i.e., the first ingredient designated
in the ingredient list of flour, or bromated flour, or enriched flour,
or self-rising flour is flour, white flour, wheat flour, or plain flour;
the first ingredient designated in the ingredient list of durum flour is
durum flour; the first ingredient designated in the ingredient list of
whole wheat flour, or bromated whole wheat flour is whole wheat flour,
graham flour, or entire wheat flour; and the first ingredient designated
in the ingredient list of whole durum wheat flour is whole durum wheat
flour.
(c) When water is added to reconstitute, completely or partially, an
ingredient permitted by paragraph (b) of this section to be declared by
a class name, the position of the ingredient class name in the
ingredient statement shall be determined by the weight of the
unreconstituted ingredient plus the weight of the quantity of water
added to reconstitute that ingredient, up to the amount of water needed
to reconstitute the ingredient to single strength. Any water added in
excess of the amount of water needed to reconstitute the ingredient to
single
[[Page 20]]
strength shall be declared as water in the ingredient statement.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 14091, Mar. 15, 1977;
60 FR 38480, July 27, 1995]
Sec. 501.5 Animal food; name and place of business of manufacturer, packer,
or distributor.
(a) The label of a food in packaged form shall specify conspicuously
the name and place of business of the manufacturer, packer, or
distributor.
(b) The requirement for declaration of the name of the manufacturer,
packer, or distributor shall be deemed to be satisfied, in the case of a
corporation, only by the actual corporate name, which may be preceded or
followed by the name of the particular division of the corporation. In
the case of an individual, partnership, or association, the name under
which the business is conducted shall be used.
(c) Where the food is not manufactured by the person whose name
appears on the label, the name shall be qualified by a phrase that
reveals the connection such person has with such food; such as
``Manufactured for ______,'' ``Distributed by ______,'' or any other
wording that expresses the facts.
(d) The statement of the place of business shall include the street
address, city, state, and ZIP Code; however, the street address may be
omitted if it is shown in a current city directory or telephone
directory. The requirement for inclusion of the ZIP Code shall apply
only to consumer commodity labels developed or revised after the
effective date of this section. In the case of nonconsumer packages, the
ZIP Code shall appear either on the label or the labeling (including
invoice).
(e) If a person manufactures, packs, or distributes a food at a
place other than his principal place of business, the label may state
the principal place of business in lieu of the actual place where such
food was manufactured or packed or is to be distributed, unless such
statement would be misleading.
Sec. 501.8 Labeling of animal food with number of servings.
(a) The label of any package of a food which bears a representation
as to the number of servings contained in such package shall bear in
immediate conjunction with such statement, and in the same size type as
is used for such statement, a statement of the net quantity (in terms of
weight, measure, or numerical count) of each such serving; however, such
statement may be expressed in terms that differ from the terms used in
the required statement of net quantity of contents (for example,
cupfuls, tablespoonfuls, etc.) when such differing term is common to
cookery and describes a constant quantity. Such statement may not be
misleading in any particular. A statement of the number of units in a
package is not in itself a statement of the number of servings.
(b) If there exists a voluntary product standard promulgated
pursuant to the procedures found in 15 CFR part 10 by the Department of
Commerce, quantitatively defining the meaning of the term serving with
respect to a particular food, then any label representation as to the
number of servings in such packaged food shall correspond with such
quantitative definition. (Copies of published standards are available
upon request from the National Bureau of Standards, Department of
Commerce, Washington, DC 20234.)
Sec. 501.15 Animal food; prominence of required statements.
(a) A word, statement, or other information required by or under
authority of the act to appear on the label may lack that prominence and
conspicuousness required by section 403(f) of the act by reason (among
other reasons) of:
(1) The failure of such word, statement, or information to appear on
the part or panel of the label which is presented or displayed under
customary conditions of purchase;
(2) The failure of such word, statement, or information to appear on
two or more parts or panels of the label, each of which has sufficient
space therefor, and each of which is so designed as to render it likely
to be,
[[Page 21]]
under customary conditions of purchase, the part or panel displayed;
(3) The failure of the label to extend over the area of the
container or package available for such extension, so as to provide
sufficient label space for the prominent placing of such word,
statement, or information;
(4) Insufficiency of label space (for the prominent placing of such
word, statement, or information) resulting from the use of label space
for any word, statement, design, or device which is not required by or
under authority of the act to appear on the label;
(5) Insufficiency of label space (for the prominent placing of such
word, statement, or information) resulting from the use of label space
to give materially greater conspicuousness to any other word, statement,
or information, or to any design or device; or
(6) Smallness or style of type in which such word, statement, or
information appears, insufficient background contrast, obscuring designs
or vignettes, or crowding with other written, printed, or graphic
matter.
(b) No exemption depending on insufficiency of label space, as
prescribed in regulations promulgated under section 403(e) or (i) of the
act, shall apply if such insufficiency is caused by:
(1) The use of label space for any word, statement, design, or
device which is not required by or under authority of the act to appear
on the label;
(2) The use of label space to give greater conspicuousness to any
word, statement, or other information that is required by section 403(f)
of the act; or
(3) The use of label space for any representation in a foreign
language.
(c)(1) All words, statements, and other information required by or
under authority of the act to appear on the label or labeling shall
appear thereon in the English language: Provided, however, That in the
case of articles distributed solely in the Commonwealth of Puerto Rico
or in a territory where the predominant language is one other than
English, the predominant language may be substituted for English.
(2) If the label contains any representation in a foreign language,
all words, statements, and other information required by or under
authority of the act to appear on the label shall appear thereon in the
foreign language.
(3) If any article of labeling (other than a label) contains any
representation in a foreign language, all words, statements, and other
information required by or under authority of the act to appear on the
label or labeling shall appear on such article of labeling.
Sec. 501.17 Animal food labeling warning statements.
(a) Self-pressurized containers. (1) The label of a food packaged in
a self-pressurized container and intended to be expelled from the
package under pressure shall bear the following warning:
Warning Avoid spraying in eyes. Contents under pressure. Do not
puncture or incinerate. Do not store at temperature above 120 [deg]F.
Keep out of reach of children.
(2) In the case of products intended for use by children, the phrase
``except under adult supervision'' may be added at the end of the last
sentence in the warning required by paragraph (a)(1) of this section.
(3) In the case of products packaged in glass containers, the word
``break'' may be substituted for the word ``puncture'' in the warning
required by paragraph (a)(1) of this section.
(4) The words ``Avoid spraying in eyes'' may be deleted from the
warning required by paragraph (a)(1) of this section in the case of a
product not expelled as a spray.
(b) Self-pressurized containers with halocarbon or hydrocarbon
propellants. (1) In addition to the warning required by paragraph (a) of
this section, the label of a food packaged in a self-pressurized
container in which the propellant consists in whole or in part of a
halocarbon or a hydrocarbon shall bear the following warning:
Warning Use only as directed. Intentional misuse by deliberately
concentrating and inhaling the contents can be harmful or fatal.
(2) The warning required by paragraph (b)(1) of this section is not
required for the following products:
(i) Products expelled in the form of a foam or cream, which contain
less than 10 percent propellant in the container.
[[Page 22]]
(ii) Products in a container with a physical barrier that prevents
escape of the propellant at the time of use.
(iii) Products of a net quantity of contents of less than 2 ozs that
are designed to release a measured amount of product with each valve
actuation.
(iv) Products of a net quantity of contents of less than \1/2\ oz.
(c) Animal food containing or manufactured with a chlorofluorocarbon
or other ozone-depleting substance. Labeling requirements for animal
foods that contain or are manufactured with a chlorofluorocarbon or
other ozone-depleting substance designated by the Environmental
Protection Agency (EPA) are set forth in 40 CFR part 82.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 22033, Apr. 29, 1977;
61 FR 20101, May 3, 1996]
Sec. 501.18 Misbranding of animal food.
(a) Among representations in the labeling of a food which render
such food misbranded is a false or misleading representation with
respect to another food or a drug, device, or cosmetic.
(b) The labeling of a food which contains two or more ingredients
may be misleading by reason (among other reasons) of the designation of
such food in such labeling by a name which includes or suggests the name
of one or more but not all such ingredients, even though the names of
all such ingredients are stated elsewhere in the labeling.
(c) Among representations in the labeling of a food which render
such food misbranded is any representation that expresses or implies a
geographical origin of the food or any ingredient of the food except
when such representation is either:
(1) A truthful representation of geographical origin.
(2) A trademark or trade name provided that as applied to the
article in question its use is not deceptively misdescriptive. A
trademark or trade name comprised in whole or in part of geographical
words shall not be considered deceptively misdescriptive if it:
(i) Has been so long and exclusively used by a manufacturer or
distributor that it is generally understood by the consumer to mean the
product of a particular manufacturer or distributor; or
(ii) Is so arbitrary or fanciful that it is not generally understood
by the consumer to suggest geographic origin.
(3) A part of the name required by applicable Federal law or
regulation.
(4) A name whose market significance is generally understood by the
consumer to connote a particular class, kind, type, or style of food
rather than to indicate geographical origin.
Subpart B_Specific Animal Food Labeling Requirements
Sec. 501.22 Animal foods; labeling of spices, flavorings, colorings,
and chemical preservatives.
(a)(1) The term artificial flavor or artificial flavoring means any
substance, the function of which is to impart flavor, which is not
derived from a spice, fruit or fruit juice, vegetable or vegetable
juice, edible yeast, herb, bark, bud, root, leaf or similar plant
material, meat, fish, poultry, eggs, dairy products, or fermentation
products thereof. Artificial flavor includes the substances listed in
Sec. Sec. 172.515(b) and 582.60 of this chapter except where these are
derived from natural sources.
(2) The term spice means any aromatic vegetable substance in the
whole, broken, or ground form, except for those substances which have
been traditionally regarded as foods, such as onions, garlic and celery;
whose significant function in food is seasoning rather than nutritional;
that is true to name; and from which no portion of any volatile oil or
other flavoring principle has been removed. Spices include the spices
listed in subpart A of part 582 of this chapter, such as the following:
Allspice, Anise, Basil, Bay leaves, Caraway seed, Cardamon, Celery seed,
Chervil, Cinnamon, Cloves, Coriander, Cumin seed, Dill seed, Fennel
seed, Fenugreek, Ginger, Horseradish, Mace, Marjoram, Mustard flour,
Nutmeg, Oregano, Paprika, Parsley, Pepper, black; Pepper, white; Pepper,
red; Rosemary, Saffron, Sage, Savory, Star aniseed, Tarragon, Thyme,
Turmeric.
Paprika, turmeric, and saffron or other spices which are also colors,
shall be declared as spice and coloring unless declared by their common
or usual name.
[[Page 23]]
(3) The term natural flavor or natural flavoring means the essential
oil, oleoresin, essence or extractive, protein hydrolysate, distillate,
or any product of roasting, heating or enzymolysis, which contains the
flavoring constituents derived from a spice, fruit or fruit juice,
vegetable or vegetable juice, edible yeast, herb, bark, bud, root, leaf
or similar plant material, meat, seafood, poultry, eggs, dairy products,
or fermentation products thereof, whose significant function in food is
flavoring rather than nutritional. Natural flavors, include the natural
essence or extractives obtained from plants listed in subpart A of part
582 of this chapter, and the substances listed in Sec. 172.510 of this
chapter.
(4) The term artificial color or artificial coloring means any color
additive as defined in Sec. 70.3(f) of this chapter.
(5) The term chemical preservative means any chemical that, when
added to food, tends to prevent or retard deterioration thereof, but
does not include common salt, sugars, vinegars, spices, or oils
extracted from spices, substances added to food by direct exposure
thereof to wood smoke, or chemicals applied for their insecticidal or
herbicidal properties.
(b) A food which is subject to the requirements of section 403(k) of
the act shall bear labeling, even though such food is not in package
form.
(c) A statement of artificial flavoring, artificial coloring, or
chemical preservative shall be placed on the food, or on its container
or wrapper, or on any two or all of these, as may be necessary to render
such statement likely to be read by the ordinary individual under
customary conditions of purchase and use of such food.
(d) A food shall be exempt from compliance with the requirements of
section 403(k) of the act if it is not in package form and the units
thereof are so small that a statement of artificial flavoring,
artificial coloring, or chemical preservative, as the case may be,
cannot be placed on such units with such conspicuousness as to render it
likely to be read by the ordinary individual under customary conditions
of purchase and use.
(e) A food shall be exempt while held for sale from the requirements
of section 403(k) of the act (requiring label statement of any
artificial flavoring, artificial coloring, or chemical preservatives) if
said food, having been received in bulk containers at a retail
establishment, is displayed to the purchaser with either (1) the
labeling of the bulk container plainly in view or (2) a counter card,
sign, or other appropriate device bearing prominently and conspicuously
the information required to be stated on the label pursuant to section
403(k) of the act.
(f) A fruit or vegetable shall be exempt from compliance with the
requirements of section 403(k) of the act with respect to a chemical
preservative applied to the fruit or vegetable as a pesticide chemical
prior to harvest.
(g) A flavor shall be labeled in the following way when shipped to a
food manufacturer or processor (but not a consumer) for use in the
manufacture of a fabricated food, unless it is a flavor for which a
standard of identity has been promulgated, in which case it shall be
labeled as provided in the standard:
(1) If the flavor consists of one ingredient, it shall be declared
by its common or usual name.
(2) If the flavor consists of two or more ingredients, the label
either may declare each ingredient by its common or usual name or may
state ``All flavor ingredients contained in this product are approved
for use in a regulation of the Food and Drug Administration.'' Any
flavor ingredient not contained in one of these regulations, and any
nonflavor ingredient, shall be separately listed on the label.
(3) In cases where the flavor contains a solely natural flavor(s),
the flavor shall be so labeled, e.g., strawberry flavor, banana flavor,
or natural strawberry flavor. In cases where the flavor contains both a
natural flavor and an artificial flavor, the flavor shall be so labeled,
e.g., natural and artificial strawberry flavor. In cases where the
flavor contains a solely artificial flavor(s), the flavor shall be so
labeled, e.g., artificial strawberry flavor.
(h) The label of a food to which flavor is added shall declare the
flavor in the statement of ingredients in the following way:
[[Page 24]]
(1) Spice, natural flavor, and artificial flavor may be declared as
spice, natural flavor, or artificial flavor, or any combination thereof,
as the case may be.
(2) An incidental additive in a food, originating in a spice or
flavor used in the manufacture of the food, need not be declared in the
statement of ingredients if it meets the requirements of Sec.
501.100(a)(3).
(3) Substances obtained by cutting, grinding, drying, pulping, or
similar processing of tissues derived from fruit, vegetable, meat, fish,
or poultry, e.g., powdered or granulated onions, garlic powder, and
celery powder, are commonly understood by consumers to be food rather
than flavor and shall be declared by their common or usual name.
(4) Any salt (sodium chloride) used as an ingredient in food shall
be declared by its common or usual name salt.
(5) Any monosodium glutamate used as an ingredient in food shall be
declared by its common or usual name monosodium glutamate.
(6) Any pyroligneous acid or other artificial smoke flavors used as
an ingredient in a food may be declared as artificial flavor or
artificial smoke flavor. No representation may be made, either directly
or implied, that a food flavored with pyroligneous acid or other
artificial smoke flavor has been smoked or has a true smoked flavor, or
that a seasoning sauce or similar product containing pyroligneous acid
or other artificial smoke flavor and used to season or flavor other
foods will result in a smoked product or one having a true smoked
flavor.
(i) If the label, labeling, or advertising of a food makes any
direct or indirect representations with respect to the primary
recognizable flavor(s), by word, vignette, e.g., depiction of a fruit,
or other means, or if for any other reason the manufacturer or
distributor of a food wishes to designate the type of flavor in the food
other than through the statement of ingredients, such flavor shall be
considered the characterizing flavor and shall be declared in the
following way:
(1) If the food contains no artificial flavor which simulates,
resembles or reinforces the characterizing flavor, the name of the food
on the principal display panel or panels of the label shall be
accompanied by the common or usual name of the characterizing flavor in
letters not less than one-half the height of the letters used in the
name of the food, except that:
(i) If the food is one that is commonly expected to contain a
characterizing food ingredient, and the food contains natural flavor
derived from such ingredient and an amount of characterizing ingredient
insufficient to independently characterize the food, or the food
contains no such ingredient, the name of the characterizing flavor may
be immediately preceded by the word natural and shall be immediately
followed by the word flavored in letters not less than one-half the
height of the letters in the name of the characterizing flavor.
(ii) If none of the natural flavor used in the food is derived from
the product whose flavor is simulated, the food in which the flavor is
used shall be labeled either with the flavor of the product from which
the flavor is derived or as artificially flavored.
(iii) If the food contains both a characterizing flavor from the
product whose flavor is simulated and other natural flavor which
simulates, resembles or reinforces the characterizing flavor, the food
shall be labeled in accordance with the introductory text and paragraph
(i)(1)(i) of this section and the name of the food shall be immediately
followed by the words with other natural flavor in letters not less than
one-half the height of the letters used in the name of the
characterizing flavor.
(2) If the food contains any artificial flavor which simulates,
resembles or reinforces the characterizing flavor, the name of the food
on the principal display panel or panels of the label shall be
accompanied by the common or usual name(s) of the characterizing flavor,
in letters not less than one-half the height of the letters used in the
name of the food and the name of the characterizing flavor shall be
accompanied by the word(s) artificial or artificially flavored, in
letters not less than one-half the height of the letters in the name of
the characterizing flavor.
(3) Wherever the name of the characterizing flavor appears on the
label
[[Page 25]]
(other than in the statement of ingredients) so conspicuously as to be
easily seen under customary conditions of purchase, the words prescribed
by this paragraph shall immediately and conspicuously precede or follow
such name, without any intervening written, printed, or graphic matter,
except:
(i) Where the characterizing flavor and a trademark or brand are
presented together, other written, printed, or graphic matter that is a
part of or is associated with the trademark or brand may intervene if
the required words are in such relationship with the trademark or brand
as to be clearly related to the characterizing flavor; and
(ii) If the finished product contains more than one flavor subject
to the requirements of this paragraph, the statements required by this
paragraph need appear only once in each statement of characterizing
flavors present in such food.
(iii) If the finished product contains three or more distinguishable
characterizing flavors, or a blend of flavors with no primary
recognizable flavor, the flavor may be declared by an appropriately
descriptive generic term in lieu of naming each flavor.
(4) A flavor supplier shall certify, in writing, that any flavor he
supplies which is designated as containing no artificial flavor does
not, to the best of his knowledge and belief, contain any artificial
flavor, and that he has added no artificial flavor to it. The
requirement for such certification may be satisfied by a guarantee under
section 303(c)(2) of the act which contains such a specific statement. A
flavor used shall be required to make such a written certification only
where he adds to or combines another flavor with a flavor which has been
certified by a flavor supplier as containing no artificial flavor, but
otherwise such user may rely upon the supplier's certification and need
make no separate certification. All such certifications shall be
retained by the certifying party throughout the period in which the
flavor is supplied and for a minimum of 3 years thereafter, and shall be
subject to the following conditions:
(i) The certifying party shall make such certifications available
upon request at all reasonable hours to any duly authorized officer, or
employee of the Food and Drug Administration or any other employee
acting on behalf of the Secretary of Health and Human Services. Such
certifications are regarded by the Food and Drug Administration as
reports to the government and as guarantees or other undertakings within
the meaning of section 301(h) of the act and subject the certifying
party to the penalties for making any false report to the government
under 18 U.S.C. 1001 and any false guarantee or undertaking under
section 303(a) of the act. The defenses provided under section 303(c)(2)
of the act shall be applicable to the certifications provided for in
this section.
(ii) Wherever possible, the Food and Drug Administration shall
verify the accuracy of a reasonable number of certifications made
pursuant to this section, constituting a representative sample of such
certifications, and shall not request all such certifications.
(iii) Where no person authorized to provide such information is
reasonably available at the time of inspection, the certifying party
shall arrange to have such person and the relevant materials and records
ready for verification as soon as practicable; provided that, whenever
the Food and Drug Administration has reason to believe that the supplier
or user may utilize this period to alter inventories or records, such
additional time shall not be permitted. Where such additional time is
provided, the Food and Drug Administration may require the certifying
party to certify that relevant inventories have not been materially
disturbed and relevant records have not been altered or concealed during
such period.
(iv) The certifying party shall provide, to an officer or
representative duly designated by the Secretary, such qualitative
statement of the composition of the flavor or product covered by the
certification as may be reasonably expected to enable the Secretary's
representatives to determine which relevant raw and finished materials
and flavor ingredient records are reasonably necessary to verify the
certifications. The examination conducted by the Secretary's
representative shall be limited to inspection and review of inventories
and ingredient records for
[[Page 26]]
those certifications which are to be verified.
(v) Review of flavor ingredient records shall be limited to the
qualitative formula and shall not include the quantitative formula. The
person verifying the certifications may make only such notes as are
necessary to enable him to verify such certification. Only such notes or
such flavor ingredient records as are necessary to verify such
certification or to show a potential or actual violation may be removed
or transmitted from the certifying party's place of business: Provided,
That, where such removal or transmittal is necessary for such purposes
the relevant records and notes shall be retained as separate documents
in Food and Drug Administration files, shall not be copied in other
reports, and shall not be disclosed publicly other than in a judicial
proceeding brought pursuant to the act or 18 U.S.C. 1001.
(j) A food to which a chemical preservative(s) is added shall,
except when exempt pursuant to Sec. 501.100, bear a label declaration
stating both the common or usual name of the ingredient(s) and a
separate description of its function, e.g., preservative, to retard
spoilage, a mold inhibitor, to help protect flavor or to promote color
retention.
(k) The label of an animal food to which any coloring has been added
shall declare the coloring in the statement of ingredients in the manner
specified in paragraphs (k)(1) and (k)(2) of this section.
(1) A color additive or the lake of a color additive subject to
certification under section 721(c) of the act shall be declared by the
name of the color additive listed in the applicable regulation in part
74 or part 82 of this chapter, except that it is not necessary to
include the ``FD&C'' prefix or the term ``No.'' in the declaration, but
the term ``Lake'' shall be included in the declaration of the lake of
the certified color additive (e.g., Blue 1 Lake). Manufacturers may
parenthetically declare an appropriate alternative name of the certified
color additive following its common or usual name as specified in part
74 or part 82 of this chapter.
(2) Color additives not subject to certification may be declared as
``Artificial Color,'' ``Artificial Color Added,'' or ``Color Added'' (or
by an equally informative term that makes clear that a color additive
has been used in the food). Alternatively, such color additives may be
declared as ``Colored with ____'' or ``____ color,'' the blank to be
filled with the name of the color additive listed in the applicable
regulation in part 73 of this chapter.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 14091, Mar. 15, 1977;
42 FR 15675, Mar. 22, 1977; 76 FR 71254, Nov. 17, 2011]
Subparts C-E [Reserved]
Subpart F_Exemptions From Animal Food Labeling Requirements
Sec. 501.100 Animal food; exemptions from labeling.
(a) The following foods are exempt from compliance with the
requirements of section 403(i)(2) of the act (requiring a declaration on
the label of the common or usual name of each ingredient when the food
is fabricated from two or more ingredients).
(1) An assortment of different items of food, when variations in the
items that make up different packages packed from such assortment
normally occur in good packing practice and when such variations result
in variations in the ingredients in different packages, with respect to
any ingredient that is not common to all packages. Such exemption,
however, shall be on the condition that the label shall bear, in
conjunction with the names of such ingredients as are common to all
packages, a statement (in terms that are as informative as practicable
and that are not misleading) indicating by name other ingredients which
may be present.
(2) A food having been received in bulk containers at a retail
establishment, if displayed to the purchaser with either (i) the
labeling of the bulk container plainly in view or (ii) a counter card,
sign, or other appropriate device bearing prominently and conspicuously
the information required to be stated on the label pursuant to section
403(i)(2) of the act.
[[Page 27]]
(3) Incidental additives that are present in a food at insignificant
levels and do not have any technical or functional effect in that food.
For the purposes of this paragraph (a)(3), incidental additives are:
(i) Substances that have no technical or functional effect but are
present in a food by reason of having been incorporated into the food as
an ingredient of another food, in which the substance did have a
functional or technical effect.
(ii) Processing aids, which are as follows:
(a) Substances that are added to a food during the processing of
such food but are removed in some manner from the food before it is
packaged in its finished form.
(b) Substances that are added to a food during processing, are
converted into constituents normally present in the food, and do not
significantly increase the amount of the constituents naturally found in
the food.
(c) Substances that are added to a food for their technical or
functional effect in the processing but are present in the finished food
at insignificant levels and do not have any technical or functional
effect in that food.
(iii) Substances migrating to food from equipment or packaging or
otherwise affecting food that are not food additives as defined in
section 201(s) of the act; or if they are food additives as so defined,
they are used in conformity with regulations established pursuant to
section 409 of the act.
(b) A food repackaged in a retail establishment is exempt from the
following provisions of the act if the conditions specified are met.
(1) Section 403(e)(1) of the act (requiring a statement on the label
of the name and place of business of the manufacturer, packer, or
distributor).
(2) Section 403(g)(2) of the act (requiring the label of a food
which purports to be or is represented as one for which a definition and
standard of identity has been prescribed to bear the name of the food
specified in the definition and standard and, insofar as may be required
by the regulation establishing the standard the common names of the
optional ingredients present in the food), if the food is displayed to
the purchaser with its interstate labeling clearly in view, or with a
counter card, sign, or other appropriate device bearing prominently and
conspicuously the information required by these provisions.
(3) Section 403(i)(1) of the act (requiring the label to bear the
common or usual name of the food), if the food is displayed to the
purchaser with its interstate labeling clearly in view, or with a
counter card, sign, or other appropriate device bearing prominently and
conspicuously the common or usual name of the food, or if the common or
usual name of the food is clearly revealed by its appearance.
(c) [Reserved]
(d) Except as provided by paragraphs (e) and (f) of this section, a
shipment or other delivery of a food which is, in accordance with the
practice of the trade, to be processed, labeled, or repacked in
substantial quantity at an establishment other than that where
originally processed or packed, shall be exempt, during the time of
introduction into and movement in interstate commerce and the time of
holding in such establishment, from compliance with the labeling
requirements of section 403 (c), (e), (g), (h), (i), (j) and (k) of the
act if:
(1) The person who introduced such shipment or delivery into
interstate commerce is the operator of the establishment where such food
is to be processed, labeled, or repacked; or
(2) In case such person is not such operator, such shipment or
delivery is made to such establishment under a written agreement, signed
by and containing the post office addresses of such person and such
operator, and containing such specifications for the processing,
labeling, or repacking, as the case may be, of such food in such
establishment as will ensure, if such specifications are followed, that
such food will not be adulterated or misbranded within the meaning of
the act upon completion of such processing, labeling, or repacking. Such
person and such operator shall each keep a copy of such agreement until
2 years after the final shipment or delivery of such food from such
establishment, and shall
[[Page 28]]
make such copies available for inspection at any reasonable hour to any
officer or employee of the Department who requests them.
(e) Conditions affecting expiration of exemptions.
(1) An exemption of a shipment or other delivery of a food under
paragraph (d)(1) of this section shall, at the beginning of the act of
removing such shipment or delivery, or any part thereof, from such
establishment become void ab initio if the food comprising such
shipment, delivery, or part is adulterated or misbranded within the
meaning of the act when so removed.
(2) An exemption of a shipment or other delivery of a food under
paragraph (d)(2) of this section shall become void ab initio with
respect to the person who introduced such shipment or delivery into
interstate commerce upon refusal by such person to make available for
inspection a copy of the agreement, as required by paragraph (d)(2) of
this section.
(3) An exemption of a shipment or other delivery of a food under
paragraph (d)(2) of this section shall expire:
(i) At the beginning of the act of removing such shipment or
delivery, or any part thereof, from such establishment if the food
comprising such shipment, delivery, or part is adulterated or misbranded
within the meaning of the act when so removed; or
(ii) Upon refusal by the operator of the establishment where such
food is to be processed, labeled, or repacked, to make available for
inspection a copy of the agreement as required by such paragraph.
(f) [Reserved]
(g) The label declaration of a harmless marker used to identify a
particular manufacturer's product may result in unfair competition
through revealing a trade secret. Exemption from the label declaration
of such a marker is granted, therefore, provided that the following
conditions are met:
(1) The person desiring to use the marker without label declaration
of its presence has submitted to the Commissioner of Food and Drugs full
information concerning the proposed usage and the reasons why he
believes label declaration of the marker should be subject to this
exemption; and
(2) The person requesting the exemption has received from the
Commissioner of Food and Drugs a finding that the marker is harmless and
that the exemption has been granted.
Sec. 501.103 Petitions requesting exemptions from or special requirements
for label declaration of ingredients.
The Commissioner of Food and Drugs, either on his own initiative or
on behalf of any interested person who has submitted a petition pursuant
to part 10 of this chapter may issue a proposal to amend Sec. 501.4 to
specify the manner in which an ingredient(s) shall be declared, i.e., by
specific or class name, or Sec. 501.100 to exempt an ingredient(s) from
the requirements for label declaration.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 15675, Mar. 22, 1977]
Sec. 501.105 Declaration of net quantity of contents when exempt.
(a) The principal display panel of a food in package form shall bear
a declaration of the net quantity of contents. This shall be expressed
in the terms of weight, measure, numerical count, or a combination of
numerical count and weight or measure. The statement shall be in terms
of fluid measure if the food is liquid, or in terms of weight if the
food is solid, semisolid, or viscous, or a mixture of solid and liquid;
except that such statement may be in terms of dry measure if the food is
a fresh fruit, fresh vegetable, or other dry commodity that is
customarily sold by dry measure. If there is a firmly established
general consumer usage and trade custom of declaring the contents of a
liquid by weight, or a solid, semisolid, or viscous product by fluid
measure, it may be used. Whenever the Commissioner determines that an
existing practice of declaring net quantity of contents by weight,
measure, numerical count, or a combination in the case of a specific
packaged food does not facilitate value comparisons by consumers and
offers opportunity for consumer confusion, he will by regulation
designate the appropriate term or terms to be used for such commodity.
[[Page 29]]
(b)(1) Statements of weight shall be in terms of avoirdupois pound
and ounce.
(2) Statements of fluid measure shall be in terms of the U.S. gallon
of 231 cubic inches and quart, pint, and fluid ounce subdivisions
thereof, and shall:
(i) In the case of frozen food that is sold and consumed in a frozen
state, express the volume at the frozen temperature.
(ii) In the case of refrigerated food that is sold in the
refrigerated state, express the volume at 40 [deg]F (4 [deg]C).
(iii) In the case of other foods, express the volume at 68 [deg]F
(20 [deg]C).
(3) Statements of dry measure shall be in terms of the U.S. bushel
of 2,150.42 cubic inches and peck, dry quart, and dry pint subdivisions
thereof.
(c) When the declaration of quantity of contents by numerical count
does not give adequate information as to the quantity of food in the
package, it shall be combined with such statement of weight, measure, or
size of the individual units of the foods as will provide such
information.
(d) The declaration may contain common or decimal fractions. A
common fraction shall be in terms of halves, quarters, eighths,
sixteenths, or thirty-seconds; except that if there exists a firmly
established general consumer usage and trade custom of employing
different common fractions in the net quantity declaration of a
particular commodity, they may be employed. A common fraction shall be
reduced to its lowest terms; a decimal fraction shall not be carried out
to more than two places. A statement that includes small fractions of an
ounce shall be deemed to permit smaller variations than one which does
not include such fractions.
(e) The declaration shall be located on the principal display panel
of the label, and with respect to packages bearing alternate principal
panels it shall be duplicated on each principal display panel.
(f) The declaration shall appear as a distinct item on the principal
display panel, shall be separated (by at least a space equal to the
height of the lettering used in the declaration) from other printed
label information appearing above or below the declaration and (by at
least a space equal to twice the width of the letter ``N'' of the style
of type used in the quantity of contents statement) from other printed
label information appearing to the left or right of the declaration. It
shall not include any term qualifying a unit of weight, measure, or
count (such as jumbo quart and full gallon) that tends to exaggerate the
amount of the food in the container. It shall be placed on the principal
display panel within the bottom 30 percent of the area of the label
panel in lines generally parallel to the base on which the package rests
as it is designed to be displayed: Provided, That on packages having a
principal display panel of 5 square inches or less, the requirement for
placement within the bottom 30 percent of the area of the label panel
shall not apply when the declaration of net quantity of contents meets
the other requirements of this part.
(g) The declaration shall accurately reveal the quantity of food in
the package exclusive of wrappers and other material packed therewith;
provided that in the case of foods packed in containers designed to
deliver the food under pressure, the declaration shall state the net
quantity of the contents that will be expelled when the instructions for
use as shown on the container are followed. The propellant is included
in the net quantity declaration.
(h) The declaration shall appear in conspicuous and easily legible
boldface print or type in distinct contrast (by typography, layout,
color, embossing, or molding) to other matter on the package; except
that a declaration of net quantity blown, embossed, or molded on a glass
or plastic surface is permissible when all label information is so
formed on the surface. Requirements of conspicuousness and legibility
shall include the specifications that:
(1) The ratio of height to width (of the letter) shall not exceed a
differential of 3 units to 1 unit (no more than 3 times as high as it is
wide).
(2) Letter heights pertain to upper case or capital letters. When
upper and lower case or all lower case letters are used, it is the lower
case letter ``o'' or its equivalent that shall meet the minimum
standards.
[[Page 30]]
(3) When fractions are used, each component numeral shall meet one-
half the minimum height standards.
(i) The declaration shall be in letters and numerals in a type size
established in relationship to the area of the principal display panel
of the package and shall be uniform for all packages of substantially
the same size by complying with the following type specifications:
(1) Not less than \1/16\ inch in height on packages the principal
display panel of which has an area of 5 square inches or less.
(2) Not less than \1/8\ inch in height on packages the principal
display panel of which has an area of more than 5 but not more than 25
square inches.
(3) Not less than \3/16\ inch in height on packages the principal
display panel of which has an area of more than 25 but not more than 100
square inches.
(4) Not less than \1/4\ inch in height on packages the principal
display panel of which has an area of more than 100 square inches,
except not less than \1/2\ inch in height if the area is more than 400
square inches.
Where the declaration is blown, embossed, or molded on a glass or
plastic surface rather than by printing, typing, or coloring, the
lettering sizes specified in paragraphs (i) (1) through (4) of this
section shall be increased by \1/16\ of an inch.
(j) On packages containing less than 4 pounds or 1 gallon and
labeled in terms of weight or fluid measure:
(1) The declaration shall be expressed both in ounces, with
identification by weight or by liquid measure and, if applicable (1
pound or 1 pint or more) followed in parentheses by a declaration in
pounds for weight units, with any remainder in terms of ounces or common
or decimal fractions of the pound (see examples set forth in paragraphs
(m) (1) and (2) of this section), or in the case of liquid measure, in
the largest whole units (quarts, quarts and pints, or pints, as
appropriate) with any remainder in terms of fluid ounces or common or
decimal fractions of the pint or quart (see examples in paragraphs (m)
(3) and (4) of this section).
(2) If the net quantity of contents declaration appears on a random
package, that is a package which is one of a lot, shipment, or delivery
of packages of the same consumer commodity with varying weights and with
no fixed weight pattern, it may, when the net weight exceeds 1 pound, be
expressed in terms of pounds and decimal fractions of the pound carried
out to not more than two decimal places. When the net weight does not
exceed 1 pound, the declaration on the random package may be in decimal
fractions of the pound in lieu of ounces (see example in paragraph
(m)(5) of this section).
(3) The declaration may appear in more than one line. The term net
weight shall be used when stating the net quantity of contents in terms
of weight. Use of the terms net or net contents in terms of fluid
measure or numerical count is optional. It is sufficient to distinguish
avoirdupois ounce from fluid ounce through association of terms; for
example, Net wt. 6 oz. or 6 oz. net wt. and 6 fl. oz. or net contents 6
fl. oz.
(k) On packages containing 4 pounds or 1 gallon or more and labeled
in terms of weight or fluid measure, the declaration shall be expressed
in pounds for weight units with any remainder in terms of ounces or
common or decimal fraction of the pound, or in the case of fluid
measure, it shall be expressed in the largest whole unit (gallons
followed by common or decimal fraction of a gallon or by the next
smaller whole unit or units (quarts, or quarts and pints)) with any
remainder in terms of fluid ounces or common or decimal fractions of the
pint or quart (see paragraph (m)(6) of this section).
(l) [Reserved]
(m) Examples: (1) A declaration of 1\1/2\ pounds weight shall be
expressed as Net Wt. 24 oz. (1 lb. 8 oz.), Net Wt. 24 oz. (1\1/2\ lb.),
or Net Wt. 24 oz. (1.5 lb.).
(2) A declaration of \3/4\ pound avoirdupois weight shall be
expressed as Net Wt. 12 oz.
(3) A declaration of 1 quart liquid measure shall be expressed as
Net 32 fl. oz. (1 qt.).
(4) A declaration of 1\3/4\ quarts liquid measure shall be expressed
as Net contents 56 fluid ounces (1 quart 1\1/2\ pints) or as Net 56
fluid oz. (1 qt. 1 pt. 8 oz.), but not in terms of quart and ounce such
as Net 56 fluid oz. (1 quart 24 ounces).
[[Page 31]]
(5) On a random package, declaration of \3/4\ pound avoirdupois may
be expressed as Net Wt. .75 lb.
(6) A declaration of 2\1/2\ gallons liquid measure shall be
expressed as Net contents 2\1/2\ gallons, Net contents 2.5 gallons, or
Net contents 2 gallons 2 quarts and not as 2 gallons 4 pints.
(n) For quantities, the following abbreviations and none other may
be employed (periods and plural forms are optional):
weight wt.
ounce oz.
pound lb.
gallon gal.
pint pt.
quart qt.
fluid fl.
(o) Nothing in this section shall prohibit supplemental statements
at locations other than the principal display panel(s) describing in
nondeceptive terms the net quantity of contents; provided, that such
supplemental statements of net quantity of contents shall not include
any term qualifying a unit of weight, measure, or count that tends to
exaggerate the amount of the food contained in the package; for example,
jumbo quart and full gallon. Dual or combination declarations of net
quantity of contents as provided for in paragraphs (a), (c), and (j) of
this section (for example, a combination of net weight plus numerical
count, net contents plus dilution directions of a concentrate, etc.) are
not regarded as supplemental net quantity statements and may be located
on the principal display panel.
(p) A separate statement of the net quantity of contents in terms of
the metric system is not regarded as a supplemental statement and an
accurate statement of the net quantity of contents in terms of the
metric system of weight or measure may also appear on the principal
display panel or on other panels.
(q) The declaration of net quantity of contents shall express an
accurate statement of the quantity of contents of the package.
Reasonable variations caused by loss or gain of moisture during the
course of good distribution practice or by unavoidable deviations in
good manufacturing practice will be recognized. Variations from stated
quantity of contents shall not be unreasonably large.
(r) [Reserved]
(s) On a multiunit retail package, a statement of the quantity of
contents shall appear on the outside of the package and shall include
the number of individual units, the quantity of each individual unit,
and, in parentheses, the total quantity of contents of the multiunit
package in terms of avoirdupois or fluid ounces, except that such
declaration of total quantity need not be followed by an additional
parenthetical declaration in terms of the largest whole units and
subdivisions thereof, as required by paragraph (j)(1) of this section. A
multiunit retail package may thus be properly labeled: 6-16 oz.
bottles--(96 fl. oz.) or 3-16 oz. cans--(net wt. 48 oz). For the
purposes of this section, multiunit retail package means a package
containing two or more individually packaged units of the identical
commodity and in the same quantity, intended to be sold as part of the
multiunit retail package but capable of being individually sold in full
compliance with all requirements of the regulations in this part. Open
multiunit retail packages that do not obscure the number of units nor
prevent examination of the labeling on each of the individual units are
not subject to this paragraph if the labeling of each individual unit
complies with the requirements of paragraphs (f) and (i) of this
section.
(t) Where the declaration of net quantity of contents is in terms of
net weight and/or drained weight or volume and does not accurately
reflect the actual quantity of the contents or the product falls below
the applicable standard of fill of container because of equipment
malfunction or otherwise unintentional product variation, and the label
conforms in all other respects to the requirements of this chapter, the
mislabeled food product may be sold by the manufacturer or processor
directly to institutions operated by Federal, State or local
governments: Provided, That:
(1) The purchaser shall sign a statement at the time of sale stating
that he is aware that the product is mislabeled to include
acknowledgement of the nature and extent of the mislabeling, e.g.,
``Actual net weight may be as low as __% below labeled
[[Page 32]]
quantity'' and that any subsequent distribution by him of said product
except for his own institutional use is unlawful. This statement shall
be kept on file at the principal place of business of the manufacturer
or processor for 2 years subsequent to the date of shipment of the
product and shall be available to the Food and Drug Administration upon
request.
(2) The product shall be labeled on the outside of its shipping
container with the statement(s):
(i) When the variation concerns net weight and/or drained weight of
volume--``Product Mislabeled. Actual net weight (drained weight or
volume where appropriate) may be as low as __% below labeled quantity.
This Product Not for Retail Distribution,'' the blank to be filled in
with the maximum percentage variance between the labeled and actual
weight or volume of contents of the individual packages in the shipping
container, and
(ii) When the variation is in regard to a fill of container
standard--``Product Mislabeled. Actual fill may be as low as __% below
standard of fill. This Product Not for Retail Distribution.''
(3) The statements required by paragraphs (t)(2) (i) and (ii) of
this section, which may be consolidated where appropriate, shall appear
prominently and conspicuously as compared to other printed matter on the
shipping container and in boldface print or type on a clear, contrasting
background in order to render them likely to be read and understood by
the purchaser under ordinary conditions of purchase.
[41 FR 38619, Sept. 10, 1976, as amended at 54 FR 18279, Apr. 28, 1989;
85 FR 72908, Nov. 16, 2020]
Sec. 501.110 Animal feed labeling; collective names for feed ingredients.
(a) An animal feed shall be exempt from the requirements of section
403(i)(2) of the act with respect to its label bearing the common or
usual names of the animal feed ingredients listed in paragraph (b) of
this section under the following prescribed conditions:
(1) The animal feed is intended solely for livestock and poultry.
(2) The label of the animal feed bears the collective name(s)
prescribed in paragraph (b) of this section in lieu of the corresponding
common or usual names of the individual feed ingredients contained
therein.
(3) The label of the animal feed otherwise conforms to the
requirements of section 403(i)(2) of the act.
(4) The ingredients of any feed listed in paragraph (b) of this
section neither contain nor are food additives as defined in section
201(s) of the act unless provided for by and in conformity with
applicable regulations established pursuant to section 409 of the act.
(b) Each collective name referred to in this paragraph may be used
for the purpose of labeling where one or more of the ingredients listed
for that collective name are present. The animal feed ingredients listed
under each of the collective names are the products defined by the
Association of American Feed Control Officials. The collective names are
as follows:
(1) Animal protein products include one or more of the following:
Animal products, marine products, and milk products.
(2) Forage products include one or more of the following: Alfalfa
meals, entire plant meals, hays, and stem meals.
(3) Grain products include one or more of the following: Barley,
grain sorghums, maize (corn), oats, rice, rye, and wheat.
(4) Plant protein products include one or more of the following:
Algae meals, coconut meals (copra), cottonseed meals, guar meal, linseed
meals, peanut meals, safflower meals, soybean meals, sunflower meals,
and yeasts.
(5) Processed grain byproducts include one or more of the following:
Brans, brewers dried grains, distillers grains, distillers solubles,
flours, germ meals, gluten feeds, gluten meals, grits, groats, hominy
feeds, malt sprouts, middlings, pearled, polishings, shorts, and wheat
mill run.
(6) Roughage products include one or more of the following: Cobs,
hulls, husks, pulps, and straws.
[[Page 33]]
PART 502_COMMON OR USUAL NAMES FOR NONSTANDARDIZED ANIMAL FOODS--
Table of Contents
Sec.
502.5 General principles.
502.19 Petitions.
Authority: 21 U.S.C. 321, 343, 371.
Sec. 502.5 General principles.
(a) The common or usual name of a food, which may be a coined term,
shall accurately identify or describe, in as simple and direct terms as
possible, the basic nature of the food or its characterizing properties
or ingredients. The name shall be uniform among all identical or similar
products and may not be confusingly similar to the name of any other
food that is not reasonably encompassed within the same name. Each class
or subclass of food shall be given its own common or usual name that
states, in clear terms, what it is in a way that distinguishes it from
different foods.
(b) The common or usual name of a food shall include the
percentage(s) of any characterizing ingredient(s) or component(s) when
the proportion of such ingredient(s) or component(s) in the food has a
material bearing on price or consumer acceptance or when the labeling or
the appearance of the food may otherwise create an erroneous impression
that such ingredient(s) or component(s) is present in an amount greater
than is actually the case. The following requirements shall apply unless
modified by a specific regulation in this part.
(1) The percentage of a characterizing ingredient or component shall
be declared on the basis of its quantity in the finished product (i.e.,
weight/weight in the case of solids, or volume/volume in the case of
liquids).
(2) The percentage of a characterizing ingredient or component shall
be declared by the words ``containing (or contains) __ percent (or %)
__'' or ``__ percent (or %) __'' with the first blank filled in with the
percentage expressed as a whole number not greater than the actual
percentage of the ingredient or component named and the second blank
filled in with the common or usual name of the ingredient or component.
The word ``containing'' (or ``contains''), when used, shall appear on a
line immediately below the part of the common or usual name of the food
required by paragraph (a) of this section. For each characterizing
ingredient or component, the words ``__ percent (or %) __''shall appear
following or directly below the word ``containing'' (or ``contains''),
or directly below the part of the common or usual name of the food
required by paragraph (a) of this section when the word ``containing''
(or ``contains'') is not used, in easily legible boldface print or type
in distinct contrast to other printed or graphic matter, and in a height
not less than the larger of the following alternatives:
(i) Not less than one-sixteenth inch in height on packages having a
principal display panel with an area of 5 square inches or less and not
less than one-eighth inch in height if the area of the principal display
panel is greater than 5 square inches; or
(ii) Not less than one-half the height of the largest type appearing
in the part of the common or usual name of the food required by
paragraph (a) of this section.
(c) The common or usual name of a food shall include a statement of
the presence or absence of any characterizing ingredient(s) or
component(s) and/or the need for the user to add any characterizing
ingredient(s) or component(s) when the presence or absence of such
ingredient(s) or component(s) in the food has a material bearing on
price or consumer acceptance or when the labeling or the appearance of
the food may otherwise create an erroneous impression that such
ingredient(s) or component(s) is present when it is not, and consumers
may otherwise be misled about the presence or absence of the
ingredient(s) or component(s) in the food. The following requirements
shall apply unless modified by a specific regulation in this part.
(1) The presence or absence of a characterizing ingredient or
component shall be declared by the words ``containing (or contains)
____'' or ``containing (or contains) _____'' or ``no _____'' or ``does
not contain _____'', with the blank being filled in with the common or
usual name of the ingredient or component.
[[Page 34]]
(2) The need for the user of a food to add any characterizing
ingredient(s) or component(s) shall be declared by an appropriate
informative statement.
(3) The statement(s) required under paragraph (c) (1) and/or (2) of
this section shall appear following or directly below the part of the
common or usual name of the food required by paragraphs (a) and (b) of
this section, in easily legible boldface print or type in distinct
contrast to other printed or graphic matter, and in a height not less
than the larger of the alternatives established under paragraph (b)(2)
(i) and (ii) of this section.
(d) A common or usual name of a food may be established by common
usage or by establishment of a regulation in this part, in a standard of
identity, or in other regulations in this chapter.
[41 FR 38627, Sept. 10, 1976. Redesignated at 42 FR 14091, Mar. 15,
1977]
Sec. 502.19 Petitions.
(a) The Commissioner of Food and Drugs, either on his own initiative
or on behalf of any interested person who has submitted a petition, may
publish a proposal to issue, amend, or revoke, under this part, a
regulation prescribing a common or usual name for a food, pursuant to
part 10 of this chapter.
(b) If the principal display panel of a food for which a common or
usual name regulation is established is too small to accommodate all
mandatory requirements, the Commissioner may establish by regulation an
acceptable alternative, e.g., a smaller type size. A petition requesting
such a regulation, which would amend the applicable regulation, shall be
submitted pursuant to part 10 of this chapter.
[42 FR 4716, Jan. 25, 1977; 42 FR 10980, Feb. 25, 1977. Redesignated at
42 FR 14091, Mar. 15, 1977, and amended at 42 FR 15675, Mar. 22, 1977;
42 FR 24254, May 13, 1977]
PART 507_CURRENT GOOD MANUFACTURING PRACTICE, HAZARD ANALYSIS,
AND RISK-BASED PREVENTIVE CONTROLS FOR FOOD FOR ANIMALS--Table of Contents
Subpart A_General Provisions
Sec.
507.1 Applicability and status.
507.3 Definitions.
507.4 Qualifications of individuals who manufacture, process, pack, or
hold animal food.
507.5 Exemptions.
507.7 Requirements that apply to a qualified facility.
507.10 Applicability of subparts C and E of this part to a facility
solely engaged in the storage of unexposed packaged animal
food.
507.12 Applicability of this part to the holding and distribution of
human food by-products for use as animal food.
Subpart B_Current Good Manufacturing Practice
507.14 Personnel.
507.17 Plant and grounds.
507.19 Sanitation.
507.20 Water supply and plumbing.
507.22 Equipment and utensils.
507.25 Plant operations.
507.27 Holding and distribution.
507.28 Holding and distribution of human food by-products for use as
animal food.
Subpart C_Hazard Analysis and Risk-Based Preventive Controls
507.31 Food safety plan.
507.33 Hazard analysis.
507.34 Preventive controls.
507.36 Circumstances in which the owner, operator, or agent in charge of
a manufacturing/processing facility is not required to
implement a preventive control.
507.37 Provision of assurances required under Sec. 507.36(a)(2), (3),
and (4).
507.38 Recall plan.
507.39 Preventive control management components.
507.40 Monitoring.
507.42 Corrective actions and corrections.
507.45 Verification.
507.47 Validation.
507.49 Verification of implementation and effectiveness.
507.50 Reanalysis.
507.51 Modified requirements that apply to a facility solely engaged in
the storage of unexposed packaged animal food.
[[Page 35]]
507.53 Requirements applicable to a preventive controls qualified
individual and a qualified auditor.
507.55 Implementation records required for this subpart.
Subpart D_Withdrawal of a Qualified Facility Exemption
507.60 Circumstances that may lead FDA to withdraw a qualified facility
exemption.
507.62 Issuance of an order to withdraw a qualified facility exemption.
507.65 Contents of an order to withdraw a qualified facility exemption.
507.67 Compliance with, or appeal of, an order to withdraw a qualified
facility exemption.
507.69 Procedure for submitting an appeal.
507.71 Procedure for requesting an informal hearing.
507.73 Requirements applicable to an informal hearing.
507.75 Presiding officer for an appeal and for an informal hearing.
507.77 Timeframe for issuing a decision on an appeal.
507.80 Revocation of an order to withdraw a qualified facility
exemption.
507.83 Final agency action.
507.85 Reinstatement of a qualified facility exemption that was
withdrawn.
Subpart E_Supply-Chain Program
507.105 Requirement to establish and implement a supply-chain program.
507.110 General requirements applicable to a supply-chain program.
507.115 Responsibilities of the receiving facility.
507.120 Using approved suppliers.
507.125 Determining appropriate supplier verification activities
(including determining the frequency of conducting the
activity).
507.130 Conducting supplier verification activities for raw materials
and other ingredients.
507.135 Onsite audit.
507.175 Records documenting the supply-chain program.
Subpart F_Requirements Applying to Records That Must Be Established and
Maintained
507.200 Records subject to the requirements of this subpart.
507.202 General requirements applying to records.
507.206 Additional requirements applying to the food safety plan.
507.208 Requirements for record retention.
507.212 Use of existing records.
507.215 Special requirements applicable to a written assurance.
Authority: 21 U.S.C. 331, 342, 343, 350d note, 350g, 350g note, 371,
374; 42 U.S.C. 243, 264, 271.
Source: 80 FR 56337, Sept. 17, 2015, unless otherwise noted.
Subpart A_General Provisions
Sec. 507.1 Applicability and status.
(a) The criteria and definitions in this part apply in determining
whether an animal food is:
(1) Adulterated within the meaning of:
(i) Section 402(a)(3) of the Federal Food, Drug, and Cosmetic Act in
that the food has been manufactured under such conditions that it is
unfit for food; or
(ii) Section 402(a)(4) of the Federal Food, Drug, and Cosmetic Act
in that the food has been prepared, packed, or held under insanitary
conditions whereby it may have become contaminated with filth, or
whereby it may have been rendered injurious to health; and
(2) In violation of section 361 of the Public Health Service Act (42
U.S.C. 264).
(b) The operation of a facility that manufactures, processes, packs,
or holds animal food for sale in the United States if the owner,
operator, or agent in charge of such facility is required to comply
with, and is not in compliance with, section 418 of the Federal Food,
Drug, and Cosmetic Act or subparts C, D, E, or F of this part and Sec.
507.7 is a prohibited act under section 301(uu) of the Federal Food,
Drug, and Cosmetic Act.
(c) Animal food covered by specific current good manufacturing
practice regulations also is subject to the requirements of those
regulations.
(d) Except as provided by Sec. 507.12, if a facility is required to
comply with subpart B of part 507 and is also required to comply with
subpart B of part 117 of this chapter because the facility manufactures,
processes, packs, or holds human food and animal food, then the facility
may choose to comply with the requirements in subpart B of part 117,
instead of subpart B of part 507, as to the manufacturing, processing,
packing, and holding of animal food at that facility. If a facility is
required to comply with subpart C of part 507 and is
[[Page 36]]
also required to comply with subpart C of part 117 of this chapter, then
the facility may choose to comply with the requirements in subpart C of
part 117 as to the manufacturing, processing, packing, and holding of
animal food at the facility, instead of subpart C of part 507, provided
the food safety plan also addresses hazards for the animal food, if
applicable, that require a preventive control. When applying the
requirements of part 117 of this chapter to animal food, the term
``food'' in part 117 includes animal food.
Sec. 507.3 Definitions.
The definitions and interpretations contained in section 201 of the
Federal Food, Drug, and Cosmetic Act apply to such terms when used in
this part. The following definitions also apply:
Adequate means that which is needed to accomplish the intended
purpose in keeping with good public (human and animal) health practice.
Affiliate means any facility that controls, is controlled by, or is
under common control with another facility.
Animal food means food for animals other than man and includes pet
food, animal feed, and raw materials and ingredients.
Audit means the systematic, independent, and documented examination
(through observation, investigation, records review, discussions with
employees of the audited entity, and, as appropriate, sampling and
laboratory analysis) to assess an audited entity's food safety processes
and procedures.
Calendar day means every day shown on the calendar.
Correction means an action to identify and correct a problem that
occurred during the production of animal food, without other actions
associated with a corrective action procedure (such as actions to reduce
the likelihood that the problem will recur, evaluate all affected animal
food for safety, and prevent affected animal food from entering
commerce).
Critical control point means a point, step, or procedure in a food
process at which control can be applied and is essential to prevent or
eliminate a food safety hazard or reduce such hazard to an acceptable
level.
Environmental pathogen means a pathogen capable of surviving and
persisting within the manufacturing, processing, packing, or holding
environment such that food for animals may be contaminated and may
result in foodborne illness if that animal food is not treated to
significantly minimize or prevent the environmental pathogen. Examples
of environmental pathogens for the purposes of this part include
Listeria monocytogenes and Salmonella spp. but do not include the spores
of pathogenic sporeforming bacteria.
Facility means a domestic facility or a foreign facility that is
required to register under section 415 of the Federal Food, Drug, and
Cosmetic Act, in accordance with the requirements of part 1, subpart H
of this chapter.
Farm means farm as defined in Sec. 1.227 of this chapter.
FDA means the Food and Drug Administration.
Food means food as defined in section 201(f) of the Federal Food,
Drug, and Cosmetic Act and includes raw materials and ingredients.
Food-contact surfaces are those surfaces that contact animal food
and those surfaces from which drainage, or other transfer, onto the
animal food or onto surfaces that contact the animal food ordinarily
occurs during the normal course of operations. ``Food-contact surfaces''
includes utensils and animal food-contact surfaces of equipment.
Full-time equivalent employee is a term used to represent the number
of employees of a business entity for the purpose of determining whether
the business qualifies for the small business exemption. The number of
full-time equivalent employees is determined by dividing the total
number of hours of salary or wages paid directly to employees of the
business entity and of all of its affiliates and subsidiaries by the
number of hours of work in 1 year, 2,080 hours (i.e., 40 hours x 52
weeks). If the result is not a whole number, round down to the next
lowest whole number.
Harvesting applies to farms and farm mixed-type facilities and means
activities that are traditionally performed on farms for the purpose of
removing raw agricultural commodities from the
[[Page 37]]
place they were grown or raised and preparing them for use as animal
food. Harvesting is limited to activities performed on raw agricultural
commodities, or on processed foods created by drying/dehydrating a raw
agricultural commodity without additional manufacturing/processing, on a
farm. Harvesting does not include activities that transform a raw
agricultural commodity into a processed food as defined in section
201(gg) of the Federal Food, Drug, and Cosmetic Act. Examples of
harvesting include cutting (or otherwise separating) the edible portion
of the raw agricultural commodity from the crop plant and removing or
trimming part of the raw agricultural commodity (e.g., foliage, husks,
roots, or stems). Examples of harvesting also include cooling, field
coring, filtering, gathering, hulling, shelling, sifting, threshing,
trimming of outer leaves of, and washing raw agricultural commodities
grown on a farm.
Hazard means any biological, chemical (including radiological), or
physical agent that has the potential to cause illness or injury in
humans or animals.
Hazard requiring a preventive control means a known or reasonably
foreseeable hazard for which a person knowledgeable about the safe
manufacturing, processing, packing, or holding of animal food would,
based on the outcome of a hazard analysis (which includes an assessment
of the severity of the illness or injury to humans or animals if the
hazard were to occur and the probability that the hazard will occur in
the absence of preventive controls), establish one or more preventive
controls to significantly minimize or prevent the hazard in an animal
food and components to manage those controls (such as monitoring,
corrections or corrective actions, verification, and records) as
appropriate to the animal food, the facility, and the nature of the
preventive control and its role in the facility's food safety system.
Holding means storage of animal food and also includes activities
performed incidental to storage of an animal food (e.g., activities
performed for the safe or effective storage of that animal food, such as
fumigating animal food during storage, and drying/dehydrating raw
agricultural commodities when the drying/dehydrating does not create a
distinct commodity (such as drying/dehydrating hay or alfalfa)). Holding
also includes activities performed as a practical necessity for the
distribution of that animal food (such as blending of the same raw
agricultural commodity and breaking down pallets), but does not include
activities that transform a raw agricultural commodity into a processed
food as defined in section 201(gg) of the Federal Food, Drug, and
Cosmetic Act. Holding facilities could include warehouses, cold storage
facilities, storage silos, grain elevators, and liquid-storage tanks.
Known or reasonably foreseeable hazard means a biological, chemical
(including radiological), or physical hazard that is known to be, or has
the potential to be, associated with the facility or the animal food.
Lot means the animal food produced during a period of time and
identified by an establishment's specific code.
Manufacturing/processing means making animal food from one or more
ingredients, or synthesizing, preparing, treating, modifying, or
manipulating animal food, including food crops or ingredients. Examples
of manufacturing/processing activities include: Baking, boiling,
bottling, canning, cooking, cooling, cutting, distilling, drying/
dehydrating raw agricultural commodities to create a distinct commodity
(such as drying/dehydrating grapes to produce raisins), evaporating,
eviscerating, extracting juice, extruding, formulating, freezing,
grinding, homogenizing, irradiating, labeling, milling, mixing,
packaging (including modified atmosphere packaging), pasteurizing,
peeling, pelleting, rendering, treating to manipulate ripening,
trimming, washing, or waxing. For farms and farm mixed-type facilities,
manufacturing/processing does not include activities that are part of
harvesting, packing, or holding.
Microorganisms means yeasts, molds, bacteria, viruses, protozoa, and
microscopic parasites and includes species that are pathogens. The term
``undesirable microorganisms'' includes those microorganisms that are
pathogens, that subject animal food to decomposition, that indicate that
animal food is
[[Page 38]]
contaminated with filth, or that otherwise may cause animal food to be
adulterated.
Mixed-type facility means an establishment that engages in both
activities that are exempt from registration under section 415 of the
Federal Food, Drug, and Cosmetic Act and activities that require the
establishment to be registered. An example of such a facility is a
``farm mixed-type facility,'' which is an establishment that is a farm,
but also conducts activities outside the farm definition that require
the establishment to be registered.
Monitor means to conduct a planned sequence of observations or
measurements to assess whether control measures are operating as
intended.
Packing means placing animal food into a container other than
packaging the animal food and also includes repacking and activities
performed incidental to packing or repacking an animal food (e.g.,
activities performed for the safe or effective packing or repacking of
that animal food (such as sorting, culling, grading, and weighing or
conveying incidental to packing or repacking)), but does not include
activities that transform a raw agricultural commodity into a processed
food as defined in section 201(gg) of the Federal Food, Drug, and
Cosmetic Act.
Pathogen means a microorganism of public (human or animal) health
significance.
Pest refers to any objectionable animals or insects including birds,
rodents, flies, and larvae.
Plant means the building or structure, or parts thereof, used for or
in connection with the manufacturing, processing, packing, or holding of
animal food.
Preventive controls means those risk-based, reasonably appropriate
procedures, practices, and processes that a person knowledgeable about
the safe manufacturing, processing, packing, or holding of animal food
would employ to significantly minimize or prevent the hazards identified
under the hazard analysis that are consistent with the current
scientific understanding of safe food manufacturing, processing,
packing, or holding at the time of the analysis.
Preventive controls qualified individual means a qualified
individual who has successfully completed training in the development
and application of risk-based preventive controls at least equivalent to
that received under a standardized curriculum recognized as adequate by
FDA, or is otherwise qualified through job experience to develop and
apply a food safety system.
Qualified auditor means a person who is a qualified individual as
defined in this part and has technical expertise obtained through
education, training, or experience (or the combination thereof)
necessary to perform the auditing function. Examples of potential
qualified auditors include:
(1) A government employee, including a foreign government employee;
and
(2) An audit agent of a certification body that is accredited in
accordance with regulations in part 1, subpart M of this chapter.
Qualified end-user, with respect to food, means the consumer of the
food (where the term consumer does not include a business); or a
restaurant or retail food establishment (as those terms are defined in
Sec. 1.227 of this chapter) that:
(1) Is located:
(i) In the same State or the same Indian reservation as the
qualified facility that sold the food to such restaurant or retail food
establishment; or
(ii) Not more than 275 miles from such facility; and
(2) Is purchasing the food for sale directly to consumers at such
restaurant or retail food establishment.
Qualified facility means (when including the sales by any
subsidiary; affiliate; or subsidiaries or affiliates, collectively, of
any entity of which the facility is a subsidiary or affiliate) a
facility that is a very small business as defined in this part, or a
facility to which both of the following apply:
(1) During the 3-year period preceding the applicable calendar year,
the average annual monetary value of the food manufactured, processed,
packed, or held at such facility that is sold directly to qualified end-
users (as defined in this part) during such period exceeded the average
annual monetary value
[[Page 39]]
of the food sold by such facility to all other purchasers; and
(2) The average annual monetary value of all food sold during the 3-
year period preceding the applicable calendar year was less than
$500,000, adjusted for inflation.
Qualified facility exemption means an exemption applicable to a
qualified facility under Sec. 507.5(d).
Qualified individual means a person who has the education, training,
or experience (or a combination thereof) necessary to manufacture,
process, pack, or hold safe animal food as appropriate to the
individual's assigned duties. A qualified individual may be, but is not
required to be, an employee of the establishment.
Raw agricultural commodity has the meaning given in section 201(r)
of the Federal Food, Drug, and Cosmetic Act.
Receiving facility means a facility that is subject to subparts C
and E of this part and that manufactures/processes a raw material or
other ingredient that it receives from a supplier.
Rework means clean, unadulterated animal food that has been removed
from processing for reasons other than insanitary conditions or that has
been successfully reconditioned by reprocessing and that is suitable for
use as animal food.
Sanitize means to adequately treat cleaned surfaces by a process
that is effective in destroying vegetative cells of pathogens, and in
substantially reducing numbers of other undesirable microorganisms, but
without adversely affecting the product or its safety for animals or
humans.
Significantly minimize means to reduce to an acceptable level,
including to eliminate.
Small business means, for purposes of this part, a business
(including any subsidiaries and affiliates) employing fewer than 500
full-time equivalent employees.
Subsidiary means any company which is owned or controlled directly
or indirectly by another company.
Supplier means the establishment that manufactures/processes the
animal food, raises the animal, or grows the food that is provided to a
receiving facility without further manufacturing/processing by another
establishment, except for further manufacturing/processing that consists
solely of the addition of labeling or similar activity of a de minimis
nature.
Supply-chain-applied control means a preventive control for a hazard
in a raw material or other ingredient when the hazard in the raw
material or other ingredient is controlled before its receipt.
Unexposed packaged animal food means packaged animal food that is
not exposed to the environment.
Validation means obtaining and evaluating scientific and technical
evidence that a control measure, combination of control measures, or the
food safety plan as a whole, when properly implemented, is capable of
effectively controlling the identified hazards.
Verification means the application of methods, procedures, tests and
other evaluations, in addition to monitoring, to determine whether a
control measure or combination of control measures is or has been
operating as intended and to establish the validity of the food safety
plan.
Very small business means, for purposes of this part, a business
(including any subsidiaries and affiliates) averaging less than
$2,500,000, adjusted for inflation, per year, during the 3-year period
preceding the applicable calendar year in sales of animal food plus the
market value of animal food manufactured, processed, packed, or held
without sale (e.g., held for a fee or supplied to a farm without sale).
Water activity (aw) means a measure of the free moisture
in an animal food and is the quotient of the water vapor pressure of the
substance divided by the vapor pressure of pure water at the same
temperature.
Written procedures for receiving raw materials and other ingredients
means written procedures to ensure that raw materials and other
ingredients are received only from suppliers approved by the receiving
facility (or, when necessary and appropriate, on a temporary basis from
unapproved suppliers whose raw materials or other ingredients are
subjected to adequate verification activities before acceptance for
use).
[[Page 40]]
You means, for purposes of this part, the owner, operator, or agent
in charge of a facility.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3717, Jan. 22, 2016]
Sec. 507.4 Qualifications of individuals who manufacture, process, pack,
or hold animal food.
(a)(1) The management of an establishment must ensure that all
individuals who manufacture, process, pack, or hold animal food subject
to subparts B and F of this part are qualified to perform their assigned
duties; and
(2) The owner, operator, or agent in charge of a facility must
ensure that all individuals who manufacture, process, pack, or hold
animal food subject to subparts C, D, E, or F of this part are qualified
to perform their assigned duties.
(b) Each individual engaged in manufacturing, processing, packing,
or holding animal food (including temporary and seasonal personnel) or
in the supervision thereof must:
(1) Be a qualified individual as that term is defined in Sec.
507.3, i.e., have the education, training, or experience (or a
combination thereof) necessary to manufacture, process, pack, or hold
safe animal food as appropriate to the individual's assigned duties; and
(2) Receive training in the principles of animal food hygiene and
animal food safety, including the importance of employee health and
personal hygiene, as appropriate to the animal food, the facility and
the individual's assigned duties.
(c) Responsibility for ensuring compliance by individuals with the
requirements of this part must be clearly assigned to supervisory
personnel who have the education, training, or experience (or a
combination thereof) necessary to supervise the production of safe
animal food.
(d) Records that document training required by paragraph (b)(2) of
this section must be established and maintained and are subject to the
recordkeeping requirements in subpart F of this part.
Sec. 507.5 Exemptions.
(a) This part does not apply to establishments, including ``farms''
(as defined in Sec. 1.227 of this chapter), that are not required to
register under section 415 of the Federal Food, Drug, and Cosmetic Act.
(b)(1) Subparts C and E of this part do not apply with respect to
activities that are subject to Sec. 500.23 and part 113 of this chapter
(Thermally Processed Low-Acid Foods Packaged in Hermetically Sealed
Containers) at an animal food facility if you are required to comply
with, and are in compliance with, part 113 of this chapter with respect
to those activities.
(2) The exemption in paragraph (b)(1) of this section is applicable
only with respect to those microbiological hazards regulated under part
113 of this chapter.
(c) Subparts C and E of this part do not apply to activities of a
facility that are subject to section 419 of the Federal Food, Drug, and
Cosmetic Act (Standards for Produce Safety).
(d) Except as provided in subpart D of this part, subparts C and E
of this part do not apply to a qualified facility. Qualified facilities
are subject to the requirements in Sec. 507.7.
(e) For a farm mixed-type facility that is a small or very small
business, subparts C and E of this part do not apply to on-farm packing
or holding of processed animal food, and Sec. 507.7 does not apply to
on-farm packing or holding of processed animal food by a very small
business, if the only packing or holding activities subject to section
418 of the Federal Food, Drug, and Cosmetic Act that the business
conducts are the following low-risk packing or holding activity/animal
food combinations--i.e., packing (or repacking) (including weighing or
conveying incidental to packing or repacking); sorting, culling, or
grading incidental to packing or storing; and storing (ambient, cold and
controlled atmosphere) of:
(1) Roughage products (e.g., alfalfa meal, entire plant meal, stem
meal, pomace, and pulp);
(2) Plant protein meals (e.g., algae, coconut (copra), guar, and
peanut);
(3) Grain by-products and processed grain products (e.g., bran,
flour, germ meal, grits, groats, hominy feed, malt
[[Page 41]]
sprouts, middlings, pearled grain, polished grain, brewers grain,
distillers grain, and gluten meal);
(4) Oilseed products (e.g., oil and meal of safflower, soybean, or
sunflower);
(5) Molasses (e.g., processed sugar cane, sugar beets, and citrus);
(6) Animal protein meals (e.g., blood, feather, meat, meat and bone,
and marine (e.g., crab, fish, shrimp));
(7) Milk products (e.g., casein, cheese rind, and lactalbumin);
(8) Animal tissue-derived products (e.g., fat);
(9) Vitamins, minerals, and concentrates;
(10) Processing aids (e.g., enzymes, preservatives, and
stabilizers); and
(11) Any other processed animal food that does not require time/
temperature control for safety.
(f) For a farm mixed-type facility that is a small or very small
business, subparts C and E of this part do not apply to on-farm
manufacturing/processing activities conducted by a small or very small
business for distribution into commerce, and Sec. 507.7 does not apply
to on-farm manufacturing/processing activities conducted by a very small
business for distribution into commerce, if the only manufacturing/
processing activities subject to section 418 of the Federal Food, Drug,
and Cosmetic Act that the business conducts consists of the following
low-risk manufacturing/processing activity/animal food combinations:
(1) Chopping or shredding hay;
(2) Cracking, crimping, flaking, pearling, peeling, shelling, or
wafering--grain (e.g., barley, sorghum, corn, oats, rice, rye, and
wheat) or oilseed (e.g., beans, canola, cottonseed, linseed, soybeans,
and sunflowers);
(3) Crushing, dry rolling, grinding, milling, pulverizing--grain,
oilseed, grain by-products and processed grain products, oilseed
products, hay, ensiled material, culled fruits and vegetables, roughage
(e.g., cobs, hulls, husks, and straws), or roughage products;
(4) Ensiling (including chopping, shredding, mixing, storing, or
fermenting), that is, making silage or haylage from forage (e.g.,
sorghum (milo), corn (maize), alfalfa, and grass), grain, culled fruits
and vegetables, or roughage;
(5) Extracting (mechanical) or wet rolling grain, oilseed, brewers
grain by-products, or distillers grain by-products;
(6) Labeling roughage products, plant protein meals, grain by-
products and processed grain products, oilseed products, molasses,
animal protein meals, milk products, animal tissue-derived products,
vitamins, minerals, concentrates, processing aids, finished animal food,
including animal food ready for consumption, or any other processed
animal food that does not require time/temperature control for safety;
and
(7) Packaging roughage products, plant protein meals, grain by-
products and processed grain products, oilseed products, molasses,
animal protein meals, milk products, animal tissue-derived products,
vitamins, minerals, concentrates, processing aids, finished animal food,
including animal food ready for consumption, or any other processed
animal food that does not require time/temperature control for safety.
(g) Subparts C and E of this part do not apply to facilities that
are solely engaged in the storage of raw agricultural commodities (other
than fruits and vegetables) intended for further distribution or
processing.
(h) Subpart B of this part does not apply to any of the following:
(1) Establishments solely engaged in the holding and/or
transportation of one or more raw agricultural commodities;
(2) Establishments solely engaged in hulling, shelling, drying,
packing, and/or holding nuts and hulls (without manufacturing/
processing, such as grinding shells or roasting nuts); and
(3) Establishments solely engaged in ginning of cotton (without
manufacturing/processing, such as extracting oil from cottonseed).
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3717, Jan. 22, 2016]
Sec. 507.7 Requirements that apply to a qualified facility.
(a) A qualified facility must submit the following attestations to
FDA:
(1) An attestation that the facility is a qualified facility as
defined in Sec. 507.3.
[[Page 42]]
For the purpose of determining whether a facility satisfies the
definition of qualified facility, the baseline year for calculating the
adjustment for inflation is 2011; and
(2)(i) An attestation that you have identified the potential hazards
associated with the animal food being produced, are implementing
preventive controls to address the hazards, and are monitoring the
performance of the preventive controls to ensure that such controls are
effective; or
(ii) An attestation that the facility is in compliance with State,
local, county, tribal, or other applicable non-Federal food safety law,
including relevant laws and regulations of foreign countries, including
an attestation based on licenses, inspection reports, certificates,
permits, credentials, certification by an appropriate agency (such as a
State department of agriculture), or other evidence of oversight.
(b) The attestations required by paragraph (a) of this section must
be submitted to FDA by any one of the following means:
(1) Electronic submission. To submit electronically, go to http://
www.fda.gov/furls and follow the instructions. This Web site is
available from wherever the Internet is accessible, including libraries,
copy centers, schools, and Internet cafes. FDA encourages electronic
submission.
(2) Submission by mail. (i) You must use Form FDA 3942b. You may
obtain a copy of this form by any of the following mechanisms:
(A) Download it from http://www.fda.gov/pcafrule;
(B) Write to the U.S. Food and Drug Administration (HFS-681), 5001
Campus Dr., College Park, MD 20740; or
(C) Request a copy of this form by phone at 1-800-216-7331 or 301-
575-0156.
(ii) Send a paper Form FDA 3942b to the U.S. Food and Drug
Administration (HFS-681), 5001 Campus Dr., College Park, MD 20740. We
recommend that you submit a paper copy only if your facility does not
have reasonable access to the Internet.
(c)(1) A facility must determine and document its status as a
qualified facility on an annual basis no later than July 1 of each
calendar year.
(2) The attestations required by paragraph (a) of this section must
be:
(i) Submitted to FDA initially:
(A) By December 16, 2019 for a facility that begins manufacturing,
processing, packing, or holding animal food before September 17, 2019;
(B) Before beginning operations, for a facility that begins
manufacturing, processing, packing, or holding animal food after
September 17, 2019; or
(C) By July 31 of the applicable calendar year, when the status of a
facility changes from ``not a qualified facility'' to ``qualified
facility'' based on the annual determination required by paragraph
(c)(1) of this section; and
(ii) Beginning in 2020, submitted to FDA every 2 years during the
period beginning on October 1 and ending on December 31.
(3) When the status of a facility changes from ``qualified
facility'' to ``not a qualified facility'' based on the annual
determination required by paragraph (c)(1) of this section, the facility
must notify FDA of that change in status using Form FDA 3942b by July 31
of the applicable calendar year.
(d) When the status of a facility changes from ``qualified
facility'' to ``not a qualified facility,'' the facility must comply
with subparts C and E of this part no later than December 31 of the
applicable calendar year unless otherwise agreed to by FDA and the
facility.
(e) A qualified facility that does not submit attestations under
paragraph (a)(2)(i) of this section must provide notification to
consumers as to the name and complete business address of the facility
where the animal food was manufactured or processed (including the
street address or P.O. Box, city, state, and zip code for domestic
facilities, and comparable full address information for foreign
facilities) as follows:
(1) If an animal food packaging label is required, the notification
required by paragraph (e) of this section must appear prominently and
conspicuously on the label of the animal food.
(2) If an animal food packaging label is not required, the
notification required by paragraph (e) of this section must appear
prominently and conspicuously, at the point of purchase, on a
[[Page 43]]
label, poster, sign, placard, or documents delivered contemporaneously
with the animal food in the normal course of business, or in an
electronic notice, in the case of Internet sales.
(f)(1) A qualified facility must maintain those records relied upon
to support the attestations that are required by paragraph (a) of this
section.
(2) The records that a qualified facility must maintain are subject
to the requirements of subpart F of this part.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3717, Jan. 22, 2016;
81 FR 49897, July 29, 2016]
Sec. 507.10 Applicability of subparts C and E of this part to a facility
solely engaged in the storage of unexposed packaged animal food.
(a) Subparts C and E of this part do not apply to a facility solely
engaged in the storage of unexposed packaged animal food that does not
require time/temperature control to significantly minimize or prevent
the growth of, or toxin production by, pathogens.
(b) A facility solely engaged in the storage of unexposed packaged
animal food, including unexposed packaged animal food that requires
time/temperature control to significantly minimize or prevent the growth
of, or toxin production by, pathogens is subject to the modified
requirements in Sec. 507.51 for any unexposed packaged animal food that
requires time/temperature control to significantly minimize or prevent
the growth of, or toxin production by, pathogens.
Sec. 507.12 Applicability of this part to the holding and distribution
of human food by-products for use as animal food.
(a) Except as provided by paragraph (b) of this section, the
requirements of this part do not apply to by-products of human food
production, or the off-farm packing and holding of raw agricultural
commodities, that are packed or held by that human food facility for
distribution as animal food if:
(1)(i) The human food facility is subject to and in compliance with
subpart B of part 117 of this chapter and in compliance with all
applicable human food safety requirements of the Federal Food, Drug, and
Cosmetic Act and implementing regulations; or
(ii) For the off-farm packing and holding of produce (as defined in
part 112 of this chapter), the human food facility is subject to and in
compliance with Sec. 117.8 of this chapter and in compliance with all
applicable human food safety requirements of the Federal Food, Drug, and
Cosmetic Act and implementing regulations; and
(2) The human food facility does not further manufacture or process
the by-products intended for use as animal food.
(b) The human food by-products for use as animal food identified in
paragraph (a) of this section must be held and distributed by that
facility in accordance with Sec. Sec. 507.28 and 117.95 of this
chapter.
Subpart B_Current Good Manufacturing Practice
Sec. 507.14 Personnel.
(a) The management of the establishment must take reasonable
measures and precautions to ensure that all persons working in direct
contact with animal food, animal food-contact surfaces, and animal food-
packaging materials conform to hygienic practices to the extent
necessary to protect against the contamination of animal food.
(b) The methods for conforming to hygienic practices and maintaining
cleanliness include:
(1) Maintaining adequate personal cleanliness;
(2) Washing hands thoroughly in an adequate hand-washing facility as
necessary and appropriate to protect against contamination;
(3) Removing or securing jewelry and other objects that might fall
into animal food, equipment, or containers;
(4) Storing clothing or other personal belongings in areas other
than where animal food is exposed or where equipment or utensils are
cleaned; and
(5) Taking any other necessary precautions to protect against the
contamination of animal food, animal food-contact surfaces, or animal
food-packaging materials.
[[Page 44]]
Sec. 507.17 Plant and grounds.
(a) The grounds around an animal food plant under the control of the
management of the establishment must be kept in a condition that will
protect against the contamination of animal food. Maintenance of grounds
must include:
(1) Properly storing equipment, removing litter and waste, and
cutting weeds or grass within the immediate vicinity of the plant that
may constitute an attractant, breeding place, or harborage for pests;
(2) Maintaining driveways, yards, and parking areas so that they do
not constitute a source of contamination in areas where animal food is
exposed;
(3) Adequately draining areas that may contribute to contamination
of animal food; and
(4) Treating and disposing of waste so that it does not constitute a
source of contamination in areas where animal food is exposed.
(b) The plant must be suitable in size, construction, and design to
facilitate cleaning, maintenance, and pest control to reduce the
potential for contamination of animal food, animal food-contact
surfaces, and animal food-packaging materials, including that the plant
must:
(1) Provide adequate space between equipment, walls, and stored
materials to permit employees to perform their duties and to allow
cleaning and maintenance of equipment;
(2) Be constructed in a manner such that drip or condensate from
fixtures, ducts, and pipes does not serve as a source of contamination;
(3) Provide adequate ventilation (mechanical or natural) where
necessary and appropriate to minimize vapors (e.g., steam) and fumes in
areas where they may contaminate animal food and in a manner that
minimizes the potential for contaminating animal food;
(4) Provide adequate lighting in hand-washing areas, toilet rooms,
areas where animal food is received, manufactured, processed, packed, or
held, and areas where equipment or utensils are cleaned; and
(5) Provide shatter-resistant light bulbs, fixtures, and skylights,
or other glass items suspended over exposed animal food in any step of
preparation, to protect against the contamination of animal food in case
of glass breakage.
(c) The plant must protect animal food stored outdoors in bulk from
contamination by any effective means, including:
(1) Using protective coverings where necessary and appropriate;
(2) Controlling areas over and around the bulk animal food to
eliminate harborages for pests; and
(3) Checking on a regular basis for pests, pest infestation, and
product condition related to safety of the animal food.
Sec. 507.19 Sanitation.
(a) Buildings, structures, fixtures, and other physical facilities
of the plant must be kept clean and in good repair to prevent animal
food from becoming adulterated.
(b) Animal food-contact and non-contact surfaces of utensils and
equipment must be cleaned and maintained and utensils and equipment
stored as necessary to protect against the contamination of animal food,
animal food-contact surfaces, or animal food-packaging materials. When
necessary, equipment must be disassembled for thorough cleaning. In
addition:
(1) When animal food-contact surfaces used for manufacturing,
processing, packing, or holding animal food are wet-cleaned, the
surfaces must, when necessary, be thoroughly dried before subsequent
use; and
(2) In wet processing of animal food, when cleaning and sanitizing
are necessary to protect against the introduction of undesirable
microorganisms into animal food, all animal food-contact surfaces must
be cleaned and sanitized before use and after any interruption during
which the animal food-contact surfaces may have become contaminated.
(c) Cleaning compounds and sanitizing agents must be safe and
adequate under the conditions of use.
(d) The following applies to toxic materials:
(1) Only the following toxic materials may be used or stored in the
plant area where animal food is manufactured, processed, or exposed:
(i) Those required to maintain clean and sanitary conditions;
[[Page 45]]
(ii) Those necessary for use in laboratory testing procedures;
(iii) Those necessary for plant and equipment maintenance and
operation; and
(iv) Those necessary for use in the plant's operations.
(2) Toxic materials described in paragraph (d)(1) of this section
(e.g., cleaning compounds, sanitizing agents, and pesticide chemicals)
must be identified, used, and stored in a manner that protects against
the contamination of animal food, animal food-contact surfaces, or
animal food-packaging materials; and
(3) Other toxic materials (such as fertilizers and pesticides not
included in paragraph (d)(1) of this section) must be stored in an area
of the plant where animal food is not manufactured, processed, or
exposed.
(e) Effective measures must be taken to exclude pests from the
manufacturing, processing, packing, and holding areas and to protect
against the contamination of animal food by pests. The use of pesticides
in the plant is permitted only under precautions and restrictions that
will protect against the contamination of animal food, animal food-
contact surfaces, and animal food-packaging materials.
(f) Trash must be conveyed, stored, and disposed of in a way that
protects against the contamination of animal food, animal food-contact
surfaces, animal food-packaging materials, water supplies, and ground
surfaces, and minimizes the potential for the trash to become an
attractant and harborage or breeding place for pests.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3717, Jan. 22, 2016]
Sec. 507.20 Water supply and plumbing.
(a) The following apply to the water supply:
(1) Water must be adequate for the operations and must be derived
from an adequate source;
(2) Running water at a suitable temperature, and under suitable
pressure as needed, must be provided in all areas where required for the
manufacturing, processing, packing, or holding of animal food, for the
cleaning of equipment, utensils, and animal food-packaging materials, or
for employee hand-washing facilities;
(3) Water that contacts animal food, animal food-contact surfaces,
or animal food-packaging materials must be safe for its intended use;
and
(4) Water may be reused for washing, rinsing, or conveying animal
food if it does not increase the level of contamination of the animal
food.
(b) Plumbing must be designed, installed, and maintained to:
(1) Carry adequate quantities of water to required locations
throughout the plant;
(2) Properly convey sewage and liquid disposable waste from the
plant;
(3) Avoid being a source of contamination to animal food, water
supplies, equipment, or utensils, or creating an unsanitary condition;
(4) Provide adequate floor drainage in all areas where floors are
subject to flooding-type cleaning or where normal operations release or
discharge water or other liquid waste on the floor; and
(5) Ensure that there is no backflow from, or cross-connection
between, piping systems that discharge waste water or sewage and piping
systems that carry water for animal food or animal food manufacturing.
(c) Sewage and liquid disposal waste must be disposed of through an
adequate sewerage system or through other adequate means.
(d) Each plant must provide employees with adequate, readily
accessible toilet facilities. Toilet facilities must be kept clean and
must not be a potential source of contamination of animal food, animal
food-contact surfaces, or animal food-packaging materials.
(e) Each plant must provide hand-washing facilities designed to
ensure that an employee's hands are not a potential source of
contamination of animal food, animal food-contact surfaces, or animal
food-packaging materials.
Sec. 507.22 Equipment and utensils.
(a) The following apply to plant equipment and utensils used in
manufacturing, processing, packing, and holding animal food:
(1) All plant equipment and utensils, including equipment and
utensils that do not come in contact with animal food, must be designed
and constructed
[[Page 46]]
of such material and workmanship to be adequately cleanable, and must be
properly maintained;
(2) Equipment and utensils must be designed, constructed, and used
appropriately to avoid the adulteration of animal food with non-food
grade lubricants, fuel, metal fragments, contaminated water, or any
other contaminants;
(3) Equipment must be installed so as to facilitate the cleaning and
maintenance of the equipment and adjacent spaces;
(4) Animal food-contact surfaces must be:
(i) Made of materials that withstand the environment of their use
and the action of animal food, and, if applicable, the action of
cleaning compounds, cleaning procedures, and sanitizing agents;
(ii) Made of nontoxic materials; and
(iii) Maintained to protect animal food from being contaminated.
(b) Holding, conveying, manufacturing, and processing systems,
including gravimetric, pneumatic, closed, and automated systems, must be
designed, constructed, and maintained in a way to protect against the
contamination of animal food.
(c) Each freezer and cold storage compartment used to hold animal
food must be fitted with an accurate temperature-measuring device.
(d) Instruments and controls used for measuring, regulating, or
recording temperatures, pH, aw, or other conditions that
control or prevent the growth of undesirable microorganisms in animal
food must be accurate, precise, adequately maintained, and adequate in
number for their designated uses.
(e) Compressed air or other gases mechanically introduced into
animal food or used to clean animal food-contact surfaces or equipment
must be used in such a way to protect against the contamination of
animal food.
Sec. 507.25 Plant operations.
(a) Management of the establishment must ensure that:
(1) All operations in the manufacturing, processing, packing, and
holding of animal food (including operations directed to receiving,
inspecting, transporting, and segregating) are conducted in accordance
with the current good manufacturing practice requirements of this
subpart;
(2) Animal food, including raw materials, other ingredients, or
rework is accurately identified;
(3) Animal food-packaging materials are safe and suitable;
(4) The overall cleanliness of the plant is under the supervision of
one or more competent individuals assigned responsibility for this
function;
(5) Adequate precautions are taken so that plant operations do not
contribute to contamination of animal food, animal food-contact
surfaces, and animal food-packaging materials;
(6) Chemical, microbial, or extraneous-material testing procedures
are used where necessary to identify sanitation failures or possible
animal food contamination;
(7) Animal food that has become adulterated is rejected, disposed
of, or if appropriate, treated or processed to eliminate the
adulteration. If disposed of, it must be done in a manner that protects
against the contamination of other animal food; and
(8) All animal food manufacturing, processing, packing, and holding
is conducted under such conditions and controls as are necessary to
minimize the potential for the growth of undesirable microorganisms to
protect against the contamination of animal food.
(b) Raw materials and other ingredients:
(1) Must be examined to ensure that they are suitable for
manufacturing and processing into animal food and must be handled under
conditions that will protect against contamination and minimize
deterioration. In addition:
(i) Shipping containers (e.g., totes, drums, and tubs) and bulk
vehicles holding raw materials and other ingredients must be examined
upon receipt to determine whether contamination or deterioration of
animal food has occurred;
(ii) Raw materials must be cleaned as necessary to minimize
contamination; and
(iii) Raw materials and other ingredients, including rework, must be
stored in containers designed and constructed
[[Page 47]]
in a way that protects against contamination and deterioration, and held
under conditions, e.g., appropriate temperature and relative humidity,
that will minimize the potential for growth of undesirable
microorganisms and prevent the animal food from becoming adulterated;
(2) Susceptible to contamination with mycotoxins or other natural
toxins must be evaluated and used in a manner that does not result in
animal food that can cause injury or illness to animals or humans; and
(3) If frozen, must be kept frozen. If thawing is required prior to
use, it must be done in a manner that minimizes the potential for the
growth of undesirable microorganisms.
(c) For the purposes of manufacturing, processing, packing, and
holding operations, the following apply:
(1) Animal food must be maintained under conditions, e.g.,
appropriate temperature and relative humidity, that will minimize the
potential for growth of undesirable microorganisms and prevent the
animal food from becoming adulterated during manufacturing, processing,
packing, and holding;
(2) Measures taken during manufacturing, processing, packing, and
holding of animal food to significantly minimize or prevent the growth
of undesirable microorganisms (e.g., heat treating, freezing,
refrigerating, irradiating, controlling pH, or controlling
aw) must be adequate to prevent adulteration of animal food;
(3) Work-in-process and rework must be handled in such a way that it
is protected against contamination and the growth of undesirable
microorganisms;
(4) Steps such as cutting, drying, defatting, grinding, mixing,
extruding, pelleting, and cooling, must be performed in a way that
protects against the contamination of animal food;
(5) Filling, assembling, packaging, and other operations must be
performed in such a way that protects against the contamination of
animal food and the growth of undesirable microorganisms;
(6) Animal food that relies principally on the control of water
activity (aw) for preventing the growth of undesirable
microorganisms must be processed to and maintained at a safe
aw level;
(7) Animal food that relies principally on the control of pH for
preventing the growth of undesirable microorganisms must be monitored
and maintained at the appropriate pH; and
(8) When ice is used in contact with animal food, it must be made
from water that is safe and must be used only if it has been
manufactured in accordance with current good manufacturing practice as
outlined in this subpart.
Sec. 507.27 Holding and distribution.
(a) Animal food held for distribution must be held under conditions
that will protect against contamination and minimize deterioration,
including the following:
(1) Containers used to hold animal food before distribution must be
designed, constructed of appropriate material, cleaned as necessary, and
maintained to protect against the contamination of animal food; and
(2) Animal food held for distribution must be held in a way that
protects against contamination from sources such as trash.
(b) The labeling for the animal food ready for distribution must
contain, when applicable, information and instructions for safely using
the animal food for the intended animal species.
(c) Shipping containers (e.g., totes, drums, and tubs) and bulk
vehicles used to distribute animal food must be examined prior to use to
protect against the contamination of animal food from the container or
vehicle when the facility is responsible for transporting the animal
food itself or arranges with a third party to transport the animal food.
(d) Animal food returned from distribution must be assessed for
animal food safety to determine the appropriate disposition. Returned
animal food must be identified as such and segregated until assessed.
(e) Unpackaged or bulk animal food must be held in a manner that
does not result in unsafe cross contamination with other animal food.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3717, Jan. 22, 2016]
[[Page 48]]
Sec. 507.28 Holding and distribution of human food by-products
for use as animal food.
(a) Human food by-products held for distribution as animal food must
be held under conditions that will protect against contamination,
including the following:
(1) Containers and equipment used to convey or hold human food by-
products for use as animal food before distribution must be designed,
constructed of appropriate material, cleaned as necessary, and
maintained to protect against the contamination of human food by-
products for use as animal food;
(2) Human food by-products for use as animal food held for
distribution must be held in a way to protect against contamination from
sources such as trash; and
(3) During holding, human food by-products for use as animal food
must be accurately identified.
(b) Labeling that identifies the product by the common or usual name
must be affixed to or accompany the human food by-products for use as
animal food when distributed.
(c) Shipping containers (e.g., totes, drums, and tubs) and bulk
vehicles used to distribute human food by-products for use as animal
food must be examined prior to use to protect against the contamination
of animal food from the container or vehicle when the facility is
responsible for transporting the human food by-products for use as
animal food itself or arranges with a third party to transport the human
food by-products for use as animal food.
Subpart C_Hazard Analysis and Risk-Based Preventive Controls
Sec. 507.31 Food safety plan.
(a) You must prepare, or have prepared, and implement a written food
safety plan.
(b) One or more preventive controls qualified individuals must
prepare, or oversee the preparation of, the food safety plan.
(c) The written food safety plan must include:
(1) The written hazard analysis as required by Sec. 507.33(a)(2);
(2) The written preventive controls as required by Sec. 507.34(b);
(3) The written supply-chain program as required by subpart E of
this part;
(4) The written recall plan as required by Sec. 507.38(a)(1);
(5) The written procedures for monitoring the implementation of the
preventive controls as required by Sec. 507.40(a);
(6) The written corrective action procedures as required by Sec.
507.42(a)(1); and
(7) The written verification procedures as required by Sec.
507.49(b).
(d) The food safety plan required by this section is a record that
is subject to the requirements of subpart F of this part.
[80 FR 56337, Sept. 17, 2015, as amended at 84 FR 12491, Apr. 2, 2019]
Sec. 507.33 Hazard analysis.
(a)(1) You must conduct a hazard analysis to identify and evaluate,
based on experience, illness data, scientific reports, and other
information, known or reasonably foreseeable hazards for each type of
animal food manufactured, processed, packed, or held at your facility to
determine whether there are any hazards requiring a preventive control;
and
(2) The hazard analysis must be written regardless of its outcome.
(b) The hazard identification must consider:
(1) Known or reasonably foreseeable hazards that include:
(i) Biological hazards, including microbiological hazards such as
parasites, environmental pathogens, and other pathogens;
(ii) Chemical hazards, including radiological hazards, substances
such as pesticide and drug residues, natural toxins, decomposition,
unapproved food or color additives, and nutrient deficiencies or
toxicities (such as inadequate thiamine in cat food, excessive vitamin D
in dog food, and excessive copper in food for sheep); and
(iii) Physical hazards (such as stones, glass, and metal fragments);
and
(2) Known or reasonably foreseeable hazards that may be present in
the animal food for any of the following reasons:
(i) The hazard occurs naturally;
[[Page 49]]
(ii) The hazard may be unintentionally introduced; or
(iii) The hazard may be intentionally introduced for purposes of
economic gain.
(c)(1) The hazard analysis must include an evaluation of the hazards
identified in paragraph (b) of this section to assess the severity of
the illness or injury to humans or animals if the hazard were to occur
and the probability that the hazard will occur in the absence of
preventive controls.
(2) The hazard evaluation required by paragraph (c)(1) of this
section must include an evaluation of environmental pathogens whenever
an animal food is exposed to the environment prior to packaging and the
packaged animal food does not receive a treatment or otherwise include a
control measure (such as a formulation lethal to the pathogen) that
would significantly minimize the pathogen.
(d) The hazard evaluation must consider the effect of the following
on the safety of the finished animal food for the intended animal:
(1) The formulation of the animal food;
(2) The condition, function, and design of the facility and
equipment;
(3) Raw materials and other ingredients;
(4) Transportation practices;
(5) Manufacturing/processing procedures;
(6) Packaging activities and labeling activities;
(7) Storage and distribution;
(8) Intended or reasonably foreseeable use;
(9) Sanitation, including employee hygiene; and
(10) Any other relevant factors such as the temporal (e.g., weather-
related) nature of some hazards (e.g., levels of some natural toxins).
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3717, Jan. 22, 2016]
Sec. 507.34 Preventive controls.
(a)(1) You must identify and implement preventive controls to
provide assurances that any hazards requiring a preventive control will
be significantly minimized or prevented and the animal food
manufactured, processed, packed, or held by your facility will not be
adulterated under section 402 of the Federal Food, Drug, and Cosmetic
Act; and
(2) Preventive controls required by paragraph (a)(1) of this section
include:
(i) Controls at critical control points (CCPs), if there are any
CCPs; and
(ii) Controls, other than those at CCPs, that are also appropriate
for animal food safety.
(b) Preventive controls must be written.
(c) Preventive controls include, as appropriate to the facility and
animal food:
(1) Process controls. Process controls include procedures,
practices, and processes to ensure the control of parameters during
operations such as heat processing, irradiating, and refrigerating
animal food. Process controls must include, as appropriate to the nature
of the applicable control and its role in the facility's food safety
system:
(i) Parameters associated with the control of the hazard; and
(ii) The maximum or minimum value, or combination of values, to
which any biological, chemical, or physical parameter must be controlled
to significantly minimize or prevent a hazard requiring a process
control.
(2) Sanitation controls. Sanitation controls include procedures,
practices, and processes to ensure that the facility is maintained in a
sanitary condition adequate to significantly minimize or prevent hazards
such as environmental pathogens and biological hazards due to employee
handling. Sanitation controls must include, as appropriate to the
facility and the animal food, procedures, practices, and processes for
the:
(i) Cleanliness of animal food-contact surfaces, including animal
food-contact surfaces of utensils and equipment; and
(ii) Prevention of cross-contamination from insanitary objects and
from personnel to animal food, animal food-packaging material, and other
animal food-contact surfaces and from raw product to processed product.
(3) Supply-chain controls. Supply-chain controls include the supply-
chain program as required by subpart E of this part;
[[Page 50]]
(4) A recall plan as required by Sec. 507.38; and
(5) Other preventive controls. These include any other procedures,
practices, and processes necessary to satisfy the requirements of
paragraph (a) of this section. Examples of other controls include
hygiene training and other current good manufacturing practices.
Sec. 507.36 Circumstances in which the owner, operator, or agent
in charge of a manufacturing/processing facility is not required
to implement a preventive control.
(a) If you are a manufacturer/processor, you are not required to
implement a preventive control when you identify a hazard requiring a
preventive control (identified hazard) and any of the following
circumstances apply:
(1) You determine and document that the type of animal food could
not be consumed without application of an appropriate control;
(2) You rely on your customer who is subject to the requirements for
hazard analysis and risk-based preventive controls in this subpart to
ensure that the identified hazard will be significantly minimized or
prevented; and you:
(i) Disclose in documents accompanying the animal food, in
accordance with the practice of the trade, that the animal food is ``not
processed to control [identified hazard]''; and
(ii) Annually obtain from your customer written assurance, subject
to the requirements of Sec. 507.37, that the customer has established
and is following procedures (identified in the written assurance) that
will significantly minimize or prevent the identified hazard (except as
provided in paragraph (c) of this section);
(3) You rely on your customer who is not subject to the requirements
for hazard analysis and risk-based preventive controls in this subpart
to provide assurance it is manufacturing, processing, or preparing the
animal food in accordance with applicable animal food safety
requirements and you:
(i) Disclose in documents accompanying the animal food, in
accordance with the practice of the trade, that the animal food is ``not
processed to control [identified hazard]''; and
(ii) Annually obtain from your customer written assurance that it is
manufacturing, processing, or preparing the animal food in accordance
with applicable animal food safety requirements;
(4) You rely on your customer to provide assurance that the animal
food will be processed to control the identified hazard by an entity in
the distribution chain subsequent to the customer and you:
(i) Disclose in documents accompanying the animal food, in
accordance with the practice of the trade, that the animal food is ``not
processed to control [identified hazard]''; and
(ii) Annually obtain from your customer written assurance, subject
to the requirements of Sec. 507.37, that your customer:
(A) Will disclose in documents accompanying the animal food, in
accordance with the practice of the trade, that the animal food is ``not
processed to control [identified hazard]''; and
(B) Will only sell to another entity that agrees, in writing, it
will:
(1) Follow procedures (identified in a written assurance) that will
significantly minimize or prevent the identified hazard (if the entity
is subject to the requirements for hazard analysis and risk-based
preventive controls in subpart C of this part), except as provided in
paragraph (d) of this section, or manufacture, process, or prepare the
animal food in accordance with applicable animal food safety
requirements (if the entity is not subject to the requirements for
hazard analysis and risk-based preventive controls in subpart C of this
part); or
(2) Obtain a similar written assurance from the entity's customer,
subject to the requirements of Sec. 507.37, as in paragraphs
(a)(4)(ii)(A) and (B) of this section, as appropriate; or
(5) You have established, documented, and implemented a system that
ensures control, at a subsequent distribution step, of the hazards in
the animal food you distribute and you document the implementation of
that system.
(b) You must document any circumstance specified in paragraph (a) of
this section that applies to you, including:
[[Page 51]]
(1) A determination in accordance with paragraph (a) of this section
that the type of animal food could not be consumed without application
of an appropriate control;
(2) The annual written assurance from your customer in accordance
with paragraph (a)(2) of this section;
(3) The annual written assurance from your customer in accordance
with paragraph (a)(3) of this section;
(4) The annual written assurance from your customer in accordance
with paragraph (a)(4) of this section; and
(5) Your system, in accordance with paragraph (a)(5) of this
section, that ensures control, at a subsequent distribution step, of the
hazards in the animal food you distribute.
(c) For the written assurance required by paragraph (a)(2)(ii) of
this section, if your customer has determined that the identified hazard
in paragraph (a) of this section is not a hazard in the animal food
intended for use for a specific animal species, your customer's written
assurance may provide this determination (including animal species and
why the identified hazard is not a hazard) instead of providing
assurance of procedures established and followed that will significantly
minimize or prevent the identified hazard.
(d) For the written assurance required by paragraph (a)(4)(ii)(B) of
this section, if the entity in the distribution chain subsequent to your
customer is subject to subpart C of this part and has determined that
the identified hazard in paragraph (a) of this section is not a hazard
in the animal food intended for use for a specific animal species, that
entity's written assurance may provide this determination (including
animal species and why the identified hazard is not a hazard) instead of
providing assurance that the identified hazard will be significantly
minimized or prevented.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3717, Jan. 22, 2016]
Sec. 507.37 Provision of assurances required
under Sec. 507.36(a)(2), (3), and (4).
A facility that provides a written assurance under Sec.
507.36(a)(2), (3), or (4) must act consistently with the assurance and
document its actions taken to satisfy the written assurance.
Sec. 507.38 Recall plan.
(a) For animal food with a hazard requiring a preventive control you
must:
(1) Establish a written recall plan for the animal food; and
(2) Assign responsibility for performing all procedures in the
recall plan.
(b) The written recall plan must include procedures that describe
the steps to perform the following actions as appropriate to the
facility:
(1) Directly notify direct consignees about the animal food being
recalled, including how to return or dispose of the affected animal
food;
(2) Notify the public about any hazard presented by the animal food
when appropriate to protect human and animal health;
(3) Conduct effectiveness checks to verify the recall has been
carried out; and
(4) Appropriately dispose of recalled animal food, e.g., through
reprocessing, reworking, diverting to another use that would not present
a safety concern, or destroying the animal food.
Sec. 507.39 Preventive control management components.
(a) Except as provided by paragraphs (b) and (c) of this section,
the preventive controls required under Sec. 507.34 are subject to the
following preventive control management components as appropriate to
ensure the effectiveness of the preventive controls, taking into account
the nature of the preventive control and its role in the facility's food
safety system:
(1) Monitoring in accordance with Sec. 507.40;
(2) Corrective actions and corrections in accordance with Sec.
507.42; and
(3) Verification in accordance with Sec. 507.45.
(b) The supply-chain program established in subpart E of this part
is subject to the following preventive control management components as
appropriate to ensure the effectiveness of the supply-chain program,
taking into account the nature of the hazard controlled before receipt
of the raw material or other ingredient:
[[Page 52]]
(1) Corrective actions and corrections in accordance with Sec.
507.42, taking into account the nature of any supplier non-conformance;
(2) Review of records in accordance with Sec. 507.49(a)(4)(ii); and
(3) Reanalysis in accordance with Sec. 507.50.
(c) The recall plan established in Sec. 507.38 is not subject to
the requirements of paragraph (a) of this section.
Sec. 507.40 Monitoring.
As appropriate to the nature of the preventive control and its role
in the facility's food safety system you must:
(a) Establish and implement written procedures, including the
frequency with which they are to be performed, for monitoring the
preventive controls; and
(b) Monitor the preventive controls with adequate frequency to
provide assurance that they are consistently performed.
(c)(1) You must document the monitoring of preventive controls in
accordance with this section in records that are subject to verification
in accordance with Sec. 507.45(a)(2) and records review in accordance
with Sec. 507.49(a)(4)(i);
(2)(i) Records of refrigeration temperature during storage of animal
food that requires time/temperature control to significantly minimize or
prevent the growth of, or toxin production by, pathogens may be
affirmative records demonstrating temperature is controlled or exception
records demonstrating loss of temperature control; and
(ii) Exception records may be adequate in circumstances other than
monitoring of refrigeration temperature.
Sec. 507.42 Corrective actions and corrections.
(a) As appropriate to the nature of the hazard and the nature of the
preventive control, except as provided by paragraph (c) of this section:
(1) You must establish and implement written corrective action
procedures that must be taken if preventive controls are not properly
implemented, including procedures to address, as appropriate:
(i) The presence of a pathogen or appropriate indicator organism in
animal food detected as a result of product testing conducted in
accordance with Sec. 507.49(a)(2); and
(ii) The presence of an environmental pathogen or appropriate
indicator organism detected through the environmental monitoring
conducted in accordance with Sec. 507.49(a)(3).
(2) The corrective action procedures must describe the steps to be
taken to ensure that:
(i) Appropriate action is taken to identify and correct a problem
that has occurred with implementation of a preventive control;
(ii) Appropriate action is taken when necessary, to reduce the
likelihood that the problem will recur;
(iii) All affected animal food is evaluated for safety; and
(iv) All affected animal food is prevented from entering into
commerce if you cannot ensure the affected animal food is not
adulterated under section 402 of the Federal Food, Drug, and Cosmetic
Act.
(b)(1) Except as provided by paragraph (c) of this section, you are
subject to the requirements of paragraph (b)(2) of this section if any
of the following circumstances apply:
(i) A preventive control is not properly implemented and a
corrective action procedure has not been established;
(ii) A preventive control, combination of preventive controls, or
the food safety plan as a whole is found to be ineffective; or
(iii) A review of records in accordance with Sec. 507.49(a)(4)
finds that the records are not complete, the activities conducted did
not occur in accordance with the food safety plan, or appropriate
decisions were not made about corrective actions.
(2) If any of the circumstances listed in paragraph (b)(1) of this
section apply, you must:
(i) Take corrective action to identify and correct the problem;
(ii) Reduce the likelihood that the problem will recur;
(iii) Evaluate all affected animal food for safety;
(iv) As necessary, prevent affected animal food from entering
commerce
[[Page 53]]
as would be done following the corrective action procedure under
paragraph (a)(2) of this section; and
(v) When appropriate, reanalyze the food safety plan in accordance
with Sec. 507.50 to determine whether modification of the food safety
plan is required.
(c) You do not need to comply with the requirements of paragraphs
(a) and (b) of this section if:
(1) You take action, in a timely manner, to identify and correct
conditions and practices that are not consistent with the sanitation
controls in Sec. 507.34(c)(2)(i) or (ii); or
(2) You take action, in a timely manner, to identify and correct a
minor and isolated problem that does not directly impact product safety.
(d) All corrective actions (and, when appropriate, corrections)
taken in accordance with this section must be documented in records.
These records are subject to verification in accordance with Sec.
507.45(a)(3) and records review in accordance with Sec.
507.49(a)(4)(i).
Sec. 507.45 Verification.
(a) Verification activities must include, as appropriate to the
nature of the preventive control and its role in the facility's food
safety system:
(1) Validation in accordance with Sec. 507.47;
(2) Verification that monitoring is being conducted as required by
Sec. 507.39 (and in accordance with Sec. 507.40);
(3) Verification that appropriate decisions about corrective actions
are being made as required by Sec. 507.39 (and in accordance with Sec.
507.42);
(4) Verification of implementation and effectiveness in accordance
with Sec. 507.49; and
(5) Reanalysis in accordance with Sec. 507.50.
(b) All verification activities conducted in accordance with this
section must be documented in records.
Sec. 507.47 Validation.
(a) You must validate that the preventive controls identified and
implemented in accordance with Sec. 507.34 are adequate to control the
hazard as appropriate to the nature of the preventive control and its
role in the facility's food safety system.
(b) The validation of the preventive controls:
(1) Must be performed (or overseen) by a preventive controls
qualified individual:
(i)(A) Prior to implementation of the food safety plan; or
(B) When necessary to demonstrate the control measures can be
implemented as designed:
(1) Within 90 calendar days after production of the applicable
animal food first begins; or
(2) Within a reasonable timeframe, provided that the preventive
controls qualified individual prepares (or oversees the preparation of)
a written justification for a timeframe that exceeds 90 calendar days
after production of the applicable animal food first begins;
(ii) Whenever a change to a control measure or combination of
control measures could impact whether the control measure or combination
of control measures, when properly implemented, will effectively control
the hazards; and
(iii) Whenever a reanalysis of the food safety plan reveals the need
to do so.
(2) Must include obtaining and evaluating scientific and technical
evidence (or, when such evidence is not available or is inadequate,
conducting studies) to determine whether the preventive controls, when
properly implemented, will effectively control the hazards.
(c) You do not need to validate:
(1) The sanitation controls in Sec. 507.34(c)(2);
(2) The recall plan in Sec. 507.38;
(3) The supply-chain program in subpart E of this part; and
(4) Other preventive controls, if the preventive controls qualified
individual prepares (or oversees the preparation of) a written
justification that validation is not applicable based on factors such as
the nature of the hazard, and the nature of the preventive control and
its role in the facility's food safety system.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3718, Jan. 22, 2016]
[[Page 54]]
Sec. 507.49 Verification of implementation and effectiveness.
(a) You must verify that the preventive controls are consistently
implemented and are effectively and significantly minimizing or
preventing the hazards. To do so, you must conduct activities that
include the following, as appropriate to the facility, the animal food,
and the nature of the preventive control and its role in the facility's
food safety system:
(1) Calibration of process monitoring and verification instruments
(or checking them for accuracy);
(2) Product testing for a pathogen (or appropriate indicator
organism) or other hazard;
(3) Environmental monitoring, for an environmental pathogen or for
an appropriate indicator organism, if contamination of an animal food
with an environmental pathogen is a hazard requiring a preventive
control, by collecting and testing environmental samples; and
(4) Review of the following records within the specified timeframes,
by (or under the oversight of) a preventive controls qualified
individual, to ensure the records are complete, the activities reflected
in the records occurred in accordance with the food safety plan, the
preventive controls are effective, and appropriate decisions were made
about corrective actions:
(i) Monitoring and corrective action records within 7-working days
after the records are created or within a reasonable timeframe, provided
that the preventive controls qualified individual prepares (or oversees
the preparation of) a written justification for a timeframe that exceeds
7-working days; and
(ii) Records of calibration, testing (e.g., product testing,
environmental monitoring), and supplier and supply-chain verification
activities, and other verification activities within a reasonable time
after the records are created; and
(5) Other activities appropriate for verification of implementation
and effectiveness.
(b) As appropriate to the facility, the food, the nature of the
preventive control, and the role of the preventive control in the
facility's food safety system, you must establish and implement written
procedures for the following activities:
(1) The method and frequency of calibrating process monitoring
instruments and verification instruments (or checking them for accuracy)
as required by paragraph (a)(1) of this section;
(2) Product testing as required by paragraph (a)(2) of this section.
Procedures for product testing must:
(i) Be scientifically valid;
(ii) Identify the test microorganism(s) or other analyte(s);
(iii) Specify the procedures for identifying samples, including
their relationship to specific lots of product;
(iv) Include the procedures for sampling, including the number of
samples and the sampling frequency;
(v) Identify the test(s) conducted, including the analytical
method(s) used;
(vi) Identify the laboratory conducting the testing; and
(vii) Include the corrective action procedures required by Sec.
507.42(a)(1).
(3) Environmental monitoring as required by paragraph (a)(3) of this
section. Procedures for environmental monitoring must:
(i) Be scientifically valid;
(ii) Identify the test microorganism(s);
(iii) Identify the locations from which samples will be collected
and the number of sites to be tested during routine environmental
monitoring. The number and location of sampling sites must be adequate
to determine whether preventive controls are effective;
(iv) Identify the timing and frequency for collecting and testing
samples. The timing and frequency for collecting and testing samples
must be adequate to determine whether preventive controls are effective;
(v) Identify the test(s) conducted, including the analytical
method(s) used;
(vi) Identify the laboratory conducting the testing; and
(vii) Include the corrective action procedures required by Sec.
507.42(a)(1)(ii).
Sec. 507.50 Reanalysis.
(a) You must conduct a reanalysis of the food safety plan as a whole
at least once every 3 years.
(b) You must conduct a reanalysis of the food safety plan as a
whole, or the
[[Page 55]]
applicable portion of the food safety plan:
(1) Whenever a significant change in the activities conducted at
your facility creates a reasonable potential for a new hazard or creates
a significant increase in a previously identified hazard;
(2) Whenever you become aware of new information about potential
hazards associated with the animal food;
(3) Whenever appropriate after an unanticipated animal food safety
problem in accordance with Sec. 507.42(b); and
(4) Whenever you find that a preventive control, combination of
preventive controls, or the food safety plan as a whole is ineffective.
(c) You must complete the reanalysis required by paragraphs (a) and
(b) of this section and validate, as appropriate to the nature of the
preventive control and its role in the facility's food safety system,
any additional preventive controls needed to address the hazard
identified:
(1) Before any change in activities (including any change in
preventive control) at the facility is operative; or
(2) When necessary to demonstrate the control measures can be
implemented as designed:
(i) Within 90 calendar days after production of the applicable
animal food first begins; or
(ii) Within a reasonable timeframe, provided that the preventive
controls qualified individual prepares (or oversees the preparation of)
a written justification for a timeframe that exceeds 90 calendar days
after production of the applicable animal food first begins.
(d) You must revise the written food safety plan if a significant
change in the activities conducted at your facility creates a reasonable
potential for a new hazard or a significant increase in a previously
identified hazard, or document the basis for the conclusion that no
revisions are needed.
(e) A preventive controls qualified individual must perform (or
oversee) the reanalysis.
(f) You must conduct a reanalysis of the food safety plan when FDA
determines it is necessary to respond to new hazards and developments in
scientific understanding.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3718, Jan. 22, 2016]
Sec. 507.51 Modified requirements that apply to a facility
solely engaged in the storage of unexposed packaged animal food.
(a) If a facility that is solely engaged in the storage of unexposed
packaged animal food stores any such refrigerated packaged animal food
that requires time/temperature control to significantly minimize or
prevent the growth of, or toxin formation by pathogens, the facility
must conduct the following activities as appropriate to ensure the
effectiveness of the temperature controls:
(1) Establish and implement temperature controls adequate to
significantly minimize or prevent the growth of, or toxin formation by,
pathogens;
(2) Monitor the temperature controls with adequate frequency to
provide assurance that the temperature controls are consistently
performed;
(3) If there is a loss of temperature control that may impact the
safety of such refrigerated packaged animal food, take appropriate
corrective actions to:
(i) Correct the problem and reduce the likelihood that the problem
will recur;
(ii) Evaluate all affected animal food for safety; and
(iii) Prevent the animal food from entering commerce, if you cannot
ensure the affected animal food is not adulterated under section 402 of
the Federal Food, Drug, and Cosmetic Act;
(4) Verify that temperature controls are consistently implemented
by:
(i) Calibrating temperature monitoring and recording devices (or
checking them for accuracy);
(ii) Reviewing records of calibration within a reasonable time after
the records are created; and
(iii) Reviewing records of monitoring and corrective actions taken
to correct a problem with the control of temperature within 7-working
days after the records are created or within a reasonable timeframe,
provided that the preventive controls qualified individual prepares (or
oversees the preparation
[[Page 56]]
of) a written justification for a timeframe that exceeds 7-working days;
and
(5) Establish and maintain the following records:
(i) Records (whether affirmative records demonstrating temperature
is controlled or exception records demonstrating loss of temperature
control) documenting the monitoring of temperature controls for any such
refrigerated packaged animal food;
(ii) Records of corrective actions taken when there is a loss of
temperature control that may impact the safety of any such refrigerated
packaged animal food; and
(iii) Records documenting the verification activities.
(b) The records that a facility must establish and maintain under
paragraph (a)(5) of this section are subject to the requirements of
subpart F of this part.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3718, Jan. 22, 2016]
Sec. 507.53 Requirements applicable to a preventive controls
qualified individual and a qualified auditor.
(a) One or more preventive controls qualified individuals must do or
oversee the following:
(1) Preparation of the food safety plan (Sec. 507.31(b));
(2) Validation of the preventive controls (Sec. 507.47(b)(1));
(3) Written justification for validation to be performed in a
timeframe that exceeds the first 90 calendar days of production of the
applicable animal food;
(4) Determination that validation is not required (Sec.
507.47(c)(4));
(5) Review of records (Sec. 507.49(a)(4));
(6) Written justification for review of records of monitoring and
corrective actions within a timeframe that exceeds 7-working days;
(7) Reanalysis of the food safety plan (Sec. 507.50(d)); and
(8) Determination that reanalysis can be completed, and additional
preventive controls validated, as appropriate to the nature of the
preventive control and its role in the facility's food safety system, in
a timeframe that exceeds the first 90 calendar days of production of the
applicable animal food.
(b) A qualified auditor must conduct an onsite audit (Sec.
507.135(a)).
(c)(1) To be a preventive controls qualified individual, the
individual must have successfully completed training in the development
and application of risk-based preventive controls at least equivalent to
that received under a standardized curriculum recognized as adequate by
FDA or be otherwise qualified through job experience to develop and
apply a food safety system. Job experience may qualify an individual to
perform these functions if such experience has provided an individual
with knowledge at least equivalent to that provided through the
standardized curriculum. This individual may be, but is not required to
be, an employee of the facility; and
(2) To be a qualified auditor, a qualified individual must have
technical expertise obtained through education, training, or experience
(or a combination thereof) necessary to perform the auditing function.
(d) All applicable training in the development and application of
risk-based preventive controls must be documented in records, including
the date of the training, the type of training, and the person(s)
trained.
Sec. 507.55 Implementation records required for this subpart.
(a) You must establish and maintain the following records
documenting implementation of the food safety plan:
(1) Documentation, as required by Sec. 507.36(b), of the basis for
not establishing a preventive control in accordance with Sec.
507.36(a);
(2) Records that document the monitoring of preventive controls;
(3) Records that document corrective actions;
(4) Records that document verification, including, as applicable,
those related to:
(i) Validation;
(ii) Verification of monitoring;
(iii) Verification of corrective actions;
(iv) Calibration of process monitoring and verification instruments;
(v) Product testing;
(vi) Environmental monitoring;
(vii) Records review; and
(viii) Reanalysis;
[[Page 57]]
(5) Records that document the supply-chain program; and
(6) Records that document applicable training for the preventive
controls qualified individual and the qualified auditor.
(b) The records that you must establish and maintain are subject to
the requirements of subpart F of this part.
Subpart D_Withdrawal of a Qualified Facility Exemption
Sec. 507.60 Circumstances that may lead FDA to withdraw
a qualified facility exemption.
(a) FDA may withdraw a qualified facility exemption under Sec.
507.5(d):
(1) In the event of an active investigation of a foodborne illness
outbreak that is directly linked to the qualified facility; or
(2) If FDA determines that it is necessary to protect the public
(human or animal) health and prevent or mitigate a foodborne illness
outbreak based on conditions or conduct associated with the qualified
facility that are material to the safety of the animal food
manufactured, processed, packed, or held at such facility.
(b) Before FDA issues an order to withdraw a qualified facility
exemption, FDA:
(1) May consider one or more other actions to protect the public
(human or animal) health or mitigate a foodborne illness outbreak,
including, a warning letter, recall, administrative detention,
suspension of registration, refusal of animal food offered for import,
seizure, and injunction;
(2) Must notify the owner, operator, or agent in charge of the
facility, in writing of circumstances that may lead FDA to withdraw the
exemption, and provide an opportunity for the owner, operator, or agent
in charge of the facility to respond in writing, within 15 calendar days
of the date of receipt of the notification, to FDA's notification; and
(3) Must consider the actions taken by the facility to address the
circumstances that may lead FDA to withdraw the exemption.
Sec. 507.62 Issuance of an order to withdraw a qualified facility exemption.
(a) An FDA Division Director in whose division the qualified
facility is located (or, in the case of a foreign facility, the Director
of the Division of Compliance in the Center for Veterinary Medicine), or
an FDA official senior to either such Director, must approve an order to
withdraw the exemption before the order is issued.
(b) Any officer or qualified employee of FDA may issue an order to
withdraw the exemption after it has been approved in accordance with
paragraph (a) of this section.
(c) FDA must issue an order to withdraw the exemption to the owner,
operator, or agent in charge of the facility.
(d) FDA must issue an order to withdraw the exemption in writing,
signed and dated by the officer or qualified employee of FDA who is
issuing the order.
[80 FR 56337, Sept. 17, 2015, as amended at 85 FR 16554, Mar. 24, 2020]
Sec. 507.65 Contents of an order to withdraw a qualified facility exemption.
An order to withdraw a qualified facility exemption under Sec.
507.5(d) must include the following information:
(a) The date of the order;
(b) The name, address, and location of the qualified facility;
(c) A brief, general statement of the reasons for the order,
including information relevant to one or both of the following
circumstances that leads FDA to issue the order:
(1) An active investigation of a foodborne illness outbreak that is
directly linked to the facility; or
(2) Conditions or conduct associated with a qualified facility that
are material to the safety of the animal food manufactured, processed,
packed, or held at such facility.
(d) A statement that the facility must either:
(1) Comply with subparts C and E of this part on the date that is
120 calendar days after the date of receipt of the order or within a
reasonable timeframe, agreed to by FDA, based on a written
justification, submitted to FDA, for a timeframe that exceeds 120
calendar days from the date of receipt of the order; or
[[Page 58]]
(2) Appeal the order within 15 calendar days of the date of receipt
of the order in accordance with the requirements of Sec. 507.69.
(e) A statement that a facility may request that FDA reinstate an
exemption that was withdrawn by following the procedures in Sec.
507.85;
(f) The text of section 418(l) of the Federal Food, Drug, and
Cosmetic Act and of this subpart;
(g) A statement that any informal hearing on an appeal of the order
must be conducted as a regulatory hearing under part 16 of this chapter,
with certain exceptions described in Sec. 507.73;
(h) The mailing address, telephone number, email address, fax
number, and name of the FDA Division Director in whose division the
facility is located (or, in the case of a foreign facility, the same
information for the Director of the Division of Compliance in the Center
for Veterinary Medicine); and
(i) The name and the title of the FDA representative who approved
the order.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3718, Jan. 22, 2016;
85 FR 16554, Mar. 24, 2020]
Sec. 507.67 Compliance with, or appeal of, an order to withdraw
a qualified facility exemption.
(a) If you receive an order under Sec. 507.65 to withdraw a
qualified facility exemption, you must either:
(1) Comply with applicable requirements of this part within 120
calendar days of the date of receipt of the order, or within a
reasonable timeframe, agreed to by FDA, based on a written
justification, submitted to FDA, for a timeframe that exceeds 120
calendar days from the date of receipt of the order; or
(2) Appeal the order within 15 calendar days of the date of receipt
of the order in accordance with the requirements of Sec. 507.69.
(b) Submission of an appeal, including submission of a request for
an informal hearing, will not operate to delay or stay any
administrative action, including enforcement action by FDA, unless the
Commissioner of Food and Drugs, as a matter of discretion, determines
that delay or a stay is in the public interest.
(c) If you appeal the order, and FDA confirms the order:
(1) You must comply with applicable requirements of this part within
120 calendar days of the date of receipt of the order, or within a
reasonable timeframe, agreed to by FDA, based on a written
justification, submitted to FDA, for a timeframe that exceeds 120
calendar days from the date of receipt of the order; and
(2) You are no longer subject to the requirements in Sec. 507.7.
Sec. 507.69 Procedure for submitting an appeal.
(a) To appeal an order to withdraw a qualified facility exemption,
you must:
(1) Submit the appeal in writing to the FDA Division Director in
whose division the facility is located (or, in the case of a foreign
facility, the Director of the Division of Compliance in the Center for
Veterinary Medicine), at the mailing address, email address, or fax
number identified in the order within 15 calendar days of the date of
receipt of confirmation of the order; and
(2) Respond with particularity to the facts and issues contained in
the order, including any supporting documentation upon which you rely.
(b) In a written appeal of the order withdrawing an exemption
provided under Sec. 507.5(d), you may include a written request for an
informal hearing as provided in Sec. 507.71.
[80 FR 56337, Sept. 17, 2015, as amended at 81 FR 3718, Jan. 22, 2016;
85 FR 16554, Mar. 24, 2020]
Sec. 507.71 Procedure for requesting an informal hearing.
(a) If you appeal the order, you:
(1) May request an informal hearing; and
(2) Must submit any request for an informal hearing together with
your written appeal submitted in accordance with Sec. 507.69 within 15
calendar days of the date of receipt of the order.
(b) A request for an informal hearing may be denied, in whole or in
part, if the presiding officer determines that no genuine and
substantial issue of material fact has been raised by the material
submitted. If the presiding officer
[[Page 59]]
determines that a hearing is not justified, written notice of the
determination will be given to you explaining the reason for the denial.
Sec. 507.73 Requirements applicable to an informal hearing.
If you request an informal hearing, and FDA grants the request:
(a) The hearing will be held within 15 calendar days after the date
the appeal is filed or, if applicable, within a timeframe agreed upon in
writing by you and FDA.
(b) The presiding officer may require that a hearing conducted under
this subpart be completed within 1 calendar day, as appropriate.
(c) FDA must conduct the hearing in accordance with part 16 of this
chapter, except that:
(1) The order withdrawing an exemption under Sec. Sec. 507.62 and
507.65, rather than the notice under Sec. 16.22(a) of this chapter,
provides notice of opportunity for a hearing under this section and is
part of the administrative record of the regulatory hearing under Sec.
16.80(a) of this chapter.
(2) A request for a hearing under this subpart must be addressed to
the FDA Division Director (or, in the case of a foreign facility, the
Director of the Division of Compliance in the Center for Veterinary
Medicine) as provided in the order withdrawing an exemption.
(3) Section 507.75, rather than Sec. 16.42(a) of this chapter,
describes the FDA employees who preside at hearings under this subpart.
(4) Section 16.60(e) and (f) of this chapter does not apply to a
hearing under this subpart. The presiding officer must prepare a written
report of the hearing. All written material presented at the hearing
will be attached to the report. The presiding officer must include as
part of the report of the hearing a finding on the credibility of
witnesses (other than expert witnesses) whenever credibility is a
material issue, and must include a proposed decision, with a statement
of reasons. The hearing participant may review and comment on the
presiding officer's report within 2 calendar days of issuance of the
report. The presiding officer will then issue the final decision.
(5) Section 16.80(a)(4) of this chapter does not apply to a
regulatory hearing under this subpart. The presiding officer's report of
the hearing and any comments on the report by the hearing participant
under paragraph (c)(4) of this section are part of the administrative
record.
(6) No party shall have the right, under Sec. 16.119 of this
chapter to petition the Commissioner of Food and Drugs for
reconsideration or a stay of the presiding officer's final decision.
(7) If FDA grants a request for an informal hearing on an appeal of
an order withdrawing an exemption, the hearing must be conducted as a
regulatory hearing under a regulation in accordance with part 16 of this
chapter, except that Sec. 16.95(b) does not apply to a hearing under
this subpart. With respect to a regulatory hearing under this subpart,
the administrative record of the hearing specified in Sec. Sec.
16.80(a)(1) through (3), and (a)(5), of this chapter, and 507.73(c)(5)
constitutes the exclusive record for the presiding officer's final
decision. For purposes of judicial review under Sec. 10.45 of this
chapter, the record of the administrative proceeding consists of the
record of the hearing and the presiding officer's final decision.
[80 FR 56337, Sept. 17, 2015, as amended at 85 FR 16554, Mar. 24, 2020]
Sec. 507.75 Presiding officer for an appeal and for an informal hearing.
The presiding officer for an appeal, and for an informal hearing,
must be an Office of Regulatory Affairs Program Director or another FDA
official senior to an FDA Division Director.
[85 FR 16555, Mar. 24, 2020]
Sec. 507.77 Timeframe for issuing a decision on an appeal.
(a) If you appeal the order without requesting a hearing, the
presiding officer must issue a written report that includes a final
decision confirming or revoking the withdrawal by the 10th calendar day
after the appeal is filed.
(b) If you appeal the order and request an informal hearing:
(1) If FDA grants the request for a hearing and the hearing is held,
the
[[Page 60]]
presiding officer must provide a 2 calendar day opportunity for the
hearing participants to review and submit comments on the report of the
hearing under Sec. 507.73(c)(4), and must issue a final decision within
10 calendar days after the hearing is held; or
(2) If FDA denies the request for a hearing, the presiding officer
must issue a final decision on the appeal confirming or revoking the
withdrawal within 10 calendar days after the date the appeal is filed.
Sec. 507.80 Revocation of an order to withdraw
a qualified facility exemption.
An order to withdraw a qualified facility exemption is revoked if:
(a) You appeal the order and request an informal hearing, FDA grants
the request for an informal hearing, and the presiding officer does not
confirm the order within the 10 calendar days after the hearing, or
issues a decision revoking the order within that time; or
(b) You appeal the order and request an informal hearing, FDA denies
the request for an informal hearing, and FDA does not confirm the order
within the 10 calendar days after the appeal is filed, or issues a
decision revoking the order within that time; or
(c) You appeal the order without requesting an informal hearing, and
FDA does not confirm the order within the 10 calendar days after the
appeal is filed, or issues a decision revoking the order within that
time.
Sec. 507.83 Final agency action.
Confirmation of a withdrawal order by the presiding officer is
considered a final agency action for purposes of 5 U.S.C. 702.
Sec. 507.85 Reinstatement of a qualified facility exemption
that was withdrawn.
(a) If the FDA Division Director in whose division your facility is
located (or, in the case of a foreign facility, the Director of the
Division of Compliance in the Center for Veterinary Medicine) determines
that a facility has adequately resolved any problems with the conditions
and conduct that are material to the safety of the animal food
manufactured, processed, packed, or held at the facility and that
continued withdrawal of the exemption is not necessary to protect public
(human and animal) health and prevent or mitigate a foodborne illness
outbreak, the FDA Division Director in whose division your facility is
located (or, in the case of a foreign facility, the Director of the
Division of Compliance in the Center for Veterinary Medicine) will, on
his or her own initiative or on the request of a facility, reinstate the
exemption.
(b) You may ask FDA to reinstate an exemption that has been
withdrawn under the procedures of this subpart as follows:
(1) Submit a request, in writing, to the FDA Division Director in
whose division your facility is located (or, in the case of a foreign
facility, the Director of the Division of Compliance in the Center for
Veterinary Medicine); and
(2) Present data and information to demonstrate that you have
adequately resolved any problems with the conditions and conduct that
are material to the safety of the animal food manufactured, processed,
packed, or held at your facility, such that continued withdrawal of the
exemption is not necessary to protect public (human and animal) health
and prevent or mitigate a foodborne illness outbreak.
(c) If your exemption was withdrawn under Sec. 507.60(a)(1) and FDA
later determines, after finishing the active investigation of a
foodborne illness outbreak, that the outbreak is not directly linked to
your facility, FDA will reinstate your exemption under Sec. 507.5(d),
and FDA will notify you in writing that your exempt status has been
reinstated.
(d) If your exemption was withdrawn under both Sec. 507.60(a)(1)
and (2) and FDA later determines, after finishing the active
investigation of a foodborne illness outbreak, that the outbreak is not
directly linked to your facility, FDA will inform you of this finding
and you may ask FDA to reinstate your exemption under Sec. 507.5(d) in
accordance with the requirements of paragraph (b) of this section.
[80 FR 56337, Sept. 17, 2015, as amended at 85 FR 16555, Mar. 24, 2020]
[[Page 61]]
Subpart E_Supply-Chain Program
Sec. 507.105 Requirement to establish and implement a supply-chain program.
(a)(1) Except as provided by paragraphs (a)(2) and (3) of this
section, the receiving facility must establish and implement a risk-
based supply-chain program for those raw materials and other ingredients
for which the receiving facility has identified a hazard requiring a
supply-chain-applied control.
(2) A receiving facility that is an importer, is in compliance with
the foreign supplier verification requirements under part 1, subpart L
of this chapter, and has documentation of verification activities
conducted under Sec. 1.506(e) of this chapter (which provides assurance
that the hazards requiring a supply-chain-applied control for the raw
material or other ingredient have been significantly minimized or
prevented) need not conduct supplier verification activities for that
raw material or other ingredient.
(3) The requirements in this subpart do not apply to animal food
that is supplied for research or evaluation use, provided that such
animal food:
(i) Is not intended for retail sale and is not sold or distributed
to the public;
(ii) Is labeled with the statement ``Animal food for research or
evaluation use'';
(iii) Is supplied in a small quantity that is consistent with a
research, analysis, or quality assurance purpose, the animal food is
used only for this purpose, and any unused quantity is properly disposed
of; and
(iv) Is accompanied with documents, in accordance with the practice
of the trade, stating that the animal food will be used for research or
evaluation purposes and cannot be sold or distributed to the public.
(b) The supply-chain program must be written.
(c) When a supply-chain-applied control is applied by an entity
other than the receiving facility's supplier (e.g., when a non-supplier
applies controls to certain produce (i.e., produce covered by part 112
of this chapter), because growing, harvesting, and packing activities
are under different management), the receiving facility must:
(1) Verify the supply-chain-applied control; or
(2) Obtain documentation of an appropriate verification activity
from another entity, review and assess the entity's applicable
documentation, and document that review and assessment.
Effective Date Note: At 80 FR 56337, Sept. 17, 2015, part 507 was
added, effective Nov. 16, 2015, with the exception of paragraph (a)(2)
in Sec. 507.105, which is not yet effective.
Sec. 507.110 General requirements applicable to a supply-chain program.
(a) The supply-chain program must include:
(1) Using approved suppliers as required by Sec. 507.120;
(2) Determining appropriate supplier verification activities
(including determining the frequency of conducting the activity) as
required by Sec. 507.125;
(3) Conducting supplier verification activities as required by
Sec. Sec. 507.130 and 507.135;
(4) Documenting supplier verification activities as required by
Sec. 507.175; and
(5) When applicable, verifying a supply-chain-applied control
applied by an entity other than the receiving facility's supplier and
documenting that verification as required by Sec. 507.175, or obtaining
documentation of an appropriate verification activity from another
entity, reviewing and assessing that documentation, and documenting the
review and assessment as required by Sec. 507.175.
(b) The following are appropriate supplier verification activities
for raw materials and other ingredients:
(1) Onsite audits;
(2) Sampling and testing of the raw material or other ingredient;
(3) Review of the supplier's relevant food safety records; and
(4) Other appropriate supplier verification activities based on
supplier performance and the risk associated with the raw material or
other ingredient.
(c) The supply-chain program must provide assurance that a hazard
requiring a supply-chain-applied control has been significantly
minimized or prevented.
[[Page 62]]
(d)(1) Except as provided by paragraph (d)(2) of this section, in
approving suppliers and determining the appropriate supplier
verification activities and the frequency with which they are conducted,
the following must be considered:
(i) The hazard analysis of the animal food, including the nature of
the hazard controlled before receipt of the raw material or other
ingredient, applicable to the raw material and other ingredients;
(ii) The entity or entities that will be applying controls for the
hazards requiring a supply-chain-applied control;
(iii) Supplier performance, including:
(A) The supplier's procedures, processes, and practices related to
the safety of the raw material and other ingredients;
(B) Applicable FDA food safety regulations and information relevant
to the supplier's compliance with those regulations, including an FDA
warning letter or import alert relating to the safety of animal food and
other FDA compliance actions related to animal food safety (or, when
applicable, relevant laws and regulations of a country whose food safety
system FDA has officially recognized as comparable or has determined to
be equivalent to that of the United States, and information relevant to
the supplier's compliance with those laws and regulations); and
(C) The supplier's food safety history relevant to the raw materials
or other ingredients that the receiving facility receives from the
supplier, including available information about results from testing raw
materials or other ingredients for hazards, audit results relating to
the safety of the animal food, and responsiveness of the supplier in
correcting problems; and
(iv) Any other factors as appropriate and necessary, such as storage
and transportation practices.
(2) Considering supplier performance can be limited to the
supplier's compliance history as required by paragraph (d)(1)(iii)(B) of
this section, if the supplier is:
(i) A qualified facility as defined by Sec. 507.3;
(ii) A farm that grows produce and is not a covered farm under part
112 of this chapter in accordance with Sec. 112.4(a), or in accordance
with Sec. Sec. 112.4(b) and 112.5; or
(iii) A shell egg producer that is not subject to the requirements
of part 118 of this chapter because it has less than 3,000 laying hens.
(e) If the owner, operator, or agent in charge of a receiving
facility determines through auditing, verification testing, document
review, relevant consumer, customer, or other complaints, or otherwise
that the supplier is not controlling hazards that the receiving facility
has identified as requiring a supply-chain-applied control, the
receiving facility must take and document prompt action in accordance
with Sec. 507.42 to ensure that raw materials or other ingredients from
the supplier do not cause animal food that is manufactured or processed
by the receiving facility to be adulterated under section 402 of the
Federal Food, Drug, and Cosmetic Act.
Sec. 507.115 Responsibilities of the receiving facility.
(a)(1) The receiving facility must approve suppliers.
(2) Except as provided by paragraphs (a)(3) and (4) of this section,
the receiving facility must determine and conduct appropriate supplier
verification activities, and satisfy all documentation requirements of
this subpart.
(3) An entity other than the receiving facility may do any of the
following, provided that the receiving facility reviews and assesses the
entity's applicable documentation, and documents that review and
assessment:
(i) Establish written procedures for receiving raw materials and
other ingredients by the entity;
(ii) Document that written procedures for receiving raw materials
and other ingredients are being followed by the entity; and
(iii) Determine, conduct, or both determine and conduct, the
appropriate supplier verification activities, with appropriate
documentation.
(4) The supplier may conduct and document sampling and testing of
raw materials and other ingredients, for the hazard controlled by the
supplier, as a supplier verification activity for a particular lot of
product and provide such documentation to the receiving
[[Page 63]]
facility, provided that the receiving facility reviews and assesses that
documentation, and documents that review and assessment.
(b) For the purposes of this subpart, a receiving facility may not
accept any of the following as a supplier verification activity:
(1) A determination by its supplier of the appropriate supplier
verification activities for that supplier;
(2) An audit conducted by its supplier;
(3) A review by its supplier of that supplier's own relevant food
safety records; or
(4) The conduct by its supplier of other appropriate supplier
verification activities for that supplier within the meaning of Sec.
507.110(b)(4).
(c) The requirements of this section do not prohibit a receiving
facility from relying on an audit provided by its supplier when the
audit of the supplier was conducted by a third-party qualified auditor
in accordance with Sec. Sec. 507.130(f) and 507.135.
Sec. 507.120 Using approved suppliers.
(a) The receiving facility must approve suppliers in accordance with
the requirements of Sec. 507.110(d), and document that approval, before
receiving raw materials and other ingredients received from those
suppliers;
(b)(1) Written procedures for receiving raw materials and other
ingredients must be established and followed;
(2) The written procedures for receiving raw materials and other
ingredients must ensure that raw materials and other ingredients are
received only from approved suppliers (or, when necessary and
appropriate, on a temporary basis from unapproved suppliers whose raw
materials or other ingredients are subjected to adequate verification
activities before acceptance for use); and
(3) Use of the written procedures for receiving raw materials and
other ingredients must be documented.
Sec. 507.125 Determining appropriate supplier verification activities
(including determining the frequency of conducting the activity).
Appropriate supplier verification activities (including the
frequency of conducting the activity) must be determined in accordance
with the requirements of Sec. 507.110(d).
Sec. 507.130 Conducting supplier verification activities for raw materials
and other ingredients.
(a) Except as provided by paragraphs (c), (d), or (e) of this
section, one or more of the supplier verification activities specified
in Sec. 507.110(b), as determined under Sec. 507.110(d), must be
conducted for each supplier before using the raw material or other
ingredient from that supplier and periodically thereafter.
(b)(1) Except as provided by paragraph (b)(2) of this section, when
a hazard in a raw material or other ingredient will be controlled by the
supplier and is one for which there is a reasonable probability that
exposure to the hazard will result in serious adverse health
consequences or death to humans or animals:
(i) The appropriate supplier verification activity is an onsite
audit of the supplier; and
(ii) The audit must be conducted before using the raw material or
other ingredient from the supplier and at least annually thereafter.
(2) The requirements of paragraph (b)(1) of this section do not
apply if there is a written determination that other verification
activities and/or less frequent onsite auditing of the supplier provide
adequate assurance that the hazards are controlled.
(c) If a supplier is a qualified facility as defined by Sec. 507.3,
the receiving facility does not need to comply with paragraphs (a) and
(b) of this section if the receiving facility:
(1) Obtains written assurance that the supplier is a qualified
facility as defined by Sec. 507.3:
(i) Before first approving the supplier for an applicable calendar
year; and
(ii) On an annual basis thereafter, by December 31 of each calendar
year, for the following calendar year; and
(2) Obtains written assurance, at least every 2 years, that the
supplier is producing the raw material or other ingredient in compliance
with applicable FDA food safety regulations (or, when applicable,
relevant laws and regulations of a country whose food safety system FDA
has officially recognized
[[Page 64]]
as comparable or has determined to be equivalent to that of the United
States). The written assurance must include either:
(i) A brief description of the preventive controls that the supplier
is implementing to control the applicable hazard in the animal food; or
(ii) A statement that the facility is in compliance with State,
local, county, tribal, or other applicable non-Federal food safety laws,
including relevant laws and regulations of foreign countries.
(d) If a supplier is a farm that grows produce and is not a covered
farm under part 112 of this chapter in accordance with Sec. 112.4(a),
or in accordance with Sec. Sec. 112.4(b) and 112.5, the receiving
facility does not need to comply with paragraphs (a) and (b) of this
section for produce that the receiving facility receives from the farm
as a raw material or other ingredient if the receiving facility:
(1) Obtains written assurance that the raw material or other
ingredient provided by the supplier is not subject to part 112 of this
chapter in accordance with Sec. 112.4(a), or in accordance with
Sec. Sec. 112.4(b) and 112.5:
(i) Before first approving the supplier for an applicable calendar
year; and
(ii) On an annual basis thereafter, by December 31 of each calendar
year, for the following calendar year; and
(2) Obtains written assurance, at least every 2 years, that the farm
acknowledges that its food is subject to section 402 of the Federal
Food, Drug, and Cosmetic Act (or, when applicable, that its food is
subject to relevant laws and regulations of a country whose food safety
system FDA has officially recognized as comparable or has determined to
be equivalent to that of the United States).
(e) If a supplier is a shell egg producer that is not subject to the
requirements of part 118 of this chapter because it has less than 3,000
laying hens, the receiving facility does not need to comply with
paragraphs (a) and (b) of this section if the receiving facility:
(1) Obtains written assurance that the shell eggs produced by the
supplier are not subject to part 118 because the shell egg producer has
less than 3,000 laying hens:
(i) Before first approving the supplier for an applicable calendar
year; and
(ii) On an annual basis thereafter, by December 31 of each calendar
year, for the following calendar year; and
(2) Obtains written assurance, at least every 2 years, that the
shell egg producer acknowledges that its food is subject to section 402
of the Federal Food, Drug, and Cosmetic Act (or, when applicable, that
its food is subject to relevant laws and regulations of a country whose
food safety system FDA has officially recognized as comparable or has
determined to be equivalent to that of the United States).
(f) There must not be any financial conflicts of interest that
influence the results of the verification activities listed in Sec.
507.110(b) and payment must not be related to the results of the
activity.
[80 FR 56337, Sept. 17, 2015, as amended at 84 FR 12491, Apr. 2, 2019]
Sec. 507.135 Onsite audit.
(a) An onsite audit of a supplier must be performed by a qualified
auditor.
(b) If the raw material or other ingredient at the supplier is
subject to one or more FDA food safety regulations, an onsite audit must
consider such regulations and include a review of the supplier's written
plan (e.g., Hazard Analysis and Critical Control Point (HACCP) plan or
other food safety plan), if any, and its implementation, for the hazard
being controlled (or, when applicable, an onsite audit may consider
relevant laws and regulations of a country whose food safety system FDA
has officially recognized as comparable or has determined to be
equivalent to that of the United States).
(c)(1) The following may be substituted for an onsite audit,
provided that the inspection was conducted within 1 year of the date
that the onsite audit would have been required to be conducted:
(i) The written results of an appropriate inspection of the supplier
for compliance with applicable FDA food safety regulations by FDA, by
representatives of other Federal Agencies (such as the United States
Department of Agriculture), or by representatives
[[Page 65]]
of State, local, tribal, or territorial agencies; or
(ii) For a foreign supplier, the written results of an inspection by
FDA or the food safety authority of a country whose food safety system
FDA has officially recognized as comparable or has determined to be
equivalent to that of the United States.
(2) For inspections conducted by the food safety authority of a
country whose food safety system FDA has officially recognized as
comparable or determined to be equivalent, the animal food that is the
subject of the onsite audit must be within the scope of the official
recognition or equivalence determination, and the foreign supplier must
be in, and under the regulatory oversight of, such country.
(d) If the onsite audit is solely conducted to meet the requirements
of this subpart by an audit agent of a certification body that is
accredited in accordance with regulations in part 1, subpart M of this
chapter, the audit is not subject to the requirements in those
regulations.
Effective Date Note: At 80 FR 56337, Sept. 17, 2015, part 507 was
added, effective Nov. 16, 2015, with the exception of paragraph (d) in
Sec. 507.135, which is not yet effective.
Sec. 507.175 Records documenting the supply-chain program.
(a) The records documenting the supply-chain program are subject to
the requirements of subpart F of this part.
(b) The receiving facility must review the records listed in
paragraph (c) of this section in accordance with Sec. 507.49(a)(4).
(c) The receiving facility must document the following in records as
applicable to its supply-chain program:
(1) The written supply-chain program;
(2) Documentation that a receiving facility that is an importer is
in compliance with the foreign supplier verification program
requirements under part 1, subpart L of this chapter, including
documentation of verification activities conducted under Sec. 1.506(e)
of this chapter;
(3) Documentation of the approval of a supplier;
(4) Written procedures for receiving raw materials and other
ingredients;
(5) Documentation demonstrating use of the written procedures for
receiving raw materials and other ingredients;
(6) Documentation of the determination of the appropriate supplier
verification activities for raw materials and other ingredients;
(7) Documentation of the conduct of an onsite audit. This
documentation must include:
(i) The name of the supplier subject to the onsite audit;
(ii) Documentation of audit procedures;
(iii) The dates the audit was conducted;
(iv) The conclusions of the audit;
(v) Corrective actions taken in response to significant deficiencies
identified during the audit; and
(vi) Documentation that the audit was conducted by a qualified
auditor;
(8) Documentation of sampling and testing conducted as a supplier
verification activity. This documentation must include:
(i) Identification of the raw material or other ingredient tested
(including lot number, as appropriate) and the number of samples tested;
(ii) Identification of the test(s) conducted, including the
analytical method(s) used;
(iii) The date(s) on which the test(s) were conducted and the date
of the report;
(iv) The results of the testing;
(v) Corrective actions taken in response to detection of hazards;
and
(vi) Information identifying the laboratory conducting the testing;
(9) Documentation of the review of the supplier's relevant food
safety records. This documentation must include:
(i) The name of the supplier whose records were reviewed;
(ii) The date(s) of review;
(iii) The general nature of the records reviewed;
(iv) The conclusions of the review; and
(v) Corrective actions taken in response to significant deficiencies
identified during the review;
(10) Documentation of other appropriate supplier verification
activities based on the supplier performance and
[[Page 66]]
the risk associated with the raw material or other ingredient;
(11) Documentation of any determination that verification activities
other than an onsite audit, and/or less frequent onsite auditing of a
supplier, provide adequate assurance that the hazards are controlled
when a hazard in a raw material or other ingredient will be controlled
by the supplier and is one for which there is a reasonable probability
that exposure to the hazard will result in serious adverse health
consequences or death to humans or animals;
(12) The following documentation of an alternative verification
activity for a supplier that is a qualified facility:
(i) The written assurance that the supplier is a qualified facility
as defined by Sec. 507.3; and
(ii) The written assurance that the supplier is producing the raw
material or other ingredient in compliance with applicable FDA food
safety regulations (or, when applicable, relevant laws and regulations
of a country whose food safety system FDA has officially recognized as
comparable or has determined to be equivalent to that of the United
States);
(13) The following documentation of an alternative verification
activity for a supplier that is a farm that supplies a raw material or
other ingredient and is not a covered farm under part 112 of this
chapter:
(i) The written assurance that supplier is not a covered farm under
part 112 of this chapter in accordance with Sec. 112.4(a), or in
accordance with Sec. Sec. 112.4(b) and 112.5; and
(ii) The written assurance that the farm acknowledges that its food
is subject to section 402 of the Federal Food, Drug, and Cosmetic Act
(or, when applicable, that its food is subject to relevant laws and
regulations of a country whose food safety system FDA has officially
recognized as comparable or has determined to be equivalent to that of
the United States);
(14) The following documentation of an alternative verification
activity for a supplier that is a shell egg producer that is not subject
to the requirements established in part 118 of this chapter because it
has less than 3,000 laying hens:
(i) The written assurance that the shell eggs provided by the
supplier are not subject to part 118 of this chapter because the
supplier has less than 3,000 laying hens; and
(ii) The written assurance that the shell egg producer acknowledges
that its food is subject to section 402 of the Federal Food, Drug, and
Cosmetic Act (or, when applicable, that its food is subject to relevant
laws and regulations of a country whose safety system FDA has officially
recognized as comparable or has determined to be equivalent to that of
the United States);
(15) The written results of an appropriate inspection of the
supplier for compliance with applicable FDA food safety regulations by
FDA, by representatives of other Federal Agencies (such as the United
States Department of Agriculture), or by representatives from State,
local, tribal, or territorial agencies, or the food safety authority of
another country when the results of such an inspection is substituted
for an onsite audit;
(16) Documentation of actions taken with respect to supplier non-
conformance;
(17) Documentation of verification of a supply-chain-applied control
applied by an entity other than the receiving facility's supplier; and
(18) When applicable, documentation of the receiving facility's
review and assessment of:
(i) Applicable documentation from an entity other than the receiving
facility that written procedures for receiving raw materials and other
ingredients are being followed;
(ii) Applicable documentation, from an entity other than the
receiving facility, of the determination of the appropriate supplier
verification activities for raw materials and other ingredients;
(iii) Applicable documentation, from an entity other than the
receiving facility, of conducting the appropriate supplier verification
activities for raw materials and other ingredients;
(iv) Applicable documentation, from its supplier, of:
(A) The results of sampling and testing conducted by the supplier;
or
(B) The results of an audit conducted by a third-party qualified
auditor in
[[Page 67]]
accordance with Sec. Sec. 507.130(f) and 507.135; and
(v) Applicable documentation, from an entity other than the
receiving facility, of verification activities when a supply-chain-
applied control is applied by an entity other than the receiving
facility's supplier.
Effective Date Note: At 80 FR 56337, Sept. 17, 2015, part 507 was
added, effective Nov. 16, 2015, with the exception of paragraph (c)(2)
in Sec. 507.175, which is not yet effective.
Subpart F_Requirements Applying to Records That Must Be Established and
Maintained
Sec. 507.200 Records subject to the requirements of this subpart.
(a) Except as provided by paragraphs (d) and (e) of this section,
all records required by this part are subject to all requirements of
this subpart.
(b) Records obtained by FDA in accordance with this part are subject
to the disclosure requirements under part 20 of this chapter.
(c) All records required by this part must be made promptly
available to a duly authorized representative of the Secretary of Health
and Human Services for official review and copying upon oral or written
request.
(d) The requirements of Sec. 507.206 apply only to the written food
safety plan.
(e) The requirements of Sec. 507.202(a)(2), (4), and (5) and (b) do
not apply to the records required by Sec. 507.7.
Sec. 507.202 General requirements applying to records.
(a) Records must:
(1) Be kept as original records, true copies (such as photocopies,
pictures, scanned copies, microfilm, microfiche, or other accurate
reproductions of the original records), or electronic records;
(2) Contain the actual values and observations obtained during
monitoring and as appropriate, during verification activities;
(3) Be accurate, indelible, and legible;
(4) Be created concurrently with performance of the activity
documented; and
(5) Be as detailed as necessary to provide history of work
performed.
(b) All records must include:
(1) Information adequate to identify the plant or facility (e.g.,
the name, and when necessary, the location of the plant or facility);
(2) The date and, when appropriate, the time of the activity
documented;
(3) The signature or initials of the person performing the activity;
and
(4) Where appropriate, the identity of the product and the lot code,
if any.
(c) Records that are established or maintained to satisfy the
requirements of this part and that meet the definition of electronic
records in Sec. 11.3(b)(6) of this chapter are exempt from the
requirements of part 11 of this chapter. Records that satisfy the
requirements of this part, but that also are required under other
applicable statutory provisions or regulations, remain subject to part
11 of this chapter.
Sec. 507.206 Additional requirements applying to the food safety plan.
The owner, operator, or agent in charge of the facility must sign
and date the food safety plan upon initial completion and upon any
modification.
Sec. 507.208 Requirements for record retention.
(a)(1) All records required by this part must be retained at the
plant or facility for at least 2 years after the date they were
prepared.
(2) Records that a facility relies on during the 3-year period
preceding the applicable calendar year to support its status as a
qualified facility must be retained at the facility as long as necessary
to support the status of a facility as a qualified facility during the
applicable calendar year.
(b) Records that relate to the general adequacy of the equipment or
processes being used by a facility, including the results of scientific
studies and evaluations, must be retained by the facility for at least 2
years after their use is discontinued (e.g., because the facility has
updated the written food safety plan (Sec. 507.31) or records that
document validation of the written food safety plan (Sec. 507.45(b))).
(c) Except for the food safety plan, offsite storage of records is
permitted if such records can be retrieved and
[[Page 68]]
provided onsite within 24 hours of request for official review. The food
safety plan must remain onsite. Electronic records are considered to be
onsite if they are accessible from an onsite location.
(d) If the plant or facility is closed for a prolonged period, the
food safety plan may be transferred to some other reasonably accessible
location but must be returned to the plant or facility within 24 hours
for official review upon request.
Sec. 507.212 Use of existing records.
(a) Existing records (e.g., records that are kept to comply with
other Federal, State, or local regulations, or for any other reason) do
not need to be duplicated if they contain all of the required
information and satisfy the requirements of this subpart. Existing
records may be supplemented as necessary to include all of the required
information and satisfy the requirements of this subpart.
(b) The information required by this part does not need to be kept
in one set of records. If existing records contain some of the required
information, any new information required by this part may be kept
either separately or combined with the existing records.
Sec. 507.215 Special requirements applicable to a written assurance.
(a) Any written assurance required by this part must contain the
following elements:
(1) Effective date;
(2) Printed names and signatures of authorized officials;
(3) The applicable assurance under:
(i) Sec. 507.36(a)(2);
(ii) Sec. 507.36(a)(3);
(iii) Sec. 507.36(a)(4);
(iv) Sec. 507.130(c)(2);
(v) Sec. 507.130(d)(2); or
(vi) Sec. 507.130(e)(2).
(b) A written assurance required under Sec. 507.36(a)(2), (3) or
(4) must include:
(1) Acknowledgement that the facility that provides the written
assurance assumes legal responsibility to act consistently with the
assurance and document its actions taken to satisfy the written
assurance; and
(2) Provision that if the assurance is terminated in writing by
either entity, responsibility for compliance with the applicable
provisions of this part reverts to the manufacturer/processor as of the
date of termination.
PART 509_UNAVOIDABLE CONTAMINANTS IN ANIMAL FOOD
AND FOOD-PACKAGING MATERIAL--Table of Contents
Subpart A_General Provisions
Sec.
509.3 Definitions and interpretations.
509.4 Establishment of tolerances, regulatory limits, and action levels.
509.5 Petitions.
509.6 Added poisonous or deleterious substances.
509.7 Unavoidability.
509.15 Use of polychlorinated biphenyls (PCB's) in establishments
manufacturing food-packaging materials.
Subpart B_Tolerances for Unavoidable Poisonous or Deleterious Substances
509.30 Temporary tolerances for polychlorinated biphenyls (PCB's).
Subpart C--Regulatory Limits for Added Poisonous or Deleterious Substances
[Reserved]
Subpart D--Naturally Occurring Poisonous or Deleterious Substances
[Reserved]
Authority: 21 U.S.C. 336, 342, 346, 346a, 348, 371.
Source: 42 FR 52821, Sept. 30, 1977, unless otherwise noted.
Subpart A_General Provisions
Sec. 509.3 Definitions and interpretations.
(a) Act means the Federal Food, Drug, and Cosmetic Act.
(b) The definitions of terms contained in section 201 of the act are
applicable to such terms when used in this part unless modified in this
section.
(c) A naturally occurring poisonous or deleterious substance is a
poisonous or deleterious substance that is an inherent natural
constituent of a food and is not the result of environmental,
agricultural, industrial, or other contamination.
[[Page 69]]
(d) An added poisonous or deleterious substance is a poisonous or
deleterious substance that is not a naturally occurring poisonous or
deleterious substance. When a naturally occurring poisonous or
deleterious substance is increased to abnormal levels through
mishandling or other intervening acts, it is an added poisonous or
deleterious substance to the extent of such increase.
(e) Food includes pet food, animal feed, and substances migrating to
food from food-contact articles.
Sec. 509.4 Establishment of tolerances, regulatory limits, and action levels.
(a) When appropriate under the criteria of Sec. 509.6, a tolerance
for an added poisonous or deleterious substance, which may be a food
additive, may be established by regulation in subpart B of this part
under the provisions of section 406 of the act. A tolerance may prohibit
any detectable amount of the substance in food.
(b) When appropriate under the criteria of Sec. 509.6, and under
section 402(a)(1) of the act, a regulatory limit for an added poisonous
or deleterious substance, which may be a food additive, may be
established by regulation in subpart C of this part under the provisions
of sections 402(a)(1) and 701(a) of the act. A regulatory limit may
prohibit any detectable amount of the substance in food. The regulatory
limit established represents the level at which food is adulterated
within the meaning of section 402(a)(1) of the act.
(c)(1) When appropriate under the criteria of Sec. 509.6, an action
level for an added poisonous or deleterious substance, which may be a
food additive, may be established to define a level of contamination at
which a food may be regarded as adulterated.
(2) Whenever an action level is established or changed, a notice
shall be published in the Federal Register as soon as practicable
thereafter. The notice shall call attention to the material supporting
the action level which shall be on file with the Division of Dockets
Management before the notice is published. The notice shall invite
public comment on the action level.
(d) A regulation may be established in subpart D of this part to
identify a food containing a naturally occurring poisonous or
deleterious substance which will be deemed to be adulterated under
section 402(a)(1) of the act. These regulations do not constitute a
complete list of such foods.
[42 FR 52821, Sept. 30, 1977, as amended at 55 FR 20786, May 21, 1990]
Sec. 509.5 Petitions.
The Commissioner of Food and Drugs, either on his own initiative or
on behalf of any interested person who has submitted a petition, may
issue a proposal to establish, revoke, or amend a regulation under this
part. Any such petition shall include an adequate factual basis to
support the petition, shall be in the form set forth in Sec. 10.30 of
this chapter, and will be published in the Federal Register for comment
if it contains reasonable grounds for the proposed regulation.
[42 FR 52821, Sept. 30, 1977, as amended at 54 FR 18280, Apr. 28, 1989]
Sec. 509.6 Added poisonous or deleterious substances.
(a) Use of an added poisonous or deleterious substance, other than a
pesticide chemical, that is also a food additive will be controlled by a
regulation issued under section 409 of the act when possible. When such
a use cannot be approved under the criteria of section 409 of the act,
or when the added poisonous or deleterious substance is not a food
additive, a tolerance, regulatory limit, or action level may be
established pursuant to the criteria in paragraphs (b), (c), or (d) of
this section. Residues resulting from the use of an added poisonous or
deleterious substance that is also a pesticide chemical will ordinarily
be controlled by a tolerance established in a regulation issued under
sections 406, 408, or 409 of the act by the U.S. Environmental
Protection Agency (EPA). When such a regulation has not been issued, an
action level for an added poisonous or deleterious substance that is
also a pesticide chemical may be established by the Food and Drug
Administration. The Food and Drug Administration will request EPA to
recommend such an action level pursuant to the criteria established in
paragraph (d) of this section.
[[Page 70]]
(b) A tolerance for an added poisonous or deleterious substance in
any food may be established when the following criteria are met:
(1) The substance cannot be avoided by good manufacturing practice.
(2) The tolerance established is sufficient for the protection of
the public health, taking into account the extent of which the presence
of the substance cannot be avoided and the other ways in which the
consumer may be affected by the same or related poisonous or deleterious
substances.
(3) No technological or other changes are foreseeable in the near
future that might affect the appropriateness of the tolerance
established. Examples of changes that might affect the appropriateness
of the tolerance include anticipated improvements in good manufacturing
practice that would change the extent to which use of the substance is
unavoidable and anticipated studies expected to provide significant new
toxicological or use data.
(c) A regulatory limit for an added poisonous or deleterious
substance in any food may be established when each of the following
criteria is met:
(1) The substance cannot be avoided by current good manufacturing
practices.
(2) There is no tolerance established for the substance in the
particular food under sections 406, 408, or 409 of the act.
(3) There is insufficient information by which a tolerance may be
established for the substance under section 406 of the act or
technological changes appear reasonably possible that may affect the
appropriateness of a tolerance. The regulatory limit established
represents the level at which food is adulterated within the meaning of
section 402(a)(1) of the act.
(d) An action level for an added poisonous or deleterious substance
in any food may be established when the criteria in paragraph (b) of
this section are met, except that technological or other changes that
might affect the appropriateness of the tolerance are foreseeable in the
near future. An action level for an added poisonous or deleterious
substance in any food may be established at a level at which the Food
and Drug Administration may regard the food as adulterated within the
meaning of section 402(a)(1) of the act, without regard to the criteria
in paragraph (b) of this section or in section 406 of the act. An action
level will be withdrawn when a tolerance or regulatory limit for the
same substance and use has been established.
(e) Tolerances will be established under authority appropriate for
action levels (sections 306, 402(a), and 701(a) of the act, together
with section 408 or 409 of the act, if appropriate) as well as under
authority appropriate for tolerances (sections 406 and 701 of the act).
In the event the effectiveness of a tolerance is stayed pursuant to
section 701(e)(2) of the act by the filing of an objection, the order
establishing the tolerance shall be deemed to be an order establishing
an action level until final action is taken upon such objection.
[42 FR 52821, Sept. 30, 1977, as amended at 55 FR 20786, May 21, 1990]
Sec. 509.7 Unavoidability.
(a) Tolerances and action levels in this part are established at
levels based on the unavoidability of the poisonous or deleterious
substance concerned and do not establish a permissible level of
contamination where it is avoidable.
(b) Compliance with tolerances, regulatory limits, and action levels
does not excuse failure to observe either the requirement in section
402(a)(4) of the act that food may not be prepared, packed, or held
under insanitary conditions or the other requirements in this chapter
that food manufacturers must observe current good manufacturing
practices. Evidence obtained through factory inspection or otherwise
indicating such a violation renders the food unlawful, even though the
amounts of poisonous or deleterious substances are lower than the
currently established tolerances, regulatory limits, or action levels.
The manufacturer of food must at all times utilize quality control
procedures which will reduce contamination to the lowest level currently
feasible.
[42 FR 52821, Sept. 30, 1977, as amended at 55 FR 20786, May 21, 1990]
[[Page 71]]
Sec. 509.15 Use of polychlorinated biphenyls (PCB's) in establishments
manufacturing food-packaging materials.
(a) Polychlorinated biphenyls (PCB's) represent a class of toxic
industrial chemicals manufactured and sold under a variety of trade
names, including: Aroclor (United States); Phenoclor (France); Colphen
(Germany); and Kanaclor (Japan). PCB's are highly stable, heat
resistant, and nonflammable chemicals. Industrial uses of PCB's include,
or did include in the past, their use as electrical transformer and
capacitor fluids, heat transfer fluids, hydraulic fluids, and
plasticizers, and in formulations of lubricants, coatings, and inks.
Their unique physical and chemical properties and widespread,
uncontrolled industrial applications have caused PCB's to be a
persistent and ubiquitous contaminant in the environment, causing the
contamination of certain foods. In addition, incidents have occurred in
which PCB's have directly contaminated animal feeds as a result of
industrial accidents (leakage or spillage of PCB fluids from plant
equipment). These accidents in turn caused the contamination of food
products intended for human consumption (meat, milk and eggs).
Investigations by the Food and Drug Administration have revealed that a
significant percentage of paper food-packaging material contains PCB's
which can migrate to the packaged food. The origin of PCB's in such
material is not fully understood. Reclaimed fibers containing carbonless
copy paper (contains 3 to 5 percent PCB's) have been identified as a
primary source of PCB's in paper products. Some virgin paper products
have also been found to contain PCB's, the source of which is generally
attributed to direct contamination from industrial accidents from the
use of PCB-containing equipment and machinery in food-packaging
manufacturing establishments. Since PCB's are toxic chemicals, the PCB
contamination of food-packaging materials as a result of industrial
accidents, which can cause the PCB contamination of food, represents a
hazard to public health. It is therefore necessary to place certain
restrictions on the industrial uses of PCB's in establishments
manufacturing food-packaging materials.
(b) The following special provisions are necessary to preclude the
accidental PCB contamination of food-packaging materials:
(1) New equipment or machinery for manufacturing food-packaging
materials shall not contain or use PCB's.
(2) On or before September 4, 1973, the management of establishments
manufacturing food-packaging materials shall:
(i) Have the heat exchange fluid used in existing equipment for
manufacturing food-packaging materials sampled and tested to determine
whether it contains PCB's or verify the absence of PCB's in such
formulations by other appropriate means. On or before Sept. 4, 1973, any
such fluid formulated with PCB's must to the fullest extent possible
commensurate with current good manufacturing practices be replaced with
a heat exchange fluid that does not contain PCB's.
(ii) Eliminate to the fullest extent possible commensurate with
current good manufacturing practices from the establishment any other
PCB-containing equipment, machinery and materials wherever there is a
reasonable expectation that such articles could cause food-packaging
materials to become contaminated with PCB's either as a result of normal
use or as a result of accident, breakage, or other mishap.
(iii) The toxicity and other characteristics of fluids selected as
PCB replacements must be adequately determined so that the least
potentially hazardous replacement is used. In making this determination
with respect to a given fluid, consideration should be given to (a) its
toxicity; (b) the maximum quantity that could be spilled onto a given
quantity of food before it would be noticed, taking into account its
color and odor; (c) possible signaling devices in the equipment to
indicate a loss of fluid, etc.; and (d) its environmental stability and
tendency to survive and be concentrated through the food chain. The
judgment as to whether a replacement fluid is sufficiently non-hazardous
is to be made on an individual installation and operation basis.
(c) The provisions of this section do not apply to electrical
transformers
[[Page 72]]
and condensers containing PCB's in sealed containers.
Subpart B_Tolerances for Unavoidable Poisonous or Deleterious Substances
Sec. 509.30 Temporary tolerances for polychlorinated biphenyls (PCB's).
(a) Polychlorinated biphenyls (PCB's) are toxic, industrial
chemicals. Because of their widespread, uncontrolled industrial
applications, PCB's have become a persistent and ubiquitous contaminant
in the environment. As a result, certain foods and animal feeds,
principally those of animal and marine origin, contain PCB's as
unavoidable, environmental contaminants. PCB's are transmitted to the
food portion (meat, milk, and eggs) of food producing animals ingesting
PCB contaminated animal feed. In addition, a significant percentage of
paper food-packaging materials contain PCB's which may migrate to the
packaged food. The source of PCB's in paper food-packaging materials is
primarily of certain types of carbonless copy paper (containing 3 to 5
percent PCB's) in waste paper stocks used for manufacturing recycled
paper. Therefore, temporary tolerances for residues of PCB's as
unavoidable environmental or industrial contaminants are established for
a sufficient period of time following the effective date of this
paragraph to permit the elimination of such contaminants at the earliest
practicable time. For the purposes of this paragraph, the term
polychlorinated biphenyls (PCB's) is applicable to mixtures of
chlorinated biphenyl compounds, irrespective of which mixture of PCB's
is present as the residue. The temporary tolerances for residues of
PCB's are as follows:
(1) 0.2 part per million in finished animal feed for food-producing
animals (except the following finished animal feeds: feed concentrates,
feed supplements, and feed premixes).
(2) 2 parts per million in animal feed components of animal origin,
including fishmeal and other by-products of marine origin and in
finished animal feed concentrates, supplements, and premixes intended
for food-producing animals.
(3) 10 parts per million in paper food-packaging material intended
for or used with finished animal feed and any components intended for
animal feeds. The tolerance shall not apply to paper food-packaging
material separated from the food therein by a functional barrier which
is impermeable to migration of PCB's.
(b) A compilation entitled ``Analytical Methodology for
Polychlorinated Biphenyls, February 1973'' for determining compliance
with the tolerances established in this section is available from the
Division of Dockets Management, Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852.
[42 FR 52821, Sept. 30, 1977, as amended at 46 FR 8460, Jan. 27, 1981;
59 FR 14365, Mar. 28, 1994; 68 FR 24879, May 9, 2003]
Subpart C--Regulatory Limits for Added Poisonous or Deleterious Substances
[Reserved]
Subpart D--Naturally Occurring Poisonous or Deleterious Substances
[Reserved]
PART 510_NEW ANIMAL DRUGS--Table of Contents
Subpart A_General Provisions
Sec.
510.3 Definitions and interpretations.
510.4 Biologics; products subject to license control.
510.7 Consignees of new animal drugs for use in the manufacture of
animal feed.
510.95 [Reserved]
Subpart B_Specific Administrative Rulings and Decisions
510.105 Labeling of drugs for use in milk-producing animals.
510.106 Labeling of antibiotic and antibiotic-containing drugs intended
for use in milk-producing animals.
510.110 Antibiotics used in food-producing animals.
510.112 Antibiotics used in veterinary medicine and for nonmedical
purposes; required data.
Subpart C_Import Tolerances for Residues of Unapproved New Animal Drugs
in Food
510.201 Scope.
510.202 Definitions.
[[Page 73]]
510.203 Initiation of a proceeding to establish or amend an import
tolerance.
510.205 Content and administration of a request.
510.206 Review of information supporting actions to establish or amend
an import tolerance.
510.207 Disclosure of information submitted in a request.
510.209 Establishment, denial, or amendment of an import tolerance.
510.210 Revocation of an import tolerance.
510.212 Administrative reconsideration of action.
510.213 Administrative stay of action.
Subpart D_Records and Reports
510.301 Records and reports concerning experience with animal feeds
bearing or containing new animal drugs for which an approved
medicated feed mill license application is in effect.
510.305 Maintenance of copies of approved medicated feed mill licenses
to manufacture animal feed bearing or containing new animal
drugs.
Subpart E_Requirements for Specific New Animal Drugs
510.410 Corticosteroids for oral, injectable, and ophthalmic use in
animals; warnings and labeling requirements.
510.440 Injectable iron preparations.
510.455 Requirements for free-choice medicated feeds.
Subpart F [Reserved]
Subpart G_Sponsors of Approved Applications
510.600 Names, addresses, and drug labeler codes of sponsors of approved
applications.
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e.
Source: 40 FR 13807, Mar. 27, 1975, unless otherwise noted.
Subpart A_General Provisions
Sec. 510.3 Definitions and interpretations.
As used in this part:
(a) The term act means the Federal Food, Drug, and Cosmetic Act, as
amended (secs. 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C.
321-392).
(b) Department means the Department of Health and Human Services.
(c) Secretary means the Secretary of Health and Human Services.
(d) Commissioner means the Commissioner of Food and Drugs.
(e) Person means individuals, partnerships, corporations, and
associations.
(f) The definitions and interpretations of terms contained in
section 201 of the act shall be applicable to such terms when used in
the regulations in this part.
(g) The term new animal drug means any drug intended for use for
animals other than man, including any drug intended for use in animal
feed but not including such animal feed:
(1) The composition of which is such that such drug is not generally
recognized, among experts qualified by scientific training and
experience to evaluate the safety and effectiveness of animal drugs, as
safe and effective for use under the conditions prescribed, recommended,
or suggested in the labeling thereof; except that such a drug not so
recognized shall not be deemed to be a new animal drug if at any time
prior to June 25, 1938, it was subject to the Food and Drug Act of June
30, 1906, as amended, and if at such time its labeling contained the
same representations concerning the conditions of its use; or
(2) The composition of which is such that such drug, as a result of
investigations to determine its safety and effectiveness for use under
such conditions, has become so recognized but which has not, otherwise
than in such investigations, been used to a material extent or for a
material time under such conditions.
(h) The term animal feed means an article which is intended for use
for food for animals other than man and which is intended for use as a
substantial source of nutrients in the diet of the animal, and is not
limited to a mixture intended to be the sole ration of the animal.
(i) The newness of an animal drug, including a new animal drug
intended for use in or on animal feed, may arise by reason of: (1) The
newness for its intended drug use of any substance of which the drug is
comprised, in whole or in part, whether it be an active substance or a
menstruum, excipient, carrier, coating, or other component; (2) the
newness for its intended drug use of
[[Page 74]]
a combination of two or more substances, none of which is itself a new
animal drug; (3) the newness for its intended drug use of the proportion
of a substance in a combination, even though such combination containing
such substance in other proportion is not a new animal drug; (4) the
newness for its intended drug use in a different species of animal; (5)
the newness of its intended drug use in diagnosing, curing, mitigating,
treating, or preventing a disease, or to affect a structure or function
of the animal body, even though such drug is not a new animal drug when
used in another disease or to affect another structure or function of
the body; or (6) the newness of a dosage, or method or duration of
administration or application, or any other condition of use prescribed,
recommended, or suggested in the labeling of such drug, even though such
drug or animal feed containing such drug when used in another dosage, or
another method or duration of administration or application, or
different condition, is not a new animal drug.
(j) Animals used only for laboratory research and laboratory
research animals mean individual animals or groups of animals intended
for use and used solely for laboratory research purposes, regardless of
species, and does not include animals intended to be used for any food
purposes or animals intended to be kept as livestock.
(k) Sponsor means the person requesting designation for a minor-use
or minor-species drug as defined in part 516 of this chapter, who must
be the real party in interest of the development and the intended or
actual production and sales of such drug (in this context, the sponsor
may be an individual, partnership, organization, or association).
Sponsor also means the person responsible for an investigation of a new
animal drug. In this context, the sponsor may be an individual,
partnership, corporation, or Government agency or may be a manufacturer,
scientific institution, or an investigator regularly and lawfully
engaged in the investigation of new animal drugs. Sponsor also means the
person submitting or receiving approval for a new animal drug
application (in this context, the sponsor may be an individual,
partnership, organization, or association). In all contexts, the sponsor
is responsible for compliance with applicable provisions of the act and
regulations.
[40 FR 13807, Mar. 27, 1975, as amended at 50 FR 7517, Feb. 22, 1985; 54
FR 22741, May 26, 1989; 64 FR 69190, Dec. 10, 1999; 72 FR 41017, July
26, 2007]
Sec. 510.4 Biologics; products subject to license control.
An animal drug produced and distributed in full conformance with the
animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21
U.S.C. 151 et seq. ) and any regulations issued thereunder shall not be
deemed to be subject to section 512 of the Federal Food, Drug, and
Cosmetic Act.
Sec. 510.7 Consignees of new animal drugs for use in the manufacture
of animal feed.
(a) A new animal drug intended for use in the manufacture of animal
feed shall be deemed to be unsafe unless at the time of its removal from
the establishment of a manufacturer, packer, or distributor of such
drug, such manufacturer, packer, or distributor has an unrevoked written
statement from the consignee of such drug, or a notice from the
Secretary, to the effect that with respect to the use of such drug in
animal feed the consignee:
(1) Holds a license issued under Sec. 515.20 of this chapter; or
(2) Will, if the consignee is not the user of the drug, ship such
drug only to a holder of an approved application under Sec. 515.10 of
this chapter.
(b) The requirements of paragraph (a) of this section do not apply:
(1) Where such drugs are intended for export and/or
(2) When the use of such drug in the manufacture of a finished feed
has been exempted from the requirements of section 512(m) of the act
under the conditions specified by regulations published in part 558 of
this chapter.
[40 FR 13807, Mar. 27, 1975, as amended at 64 FR 63203, Nov. 19, 1999]
[[Page 75]]
Sec. 510.95 [Reserved]
Subpart B_Specific Administrative Rulings and Decisions
Sec. 510.105 Labeling of drugs for use in milk-producing animals.
(a) Part 526 of this chapter provides for new animal drugs intended
for intramammary use in animals and includes conditions of use intended
to prevent the contamination of milk from the use of such drugs.
(b) Preparations containing antibiotics and other potent drugs
labeled with directions for use in milk-producing animals will be
misbranded under section 502(f)(2) of the act unless their labeling
bears appropriate warnings and directions for use to avoid adulteration
of milk under section 402(a)(2)(c)(ii) of the act.
(c) It is the position of the Food and Drug Administration that the
labeling for such preparations should bear a clear warning that either:
(1) The article should not be administered to animals producing
milk, since to do so would result in contamination of the milk; or
(2) The label should bear the following statement: ``Warning: Milk
that has been taken from animals during treatment and for __ hours after
the latest treatment must not be used for food'', the blank being filled
in with the figure that the manufacturer has determined by appropriate
investigation is needed to insure that the milk will not carry violative
residues resulting from use of the preparation. If the use of the
preparation as recommended does not result in contamination of the milk,
neither of the above warning statements is required.
[40 FR 13807, Mar. 27, 1975, as amended at 63 FR 32980, June 17, 1998;
64 FR 51241, Sept. 22, 1999]
Sec. 510.106 Labeling of antibiotic and antibiotic-containing drugs
intended for use in milk-producing animals.
Whenever the labeling of an antibiotic drug included in the
regulations in this chapter suggests or recommends its use in milk-
producing animals, the label of such drugs shall bear either the
statement ``Warning: Not for use in animals producing milk, since this
use will result in contamination of the milk'' or the statement
``Warning: Milk that has been taken from animals during treatment and
for __hours after the latest treatment must not be used for food'', the
blank being filled in with the figure that the Commissioner has
authorized the manufacturer of the drug to use. The Commissioner shall
determine what such figures shall be from information submitted by the
manufacturer and which the Commissioner considers is adequate to prove
that period of time after the latest treatment that the milk from
treated animals will contain no violative residues from use of the
preparation. If the Commissioner determines from the information
submitted that the use of the antibiotic drug as recommended does not
result in its appearance in the milk, the Commissioner may exempt the
drug from bearing either of the above warning statements.
[63 FR 32980, June 17, 1998]
Sec. 510.110 Antibiotics used in food-producing animals.
(a) The Food and Drug Administration in the interest of fulfilling
its responsibilities with regard to protection of the public health has
requested an evaluation of the public health aspects of the use of
antibiotics in veterinary medical and nonmedical uses. There is
particular concern with regard to the potential hazards associated with
the extensive use of antibiotics administered to food-producing animals.
Accordingly, an ad hoc committee on the Veterinary Medical and
Nonmedical Uses of Antibiotics was established by the Food and Drug
Administration to study and advise the Commissioner of Food and Drugs on
the uses of antibiotics in veterinary medicine and for various
nonmedical purposes as such uses may affect the enforcement of the
Federal Food, Drug, and Cosmetic Act with respect to their safety and
effectiveness.
(b) Based upon an evaluation of the conclusions of said Committee
and other relevant material, Sec. 510.112 was published in the Federal
Register of August 23, 1966 (31 FR 11141), asking
[[Page 76]]
sponsors of drugs containing any antibiotic intended for use in food-
producing animals to submit data to establish whether such antibiotic
and its metabolites are present as residues in edible tissues, milk, and
eggs from treated animals. The data on the residues of antibiotics in
milk from intramammary infusion preparations were requested within 60
days and the data on all other products were requested within 180 days
following the date of publication of Sec. 510.112 in the Federal
Register.
(c) An evaluation of the data now available shows that use of many
antibiotic preparations cause residues in edible products of treated
animals for varying and, in some cases, for long periods of time
following the last administration. Because of the accumulation of new
information with regard to the development of resistance of bacteria to
antibiotics, the ability of bacteria to transfer this resistance, and
the development of sensitivity to antibiotics in humans, unauthorized
and unsafe residues of antibiotics cannot be permitted in food obtained
from treated animals.
(d) Based on evaluation of information available, including the
conclusions of the aforementioned ad hoc Committee, the Commissioner
concludes that antibiotic preparations intended for use in food-
producing animals, other than topical and ophthalmic preparations, are
not generally recognized among qualified experts as having been shown to
be safe for their intended use(s) within the meaning of section 201(s)
of the Federal Food, Drug, and Cosmetic Act.
(e) Therefore, all exemptions from the provisions of section 409 of
the act for use of antibiotics in food-producing animals based on
sanctions or approvals granted prior to enactment of the Food Additives
Amendment of 1958 (Pub. L. 85-929; 72 Stat. 1784) will be revoked and
the uses which are concluded to be safe will be covered by food additive
regulations. On those products for which there are inadequate residue
data, actions will be initiated to withdraw approval of new-drug
applications under the provisions of section 505 of the act. Antibiotic
preparations, other than those for topical and ophthalmic application in
food-producing animals, which are not covered by food additive
regulations will be subject to regulatory action within 180 days after
publication of the forthcoming revocation order.
(f) Because of the variation in the period of time that antibiotic
residues may remain in edible products from treated animals, all
injectable, intramammary infusion, intrauterine, and oral preparations,
including medicated premixes intended for use in food-producing animals,
are deemed to be new drugs as well as food additives.
[40 FR 13807, Mar. 27, 1975, as amended at 54 FR 18280, Apr. 28, 1989;
64 FR 403, Jan. 5, 1999]
Sec. 510.112 Antibiotics used in veterinary medicine
and for nonmedical purposes; required data.
(a) An ad hoc committee, Committee on the Veterinary Medical and
Nonmedical Uses of Antibiotics, was formed by the Food and Drug
Administration to study, and advise the Commissioner on, the use of
antibiotics in veterinary medicine and for various nonmedical purposes
as such uses may affect the enforcement of the Federal Food, Drug, and
Cosmetic Act with respect to the safety and effectiveness of such
substances. A copy of the report may be obtained from the Food and Drug
Administration, Office of Public Affairs, Room 15-05, Parklawn Building,
5600 Fishers Lane, Rockville, MD 20857.
(b) On the basis of the report of the Committee and other
information, sponsors of drugs containing any antibiotic intended for
use in food-producing animals shall submit data for determining whether
or not such antibiotics and their metabolites are present as residues in
edible tissues, milk, and eggs from treated animals; however, in the
case of a drug for which such data have already been submitted and for
which a regulation has been promulgated under section 409 of the act,
only such data as has been accumulated since the issuance of the
regulation need be submitted.
(c) The required data shall be submitted within 180 days of the date
of publication of this section in the Federal Register; except that in
the case of data on intramammary infusion
[[Page 77]]
preparations the data shall be submitted within 60 days of such
publication. Data demonstrating the absence in milk of residues of
intramammary infusion preparations when used as directed in their
labeling are needed within the 60-day period because of the importance
of milk in the human diet.
(d) Regulatory proceedings including revocation of prior sanctions,
or actions to suspend or amend new drug or antibiotic approvals granted
prior to passage of the Food Additives Amendment of 1958 (72 Stat.
1784), may be initiated with regard to the continued marketing of any
antibiotic preparation on which the required information is not
submitted within the period of time prescribed by paragraph (c) of this
section.
(e) Questions relating to the acceptability of proposed research
protocols and assay methods for determining the amount of antibiotic
residues in food should be directed to the Director, Center for
Veterinary Medicine, Food and Drug Administration, 7500 Standish Pl.,
Rockville, MD 20855.
[40 FR 13807, Mar. 27, 1975, as amended at 46 FR 8460, Jan. 27, 1981; 54
FR 18280, Apr. 28, 1989; 57 FR 6475, Feb. 25, 1992]
Subpart C_Import Tolerances for Residues of Unapproved New Animal Drugs
in Food
Source: 86 FR 52410, Sept. 21, 2021, unless otherwise noted.
Sec. 510.201 Scope.
This subpart applies to tolerances for residues of new animal drugs
not approved or conditionally approved for use in the United States, but
lawfully used in another country and present in imported, animal-derived
food and food products.
Sec. 510.202 Definitions.
The following definitions of terms apply when used in this subpart:
CNADA means an application for conditional approval of a new animal
drug submitted under section 571 of the Federal Food, Drug, and Cosmetic
Act, and includes all amendments and permissible supplements.
Import tolerance means a tolerance for a residue of a new animal
drug not approved or conditionally approved for use in the United
States, but present in any imported edible portion of any animal.
NADA means a new animal drug application submitted under section 512
of the Federal Food, Drug, and Cosmetic Act, including all amendments
and permissible supplements, for approval of a new animal drug.
Request means a request to establish or amend an import tolerance.
Sec. 510.203 Initiation of a proceeding to establish or amend
an import tolerance.
(a) Any interested person may request that the Commissioner
establish or amend an import tolerance. Such a request must be in the
form specified in Sec. 510.205 of this chapter.
(b) The Commissioner may initiate a proceeding to establish or amend
an import tolerance on his or her own initiative pursuant to Sec.
10.25(b) of this chapter.
Sec. 510.205 Content and administration of a request.
(a) Pertinent information previously submitted to and currently
retained in the files of the Food and Drug Administration (FDA) may be
incorporated in, and will be considered as part of, a request on the
basis of specific reference to such information. If the requester refers
to any nonpublic information other than its own, the requester shall
obtain a written right of reference to that nonpublic information and
submit the right of reference with the request. Any reference to
published information offered in support of a request should be
accompanied by reprints or copies of such references.
(b) Requests shall be submitted and addressed to the Document
Control Unit (HFV-199), Center for Veterinary Medicine, Food and Drug
Administration, 7500 Standish Pl., Rockville, MD 20855. Requests may be
submitted in an electronic format as authorized by FDA. See FDA[min]s
Electronic Submissions Gateway website: https://www.fda.gov/industry /
electronic-submissions-gateway.
[[Page 78]]
(c) Any material submitted in a foreign language shall be
accompanied by a complete and accurate English translation. Translations
of literature printed in a language other than English shall be
accompanied by copies of the original publication.
(d) The request must be dated and must be signed by the requester or
by his or her authorized attorney, agent, or official and shall state
the requester's correspondence address. If the requester or such
authorized representative does not reside or have a place of business
within the United States, the requester must also furnish the name and
post office address of, and the request must be countersigned by, an
authorized attorney, agent, or official residing or maintaining a place
of business within the United States.
(e) The request must include the following information:
(1) The established name and all pertinent information concerning
the new animal drug, including chemical identity and composition of the
new animal drug, and its physical, chemical, and biological properties;
(2) The conditions of use for the new animal drug, including the
route of administration and dosage, together with all labeling,
directions, and recommendations regarding the uses in countries in which
the new animal drug is lawfully used;
(3) The proposed import tolerance(s) for residues of the new animal
drug;
(4) Human food safety information to support the proposed import
tolerance(s) in either of the following forms:
(i) If a permanent maximum residue limit (MRL) has been established
by the Codex Alimentarius Committee (Codex MRL), the requester shall
provide the permanent Codex MRL and monographs and reports from the
Joint Expert Committee on Food Additives (JECFA) of the Food and
Agriculture Organization (FAO) and the World Health Organization (WHO)
of the United Nations and/or monographs and reports from the Joint FAO/
WHO Meeting on Pesticide Residues (JMPR) that support the development of
the permanent Codex MRL. FDA may request additional information as
needed.
(ii) If no permanent Codex MRL has been established, or upon
notification by FDA, the requester must provide full reports of
investigations made with respect to the human food safety of the new
animal drug. A request may be regarded as incomplete unless it includes
full reports of adequate tests by all methods reasonably applicable to
show whether or not any imported edible portion of any animal receiving
the new animal drug will be safe for human consumption. The reports must
include detailed data derived from appropriate animal and other
biological experiments in which the methods used and the results
obtained are clearly set forth, including data submitted to the
appropriate regulatory authority in any country where the new animal
drug is lawfully used. The request must also include a statement that
all such reports have been submitted or contain an explanation of why
such reports were not submitted. With respect to each nonclinical
laboratory study contained in the request, the requestor must submit
either a statement that the study was conducted in compliance with the
good laboratory practice regulations set forth in part 58 of this
chapter, or, if the study was not conducted in compliance with such
regulations, a brief statement of the reason for the noncompliance, and
how this may have impacted the study;
(5) Other human food safety information as deemed necessary by the
Commissioner;
(6) A description of practicable methods for determining the
quantity, if any, of the new animal drug in or on food, and any
substance formed in or on food because of its use;
(7) An environmental assessment under Sec. 25.40 of this chapter;
and
(8) Any information required under Sec. Sec. 500.80 through 500.92
of this chapter (Subpart E, Regulation of Carcinogenic Compounds Used in
Food-Producing Animals), where applicable.
(f) A request to amend an established import tolerance must contain
information to support each proposed change. The request may omit
statements made in the original request for which no change is proposed.
(g) The requester may withdraw the request at any time before the
notification provided for in Sec. 510.207(a) of this
[[Page 79]]
chapter has been made publicly available.
Sec. 510.206 Review of information supporting actions to establish
or amend an import tolerance.
In establishing or amending an import tolerance, the Commissioner
shall rely on data sufficient to demonstrate that a proposed tolerance
is safe based on similar food safety criteria used by the Commissioner
to establish tolerances for applications for new animal drugs filed
under section 512(b)(1) of the Federal Food, Drug, and Cosmetic Act. In
establishing or amending an import tolerance, the Commissioner will give
appropriate consideration to the anticipated residue concentrations and
conditions of use of the new animal drug specified.
Sec. 510.207 Disclosure of information submitted in a request.
(a) When a request is determined to be complete for FDA's
consideration, the Commissioner will provide public notification of the
request containing the name of the requester and a brief description of
the request in general terms. A copy of the notification will be sent to
the requester at the time the information is made available to the
public.
(b) Any notification establishing, amending, or revoking an import
tolerance will be made publicly available. A summary of the basis for
the decision will be publicly released in accordance with the provisions
of part 20 of this chapter. If FDA determines that the new animal drug
referred to in the request is a new animal drug that induces cancer when
ingested by people or animals, and the requester complies with the
requirements of Sec. Sec. 500.80 through 500.92 of this chapter
(Subpart E, Regulation of Carcinogenic Compounds Used in Food-Producing
Animals), the regulatory method for ascertaining the marker residue in
the target tissue will be made publicly available. All information and
safety data submitted with the request, or previously submitted
information incorporated in, and considered as part of, a request on the
basis of specific reference to such information, shall be available for
public disclosure, also in accordance with the provisions of part 20 of
this chapter. Trade secrets and confidential commercial or financial
information are exempted from release under Sec. 20.61 of this chapter.
Sec. 510.209 Establishment, denial, or amendment of an import tolerance.
(a) If an import tolerance is established or amended, the
Commissioner will provide public notification of the action, which will
be effective from the date of public notification. A copy of the
notification will be sent to any requestor at the time the information
is made available to the public.
(b) If a request to establish or amend an import tolerance is
denied, a notification of the denial will be made publicly available,
and a copy of the denial letter, including the reasons for such action,
will be sent to the requester.
(c) A tolerance established in an approved NADA or conditionally
approved CNADA will supersede an existing import tolerance. In the event
the conditionally approved CNADA is not renewed or is withdrawn, or such
drug does not achieve approval under section 512 of the Federal Food,
Drug, and Cosmetic Act within 5 years following the date of the
conditional approval, the Agency will reinstate the import tolerance
unless Sec. 510.210(a)(1) or (a)(2) is applicable at that time.
Sec. 510.210 Revocation of an import tolerance.
(a) The Commissioner, on his or her own initiative or on the
petition of an interested person, under Sec. 10.25 of this chapter, may
revoke an import tolerance if:
(1) Scientific evidence shows an import tolerance to be unsafe; or
(2) Information demonstrates that the use of a new animal drug under
actual use conditions results in food being imported into the United
States with residues exceeding the import tolerance.
(b) The Commissioner will provide public notification under Sec.
510.207(b) that will specify the basis for the decision and will be
effective at the time the information is made available to the public.
[[Page 80]]
(c) A petition for revocation must be submitted in the form
specified in Sec. 10.30 of this chapter.
Sec. 510.212 Administrative reconsideration of action.
(a) The Commissioner may at any time, on his or her own initiative
or on the petition of an interested person under part 10 of this
chapter, reconsider part or all of a decision to establish, not
establish, amend, or revoke an import tolerance.
(b) A petition for reconsideration must be submitted in accordance
with Sec. 10.20 of this chapter and in the form specified in Sec.
10.33 of this chapter no later than 30 days after the date of public
notification of the decision involved. The Commissioner may, for good
cause, permit a petition to be filed more than 30 days after public
notification of the decision. The petition for reconsideration must
demonstrate that relevant information contained in the administrative
record was not previously or not adequately considered by the
Commissioner. No new information may be included in a petition for
reconsideration.
(c) An interested person who wishes to rely on information not
included in the administrative record shall submit either a petition to
amend an import tolerance under Sec. 510.205 or to revoke an import
tolerance under Sec. 510.210 and Sec. 10.25 of this chapter.
Sec. 510.213 Administrative stay of action.
(a) The Commissioner may at any time, on his or her own initiative
or on the request of an interested person under part 10 of this chapter,
stay or extend the effective date of a decision to establish, not
establish, amend, or revoke an import tolerance.
(b) A request for stay must be submitted in accordance with Sec.
10.20 of this chapter and in the form specified in Sec. 10.35 of this
chapter no later than 30 days after public notification of the decision
involved. The Commissioner may, for good cause, permit a petition to be
filed more than 30 days after public notification of the decision.
Subpart D_Records and Reports
Sec. 510.301 Records and reports concerning experience with animal feeds
bearing or containing new animal drugs for which an approved medicated
feed mill license application is in effect.
Records and reports of clinical and other experience with the new
animal drug will be maintained and reported, appropriately identified
with the new animal drug application(s) or index listing(s) to which
they relate, to the Center for Veterinary Medicine in duplicate in
accordance with the following:
(a) Immediately upon receipt by the applicant, complete records or
reports covering information of the following kinds:
(1) Information concerning any mixup in the new animal drug or its
labeling with another article.
(2) Information concerning any bacteriological or any significant
chemical, physical, or other change or deterioration in the drug, or any
failure of one or more distributed batches of the drug to meet the
specifications established for it in the new animal drug application or
request for determination of eligibility for indexing.
(b) As soon as possible, and in any event within 15 working days of
its receipt by the applicant, complete records or reports concerning any
information of the following kinds:
(1) Information concerning any unexpected side effect, injury,
toxicity, or sensitivity reaction or any unexpected incidence or
severity thereof associated with clinical uses, studies, investigations,
or tests, whether or not determined to be attributable to the new animal
drug, except that this requirement shall not apply to the submission of
information described in a written communication to the applicant from
the Food and Drug Administration as types of information that may be
submitted at other designated intervals. Unexpected as used in this
paragraph refers to conditions or developments not previously submitted
as part of the new animal drug application or in support of the index
listing or not encountered during clinical trials of the drug,
[[Page 81]]
or conditions or developments occurring at a rate higher than shown by
information previously submitted as part of the new animal drug
application or in support of the index listing or at a rate higher than
encountered during such clinical trials.
(2) Information concerning any unusual failure of the new animal
drug to exhibit its expected pharmacological activity.
[40 FR 13807, Mar. 27, 1975, as amended at 54 FR 18280, Apr. 28, 1989;
72 FR 69121, Dec. 6, 2007]
Sec. 510.305 Maintenance of copies of approved medicated feed mill licenses
to manufacture animal feed bearing or containing new animal drugs.
Each applicant shall maintain in a single accessible location:
(a) A copy of the approved medicated feed mill license (Form FDA
3448) on the premises of the manufacturing establishment; and
(b) Approved or index listed labeling for each Type B and/or Type C
feed being manufactured on the premises of the manufacturing
establishment or the facility where the feed labels are generated.
[64 FR 63203, Nov. 19, 1999, as amended at 72 FR 69121, Dec. 6, 2007]
Subpart E_Requirements for Specific New Animal Drugs
Sec. 510.410 Corticosteroids for oral, injectable, and ophthalmic use
in animals; warnings and labeling requirements.
(a) The Food and Drug Administration has received reports of side
effects associated with the oral, injectable, and ophthalmic use of
corticosteroid animal drugs. The use of these drugs administered orally
or by injection has resulted in premature parturition when administered
during the last trimester of pregnancy. Premature parturition may be
followed by dystocia, fetal death, retained placenta, and metritis.
Additionally, corticosteroids used in dogs, rabbits, and rodents during
pregnancy have produced cleft palate in offspring. Use in dogs has
resulted in other congenital anomalies, including deformed forelegs,
phocomelia, and anasarca. Drugs subject to this section are required to
carry the veterinary prescription legend and are subject to the labeling
requirements of Sec. 201.105 of this chapter.
(b) In view of these potentially serious side effects, the Food and
Drug Administration has concluded that the labeling on or within
packaged corticosteroid-containing preparations intended for animal use
shall bear conspicuously the following warning statement:
Warning: Clinical and experimental data have demonstrated that
corticosteroids administered orally or by injection to animals may
induce the first stage of parturition if used during the last trimester
of pregnancy and may precipitate premature parturition followed by
dystocia, fetal death, retained placenta, and metritis.
Additionally, corticosteroids administered to dogs, rabbits, and
rodents during pregnancy have resulted in cleft palate in offspring.
Corticosteroids administered to dogs during pregnancy have also resulted
in other congenital anomalies, including deformed forelegs, phocomelia,
and anasarca.
[49 FR 48535, Dec. 13, 1984]
Sec. 510.440 Injectable iron preparations.
There has been an increasing interest in the use of injectable iron
compounds for the prevention or treatment of iron-deficiency anemia in
animals. Although some such preparations have been shown to be safe,
such articles are regarded as new animal drugs within the meaning of the
Federal Food, Drug, and Cosmetic Act. Accordingly, an approved new
animal drug application is required prior to the marketing of such
preparations within the jurisdiction of the act. In addition to the need
for demonstrating the safety of such articles, the labeling of such
preparations should not only recommend appropriate dosages of iron but
also declare the amount (in milligrams) of available iron (Fe) per
milliliter of the subject product.
Sec. 510.455 Requirements for free-choice medicated feeds.
(a) What is free-choice medicated feed? For the purpose of this
part, free-choice medicated feed is medicated feed that is placed in
feeding or grazing areas and is not intended to be consumed fully at a
single feeding or to
[[Page 82]]
constitute the entire diet of the animal. Free-choice feeds include, but
are not limited to, medicated blocks (agglomerated feed compressed or
rendered into a solid mass and cohesive enough to hold its form),
mineral mixes, and liquid feed tank supplements (``lick tank''
supplements) containing one or more new animal drugs. The manufacture of
medicated free-choice feeds is subject to the current good manufacturing
practice regulations in part 225 of this chapter for medicated feeds.
(b) What is required for new animal drugs intended for use in free-
choice feed? Any new animal drug intended for use in free-choice feed
must be approved for such use under section 512 of the Federal Food,
Drug, and Cosmetic Act (the act) (21 U.S.C. 360(b)) or listed in the
index under section 572 of the act (21 U.S.C. 360ccc-1). Such approvals
under section 512 of the act must be:
(1) An original new animal drug application (NADA),
(2) A supplemental NADA, or
(3) An abbreviated NADA.
(c) What are the approval requirements under section 512 of the act
for new animal drugs intended for use in free-choice feed? An approval
under section 512 of the act for a Type A medicated article intended for
use in free-choice feed must contain the following information:
(1) Data, or reference to data in a master file (MF), showing that
the target animal consumes the new animal drug in the Type C free-choice
feed in an amount that is safe and effective (consumption/effectiveness
data); and
(2) Data, or reference to data in an MF, showing the relevant ranges
of conditions under which the drug will be chemically and physically
stable in the Type C free-choice feed under field conditions.
(d) How are consumption/effectiveness and/or stability data to be
submitted? The data must be submitted as follows:
(1) Directly in the NADA, by a sponsor; and/or
(2) To an MF that a sponsor may then reference in its NADA with
written consent of the MF holder.
(e) What will be stated in the published approval for a new animal
drug intended for use in free-choice feed? The approval of a new animal
drug intended for use in free-choice feed, as published in this
subchapter, will include:
(1) The formula and/or specifications of the free-choice medicated
feed, where the owner of this information requests such publication, or
(2) A statement that the approval has been granted for a proprietary
formula and/or specifications.
(f) When is a medicated feed mill license required for the
manufacture of a free-choice medicated feed? An approved medicated feed
mill license is required for the manufacture of the following types of
feeds:
(1) All free-choice medicated feeds that contain a Category II drug,
and
(2) Free-choice medicated feeds that contain a Category I drug and
use a proprietary formula and/or specifications.
[69 FR 30197, May 27, 2004, as amended at 72 FR 69121, Dec. 6, 2007]
Subpart F [Reserved]
Subpart G_Sponsors of Approved Applications
Sec. 510.600 Names, addresses, and drug labeler codes of sponsors
of approved applications.
(a) Section 512(i) of the act requires publication of names and
addresses of sponsors of approved applications for new animal drugs.
(b) In this section each name and address is identified by a
numerical drug labeler code. The labeler codes identify the sponsors of
the new animal drug applications associated with the regulations
published pursuant to section 512(i) of the act. The codes appear in the
appropriate regulations and serve as a reference to the names and
addresses listed in this section. The drug labeler code is established
pursuant to section 510 of the act.
(c) The names, addresses, and drug labeler codes of sponsors of
approved new animal drug applications are as follows:
[[Page 83]]
(1) Alphabetical Listing of Sponsors
------------------------------------------------------------------------
Drug labeler
Firm name and address code
------------------------------------------------------------------------
A & G Pharmaceuticals, Inc., 1030 West Commodore Blvd., 057699
Jackson, NJ 08527......................................
Accord Healthcare, Inc., 1009 Slater Rd., suite 210-B, 016729
Durham, NC 27703.......................................
ADM Animal Nutrition, Inc., 1000 North 30th St., Quincy, 012286
IL 62305-3115..........................................
Agri Laboratories, Ltd., P.O. Box 3103, St. Joseph, MO 057561
64503..................................................
Agri-Tech, Inc., 4722 Broadway, Kansas City, MO 64112... 017762
Akorn Animal Health, Inc., 1925 West Field Ct., suite 059399
300, Lake Forest, IL 60045.............................
Alexion Pharmaceuticals, Inc., 121 Seaport Blvd., 069334
Boston, MA 02210.......................................
American Regent, Inc., Animal Health Division, Shirley, 010797
NY 11967...............................................
Anika Therapeutics Inc., 236 West Cummings Park, Woburn, 060865
MA 01801...............................................
Anivive Lifesciences, Inc., 3250 Airflite Way, Suite 086121
400, Long Beach, CA 90807..............................
Anzac Animal Health, LLC, 218 Millwell Dr., Suite B, 086073
Maryland Heights, MO 63043.............................
AquaBounty Technologies, Inc., 2 Mill and Main Pl., 086053
Suite 395, Maynard, MA 01754...........................
Ark Sciences, Inc., 1101 East 33rd St., suite B304, 076175
Baltimore, MD 21218....................................
Aurora Pharmaceutical, Inc., 1196 Highway 3 South, 051072
Northfield, MN 55057-3009..............................
Axcentive SARL, Chemin de Champouse, Quartier Violesi, 086009
13320 Bouc Bel Air, France.............................
B.L. Mitchell, Inc., 103 Hwy. 82 E., Leland, MS 38756... 067188
Bausch Health US, LLC, 400 Somerset Corporate Blvd., 099207
Bridgewater, NJ 08807..................................
Belcher Pharmaceuticals, LLC, 6911 Bryan Dairy Rd., 062250
Largo, FL 33777........................................
Bimeda Animal Health Ltd., 1B The Herbert Building, The 061133
Park, Carrickmines, Dublin 18, Ireland.................
Boehringer Ingelheim Animal Health USA, Inc., 3239 000010
Satellite Blvd., Duluth, GA 30096......................
Cephazone Pharma, LLC, 250 East Bonita Ave., Pomona, CA 068330
91767..................................................
Ceva Sante Animale, 10 Avenue de la Ballasti[egrave]re, 013744
33500 Libourne, France.................................
Chanelle Pharmaceuticals Manufacturing Ltd., Loughrea, 061651
County Galway, Ireland.................................
Cronus Pharma Specialities India Private Ltd., Sy No-99/ 069043
1, M/s GMR Hyderabad Aviation SEZ Ltd., Mamidipalli
Village, Shamshabad Mandal, Ranga Reddy, Hyderabad,
Telangana, 501218, India...............................
Dechra, Ltd., Snaygill Industrial Estate, Keighley Rd., 043264
Skipton, North Yorkshire, BD23 2RW, United Kingdom.....
Dechra Veterinary Products LLC, 7015 College Blvd., 017033
Suite 525, Overland Park, KS 66211.....................
ECO LLC, 344 Nassau St., Princeton, NJ 08540............ 066916
Elanco US Inc., 2500 Innovation Way, Greenfield, IN 058198
46140..................................................
Farnam Companies, Inc., 301 West Osborn, Phoenix, AZ 017135
85013-3928.............................................
Felix Pharmaceuticals Pvt. Ltd., 25-28 North Wall Quay, 086101
Dublin 1, Ireland......................................
First Priority, Inc., 1590 Todd Farm Dr., Elgin, IL 058829
60123..................................................
Fougera Pharmaceuticals, Inc., P.O. Box 2006, 60 Baylis 025463
Rd., Melville, NY 11747................................
GTC Biotherapeutics, Inc., 175 Crossing Blvd., 042976
Framingham, MA 01702...................................
Halocarbon Products Corp., 6525 The Corners Pkwy., Suite 012164
200, Peachtree Corners, GA 30092.......................
Happy Jack, Inc., Snow Hill, NC 28580................... 023851
Hemoglobin Oxygen Therapeutics, LLC, 674 Souder Rd., 063075
Souderton, PA 18964....................................
Heska Corp., 1825 Sharp Point Dr., Fort Collins, CO 063604
80525..................................................
HQ Specialty Pharma Corp., 120 Rte. 17 North, suite 130, 042791
Paramus, NJ 07652......................................
Huvepharma EOOD, 5th Floor, 3A Nikolay Haytov Str., 1113 016592
Sofia, Bulgaria........................................
IMPAX Laboratories, Inc., 30831 Huntwood Ave., Hayward, 000115
CA 94544...............................................
Intervet, Inc., 2 Giralda Farms, Madison, NJ 07940...... 000061
Ivaoes Animal Health, 4300 SW 73rd Ave., Suite 110, 086064
Miami, FL 33155........................................
Jaguar Animal Health, 200 Pine St., Suite 600, San 086149
Francisco, CA 94104....................................
Jurox Pty. Ltd., 85 Gardiner St., Rutherford, NSW 2320, 049480
Australia..............................................
Kindred Biosciences, Inc., 1555 Bayshore Hwy., Suite 086078
200, Burlingame, CA 94010..............................
Kinetic Technologies, LLC, 961 Beasley St., suite 270, 051031
Lexington, KY 40509....................................
LFB USA, Inc., 175 Crossing Blvd., Framingham, MA 01702. 086047
Lloyd, Inc., 604 W. Thomas Ave., Shenandoah, IA 51601... 061690
Med-Pharmex, Inc., 2727 Thompson Creek Rd., Pomona, CA 054925
91767-1861.............................................
Mizner Bioscience LLC, 225 NE Mizner Blvd., Suite 760, 086039
Boca Raton, FL 33432...................................
Modern Veterinary Therapeutics, LLC, 14343 SW 119th 015914
Ave., Miami, FL 33186..................................
Mylan Institutional, Inc., 12720 Dairy Ashford Rd., 051079
Sugar Land, TX 77478...................................
Mylan Institutional LLC, 4901 Hiawatha Dr., Rockford, IL 063286
61103..................................................
Natchez Animal Supply Co., 201 John R. Junkin Dr., 049968
Natchez, MS 39120......................................
Neogen Corp., 944 Nandino Blvd., Lexington, KY 40511.... 059051
Norbrook Laboratories, Ltd., Station Works, Newry BT35 055529
6JP, Northern Ireland..................................
Oasmia Pharmaceutical AB, Vallongatan 1, 75228 Uppsala, 052818
Sweden.................................................
Orion Corp., Orionintie 1, 02200 Espoo, Finland......... 052483
Parnell Technologies Pty. Ltd., unit 4, 476 Gardeners 068504
Rd., Alexandria, New South Wales 2015, Australia.......
Pegasus Laboratories, Inc., 8809 Ely Rd., Pensacola, FL 055246
32514..................................................
Pharmaceutical Ventures, Ltd., P.O. Box D1400, Pomona, 050057
NY 10970...............................................
Pharmacosmos, Inc., 776 Mountain Blvd., Watchung, NJ 042552
07069..................................................
Pharmaq AS, Skogmo Industriomrade, N-7863 Overhalla, 015331
Norway.................................................
Pharmgate Inc., 1800 Sir Tyler Dr., Wilmington, NC 28405 069254
Phibro Animal Health Corp., GlenPointe Centre East, 3d 066104
floor, 300 Frank W. Burr Blvd., suite 21, Teaneck, NJ
07666..................................................
Piramal Critical Care, Inc., 3850 Schelden Circle, 066794
Bethlehem, PA 18017....................................
Piramal Pharma Ltd., Ground Floor, Piramal Ananta, 065085
Agastya Corporate Park, Mumbai, Maharashtra, 400070,
India..................................................
Planalquimica Industrial Ltda., Rua das Magnolias nr. 060728
2405, Jardim das Bandeiras, CEP 13053-120, Campinas,
Sao Paulo, Brazil......................................
[[Page 84]]
Purina Animal Nutrition LLC, 4001 Lexington Ave., North 017800
Arden Hills, MN 55126-2910.............................
QBiotics Group Ltd., Suite 3A, Level 1, 165 Moggill Rd., 086132
Taringa, Queensland 4068, Australia....................
Quo Vademus, LLC, 277 Faison McGowan Rd., Kenansville, 076475
NC 28349...............................................
Revivicor, Inc., a wholly owned subsidiary of United 086134
Therapeutics Corp., 1700 Kraft Dr., Suite 2400,
Blacksburg, VA 24060...................................
Ridley USA, Inc., 111 W Cherry St., Suite 500, Mankato, 067949
MN 56001...............................................
Sergeant's Pet Care Products, Inc., 10077 S. 134th St., 021091
Omaha, NE 68138........................................
Sparhawk Laboratories, Inc., 12340 Santa Fe Trail Dr., 058005
Lenexa, KS 66215.......................................
Squire Laboratories, Inc., 100 Mill St., Revere, MA 017153
02151..................................................
Summit Hill Laboratories, P.O. Box 535, Navesink, NJ 037990
07752..................................................
Superior Equine Pharmaceuticals, Inc., Pleasant Grove, 027053
UT 84062...............................................
Syndel USA, 1441 W. Smith Rd., Ferndale, WA 98248....... 050378
Taro Pharmaceuticals U.S.A., Inc., 3 Skyline Dr., 051672
Hawthorne, NY 10532....................................
Therio, Inc., 8801 Anderson Ave., Manhattan, KS 66503... 052923
Union Agener, Inc., 1788 Lovers Ln., Augusta, GA 30901.. 086106
United-AH II LLC, 322 S Main St., Sheridan, IN 46069.... 051233
VetDC, Inc., 320 E. Vine Dr., suite 218, Fort Collins, 086072
CO 80524...............................................
V[eacute]toquinol N.-A., Inc., 2000 chemin Georges, 059320
Lavaltrie (PQ), Canada, J5T 3S5........................
V[eacute]toquinol USA, Inc., 4250 N. Sylvania Ave., Fort 017030
Worth, TX 76137........................................
Virbac AH, Inc., PO Box 162059, Fort Worth, TX 76161.... 051311
Wildcat Feeds, 215 NE Strait Ave., Topeka, KS 66616..... 086113
Wildlife Laboratories, Inc., 1230 W. Ash St., suite D, 053923
Windsor, CO 80550......................................
Zoetis Inc., 333 Portage St., Kalamazoo, MI 49007....... 054771
------------------------------------------------------------------------
(2) Numerical Listing of Sponsors
------------------------------------------------------------------------
Drug labeler
code Firm name and address
------------------------------------------------------------------------
000010 Boehringer Ingelheim Animal Health USA, Inc., 3239
Satellite Blvd., Duluth, GA 30096.
000061 Intervet, Inc., 2 Giralda Farms, Madison, NJ 07940.
000115 IMPAX Laboratories, Inc., 30831 Huntwood Ave., Hayward,
CA 94544.
010797 American Regent, Inc., Animal Health Division, Shirley,
NY 11967.
012164 Halocarbon Products Corp., 6525 The Corners Pkwy., Suite
200, Peachtree Corners, GA 30092.
012286 ADM Animal Nutrition, Inc., 1000 North 30th St., Quincy,
IL 62305-3115.
012578 Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340
Beerse, Belgium.
013744 Ceva Sante Animale, 10 Avenue de la Ballasti[egrave]re,
33500 Libourne, France.
015331 Pharmaq AS, Skogmo Industriomrade, N-7863 Overhalla,
Norway.
015914 Modern Veterinary Therapeutics, LLC, 14343 SW 119th
Ave., Miami, FL 33186.
016592 Huvepharma EOOD, 5th Floor, 3A Nikolay Haytov Str., 1113
Sofia, Bulgaria.
016729 Accord Healthcare, Inc., 1009 Slater Rd., suite 210-B,
Durham, NC 27703.
017030 V[eacute]toquinol USA, Inc., 4250 N. Sylvania Ave., Fort
Worth, TX 76137.
017033 Dechra Veterinary Products LLC, 7015 College Blvd.,
Suite 525, Overland Park, KS 66211.
017135 Farnam Companies, Inc., 301 West Osborn, Phoenix, AZ
85013-3928.
017153 Squire Laboratories, Inc., 100 Mill St., Revere, MA
02151.
017762 Agri-Tech, Inc., 4722 Broadway, Kansas City, MO 64112.
017800 Purina Animal Nutrition LLC, 4001 Lexington Ave., North
Arden Hills, MN 55126-2910.
021091 Sergeant's Pet Care Products, Inc., 10077 S. 134th St.,
Omaha, NE 68138.
023851 Happy Jack, Inc., Snow Hill, NC 28580.
025463 Fougera Pharmaceuticals, Inc., P.O. Box 2006, 60 Baylis
Rd., Melville, NY 11747.
027053 Superior Equine Pharmaceuticals, Inc., Pleasant Grove,
UT 84062.
037990 Summit Hill Laboratories, P.O. Box 535, Navesink, NJ
07752.
042552 Pharmacosmos, Inc., 776 Mountain Blvd., Watchung, NJ
07069.
042791 HQ Specialty Pharma Corp., 120 Rte. 17 North, suite 130,
Paramus, NJ 07652.
042976 GTC Biotherapeutics, Inc., 175 Crossing Blvd.,
Framingham, MA 01702.
043264 Dechra, Ltd., Snaygill Industrial Estate, Keighley Rd.,
Skipton, North Yorkshire, BD23 2RW, United Kingdom.
049480 Jurox Pty. Ltd., 85 Gardiner St., Rutherford, NSW 2320,
Australia.
049968 Natchez Animal Supply Co., 201 John R. Junkin Dr.,
Natchez, MS 39120.
050057 Pharmaceutical Ventures, Ltd., P.O. Box D1400, Pomona,
NY 10970.
050378 Syndel USA, 1441 W. Smith Rd., Ferndale, WA 98248.
051031 Kinetic Technologies, LLC, 961 Beasley St., suite 270,
Lexington, KY 40509.
051072 Aurora Pharmaceutical, Inc., 1196 Highway 3 South,
Northfield, MN 55057-3009.
051079 Mylan Institutional, Inc., 12720 Dairy Ashford Rd.,
Sugar Land, TX 77478.
051233 United-AH II LLC, 322 S Main St., Sheridan, IN 46069.
051311 Virbac AH, Inc., PO Box 162059, Fort Worth, TX 76161.
051672 Taro Pharmaceuticals U.S.A., Inc., 3 Skyline Dr.,
Hawthorne, NY 10532.
052483 Orion Corp., Orionintie 1, 02200 Espoo, Finland.
052818 Oasmia Pharmaceutical AB, Vallongatan 1, 75228 Uppsala,
Sweden.
052923 Therio, Inc., 8801 Anderson Ave., Manhattan, KS 66503.
053923 Wildlife Laboratories, Inc., 1230 W. Ash St., suite D,
Windsor, CO 80550.
054771 Zoetis Inc., 333 Portage St., Kalamazoo, MI 49007.
[[Page 85]]
054925 Med-Pharmex, Inc., 2727 Thompson Creek Rd., Pomona, CA
91767-1861.
055246 Pegasus Laboratories, Inc., 8809 Ely Rd., Pensacola, FL
32514.
055529 Norbrook Laboratories, Ltd., Station Works, Newry BT35
6JP, Northern Ireland.
057561 Agri Laboratories, Ltd., P.O. Box 3103, St. Joseph, MO
64503.
057699 A & G Pharmaceuticals, Inc., 1030 West Commodore Blvd.,
Jackson, NJ 08527.
058005 Sparhawk Laboratories, Inc., 12340 Santa Fe Trail Dr.,
Lenexa, KS 66215.
058198 Elanco US Inc., 2500 Innovation Way, Greenfield, IN
46140.
058829 First Priority, Inc., 1590 Todd Farm Dr., Elgin, IL
60123.
059051 Neogen Corp., 944 Nandino Blvd., Lexington, KY 40511.
059320 V[eacute]toquinol N.-A., Inc., 2000 chemin Georges,
Lavaltrie (PQ), Canada, J5T 3S5.
059399 Akorn Animal Health, Inc., 1925 West Field Ct., suite
300, Lake Forest, IL 60045.
060728 Planalquimica Industrial Ltda., Rua das Magnolias nr.
Jardim das Bandeiras, CEP 13053-120, Campinas, Sao
Alto, Brazil.
060865 Anika Therapeutics Inc., 236 West Cummings Park, Woburn,
MA 01801.
061133 Bimeda Animal Health Ltd., 1B The Herbert Building, The
Park, Carrickmines, Dublin 18, Ireland.
061651 Chanelle Pharmaceuticals Manufacturing Ltd., Loughrea,
County Galway, Ireland.
061690 Lloyd, Inc., 604 W. Thomas Ave., Shenandoah, IA 51601.
062250 Belcher Pharmaceuticals, LLC, 6911 Bryan Dairy Rd.,
Largo, FL 33777.
062794 Mylan Bertek Pharmaceuticals, Inc., 12720 Dairy Ashford,
Sugar Land, TX 77478.
063075 Hemoglobin Oxygen Therapeutics, LLC, 674 Souder Rd.,
Souderton, PA 18964.
063286 Mylan Institutional, LLC, 4901 Hiawatha Dr., Rockford,
IL 61103.
063604 Heska Corp., 1825 Sharp Point Dr., Fort Collins, CO
80525.
065085 Piramal Pharma Ltd., Ground Floor, Piramal Ananta,
Agastya Corporate Park, Mumbai, Maharashtra, 400070,
India.
066104 Phibro Animal Health Corp., GlenPointe Centre East, 3d
floor, 300 Frank W. Burr Blvd., suite 21, Teaneck, NJ
07666.
066794 Piramal Critical Care, Inc., 3850 Schelden Circle,
Bethlehem, PA 18017.
066916 ECO LLC, 344 Nassau St., Princeton, NJ 08540.
067188 B.L. Mitchell, Inc., 103 Hwy. 82 E., Leland, MS 38756.
067949 Ridley USA, Inc., 111 W Cherry St., Suite 500, Mankato,
MN 56001.
068330 Cephazone Pharma, LLC, 250 East Bonita Ave., Pomona, CA
91767.
068504 Parnell Technologies Pty. Ltd., unit 4, 476 Gardeners
Rd., Alexandria, New South Wales 2015, Australia.
069043 Cronus Pharma Specialities India Private Ltd., Sy No-99/
1, M/s GMR Hyderabad Aviation SEZ Ltd., Mamidipalli
Village, Shamshabad Mandal, Ranga Reddy, Hyderabad,
Telangana, 501218, India.
069254 Pharmgate Inc., 1800 Sir Tyler Dr., Wilmington, NC
28405.
069334 Alexion Pharmaceuticals, Inc., 121 Seaport Blvd.,
Boston, MA 02210.
076175 Ark Sciences, Inc., 1101 East 33rd St., suite B304,
Baltimore, MD 21218.
076475 Quo Vademus, LLC, 277 Faison McGowan Rd., Kenansville,
NC 28349.
086009 Axcentive SARL, Chemin de Champouse, Quartier Violesi,
13320 Bouc Bel Air, France.
086039 Mizner Bioscience LLC, 225 NE Mizner Blvd., Suite 760,
Boca Raton, FL 33432.
086047 LFB USA, Inc., 175 Crossing Blvd., Framingham, MA 01702.
086053 AquaBounty Technologies, Inc., 2 Mill and Main Pl.,
Suite 395, Maynard, MA 01754.
086064 Ivaoes Animal Health, 4300 SW 73rd Ave., suite 110,
Miami, FL 33155.
086072 VetDC, Inc., 320 E Vine Dr., suite 218, Fort Collins, CO
80524.
086073 Anzac Animal Health, LLC, 218 Millwell Dr., Suite B,
Maryland Heights, MO 63043.
086078 Kindred Biosciences, Inc., 1555 Bayshore Hwy., Suite
200, Burlingame, CA 94010.
086101 Felix Pharmaceuticals Pvt. Ltd., 25-28 North Wall Quay,
Dublin 1, Ireland.
086106 Union Agener, Inc., 1788 Lovers Ln., Augusta, GA 30901.
086113 Wildcat Feeds, 215 NE Strait Ave., Topeka, KS 66616.
086121 Anivive Lifesciences, Inc., 3250 Airflite Way, Suite
400, Long Beach, CA 90807.
086132 QBiotics Group Ltd., Suite 3A, Level 1, 165 Moggill Rd.,
Taringa, Queensland 4068, Australia.
086134 Revivicor, Inc., a wholly owned subsidiary of United
Therapeutics Corp., 1700 Kraft Dr., Suite 2400,
Blacksburg, VA 24060.
086149 Jaguar Animal Health, 200 Pine St., Suite 600, San
Francisco, CA 94104.
099207 Bausch Health US, LLC, 400 Somerset Corporate Blvd.,
Bridgewater, NJ 08807.
------------------------------------------------------------------------
[40 FR 13807, Mar. 27, 1975]
Editorial Notes: 1. For Federal Register citations affecting Sec.
510.600, see the List of CFR Sections Affected, which appears in the
Finding Aids section of the printed volume and at www.govinfo.gov.
2. At 77 FR 46613, Aug. 6, 2012, Sec. 510.600 was amended by
removing the entry for ``012758'' in the table in paragraph (c)(2);
however, the amendment could not be incorporated because ``012758''
didn't exist.
[[Page 86]]
PART 511_NEW ANIMAL DRUGS FOR INVESTIGATIONAL USE--Table of Contents
Sec.
511.1 New animal drugs for investigational use exempt from section
512(a) of the Federal Food, Drug, and Cosmetic Act.
511.3 Definitions.
Authority: 21 U.S.C. 321, 351, 352, 353, 360b, 371.
Sec. 511.1 New animal drugs for investigational use exempt
from section 512(a) of the Federal Food, Drug, and Cosmetic Act.
(a) New animal drugs for tests in vitro and in laboratory research
animals. (1) A shipment or other delivery of a new animal drug or animal
feed bearing or containing a new animal drug intended solely for tests
in vitro or in animals used only for laboratory research purposes shall
be exempt from section 512 (a) and (m) of the act if it is labeled as
follows:
Caution. Contains a new animal drug for investigational use only in
laboratory research animals or for tests in vitro. Not for use in
humans.
(2) The person distributing or causing the distribution of new
animal drugs for tests in vitro or in animals used only for laboratory
research purposes under this exemption shall use due diligence to assure
that the consignee is regularly engaged in conducting such tests and
that the shipment of the new animal drug will actually be used for tests
in vitro or in animals used only for laboratory research.
(3) The person who introduced such shipment or who delivered the new
animal drug for introduction into interstate commerce shall maintain
adequate records showing the name and post office address of the expert
or expert organization to whom the new animal drug is shipped and the
date, quantity, and batch or code mark of each shipment and delivery for
a period of 2 years after such shipment and delivery. Upon the request
of a properly authorized employee of the Department at reasonable times,
he shall make such records available for inspection and copying.
(4) The exemption allowed in this paragraph shall not apply to any
new animal drug intended for in vitro use in the regular course of
diagnosing or treating disease, including antibacterial sensitivity
discs impregnated with any new animal drug or drugs, which discs are
intended for use in determining susceptibility of microorganisms to the
new animal drug or drugs.
(b) New animal drugs for clinical investigation in animals. A
shipment or other delivery of a new animal drug or an animal feed
containing a new animal drug intended for clinical investigational use
in animals shall be exempt from section 512(a) and (m) of the act if all
the following conditions are met:
(1) The label shall bear the statements:
Caution. Contains a new animal drug for use only in investigational
animals in clinical trials. Not for use in humans. Edible products of
investigational animals are not to be used for food unless authorization
has been granted by the U.S. Food and Drug Administration or by the U.S.
Department of Agriculture.
In the case of containers too small or otherwise unable to
accommodate a label with sufficient space to bear the caution statements
required by paragraph (a) or (b) of this section, the statements may be
included on the carton label and other labeling on or within the package
from which the new animal drug is to be dispensed.
(2) The person or firm distributing or causing the distribution of
the new animal drug or animal feed containing a new animal drug shall
use due diligence to assure that the new animal drug or animal feed
containing a new animal drug will actually be used for tests in animals
and is not used in humans.
(3) The person who introduced such shipment or who delivered the new
animal drug or animal feed containing a new animal drug for introduction
into interstate commerce shall maintain adequate records showing the
name and post office address of the investigator to whom the new animal
drug or animal feed containing a new animal drug is shipped and the
date, quantity, and batch or code mark of each shipment and delivery for
a period of 2 years after such shipment and delivery.
[[Page 87]]
Upon the request of a properly authorized employee of the Department at
reasonable times, such records shall be made available for inspection
and copying.
(4) Prior to shipment of the new animal drug for clinical tests in
animals, the sponsor of the investigation shall submit in triplicate to
FDA a ``Notice of Claimed Investigational Exemption for a New Animal
Drug'' including a signed statement containing the following
information:
(i) The identity of the new animal drug.
(ii) All labeling and other pertinent information to be supplied to
the investigators. When such pertinent information includes nonclinical
laboratory studies, the information shall include, with respect to each
nonclinical study, either a statement that the study was conducted in
compliance with the requirements set forth in part 58 of this chapter,
or, if the study was not conducted in compliance with such regulations,
a brief statement of the reason for the noncompliance.
(iii) The name and address of each clinical investigator.
(iv) The approximate number of animals to be treated (or if not
available, the amount of new animal drug to be shipped).
(v) If the new animal drug is given to food-producing animals, the
statement shall contain the following additional information:
(a) A commitment that the edible products from such animals shall
not be used for food without prior authorization in accordance with the
provisions prescribed in this section.
(b) Approximate dates of the beginning and end of the experiment or
series of experiments.
(c) The maximum daily dose(s) to be administered to a given species,
the size of animal, maximum duration of administration, method(s) of
administration, and proposed withdrawal time, if any.
(vi) If a sponsor has transferred any obligations for the conduct of
any clinical study to a contract research organization, a statement
containing the name and address of the contract research organization,
identification of the clinical study, and a listing of the obligations
transferred. If all obligations governing the conduct of the study have
been transferred, a general statement of this transfer--in lieu of a
listing of the specific obligations transferred--may be submitted.
(5) Authorization for use of edible products derived from a treated
food-producing animal may be granted under the provisions of this
section and when the following specified conditions are met, except that
in the case of an animal administered any unlicensed experimental
veterinary biological product regulated under the viruses, serums,
toxins statute (21 U.S.C., chapter V, sec. 151 et seq. ) the product
shall be exempt from the requirements of this section when U.S.
Department of Agriculture approval has been obtained as provided in 9
CFR 103.2. Conditional authorization may be granted in advance of
identification of the name(s) and address(es) of the clinical
investigator(s) as required by paragraph (b)(4)(iii) of this section.
Information required for authorization shall include, in addition to all
other requirements of this section, the following:
(i) Data to show that consumption of food derived from animals
treated at the maximum levels with the minimum withdrawal periods, if
any, specified in accordance with paragraph (b)(4)(v)(c) of this
section, will not be inconsistent with the public health; or
(ii) Data to show that food derived from animals treated at the
maximum levels and with the minimum withdrawal periods, if any,
specified in accordance with paragraph (b)(4)(v)(c) of this section,
does not contain drug residues or metabolites.
(iii) The name and location of the packing plant where the animals
will be processed, except that this requirement may be waived, on
request, by the terms of the authorization.
Authorizations granted under this paragraph do not exempt
investigational animals and their products from compliance with other
applicable inspection requirements. Any person who contests a refusal to
grant such authorization shall have an opportunity for a regulatory
hearing before FDA pursuant to part 16 of this chapter.
[[Page 88]]
(6) On written request of FDA, the sponsor shall submit any
additional information reported to or otherwise received by him with
respect to the investigation deemed necessary to facilitate a
determination whether there are grounds in the interest of public health
for terminating the exemption.
(7) The sponsor shall assure himself that the new animal drug is
shipped only to investigators who:
(i) Are qualified by scientific training and/experience to evaluate
the safety and/or effectiveness of the new animal drug.
(ii) Shall maintain complete records of the investigations,
including complete records of the receipt and disposition of each
shipment or delivery of the new animal drug under investigation. Copies
of all records of the investigation shall be retained by the
investigator for 2 years after the termination of the investigation or
approval of a new animal drug application.
(iii) Shall furnish adequate and timely reports of the investigation
to the sponsor.
(8) The sponsor:
(i) Shall retain all reports received from investigators for 2 years
after the termination of the investigation or approval of a new animal
drug application and make such reports available to a duly authorized
employee of the Department for inspection at all reasonable times.
(ii) Shall provide for current monitoring of the investigation by a
person qualified by scientific training and experience to evaluate
information obtained from the investigation, and shall promptly
investigate and report to FDA and to all investigators any findings
associated with use of the new animal drug that may suggest significant
hazards pertinent to the safety of the new animal drug.
(iii) Shall not unduly prolong distribution of the new animal drug
for investigational use.
(iv) Shall not, nor shall any person acting for or on behalf of the
sponsor, represent that the new animal drug is safe or effective for the
purposes for which it is under investigation. This requirement is not
intended to restrict the full exchange of scientific information.
(v) Shall not commercially distribute nor test-market the new animal
drug until a new animal drug application is approved pursuant to section
512(c) of the act.
(9) If the shipment or other delivery of the new animal drug is
imported or offered for importation into the United States for clinical
investigational use in animals, it shall also meet the following
conditions:
(i) The importer of all such shipments or deliveries is an agent of
the foreign exporter residing in the United States or the ultimate
consignee, which person has, prior to such shipments and deliveries,
informed FDA of his intention to import the new animal drug as sponsor
in compliance with the conditions prescribed in this subdivision; or
(ii) The new animal drug is shipped directly to a scientific
institution with adequate facilities and qualified personnel to conduct
laboratory or clinical investigations and is intended solely for use in
such institutions and which institution has submitted a statement as
sponsor of the investigation.
(10) The sponsor shall submit either a claim for categorical
exclusion under Sec. 25.30 or Sec. 25.33 of this chapter or an
environmental assessment under Sec. 25.40 of this chapter.
(c) Disqualification of a clinical investigator. (1) If FDA has
information indicating that an investigator (including a sponsor-
investigator) has repeatedly or deliberately failed to comply with the
conditions of these exempting regulations or has repeatedly or
deliberately submitted to FDA or to the sponsor false information in any
required report, the Center for Veterinary Medicine will furnish the
investigator written notice of the matter complained of and offer the
investigator an opportunity to explain the matter in writing, or, at the
option of the investigator, in an informal conference. If an explanation
is offered and accepted by the Center for Veterinary Medicine, the
Center will discontinue the disqualification proceeding. If an
explanation is offered but not accepted by the Center for Veterinary
Medicine, the investigator will be given an opportunity for a regulatory
hearing under
[[Page 89]]
part 16 of this chapter on the question of whether the investigator is
eligible to receive test articles under this part and eligible to
conduct:
(i) Any clinical investigation that supports an application for a
research or marketing permit for products regulated by FDA; and
(ii) Any nonclinical laboratory study intended to support an
application for a research or marketing permit for a new animal drug.
(2) After evaluating all available information, including any
explanation presented by the investigator, if the Commissioner
determines that the investigator has repeatedly or deliberately failed
to comply with the conditions of the exempting regulations in this
subchapter, or has repeatedly or deliberately submitted to FDA or to the
sponsor false information in any required report, the Commissioner will
notify the investigator and the sponsor of any investigation in which
the investigator has been named as a participant that the investigator
is not eligible to receive test articles under this part. The
notification to the investigator and sponsor will provide a statement of
the basis for such determination. The notification also will explain
that an investigator determined to be ineligible to receive test
articles under this part will be ineligible to conduct:
(i) Any clinical investigation that supports an application for a
research or marketing permit for products regulated by FDA, including
drugs, biologics, devices, new animal drugs, foods, including dietary
supplements, that bear a nutrient content claim or a health claim,
infant formulas, food and color additives, and tobacco products; and
(ii) Any nonclinical laboratory study intended to support an
application for a research or marketing permit for a new animal drug.
(3) Each application or submission to FDA under the provisions of
this chapter containing data reported by an investigator who has been
determined to be ineligible to receive FDA-regulated test articles is
subject to examination to determine whether the investigator has
submitted unreliable data that are essential to the continuation of an
investigation or essential to the approval of a marketing application,
or essential to the continued marketing of an FDA-regulated product.
(4) If the Commissioner determines, after the unreliable data
submitted by the investigator are eliminated from consideration, that
the data remaining are inadequate to support a conclusion that it is
reasonably safe to continue the investigation, the Commissioner will
notify the sponsor, who shall have an opportunity for a regulatory
hearing under part 16 of this chapter. If a danger to the public health
exists, however, the Commissioner shall terminate the exemption
immediately and notify the sponsor of the termination. In such case, the
sponsor shall have an opportunity for a regulatory hearing before FDA
under part 16 on the question of whether the exemption should be
reinstated. The determination that an investigation may not be
considered in support of a research or marketing application or a
notification or petition submission does not, however, relieve the
sponsor of any obligation under any other applicable regulation to
submit to FDA the results of the investigation.
(5) If the Commissioner determines, after the unreliable data
submitted by the investigator are eliminated from consideration, that
the continued approval of the product for which the data were submitted
cannot be justified, the Commissioner will proceed to withdraw approval
of the product in accordance with the applicable provisions of the
relevant statutes.
(6) An investigator who has been determined to be ineligible under
paragraph (c)(2) of this section may be reinstated as eligible when the
Commissioner determines that the investigator has presented adequate
assurances that the investigator will employ all test articles, and will
conduct any clinical investigation that supports an application for a
research or marketing permit for products regulated by FDA and any
nonclinical laboratory study intended to support an application for a
research or marketing permit for a new animal drug, solely in compliance
with the applicable provisions of this chapter.
(d) Termination of exemption. If the Commissioner finds that:
[[Page 90]]
(1) The sponsor of the investigation has failed to comply with any
of the conditions for the exemption established under this section, or
(2) The continuance of the investigation is unsafe or otherwise
contrary to the public interest or the drug is being or has been used
for purposes other than bona fide scientific investigation, he shall
first notify the sponsor and invite his immediate correction. If the
conditions of the exemption are not immediately met, the sponsor shall
have an opportunity for a regulatory hearing before FDA pursuant of part
16 of this chapter on whether the exemption should be terminated. If the
exemption is terminated the sponsor shall recall or have destroyed the
unused supplies of the new animal drug.
(e) Statements and requests. ``Notice(s) of Claimed Investigational
Exemption for a New Animal Drug'' and requests for authorization to use
investigational animals and their products for food should be addressed
to the Department of Health and Human Services, Food and Drug
Administration, Center for Veterinary Medicine, 7500 Standish Pl.,
Rockville, MD 20855.
(f) Contract research organizations. (1) For purposes of this part
and part 514, contract research organization means a person that
assumes, as an independent contractor with the sponsor, one or more of
the obligations of a sponsor, e.g., design of a protocol, selection or
monitoring of investigations, evaluation of reports, and preparation of
materials to be submitted to FDA.
(2) A sponsor may transfer responsibility for any or all of the
obligations set forth in this part to a contract research organization.
Any such transfer shall be in writing and, if not all obligations are
transferred, shall describe each of the obligations being assumed by the
contract research organization. If all obligations are transferred, a
general statement that all obligations have been transferred is
acceptable. Any obligation not covered by the written description shall
be deemed not to have been transferred.
(3) A contract research organization that assumes any obligation of
a sponsor shall comply with the specific regulations in this chapter
applicable to this obligation and shall be subject to the same
regulatory action as a sponsor for failure to comply with any obligation
assumed under these regulations. Thus, all references to sponsor in this
part apply to a contract research organization to the extent that it
assumes one or more obligations of the sponsor.
(g) Index of legally marketed unapproved new animal drugs for minor
species. All provisions of part 511 apply to new animal drugs for
investigational use in support of indexing, as described in section 572
of the act, subject to the provisions of Sec. 516.125 of this chapter.
[40 FR 13823, Mar. 27, 1975, as amended at 41 FR 48268, Nov. 2, 1976; 42
FR 15675, Mar. 22, 1977; 50 FR 7517, Feb. 22, 1985; 50 FR 16668, Apr.
26, 1985; 52 FR 8847, Mar. 19, 1987; 54 FR 18280, Apr. 28, 1989; 57 FR
6475, Feb. 25, 1992; 62 FR 40599, July 29, 1997; 72 FR 69121, Dec. 6,
2007; 77 FR 25359, Apr. 30, 2012; 82 FR 61446, Dec. 28, 2017]
Sec. 511.3 Definitions.
As used in this part:
Contract research organization means a person that assumes, as an
independent contractor with the sponsor, one or more of the obligations
of a sponsor, e.g., design of a protocol, selection or monitoring of
investigations, evaluation of reports, and preparation of materials to
be submitted to the Food and Drug Administration.
Investigator means an individual who actually conducts a clinical
investigation (i.e., under whose immediate direction the drug is
administered or dispensed to a subject). In the event an investigation
is conducted by a team of individuals, the investigator is the
responsible leader of the team. ``Subinvestigator'' includes any other
individual member of that team.
Sponsor means a person who takes responsibility for and initiates a
clinical investigation. The sponsor may be an individual or
pharmaceutical company, governmental agency, academic institution,
private organization, or other organization. The sponsor does not
actually conduct the investigation unless the sponsor is a sponsor-
investigator. A person other than an individual that uses one or more of
its own employees to conduct an investigation that it has
[[Page 91]]
initiated is a sponsor, not a sponsor-investigator, and the employees
are investigators.
Sponsor-Investigator means an individual who both initiates and
conducts an investigation, and under whose immediate direction the
investigational drug is administered or dispensed. The term does not
include any person other than an individual. The requirements applicable
to a sponsor-investigator under this part include both those applicable
to an investigator and a sponsor.
[77 FR 25359, Apr. 30, 2012]
PART 514_NEW ANIMAL DRUG APPLICATIONS--Table of Contents
Subpart A_General Provisions
Sec.
514.1 Applications.
514.3 Definitions.
514.4 Substantial evidence.
514.5 Presubmission conferences.
514.6 Amended applications.
514.7 Withdrawal of applications without prejudice.
514.8 Supplements and other changes to an approved application.
514.11 Confidentiality of data and information in a new animal drug
application file.
514.12 Confidentiality of data and information in an investigational new
animal drug notice.
514.15 Untrue statements in applications.
Subpart B_Administrative Actions on Applications
514.80 Records and reports concerning experience with approved new
animal drugs.
514.87 Annual reports for antimicrobial animal drug sales and
distribution.
514.100 Evaluation and comment on applications.
514.105 Approval of applications.
514.106 Approval of supplemental applications.
514.110 Reasons for refusing to file applications.
514.111 Refusal to approve an application.
514.115 Withdrawal of approval of applications.
514.116 Notice of withdrawal of approval of application.
514.117 Adequate and well-controlled studies.
514.120 Revocation of order refusing to approve an application or
suspending or withdrawing approval of an application.
514.121 Service of notices and orders.
Subpart C_Hearing Procedures
514.200 Notice of opportunity for hearing; notice of participation and
requests for hearing; grant or denial of hearing.
514.201 Procedures for hearings.
Subparts D-E [Reserved]
Subpart F_Judicial Review
514.235 Judicial review.
Authority: 21 U.S.C. 321, 331, 351, 352, 354, 356a, 360b, 360ccc,
371, 379e, 381.
Source: 40 FR 13825, Mar. 27, 1975, unless otherwise noted.
Subpart A_General Provisions
Sec. 514.1 Applications.
(a) Applications to be filed under section 512(b) of the act shall
be submitted in the form and contain the information described in
paragraph (b) of this section, as appropriate to support the particular
submission. If any part of the application is in a foreign language, an
accurate and complete English translation shall be appended to such
part. Translations of literature printed in a foreign language shall be
accompanied by copies of the original publication. The application must
be signed by the applicant or by an authorized attorney, agent, or
official. If the applicant or such authorized representative does not
reside or have a place of business within the United States, the
application must also furnish the name and post office address of, and
must be countersigned by, an authorized attorney, agent, or official
residing or maintaining a place of business within the United States.
Pertinent information may be incorporated in, and will be considered as
part of, an application on the basis of specific reference to such
information, including information submitted under the provisions of
Sec. 511.1 of this chapter, in the files of the Food and Drug
Administration; however, the reference must be specific in identifying
the information. Any reference to information furnished by a person
other than the applicant may not be considered unless its use is
authorized in a written statement signed by the person who submitted it.
[[Page 92]]
(b) Applications for new animal drugs shall be submitted in
triplicate and assembled in the manner prescribed by paragraph (b)(15)
of this section, and shall include the following information, as
appropriate to support the particular submission:
(1) Identification. Whether the submission is an original or
supplemental application; the name and the address of the applicant; the
date of the application; the trade name(s) (if one has been proposed)
and chemical name(s) of the new animal drug. Upon receipt, the
application will be assigned a number NADA __, which shall be used for
all correspondence with respect to the application.
(2) Table of contents and summary. The application shall be
organized in a cohesive fashion, shall contain a table of contents which
identifies the data and other material submitted, and shall contain a
well-organized summary and evaluation of the data in the following form:
(i) Chemistry:
(a) Chemical structural formula or description for any new animal
drug substance.
(b) Relationship to other chemically or pharmacologically related
drugs.
(c) Description of dosage form and quantitative composition.
(ii) Scientific rationale and purpose the new animal drug is to
serve:
(a) Clinical purpose.
(b) Highlights of laboratory studies: The reasons why certain types
of studies were done or omitted as related to the proposed conditions of
use and to information already known about this class of compounds.
Emphasize any unusual or particularly significant pharmacological
effects or toxicological findings.
(c) Highlights of clinical studies: The rationale of the clinical
study plan showing why types of studies were done, amended, or omitted
as related to laboratory studies and prior clinical experience.
(d) Conclusions: A short statement of conclusions combining the
major points of effectiveness and safety as they relate to the use of
the new animal drug.
(3) Labeling. Three copies of each piece of all labeling to be used
for the article (total of 9).
(i) All labeling should be identified to show its position on, or
the manner in which it is to accompany the market package.
(ii) Labeling for nonprescription new animal drugs should include
adequate directions for use by the layman under all conditions of use
for which the new animal drug is intended, recommended, or suggested in
any of the labeling or advertising sponsored by the applicant.
(iii) Labeling for prescription veterinary drugs should bear
adequate information for use under which veterinarians can use the new
animal drug safely and for the purposes for which it is intended,
including those purposes for which it is to be advertised or
represented, in accord with Sec. 201.105 of this chapter.
(iv) All labeling for prescription or nonprescription new animal
drugs shall be submitted with any necessary use restrictions prominently
and conspicuously displayed.
(v) Labeling for new animal drugs intended for use in the
manufacture of medicated feeds shall include:
(a) Specimens of labeling to be used for such new animal drug with
adequate directions for the manufacture and use of finished feeds for
all conditions for which the new animal drug is intended, recommended,
or suggested in any of the labeling, including advertising, sponsored by
the applicant. Ingredient labeling may utilize collective names as
provided in Sec. 501.110 of this chapter.
(b) Representative labeling proposed to be used for Type B and Type
C medicated feeds containing the new animal drug.
(vi) Draft labeling may be submitted for preliminary consideration
of an application. Final printed labeling will ordinarily be required
prior to approval of an application. Proposed advertising for veterinary
prescription drugs may be submitted for comment or approval.
(4) Components and composition. A complete list of all articles used
for production of the new animal drug including a full list of the
composition of each article:
[[Page 93]]
(i) A full list of the articles used as components of the new animal
drug. This list should include all substances used in the synthesis,
extraction, or other method of preparation of any new animal drug and in
the preparation of the finished dosage form, regardless of whether they
undergo chemical change or are removed in the process. Each component
should be identified by its established name, if any, or complete
chemical name, using structural formulas when necessary for specific
identification. If any proprietary name is used, it should be followed
by a complete quantitative statement of composition. Reasonable
alternatives for any listed component may be specified.
(ii) A full statement of the composition of the new animal drug. The
statement shall set forth the name and amount of each ingredient,
whether active or not, contained in a stated quantity of the new animal
drug in the form in which it is to be distributed (for example, amount
per tablet or milliliter) and a batch formula representative of that to
be employed for the manufacture of the finished dosage form. All
components should be included in the batch formula regardless of whether
they appear in the finished product. Any calculated excess of an
ingredient over the label declaration should be designated as such and
percent excess shown. Reasonable variation may be specified.
(iii) If it is a new animal drug produced by fermentation:
(a) Source and type of microorganism used to produce the new animal
drug.
(b) Composition of media used to produce the new animal drug.
(c) Type of precursor used, if any, to guide or enhance production
of the antibiotic during fermentation.
(d) Name and composition of preservative, if any, used in the broth.
(e) A complete description of the extraction and purification
processes including the names and compositions of the solvents,
precipitants, ion exchange resins, emulsifiers, and all other agents
used.
(f) If the new animal drug is produced by a catalytic hydrogenation
process (such as tetracycline from chlortetracycline), a complete
description of each chemical reaction with graphic formulas used to
produce the new animal drug, including the names of the catalyst used,
how it is removed, and how the new animal drug is extracted and
purified.
(5) Manufacturing methods, facilities, and controls. A full
description of the methods used in, and the facilities and controls used
for, the manufacture, processing, and packing of the new animal drug.
This description should include full information with respect to any new
animal drug in sufficient detail to permit evaluation of the adequacy of
the described methods of manufacture, processing, and packing, and the
described facilities and controls to determine and preserve the
identity, strength, quality, and purity of the new animal drug, and the
following:
(i) If the applicant does not himself perform all the manufacturing,
processing, packaging, labeling, and control operations for any new
animal drug, he shall: Identify each person who will perform any part of
such operations and designate the part; and provide a signed statement
from each such person fully describing, directly or by reference, the
methods, facilities, and controls he will use in his part of the
operation. The statement shall include a commitment that no changes will
be made without prior approval by the Food and Drug Administration,
unless permitted under Sec. 514.8.
(ii) A description of the qualifications, including educational
background and experience, of the technical and professional personnel
who are responsible for assuring that the new animal drug has the
identity, strength, quality, and purity it purports or is represented to
possess, and a statement of their responsibilities.
(iii) A description of the physical facilities including building
and equipment used in manufacturing, processing, packaging, labeling,
storage, and control operations.
(iv) The methods used in the synthesis, extraction, isolation, or
purification of any new animal drug. When the specifications and
controls applied to such new animal drugs are inadequate in themselves
to determine its identity, strength, quality, and purity,
[[Page 94]]
the methods should be described in sufficient detail, including
quantities used, times, temperature, pH, solvents, etc., to determine
these characteristics. Alternative methods or variations in methods
within reasonable limits that do not affect such characteristics of the
new animal drug may be specified. A flow sheet and indicated equations
should be submitted when needed to explain the process.
(v) Precautions to insure proper identity, strength, quality, and
purity of the raw materials, whether active or not, including:
(a) The specifications for acceptance and methods of testing for
each lot of raw material.
(b) A statement as to whether or not each lot of raw materials is
given a serial number to identify it, and the use made of such numbers
in subsequent plant operations.
(vi) The instructions used in the manufacturing, processing,
packaging, and labeling of each dosage form of the new animal drug,
including:
(a) The method of preparation of the master formula records and
individual batch records and the manner in which these records are used.
(b) The number of individuals checking weight or volume of each
individual ingredient entering into each batch of the new animal drug.
(c) A statement as to whether or not the total weight or volume of
each batch is determined at any stage of the manufacturing process
subsequent to making up a batch according to the formula card and, if
so, at what stage and by whom it is done.
(d) The precautions used in checking the actual package yield
produced from a batch of the new animal drug with the theoretical yield.
This should include a description of the accounting for such items as
discards, breakage, etc., and the criteria used in accepting or
rejecting batches of drugs in the event of an unexplained discrepancy.
(e) The precautions used to assure that each lot of the new animal
drug is packaged with the proper label and labeling, including
provisions for labeling storage and inventory control.
(f) Any special precautions used in the operations.
(vii) The analytical controls used during the various stages of the
manufacturing, processing, packaging, and labeling of the new animal
drug, including a detailed description of the collection of samples and
the analytical procedures to which they are subjected. The analytical
procedures should be capable of determining the active components within
a reasonable degree of accuracy and of assuring the identity of such
components.
(a) A description of practicable methods of analysis of adequate
sensitivity to determine the amount of the new animal drug in the final
dosage form should be included. The dosage form may be a finished
pharmaceutical product, a Type A medicated article, a Type B or a Type C
medicated feed, or a product for use in animal drinking water. Where two
or more active ingredients are included, methods should be quantitative
and specific for each active ingredient.
(b) If the article is one that is represented to be sterile, the
same information with regard to the manufacturing, processing,
packaging, and the collection of samples of the drug should be given for
sterility controls. Include the standards used for acceptance of each
lot of the finished drug.
(viii) An explanation of the exact significance of any batch control
numbers used in the manufacturing, processing, packaging, and labeling
of the new animal drug, including such control numbers that may appear
on the label of the finished article. State whether these numbers enable
determination of the complete manufacturing history of the product.
Describe any methods used to permit determination of the distribution of
any batch if its recall is required.
(ix) Adequate information with respect to the characteristics of and
the test methods employed for the container, closure, or other component
parts of the drug package to assure their suitability for the intended
use.
(x) A complete description of, and data derived from, studies of the
stability of the new animal drug in the final dosage form, including
information showing the suitability of the analytical methods used. A
description of
[[Page 95]]
any additional stability studies underway or planned. Stability data for
the finished dosage form of the new animal drug in the container in
which it is to be marketed, including any proposed multiple dose
container, and, if it is to be put into solution at the time of
dispensing, for the solution prepared as directed. If the new animal
drug is intended for use in the manufacture of Type C medicated feed as
defined in Sec. 558.3 of this chapter, stability data derived from
studies in which representative formulations of the medicated feed
articles are used. Similar data may be required for Type B medicated
feeds as determined by the Food and Drug Administration on a case-by-
case basis. Expiration dates shall be proposed for finished
pharmaceutical dosage forms and Type A medicated articles. If the data
indicate that an expiration date is needed for Type B or Type C
medicated feeds, the applicant shall propose such expiration date. If no
expiration date is proposed for Type B or Type C medicated feeds, the
applicant shall justify its absence with data.
(xi) Additional procedures employed which are designed to prevent
contamination and otherwise assure proper control of the product. An
application may be refused unless it includes adequate information
showing that the methods used in, and the facilities and controls used
for, the manufacturing, processing, and packaging of the new animal drug
are adequate to preserve its identity, strength, quality, and purity in
conformity with good manufacturing practice and identifies each
establishment, showing the location of the plant conducting these
operations.
(6) Samples. Samples of the new animal drug and articles used as
components and information concerning them may be requested by the
Center for Veterinary Medicine as follows:
(i) Each sample shall consist of four identical, separately packaged
subdivisions, each containing at least three times the amount required
to perform the laboratory test procedures described in the application
to determine compliance with its control specifications for identity and
assays. Each of the samples submitted shall be appropriately packaged
and labeled to preserve its characteristics, to identify the material
and the quantity in each subdivision of the sample, and to identify each
subdivision with the name of the applicant and the new animal drug
application to which it relates. Included are:
(a) A sample or samples of any reference standard and blank used in
the procedures described in the application for assaying each new animal
drug and other assayed components of the finished new animal drug.
(b) A representative sample or samples of each strength of the
finished dosage form proposed in the application and employed in the
clinical investigations and a representative sample or samples of each
new animal drug from the batch(es) employed in the production of such
dosage form.
(c) A representative sample or samples of finished market packages
of each strength of the dosage form of the new animal drug prepared for
initial marketing and, if any such sample is not from a representative
commercial-scale production batch, such a sample from a representative
commercial-scale production batch, and a representative sample or
samples of each new animal drug from the batch(es) employed in the
production of such dosage form, provided that in the case of new animal
drugs marketed in large packages the sample should contain only three
times a sufficient quantity of the new animal drug to allow for
performing the control tests for drug identity and assays.
(ii) The following information shall be included for the samples
when requested:
(a) For each sample submitted, full information regarding its
identity and the origin of any new animal drug contained therein
(including a statement whether it was produced on a laboratory, pilot-
plant, or full-production scale) and detailed results of all laboratory
tests made to determine the identity, strength, quality, and purity of
the batch represented by the sample, including assays.
(b) For any reference standard submitted, a complete description of
its preparation and the results of all laboratory tests on it. If the
test methods used differed from those described in the application, full
details of the
[[Page 96]]
methods employed in obtaining the reporting results.
(7) Analytical methods for residues. Applications shall include a
description of practicable methods for determining the quantity, if any,
of the new animal drug in or on food, and any substance formed in or on
food because of its use, and the proposed tolerance or withdrawal period
or other use restrictions to ensure that the proposed use of this drug
will be safe. When data or other adequate information establish that it
is not reasonable to expect the new animal drug to become a component of
food at concentrations considered unsafe, a regulatory method is not
required.
(i) The kind of information required by this subdivision may
include: Complete experimental protocols for determining drug residue
levels in the edible products, and the length of time required for
residues to be eliminated from such products following the drug's use;
residue studies conducted under appropriate (consistent with the
proposed usage) conditions of dosage, time, and route of administration
to show levels, if any, of the drug and/or its metabolites in test
animals during and upon cessation of treatment and at intervals
thereafter in order to establish a disappearance curve; if the drug is
to be used in combination with other drugs, possible effects of
interaction demonstrated by the appropriate disappearance curve or
depletion patterns after drug withdrawal under appropriate (consistent
with the proposed usage) conditions of dosage, time, and route of
administration; if the drug is given in the feed or water, appropriate
consumption records of the medicated feed or water and appropriate
performance data in the treated animal; if the drug is to be used in
more than one species, drug residue studies or appropriate metabolic
studies conducted for each species that is food-producing. To provide
these data, a sufficient number of birds or animals should be used at
each sample interval. Appropriate use of labeled compounds (e.g.
radioactive tracers), may be utilized to establish metabolism and
depletion curves. Drug residue levels ordinarily should be determined in
muscle, liver, kidney, and fat and where applicable, in skin, milk, and
eggs (yolk and egg white). As a part of the metabolic studies, levels of
the drug or metabolite should be determined in blood where feasible.
Samples may be combined where necessary. Where residues are suspected or
known to be present in litter from treated animals, it may be necessary
to include data with respect to such residues becoming components of
other agricultural commodities because of use of litter from treated
animals.
(ii) A new animal drug that has the potential to contaminate human
food with residues whose consumption could present a risk of cancer to
people must satisfy the requirements of subpart E of part 500 of this
chapter.
(8) Evidence to establish safety and effectiveness. (i) An
application may be refused unless it contains full reports of adequate
tests by all methods reasonably applicable to show whether or not the
new animal drug is safe and effective for use as suggested in the
proposed labeling.
(ii) An application may be refused unless it includes substantial
evidence of the effectiveness of the new animal drug as defined in Sec.
514.4.
(iii) An application may be refused unless it contains detailed
reports of the investigations, including studies made on laboratory
animals, in which the purpose, methods, and results obtained are clearly
set forth of acute, subacute, and chronic toxicity, and unless it
contains appropriate clinical laboratory results related to safety and
efficacy. Such information should include identification of the person
who conducted each investigation, a statement of where the
investigations were conducted, and where the raw data are available in
the application.
(iv) All information pertinent to an evaluation of the safety and
effectiveness of the new animal drug received or otherwise obtained by
the applicant from any source, including information derived from other
investigations or commercial marketing (for example, outside the United
States), or reports in the scientific literature, both favorable and
unfavorable, involving the new animal drug that is the subject of the
application and related new animal drugs shall be submitted. An adequate
summary may be acceptable in lieu of
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a reprint of a published report that only supports other data submitted.
Include any evaluation of the safety or effectiveness of the new animal
drug that has been made by the applicant's veterinary or medical
department, expert committee, or consultants.
(v) If the new animal drug is a combination of active ingredients or
animal drugs, an application may be refused unless it includes
substantial evidence of the effectiveness of the combination new animal
drug as required in Sec. 514.4.
(vi) An application shall include a complete list of the names and
post office addresses of all investigators who received the new animal
drug. This may be incorporated in whole or in part by reference to
information submitted under the provisions of Sec. 511.1 of this
chapter.
(vii) Explain any omission of reports from any investigator to whom
the investigational new animal drug has been made available. The
unexplained omission of any reports of investigations made with the new
animal drug by the applicant or submitted to him by an investigator or
the unexplained omission of any pertinent reports of investigations or
clinical experience received or otherwise obtained by the applicant from
published literature or other sources that would bias an evaluation of
the safety of the new animal drug or its effectiveness in use,
constitutes grounds for the refusal or withdrawal of the approval of an
application.
(viii) If a sponsor has transferred any obligations for the conduct
of any clinical study to a contract research organization, the
application is required to include a statement containing the name and
address of the contract research organization, identifying the clinical
study, and listing the obligations transferred. If all obligations
governing the conduct of the study have been transferred, a general
statement of this transfer--in lieu of a listing of the specific
obligations transferred--may be submitted.
(ix) If original subject records were audited or reviewed by the
sponsor in the course of monitoring any clinical study to verify the
accuracy of the case reports submitted to the sponsor, a list
identifying each clinical study so audited or reviewed.
(9) Veterinary feed directive. Three copies of a veterinary feed
directive (VFD) must be submitted in a form that accounts for the
information described under Sec. 558.6(b)(3) and 558.6(b)(4) of this
chapter.
(10) Supplemental applications. If it is a supplemental application,
full information shall be submitted on each proposed change concerning
any statement made in the approved application.
(11) Applicant's commitment. It is understood that the labeling and
advertising for the new animal drug will prescribe, recommend, or
suggest its use only under the conditions stated in the labeling which
is part of this application and if the article is a prescription new
animal drug, it is understood that any labeling which furnishes or
purports to furnish information for use or which prescribes, recommends,
or suggests a dosage for use of the new animal drug will also contain,
in the same language and emphasis, information for its use including
indications, effects, dosages, routes, methods, and frequency and
duration of administration, any relevant hazards, contraindications,
side effects, and precautions contained in the labeling which is part of
this application. It is understood that all representations in this
application apply to the drug produced until changes are made in
conformity with Sec. 514.8.
(12) Additional commitments. (i) New animal drugs as defined in
Sec. 510.3 of this chapter, intended for use in the manufacture of
animal feeds in any State will be shipped only to persons who may
receive such drugs in accordance with Sec. 510.7 of this chapter.
(ii) The methods, facilities, and controls described under item 5 of
this application conform to the current good manufacturing practice
regulations in subchapter C of this chapter.
(iii) With respect to each nonclinical laboratory study contained in
the application, either a statement that the study was conducted in
compliance with the good laboratory practice regulations set forth in
part 58 of this chapter, or, if the study was not conducted in
compliance with such regulations, a
[[Page 98]]
brief statement of the reason for the noncompliance.
(13) [Reserved]
(14) Environmental assessment. The applicant is required to submit
either a claim for categorical exclusion under Sec. 25.30 or Sec.
25.33 of this chapter or an environmental assessment under Sec. 25.40
of this chapter.
(15) Assembling and binding the application. Assemble and bind an
original and two copies of the application as follows:
(i) Bind the original or ribbon copy of the application as copy No.
1.
(ii) Bind two identical copies as copy No. 2 and copy No. 3.
(iii) Identify each front cover with the name of the applicant, new
animal drug, and the copy number.
(iv) Number each page of the application sequentially in the upper
right hand corner or in another location so that the page numbers remain
legible after the application has been bound, and organize the
application consistent with paragraphs (b) (1) through (14) of this
section. Each copy should bear the same page numbering, whether
sequential in each volume or continuous and sequential throughout the
application.
(v) Include complete labeling in each of the copies. It is suggested
that labeling be identified by date of printing or date of preparation.
(vi) Submit separate applications for each different dosage form of
the drug proposed. Repeating basic information pertinent to all dosage
forms in each application is unnecessary if reference is made to the
application containing such information. Include in each application
information applicable to the specific dosage form, such as labeling,
composition, stability data, and method of manufacture.
(vii) Submit in folders amendments, supplements, and other
correspondence sent after submission of an original application. The
front cover of these submissions should be identified with the name of
the applicant, new animal drug, copy number, and the new animal drug
application number, if known.
(c) When a new animal drug application is submitted for a new animal
drug which has a stimulant, depressant, or hallucinogenic effect on the
central nervous system, if it appears that the drug has a potential for
abuse, the Commissioner shall forward that information to the Attorney
General of the United States.
[40 FR 13825, Mar. 27, 1975]
Editorial Note: For Federal Register citations affecting Sec.
514.1, see the List of CFR Sections Affected, which appears in the
Finding Aids section of the printed volume and at www.govinfo.gov.
Sec. 514.3 Definitions.
The definition and interpretation of terms contained in this section
apply to those terms as used throughout subchapter E.
Adverse drug experience is any adverse event associated with the use
of a new animal drug, whether or not considered to be drug related, and
whether or not the new animal drug was used in accordance with the
approved labeling (i.e., used according to label directions or used in
an extralabel manner, including but not limited to different route of
administration, different species, different indications, or other than
labeled dosage). Adverse drug experience includes, but is not limited
to:
(1) An adverse event occurring in animals in the course of the use
of an animal drug product by a veterinarian or by a livestock producer
or other animal owner or caretaker.
(2) Failure of a new animal drug to produce its expected
pharmacological or clinical effect (lack of expected effectiveness).
(3) An adverse event occurring in humans from exposure during
manufacture, testing, handling, or use of a new animal drug.
ANADA is an abbreviated new animal drug application including all
amendments and supplements.
Applicant is a person or entity who owns or holds on behalf of the
owner the approval for an NADA or an ANADA, and is responsible for
compliance with applicable provisions of the act and regulations.
Increased frequency of adverse drug experience is an increased rate
of occurrence of a particular serious adverse drug event, expected or
unexpected, after appropriate adjustment for drug exposure.
[[Page 99]]
NADA is a new animal drug application including all amendments and
supplements.
Nonapplicant is any person other than the applicant whose name
appears on the label and who is engaged in manufacturing, packing,
distribution, or labeling of the product.
Potential applicant means any person:
(1) Intending to investigate a new animal drug under section 512(j)
of the Federal Food, Drug, and Cosmetic Act (the act),
(2) Investigating a new animal drug under section 512(j) of the act,
(3) Intending to file a new animal drug application (NADA) or
supplemental NADA under section 512(b)(1) of the act, or
(4) Intending to file an abbreviated new animal drug application
(ANADA) under section 512(b)(2) of the act.
Presubmission conference means one or more conferences between a
potential applicant and FDA to reach a binding agreement establishing a
submission or investigational requirement.
Presubmission conference agreement means that section of the
memorandum of conference headed ``Presubmission Conference Agreement''
that records any agreement on the submission or investigational
requirement reached by a potential applicant and FDA during the
presubmission conference.
Product defect/manufacturing defect is the deviation of a
distributed product from the standards specified in the approved
application, or any significant chemical, physical, or other change, or
deterioration in the distributed drug product, including any microbial
or chemical contamination. A manufacturing defect is a product defect
caused or aggravated by a manufacturing or related process. A
manufacturing defect may occur from a single event or from deficiencies
inherent to the manufacturing process. These defects are generally
associated with product contamination, product deterioration,
manufacturing error, defective packaging, damage from disaster, or
labeling error. For example, a labeling error may include any incident
that causes a distributed product to be mistaken for, or its labeling
applied to, another product.
Serious adverse drug experience is an adverse event that is fatal,
or life-threatening, or requires professional intervention, or causes an
abortion, or stillbirth, or infertility, or congenital anomaly, or
prolonged or permanent disability, or disfigurement.
Unexpected adverse drug experience is an adverse event that is not
listed in the current labeling for the new animal drug and includes any
event that may be symptomatically and pathophysiologically related to an
event listed on the labeling, but differs from the event because of
greater severity or specificity. For example, under this definition
hepatic necrosis would be unexpected if the labeling referred only to
elevated hepatic enzymes or hepatitis.
[68 FR 15365, Mar. 31, 2003, as amended at 69 FR 51170, Aug. 18, 2004]
Sec. 514.4 Substantial evidence.
(a) Definition of substantial evidence. Substantial evidence means
evidence consisting of one or more adequate and well-controlled studies,
such as a study in a target species, study in laboratory animals, field
study, bioequivalence study, or an in vitro study, on the basis of which
it could fairly and reasonably be concluded by experts qualified by
scientific training and experience to evaluate the effectiveness of the
new animal drug involved that the new animal drug will have the effect
it purports or is represented to have under the conditions of use
prescribed, recommended, or suggested in the labeling or proposed
labeling thereof. Substantial evidence shall include such adequate and
well-controlled studies that are, as a matter of sound scientific
judgment, necessary to establish that a new animal drug will have its
intended effect.
(b) Characteristics of substantial evidence--(1) Qualifications of
experts. Any study that is intended to be part of substantial evidence
of the effectiveness of a new animal drug shall be conducted by experts
qualified by scientific training and experience.
(2) Intended uses and conditions of use. Substantial evidence of
effectiveness of a new animal drug shall demonstrate that the new animal
drug is effective for each intended use and associated
[[Page 100]]
conditions of use for and under which approval is sought.
(i) Dose range labeling. Sponsors should, to the extent possible,
provide for a dose range because it increases the utility of the new
animal drug by providing the user flexibility in the selection of a safe
and effective dose. In general, substantial evidence to support dose
range labeling for a new animal drug intended for use in the diagnosis,
cure, mitigation, treatment, or prevention of disease must consist of at
least one adequate and well-controlled study on the basis of which
qualified experts could fairly and reasonably conclude that the new
animal drug will be effective for the intended use at the lowest dose of
the dose range suggested in the proposed labeling for that intended use.
Substantial evidence to support dose range labeling for a new animal
drug intended to affect the structure or function of the body of an
animal generally must consist of at least one adequate and well-
controlled study on the basis of which qualified experts could fairly
and reasonably conclude that the new animal drug will be effective for
the intended use at all doses within the range suggested in the proposed
labeling for the intended use.
(ii) [Reserved]
(3) Studies--(i) Number. Substantial evidence of the effectiveness
of a new animal drug for each intended use and associated conditions of
use shall consist of a sufficient number of current adequate and well-
controlled studies of sufficient quality and persuasiveness to permit
qualified experts:
(A) To determine that the parameters selected for measurement and
the measured responses reliably reflect the effectiveness of the new
animal drug;
(B) To determine that the results obtained are likely to be
repeatable, and that valid inferences can be drawn to the target animal
population; and
(C) To conclude that the new animal drug is effective for the
intended use at the dose or dose range and associated conditions of use
prescribed, recommended, or suggested in the proposed labeling.
(ii) Types. Adequate and well-controlled studies that are intended
to provide substantial evidence of the effectiveness of a new animal
drug may include, but are not limited to, published studies, foreign
studies, studies using models, and studies conducted by or on behalf of
the sponsor. Studies using models shall be validated to establish an
adequate relationship of parameters measured and effects observed in the
model with one or more significant effects of treatment.
(c) Substantial evidence for combination new animal drugs--(1)
Definitions. The following definitions of terms apply to this section:
(i) Combination new animal drug means a new animal drug that
contains more than one active ingredient or animal drug that is applied
or administered simultaneously in a single dosage form or simultaneously
in or on animal feed or drinking water.
(ii) Dosage form combination new animal drug means a combination new
animal drug intended for use other than in animal feed or drinking
water.
(iii) Antibacterial with respect to a particular target animal
species means an active ingredient or animal drug: That is approved in
that species for the diagnosis, cure, mitigation, treatment, or
prevention of bacterial disease; or that is approved for use in that
species for any other use that is attributable to its antibacterial
properties. But, antibacterial does not include ionophores or arsenicals
intended for use in combination in animal feed or drinking water.
(iv) Appropriate concurrent use exists when there is credible
evidence that the conditions for which the combination new animal drug
is intended can occur simultaneously.
(2) Combination new animal drugs that contain only active
ingredients or animal drugs that have previously been separately
approved. (i) For dosage form combination new animal drugs, except for
those that contain a nontopical antibacterial, that contain only active
ingredients or animal drugs that have previously been separately
approved for the particular uses and conditions of use for which they
are intended in combination, a sponsor shall demonstrate:
(A) By substantial evidence, as defined in this section, that any
active ingredient or animal drug intended only for the same use as
another active
[[Page 101]]
ingredient or animal drug in the combination makes a contribution to the
effectiveness of the combination new animal drug;
(B) That each active ingredient or animal drug intended for at least
one use that is different from all the other active ingredients or
animal drugs used in the combination provides appropriate concurrent use
for the intended target animal population; and
(C) That the active ingredients or animal drugs are physically
compatible and do not have disparate dosing regimens if FDA, based on
scientific information, has reason to believe the active ingredients or
animal drugs are physically incompatible or have disparate dosing
regimens.
(ii) For combination new animal drugs intended for use in animal
feed or drinking water that contain only active ingredients or animal
drugs that have previously been separately approved for the particular
uses and conditions of use for which they are intended in combination,
the sponsor shall demonstrate:
(A) By substantial evidence, as defined in this section, that any
active ingredient or animal drug intended only for the same use as
another active ingredient or animal drug in the combination makes a
contribution to the effectiveness of the combination new animal drug;
(B) For such combination new animal drugs that contain more than one
antibacterial ingredient or animal drug, by substantial evidence, as
defined in this section, that each antibacterial makes a contribution to
labeled effectiveness;
(C) That each active ingredient or animal drug intended for at least
one use that is different from all other active ingredients or animal
drugs used in the combination provides appropriate concurrent use for
the intended target animal population; and
(D) That the active ingredients or animal drugs intended for use in
drinking water are physically compatible if FDA, based on scientific
information, has reason to believe the active ingredients or animal
drugs are physically incompatible.
(3) Other combination new animal drugs. For all other combination
new animal drugs, the sponsor shall demonstrate by substantial evidence,
as defined in this section, that the combination new animal drug will
have the effect it purports or is represented to have under the
conditions of use prescribed, recommended, or suggested in the proposed
labeling and that each active ingredient or animal drug contributes to
the effectiveness of the combination new animal drug.
[64 FR 40756, July 28, 1999]
Sec. 514.5 Presubmission conferences.
(a) General principle underlying the conduct of a presubmission
conference. The general principle underlying the conduct of any
presubmission conference is that there should be candid, full, and open
communication.
(b) Requesting a presubmission conference. A potential applicant is
entitled to one or more conferences prior to the submission of an NADA,
supplemental NADA, or an ANADA to reach an agreement establishing part
or all of a submission or investigational requirement. A potential
applicant's request for a presubmission conference must be submitted to
FDA in a signed letter. The letter must include a proposed agenda that
clearly outlines the scope, purpose, and objectives of the presubmission
conference and must list the names and positions of the representatives
who are expected to attend the presubmission conference on behalf of the
applicant.
(c) Timing. A potential applicant may request one or more
presubmission conferences at any time prior to the filing of a NADA,
supplemental NADA, or an ANADA. A request for a presubmission conference
must be received by FDA at least 30 calendar days in advance of the
requested conference date. FDA will schedule the presubmission
conference at a time agreeable to both FDA and the potential applicant.
(d) Advance information. The potential applicant must provide to
FDA, at least 30 calendar days before a scheduled presubmission
conference, a detailed agenda, a copy of any materials to be presented
at the conference, a list of proposed indications and, if available, a
copy of the proposed labeling for the product under consideration, and
copies of materials evaluated or referenced relative to issues listed in
[[Page 102]]
the agenda for the conference. If the materials are not provided or are
not sufficient to provide the basis for meaningful discussion, FDA may
elect to postpone part or all of the meeting until sufficient materials
are provided to FDA.
(e) Conduct of a presubmission conference. The potential applicant
and FDA may each bring consultants to the presubmission conference. The
presubmission conference(s) will be directed primarily at establishing
agreement between FDA and the potential applicant regarding a submission
or investigational requirement. The submission or investigational
requirement may include, among other things, the number, types, and
general design of studies that are necessary to demonstrate the safety
and effectiveness of a new animal drug for the intended uses and
conditions of use prescribed, recommended, or suggested in the proposed
labeling for the new animal drug.
(f) Documentation of a presubmission conference--(1) Memorandum of
conference--(i) Preparation. FDA will prepare a memorandum for each
presubmission conference that will include, among other things, any
background pertinent to the request for meeting; a summary of the key
points of discussion; agreements; and action items and assignments of
responsibility. That portion of the memorandum of conference that
documents any agreements reached regarding all or part of a submission
or investigational requirement will be included under the heading
``Presubmission Conference Agreement.'' If the presubmission conference
agreement section of the memorandum is silent on an issue, including one
that was discussed in the conference or addressed by materials provided
for the conference, such silence does not constitute agreement between
FDA and the potential applicant on the issue.
(ii) Sending a copy to the potential applicant. FDA will send a copy
of the memorandum to the potential applicant for review no later than 45
calendar days after the date of the conference
(iii) Requests for changes or clarification. If a potential
applicant requests changes to, or clarification of, the substance of the
memorandum, the request must be sent to FDA within 30 calendar days from
the date a copy of the memorandum is sent to the applicant. If the
potential applicant requests changes or clarification, FDA will send the
potential applicant a response to their request no later than 45
calendar days after the date of receipt of the request.
(iv) Administrative record. A copy of FDA's original memorandum of
conference and, as appropriate, a copy of an amended memorandum to
correct or clarify the content of the original memorandum will be made
part of the administrative file.
(2) Field studies. If FDA requires more than one field study to
establish by substantial evidence that the new animal drug is effective
for its intended uses under the conditions of use prescribed,
recommended, or suggested in the proposed labeling, FDA will provide
written scientific justification for requiring more than one field
study. Such justification must be provided no later than 25 calendar
days after the date of the conference at which the requirement for more
than one field study is established. If FDA does not believe more than
one field study is required but the potential applicant voluntarily
proposes to conduct more than one field study, FDA will not provide such
written justification. If FDA requires one field study to be conducted
at multiple locations, FDA will provide justification for requiring
multiple locations verbally during the presubmission conference and in
writing as part of the memorandum of conference.
(g) Modification of presubmission conference agreements. An
agreement made under a presubmission conference requested under section
512(b)(3) of the act and documented in a memorandum of conference is
binding on the potential applicant and FDA and may only be modified if:
(1) FDA and the potential applicant mutually agree to modify, in
part or in whole, the agreement and such modification is documented and
provided to the potential applicant as described in paragraph (f)(1) of
this section; or
[[Page 103]]
(2) FDA by written order determines that a substantiated scientific
requirement essential to the determination of safety or effectiveness of
the new animal drug appeared after the conference.
(h) When the terms of a presubmission conference agreement are not
valid. (1) A presubmission conference agreement will no longer be valid
if:
(i) The potential applicant makes to FDA, before, during, or after
the presubmission conference, any untrue statement of material fact; or
(ii) The potential applicant fails to follow any material term of
the agreement; and
(2) A presubmission conference may no longer be valid if the
potential applicant submits false or misleading data relating to a new
animal drug to FDA.
(i) Dispute resolution. FDA is committed to resolving differences
between a potential applicant and FDA reviewing divisions with respect
to requirements for the investigation of new animal drugs and for NADAs,
supplemental NADAs, and ANADAs as quickly and amicably as possible
through a cooperative exchange of information and views. When
administrative or procedural disputes arise, a potential applicant
should first attempt to resolve the matter within the appropriate review
division beginning with the individual(s) most directly assigned to the
review of the application or investigational exemption. If the dispute
cannot be resolved after such attempts, the dispute shall be evaluated
and administered in accordance with applicable regulations (21 CFR
10.75). Dispute resolution procedures may be further explained by
guidance available from the Center for Veterinary Medicine.
[69 FR 51170, Aug. 18, 2004]
Sec. 514.6 Amended applications.
The applicant may submit an amendment to an application that is
pending, including changes that may alter the conditions of use, the
labeling, safety, effectiveness, identity, strength, quality, or purity
of the drug or the adequacy of the manufacturing methods, facilities,
and controls to preserve them, in which case the unamended application
may be considered as withdrawn and the amended application may be
considered resubmitted on the date on which the amendment is received by
the Food and Drug Administration. The applicant will be notified of such
date.
Sec. 514.7 Withdrawal of applications without prejudice.
The sponsor may withdraw his pending application from consideration
as a new animal drug application upon written notification to the Food
and Drug Administration. Such withdrawal may be made without prejudice
to a future filing. Upon resubmission, the time limitation will begin to
run from the date the resubmission is received by the Food and Drug
Administration. The original application will be retained by the Food
and Drug Administration although it is considered withdrawn. The
applicant shall be furnished a copy at cost on request.
Sec. 514.8 Supplements and other changes to an approved application.
(a) Definitions. (1) The definitions and interpretations contained
in section 201 of the Federal Food, Drug, and Cosmetic Act (the act)
apply to those terms when used in this part.
(2) The following definitions of terms apply to this part:
(i) Assess the effects of the change means to evaluate the effects
of a manufacturing change on the identity, strength, quality, purity,
and potency of a drug as these factors may relate to the safety or
effectiveness of the drug.
(ii) Drug substance means an active ingredient as defined under
Sec. 210.3(b)(7) of this chapter.
(iii) Minor changes and stability report (MCSR) means an annual
report that is submitted to the application once each year within 60
days before or after the anniversary date of the application's original
approval or on a mutually agreed upon date. The report must include
minor manufacturing and control changes made according to Sec.
514.8(b)(4) or state that no changes were made; and stability data
generated on commercial or production batches according to an approved
stability protocol or commitment.
[[Page 104]]
(iv) Specification means the quality standard (i.e., tests,
analytical procedures, and acceptance criteria) provided in an approved
application to confirm the quality of drugs including, for example, drug
substances, Type A medicated articles, drug products, intermediates, raw
materials, reagents, components, in-process materials, container closure
systems, and other materials used in the production of a drug. For the
purpose of this definition, the term ``acceptance criteria'' means
numerical limits, ranges, or other criteria for the tests described.
(b) Manufacturing changes to an approved application--(1) General
provisions. (i) The applicant must notify FDA about each change in each
condition established in an approved application beyond the variations
already provided for in the application. The notice is required to
describe the change fully. Depending on the type of change, the
applicant must notify FDA about it in a supplement under paragraph
(b)(2) or (b)(3) of this section or by inclusion of the information in
the annual report to the application under paragraph (b)(4) of this
section.
(ii) The holder of an approved application under section 512 of the
act must assess the effects of the change before distributing a drug
made with a manufacturing change.
(iii) Notwithstanding the requirements of paragraphs (b)(2) and
(b)(3) of this section, an applicant must make a change provided for in
those paragraphs in accordance with a regulation or guidance that
provides for a less burdensome notification of the change (for example,
by submission of a supplement that does not require approval prior to
distribution of the drug, or by notification in the next annual report
described in paragraph (b)(4) of this section).
(iv) In each supplement and amendment to a supplement providing for
a change under paragraph (b)(2) or (b)(3) of this section, the applicant
must include a statement certifying that a field copy has been provided
to the appropriate FDA district office. No field copy is required for a
supplement providing for a change made to a drug manufactured outside of
the United States.
(v) A supplement or annual report described in paragraph (b)(4) of
this section must include a list of all changes contained in the
supplement or annual report. For supplements, this list must be provided
in the cover letter.
(2) Changes requiring submission and approval of a supplement prior
to distribution of the drug made using the change (major changes). (i) A
supplement must be submitted for any change in the drug, production
process, quality controls, equipment, or facilities that has a
substantial potential to have an adverse effect on the identity,
strength, quality, purity, or potency of the drug as these factors may
relate to the safety or effectiveness of the drug.
(ii) These changes include, but are not limited to:
(A) Except those described in paragraphs (b)(3) and (b)(4) of this
section, changes in the qualitative or quantitative formulation of the
drug, including inactive ingredients, or in the specifications provided
in the approved application;
(B) Changes requiring completion of appropriate clinical studies to
demonstrate the equivalence of the drug to the drug as manufactured
without the change;
(C) Changes that may affect drug substance or drug product sterility
assurance, such as changes in drug substance, drug product or component
sterilization method(s) or an addition, deletion, or substitution of
steps in an aseptic processing operation;
(D) Changes in the synthesis or manufacture of the drug substance
that may affect the impurity profile and/or the physical, chemical, or
biological properties of the drug substance;
(E) Changes in a drug product container closure system that controls
the drug delivered to the animal or changes in the type or composition
of a packaging component that may affect the impurity profile of the
drug product;
(F) Changes solely affecting a natural product, a recombinant DNA-
derived protein/polypeptide, or a complex or conjugate of a drug
substance with a monoclonal antibody for the following:
(1) Changes in the virus or adventitious agent removal or
inactivation method(s),
[[Page 105]]
(2) Changes in the source material or cell line, and
(3) Establishment of a new master cell bank or seed;
(G) Changes to a drug under an application that is subject to a
validity assessment because of significant questions regarding the
integrity of the data supporting that application.
(iii) The applicant must obtain approval of a supplement from FDA
prior to distribution of a drug made using a change under paragraph
(b)(2) of this section. The supplement must be labeled ``Prior Approval
Supplement.'' Except for submissions under paragraph (b)(2)(v) of this
section, the following information must be contained in the supplement:
(A) A completed Form FDA 356V;
(B) A detailed description of the proposed change;
(C) The drug(s) involved;
(D) The manufacturing site(s) or area(s) affected;
(E) A description of the methods used and studies performed to
assess the effects of the change;
(F) The data derived from such studies;
(G) Appropriate documentation (for example, updated master batch
records, specification sheets) including previously approved
documentation (with the changes highlighted) or references to previously
approved documentation;
(H) For a natural product, a recombinant DNA-derived protein/
polypeptide, or a complex or conjugate of a drug substance with a
monoclonal antibody, relevant validation protocols and standard
operating procedures must be provided in addition to the requirements in
paragraphs (b)(2)(iii)(E) and (b)(2)(iii)(F) of this section;
(I) For sterilization process and test methodologies related to
sterilization process validation, relevant validation protocols and a
list of relevant standard operating procedures must be provided in
addition to the requirements in paragraphs (b)(2)(iii)(E) and
(b)(2)(iii)(F) of this section; and
(J) Any other information as directed by FDA.
(iv) An applicant may ask FDA to expedite its review of a supplement
for public health reasons or if a delay in making the change described
in it would impose an extraordinary hardship on the applicant. Such a
supplement and its mailing cover must be plainly marked: ``Prior
Approval Supplement-Expedited Review Requested.''
(v) Comparability Protocols. An applicant may submit one or more
protocols describing the specific tests and studies and acceptance
criteria to be achieved to demonstrate the lack of adverse effect for
specified types of manufacturing changes on the identity, strength,
quality, purity, and potency of the drug as these factors may relate to
the safety or effectiveness of the drug. Any such protocols, if not
included in the approved application, or changes to an approved
protocol, must be submitted as a supplement requiring approval from FDA
prior to distribution of the drug produced with the manufacturing
change. The supplement, if approved, may subsequently justify a reduced
reporting category for the particular change because the use of the
protocol for that type of change reduces the potential risk of an
adverse effect. A comparability protocol supplement must be labeled
``Prior Approval Supplement--Comparability Protocol.''
(3) Changes requiring submission of a supplement at least 30 days
prior to distribution of the drug made using the change (moderate
changes). (i) A supplement must be submitted for any change in the drug,
production process, quality controls, equipment, or facilities that has
a moderate potential to have an adverse effect on the identity,
strength, quality, purity, or potency of the drug as these factors may
relate to the safety or effectiveness of the drug.
(ii) These changes include, but are not limited to:
(A) A change in the container closure system that does not affect
the quality of the drug except as otherwise described in paragraphs
(b)(2) and (b)(4) of this section;
(B) Changes solely affecting a natural protein, a recombinant DNA-
derived protein/polypeptide or a complex or conjugate of a drug
substance with a monoclonal antibody, including:
(1) An increase or decrease in production scale during finishing
steps that involves different equipment, and
[[Page 106]]
(2) Replacement of equipment with that of a different design that
does not affect the process methodology or process operating parameters.
(C) Relaxation of an acceptance criterion or deletion of a test to
comply with an official compendium that is consistent with FDA statutory
and regulatory requirements.
(iii) A supplement submitted under paragraph (b)(3)(i) or (b)(3)(vi)
of this section is required to give a full explanation of the basis for
the change and identify the date on which the change is made. The
supplement submitted under paragraph (b)(3)(i) must be labeled
``Supplement-Changes Being Effected in 30 Days.''
(iv) Pending approval of the supplement by FDA and except as
provided in paragraph (b)(3)(vi) of this section, distribution of the
drug made using the change may begin not less than 30 days after receipt
of the supplement by FDA. The information listed in paragraphs
(b)(2)(iii)(A) through (b)(2)(iii)(J) of this section must be contained
in the supplement.
(v) The applicant must not distribute the drug made using the change
if within 30 days following FDA's receipt of the supplement, FDA informs
the applicant that either:
(A) The change requires approval prior to distribution of the drug
in accordance with paragraph (b)(2) of this section; or
(B) Any of the information required under paragraph (b)(3)(iv) of
this section is missing. In this case, the applicant must not distribute
the drug made using the change until the supplement has been amended to
provide the missing information.
(vi) The agency may designate a category of changes for the purpose
of providing that, in the case of a change in such category, the holder
of an approved application may commence distribution of the drug
involved upon receipt by the agency of a supplement for the change. The
information listed in paragraphs (b)(2)(iii)(A) through (b)(2)(iii)(J)
of this section must be contained in the supplement. The supplement must
be labeled ``Supplement-Changes Being Effected.'' These changes include,
but are not limited to:
(A) Addition to a specification or changes in the methods or
controls to provide increased assurance that the drug will have the
characteristics of identity, strength, quality, purity, or potency that
it purports or is represented to possess; and
(B) A change in the size and/or shape of a container for a
nonsterile drug product, except for solid dosage forms, without a change
in the labeled amount of drug product or from one container closure
system to another.
(vii) If the agency disapproves the supplemental application, it may
order the manufacturer to cease distribution of the drug(s) made with
the manufacturing change.
(4) Changes and updated stability data to be described and submitted
in an annual report (minor changes). (i) Changes in the drug, production
process, quality controls, equipment, or facilities that have a minimal
potential to have an adverse effect on the identity, strength, quality,
purity, or potency of the drug as these factors may relate to the safety
or effectiveness of the drug must be documented by the applicant in an
annual report to the application as described under paragraph
(a)(2)(iii) of this section. The report must be labeled ``Minor Changes
and Stability Report.''
(ii) These changes include but are not limited to:
(A) Any change made to comply with a change to an official
compendium, except a change in paragraph (b)(3)(ii)(C) of this section,
that is consistent with FDA statutory and regulatory requirements;
(B) The deletion or reduction of an ingredient intended to affect
only the color of the drug product;
(C) Replacement of equipment with that of the same design and
operating principles except for those equipment changes described in
paragraph (b)(3)(ii)(B)(2) of this section;
(D) A change in the size and/or shape of a container containing the
same number of dosage units for a nonsterile solid dosage form drug
product, without a change from one container closure system to another;
(E) A change within the container closure system for a nonsterile
drug product, based upon a showing of
[[Page 107]]
equivalency to the approved system under a protocol approved in the
application or published in an official compendium;
(F) An extension of an expiration dating period based upon full
shelf-life data on production batches obtained from a protocol approved
in the application;
(G) The addition or revision of an alternative analytical procedure
that provides the same or increased assurance of the identity, strength,
quality, purity, or potency of the drug being tested as the analytical
procedure described in the approved application, or deletion of an
alternative analytical procedure; and
(H) The addition by embossing, debossing, or engraving of a code
imprint to a solid oral dosage form drug product other than a modified
release dosage form, or a minor change in an existing code imprint.
(iii) For changes under this category, the applicant is required to
submit in the annual report:
(A) A completed Form FDA 356V;
(B) A statement by the holder of the approved application that the
effects of the change have been assessed;
(C) A detailed description of the change(s);
(D) The manufacturing site(s) or area(s) involved;
(E) The date each change was implemented;
(F) Data from studies and tests performed to assess the effects of
the change;
(G) For a natural product, recombinant DNA-derived protein/
polypeptide, complex or conjugate of a drug substance with a monoclonal
antibody, sterilization process or test methodology related to
sterilization process validation, relevant validation protocols and/or
standard operating procedures;
(H) Appropriate documentation (for example, updated master batch
records, specification sheets, etc.) including previously approved
documentation (with the changes highlighted) or references to previously
approved documentation;
(I) Updated stability data generated on commercial or production
batches according to an approved stability protocol or commitment; and
(J) Any other information as directed by FDA.
(c) Labeling and other changes to an approved application--(1)
General provisions. The applicant must notify FDA about each change in
each condition established in an approved application beyond the
variations already provided for in the application. The notice is
required to describe the change fully.
(2) Labeling changes requiring the submission and approval of a
supplement prior to distribution of the drug made using the change
(major changes). (i) Addition of intended uses and changes to package
labeling require a supplement. These changes include, but are not
limited to:
(A) Revision in labeling, such as updating information pertaining to
effects, dosages, adverse reactions, contraindications, which includes
information headed ``adverse reactions,'' ``warnings,'' ``precautions,''
and ``contraindications,'' except ones described in (c)(3) of this
section;
(B) Addition of an intended use;
(C) If it is a prescription drug, any mailing or promotional piece
used after the drug is placed on the market is labeling requiring a
supplemental application, unless:
(1) The parts of the labeling furnishing directions, warnings, and
information for use of the drug are the same in language and emphasis as
labeling approved or permitted; and
(2) Any other parts of the labeling are consistent with and not
contrary to such approved or permitted labeling.
(3) Prescription drug labeling not requiring an approved
supplemental application is submitted in accordance with Sec.
514.80(b)(5)(ii).
(D) Any other changes in labeling, except ones described in
paragraph (c)(3) of this section.
(ii) The applicant must obtain approval of the supplement from FDA
prior to distribution of the drug. The supplement must contain the
following:
(A) A completed Form FDA 356V;
(B) A detailed description of the proposed change;
(C) The drug(s) involved;
[[Page 108]]
(D) The data derived from studies in support of the change; and
(E) Any other information as directed by FDA.
(3) Labeling changes to be placed into effect prior to receipt of a
written notice of approval of a supplemental application. (i) Labeling
changes of the following kinds that increase the assurance of drug
safety proposed in supplemental applications must be placed into effect
immediately:
(A) The addition to package labeling, promotional labeling, or
prescription drug advertising of additional warning, contraindication,
adverse reaction, and precaution information;
(B) The deletion from package labeling, promotional labeling, or
drug advertising of false, misleading, or unsupported intended uses or
claims for effectiveness; and
(C) Any other changes as directed by FDA.
(ii) Labeling changes (for example, design and style) that do not
decrease safety of drug use proposed in supplemental applications may be
placed into effect prior to written notice of approval from FDA of a
supplemental application.
(iii) A supplement submitted under paragraph (c)(3) of this section
must include the following information:
(A) A full explanation of the basis for the changes, the date on
which such changes are being effected, and plainly marked on the mailing
cover and on the supplement, ``Supplement--Labeling Changes Being
Effected'';
(B) Two sets of printed copies of any revised labeling to be placed
in use, identified with the new animal drug application number; and
(C) A statement by the applicant that all promotional labeling and
all drug advertising will promptly be revised consistent with the
changes made in the labeling on or within the new animal drug package no
later than upon approval of the supplemental application.
(iv) If the supplemental application is not approved and the drug is
being distributed with the proposed labeling, FDA may initiate an
enforcement action because the drug is misbranded under section 502 of
the act and/or adulterated under section 501 of the act. In addition,
under section 512(e) of the act, FDA may, after due notice and
opportunity for a hearing, issue an order withdrawing approval of the
application.
(4) Changes providing for additional distributors to be reported
under Records and reports concerning experience with approved new animal
drugs (Sec. 514.80). Supplemental applications as described under
paragraph (c)(2) of this section will not be required for an additional
distributor to distribute a drug that is the subject of an approved new
animal drug application or abbreviated new animal drug application if
the conditions described under Sec. 514.80(b)(5)(iii) are met.
(d) Patent information. The applicant must comply with the patent
information requirements under section 512(c)(3) of the act.
(e) Claimed exclusivity. If an applicant claims exclusivity under
section 512(c)(2)(F) of the act upon approval of a supplemental
application for a change in its previously approved drug, the applicant
must include such a statement.
(f) Good laboratory practice for nonclinical laboratory studies. A
supplemental application that contains nonclinical laboratory studies
must include, with respect to each nonclinical study, either a statement
that the study was conducted in compliance with the requirements set
forth in part 58 of this chapter, or, if the study was not conducted in
compliance with such regulations, a brief statement of the reason for
the noncompliance.
[71 FR 74782, Dec. 13, 2006]
Sec. 514.11 Confidentiality of data and information
in a new animal drug application file.
(a) For purposes of this section the NADA file includes all data and
information submitted with or incorporated by reference in the NADA,
INAD's incorporated into the NADA, supplemental NADA's, reports under
Sec. Sec. 514.80 and 510.301 of this chapter, master files, and other
related submissions. The availability for public disclosure of any
record in the NADA file shall be handled in accordance with the
provisions of this section.
[[Page 109]]
(b) The existence of an NADA file will not be disclosed by the Food
and Drug Administration before the application has been approved, unless
it has been previously disclosed or acknowledged.
(c) If the existence of an NADA file has not been publicly disclosed
or acknowledged, no data or information in the NADA file is available
for public disclosure.
(d) If the existence of an NADA file has been publicly disclosed or
acknowledged before the application has been approved, no data or
information contained in the file is available for public disclosure,
but the Commissioner may, in his discretion, disclose a summary of such
selected portions of the safety and effectiveness data as are
appropriate for public consideration of a specific pending issue, i.e.,
at an open session of a Food and Drug Administration advisory committee
or pursuant to an exchange of important regulatory information with a
foreign government.
(e) After an application has been approved, the following data and
information in the NADA file are immediately available for public
disclosure unless extraordinary circumstances are shown:
(1) All safety and effectiveness data and information previously
disclosed to the public, as defined in Sec. 20.81 of this chapter.
(2) A summary or summaries of the safety and effectiveness data and
information submitted with or incorporated by reference in the NADA
file. Such summaries do not constitute the full reports of
investigations under section 512(b)(1) of the act (21 U.S.C. 360b(b)(1))
on which the safety or effectiveness of the drug may be approved. Such
summaries shall consist of the following:
(i) For an NADA approved prior to July 1, 1975, internal agency
records that describe such data and information, e.g., a summary of
basis for approval or internal reviews of the data and information,
after deletion of:
(a) Names and any information that would identify the investigators.
(b) Any inappropriate gratuitous comments unnecessary to an
objective analysis of the data and information.
(ii) For an NADA approved after July 1, 1975, a summary of such data
and information prepared in one of the following two alternative ways
shall be publicly released when the application is approved.
(a) The Center for Veterinary Medicine may at an appropriate time
prior to approval of the NADA require the applicant to prepare a summary
of such data and information, which will be reviewed and, where
appropriate, revised by the Center.
(b) The Center for Veterinary Medicine may prepare its own summary
of such data and information.
(3) A protocol for a test or study, unless it is shown to fall
within the exemption established for trade secrets and confidential
commercial information in Sec. 20.61 of this chapter.
(4) Adverse reaction reports, product experience reports, consumer
complaints, and other similar data and information, after deletion of:
(i) Names and any information that would identify the person using
the product.
(ii) Names and any information that would identify any third party
involved with the report, such as a physician, hospital, or other
institution.
(5) A list of all active ingredients and any inactive ingredients
previously disclosed to the public as defined in Sec. 20.81 of this
chapter.
(6) An assay method or other analytical method, unless it serves no
regulatory or compliance purpose and is shown to fall within the
exemption established in Sec. 20.61 of this chapter.
(7) All correspondence and written summaries of oral discussions
relating to the NADA, in accordance with the provisions of part 20 of
this chapter.
(f) All safety and effectiveness data and information not previously
disclosed to the public are available for public disclosure at the time
any one of the following events occurs unless extraordinary
circumstances are known:
(1) The NADA has been abandoned and no further work is being
undertaken with respect to it.
(2) A final determination is made that the NADA is not approvable,
and all legal appeals have been exhausted.
(3) Approval of the NADA is withdrawn, and all legal appeals have
been exhausted.
[[Page 110]]
(4) A final determination has been made that the animal drug is not
a new animal drug.
(5) A final determination has been made that the animal drug may be
marketed without submission of such safety and/or effectiveness data and
information.
(g) The following data and information in an NADA file are not
available for public disclosure unless they have been previously
disclosed to the public as defined in Sec. 20.81 of this chapter or
they relate to a product or ingredient that has been abandoned and they
no longer represent a trade secret or confidential commercial or
financial information as defined in Sec. 20.61 of this chapter:
(1) Manufacturing methods or processes, including quality control
procedures.
(2) Production, sales, distribution, and similar data and
information, except that any compilation of such data and information
aggregated and prepared in a way that does not reveal data or
information which is not available for public disclosure under this
provision is available for public disclosure.
(3) Quantitative or semiquantitative formulas.
(h) For purposes of this regulation, safety and effectiveness data
include all studies and tests of an animal drug on animals and all
studies and tests on the animal drug for identity, stability, purity,
potency, and bioavailability.
[40 FR 13825, Mar. 27, 1975, as amended at 42 FR 3109, Jan. 14, 1977; 42
FR 15675, Mar. 22, 1977; 54 FR 18280, Apr. 28, 1989; 68 FR 15365, Mar.
31, 2003; 79 FR 14611, Mar. 17, 2014]
Sec. 514.12 Confidentiality of data and information in
an investigational new animal drug notice.
(a) The existence of an INAD notice will not be disclosed by the
Food and Drug Administration unless it has previously been publicly
disclosed or acknowledged.
(b) The availability for public disclosure of all data and
information in an INAD file shall be handled in accordance with
provisions established in Sec. 514.11.
Sec. 514.15 Untrue statements in applications.
Among the reasons why an application for a new animal drug or animal
feed bearing or containing a new animal drug may contain an untrue
statement of a material fact are:
(a) Differences in:
(1) Conditions of use prescribed, recommended, or suggested by the
applicant for the product from the conditions of such use stated in the
application;
(2) Articles used as components of the product from those listed in
the application;
(3) Composition of the product from that stated in the application;
(4) Methods used in or the facilities and controls used for the
manufacture, processing, or packing of the product from such methods,
facilities, and controls described in the application;
(5) Labeling from the specimens contained in the application; or
(b) The unexplained omission in whole or in part from an application
or from an amendment or supplement to an application or from any record
or report required under the provisions of section 512 of the act and
Sec. 514.80 or Sec. 510.301 of this chapter of any information
obtained from:
(1) Investigations as to the safety, effectiveness, identity,
strength, quality, or purity of the drug, made by the applicant on the
drug, or
(2) Investigations or experience with the product that is the
subject of the application, or any related product, available to the
applicant from any source if such information is pertinent to an
evaluation of the safety, effectiveness, identity, strength, quality, or
purity of the drug, when such omission would bias an evaluation of the
safety or effectiveness of the product.
(c) Any nonclinical laboratory study contained in the application
was not conducted in compliance with the good laboratory practice
regulations as set forth in part 58 of this chapter, and the application
fails to include a brief
[[Page 111]]
statement of the reason for the noncompliance.
[40 FR 13825, Mar. 27, 1975, as amended at 49 FR 7226, Feb. 28, 1984; 50
FR 7517, Feb. 22, 1985; 68 FR 15365, Mar. 31, 2003]
Subpart B_Administrative Actions on Applications
Sec. 514.80 Records and reports concerning experience
with approved new animal drugs.
The following table outlines the purpose for each paragraph of this
section:
------------------------------------------------------------------------
Purpose 21 CFR Paragraph and Title
------------------------------------------------------------------------
What information must be reported 514.80(a) Applicability.
concerning approved NADAs or ANADAs?
------------------------------------------------------------------------
What authority does FDA have for 514.80(a)(1).
requesting records and reports?
Who is required to establish, maintain,
and report required information
relating to experiences with a new
animal drug?
Is information from foreign sources
required?
------------------------------------------------------------------------
What records must be established and 514.80(a)(2).
maintained and what reports filed with
FDA?
------------------------------------------------------------------------
What is FDA's purpose for requiring 514.80(a)(3).
reports?
------------------------------------------------------------------------
Do applicants of Type A medicated 514.80(a)(4).
articles have to establish, maintain,
and report information required under
Sec. 514.80?
------------------------------------------------------------------------
How do the requirements under Sec. 514.80(a)(5).
514.80 relate to current good
manufacturing practices?
------------------------------------------------------------------------
514.80(b) Reporting
requirements.
------------------------------------------------------------------------
What are the requirements for reporting 514.80(b)(1) Three-day NADA/
product/manufacturing defects? ANADA field alert report.
------------------------------------------------------------------------
514.80(b)(2) Fifteen-day NADA/
ANADA alert report.
------------------------------------------------------------------------
What are the requirements for reporting 514.80(b)(2)(i) Initial
serious and unexpected adverse drug report.
experiences?
------------------------------------------------------------------------
What are the requirements for followup 514.80(b)(2)(ii) Followup
reporting of serious and unexpected report.
adverse drug experiences?
------------------------------------------------------------------------
What are the requirements for 514.80(b)(3) Nonapplicant
nonapplicants for reporting adverse report.
drug experiences?
------------------------------------------------------------------------
What are the general requirements for 514.80(b)(4) Periodic drug
submission of periodic drug experience experience report.
reports, e.g., method of submission,
submission date and frequency, when is
it to be submitted, how many copies?
How do I petition to change the date of
submission or frequency of submissions?
------------------------------------------------------------------------
What must be submitted in the periodic 514.80(b)(4)(i) through
drug experience reports? (b)(4)(iv).
------------------------------------------------------------------------
What distribution data must be 514.80(b)(4)(i) Distribution
submitted? data.
How should the distribution data be
submitted?
------------------------------------------------------------------------
What labeling materials should be 514.80(b)(4)(ii) Labeling.
submitted?
How do I report changes to the labeling
materials since the last report?
------------------------------------------------------------------------
514.80(b)(4)(iii) Nonclinical
laboratory studies and
clinical data not previously
reported.
------------------------------------------------------------------------
What are the requirements for submission 514.80(b)(4)(iii)(A).
of nonclinical laboratory studies?
------------------------------------------------------------------------
What are the requirements for submission 514.80(b)(4)(iii)(B).
of clinical laboratory data?
------------------------------------------------------------------------
When must results of clinical trials 514.80(b)(4)(iii)(C).
conducted by or for the applicant be
reported?
------------------------------------------------------------------------
[[Page 112]]
514.80(b)(4)(iv) Adverse drug
experiences.
------------------------------------------------------------------------
How do I report product/manufacturing 514.80(b)(4)(iv)(A).
defects and adverse drug experiences
not previously reported to FDA?
------------------------------------------------------------------------
What are the requirements for submitting 514.80(b)(4)(iv)(B).
adverse drug experiences cited in
literature?
------------------------------------------------------------------------
What are the requirements for submitting 514.80(b)(4)(iv)(C).
adverse drug experiences in
postapproval studies and clinical
trials?
------------------------------------------------------------------------
What are the requirements for reporting 514.80(b)(4)(v) Summary report
increases in the frequency of serious, of increased frequency of
expected, and unexpected adverse drug adverse drug experience.
experiences?
------------------------------------------------------------------------
514.80(b)(5) Other reporting.
------------------------------------------------------------------------
Can FDA request that an applicant submit 514.80(b)(5)(i) Special drug
information at different times than experience report.
stated specifically in this regulation?
------------------------------------------------------------------------
What are the requirements for submission 514.80(b)(5)(ii)
of advertisement and promotional Advertisements and
labeling to FDA? promotional labeling.
------------------------------------------------------------------------
What are the requirements for adding a 514.80(b)(5)(iii)
new distributor to the approved Distributor's statement.
application?
------------------------------------------------------------------------
What labels and how many labels need to 514.80(b)(5)(iii)(A).
be submitted for review?
------------------------------------------------------------------------
What changes are required and allowed to 514.80(b)(5)(iii)(A)(1).
distributor labeling?
------------------------------------------------------------------------
What are the requirements for making 514.80(b)(5)(iii)(A)(2).
other changes to the distributor
labeling?
------------------------------------------------------------------------
What information should be included in 514.80(b)(5)(iii)(B)(1)
each new distributor's signed through (b)(5)(iii)(B)(5).
statement?
------------------------------------------------------------------------
What are the conditions for submitting 514.80(c) Multiple
information that is common to more than applications.
one application? (i.e., can I submit
common information to one application?)
------------------------------------------------------------------------
What information has to be submitted to 514.80(c)(1) through (c)(4).
the common application and related
application?
------------------------------------------------------------------------
What reports must be submitted to FDA 514.80(d) Format for
electronically? Submissions.
How can I apply for a waiver from the
electronic reporting requirements?
How do I obtain Form FDA 1932 and Form
FDA 2301?
------------------------------------------------------------------------
How long must I maintain records and 514.80(e) Records to be
reports required by this section? maintained.
------------------------------------------------------------------------
What are the requirements for allowing 514.80(f) Access to records
access to these records and reports, and reports.
and copying by authorized FDA officer
or employee?
------------------------------------------------------------------------
Where do I mail reports that are not 514.80(g) Mailing addresses.
required to be submitted
electronically?
------------------------------------------------------------------------
What happens if the applicant fails to 514.80(h) Withdrawal of
establish, maintain, or make the approval.
required reports?
What happens if the applicant refuses to
allow FDA access to, and/or copying and/
or verify records and reports?
------------------------------------------------------------------------
Does an adverse drug experience reflect 514.80(i) Disclaimer.
a conclusion that the report or
information constitutes an admission
that the drug caused an adverse effect?
------------------------------------------------------------------------
(a) Applicability. (1) Each applicant must establish and maintain
indexed and complete files containing full records of all information
pertinent to safety or effectiveness of a new animal drug that has not
been previously submitted as part of the NADA or ANADA. Such records
must include information from domestic as well as foreign sources. Each
nonapplicant must establish and maintain indexed and complete files
containing full records of all information pertinent to safety or
effectiveness of a new animal drug that
[[Page 113]]
is received or otherwise obtained by the nonapplicant. Such records must
include information from domestic as well as foreign sources.
(2) Each applicant must submit reports of data, studies, and other
information concerning experience with new animal drugs to the Food and
Drug Administration (FDA) for each approved NADA and ANADA, as required
in this section. A nonapplicant must submit data, studies, and other
information concerning experience with new animal drugs to the
appropriate applicant, as required in this section. The applicant, in
turn, must report the nonapplicant's data, studies, and other
information to FDA. Applicants and nonapplicants must submit data,
studies, and other information described in this section from domestic,
as well as foreign sources.
(3) FDA reviews the records and reports required in this section to
facilitate a determination under section 512(e) of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 360b(e)) as to whether there may be
grounds for suspending or withdrawing approval of the NADA or ANADA.
(4) The requirements of this section also apply to any approved Type
A medicated article. In addition, the requirements contained in Sec.
514.80(b)(1), (b)(2), (b)(4)(iv), and (b)(4)(v) apply to any approved
Type A medicated article incorporated in animal feeds.
(5) The records and reports referred to in this section are in
addition to those required by the current good manufacturing practice
regulations in parts 211, 225, and 226 of this chapter.
(b) Reporting requirements--(1) Three-day NADA/ANADA field alert
report. This report provides information pertaining to product and
manufacturing defects that may result in serious adverse drug events.
The applicant (or nonapplicant through the applicant) must submit the
report to the appropriate FDA District Office or local FDA resident post
within 3 working days of first becoming aware that a defect may exist.
The information initially may be provided by telephone or other
telecommunication means, with prompt written followup using Form FDA
1932 ``Veterinary Adverse Drug Reaction, Lack of Effectiveness, Product
Defect Report.'' The mailing cover for these reports must be plainly
marked ``3-Day NADA/ANADA Field Alert Report.'' If the applicant elects
to also report directly to the FDA's Center for Veterinary Medicine
(CVM), the applicant must submit the report to CVM in electronic format
as described in paragraph (d)(1) of this section, unless the applicant
obtains a waiver under paragraph (d)(2) of this section or FDA requests
the report in an alternate format.
(2) Fifteen-day NADA/ANADA alert report--(i) Initial report. This
report provides information on each serious, unexpected adverse drug
event, regardless of the source of the information. The applicant (or
nonapplicant through the applicant) must submit the report to FDA within
15 working days of first receiving the information. The report must be
submitted to FDA in electronic format as described in paragraph (d)(1)
of this section, unless the applicant obtains a waiver under paragraph
(d)(2) of this section or FDA requests the report in an alternate
format.
(ii) Followup report. The applicant must promptly investigate all
adverse drug events that are the subject of 15-day NADA/ANADA alert
reports. If this investigation reveals significant new information, a
followup report must be submitted within 15 working days of receiving
such information. A followup report must be submitted to FDA in
electronic format as described in paragraph (d)(1) of this section,
unless the applicant obtains a waiver under paragraph (d)(2) of this
section or FDA requests the report in an alternate format. The followup
report must state the date of the initial report and provide the
additional information. If additional information is sought but not
obtained within 3 months of the initial report, a followup report is
required describing the steps taken and why additional information was
not obtained.
(3) Nonapplicant report. Nonapplicants must forward reports of
adverse drug experiences to the applicant within 3 working days of first
receiving the information. The applicant must then submit the report(s)
to FDA as required in this section. The nonapplicant must maintain
records of all nonapplicant reports, including the
[[Page 114]]
date the nonapplicant received the information concerning adverse drug
experiences, the name and address of the applicant, and a copy of the
adverse drug experience report including the date such report was
submitted to the applicant. If the nonapplicant elects to also report
directly to FDA, the nonapplicant must submit the report to FDA in
electronic format as described in paragraph (d)(1) of this section,
unless the nonapplicant obtains a waiver under paragraph (d)(2) of this
section or FDA requests the report in an alternate format.
(4) Periodic drug experience report. This report must be accompanied
by a completed Form FDA 2301 ``Transmittal of Periodic Reports and
Promotional Materials for New Animal Drugs.'' It must be submitted every
6 months for the first 2 years following approval of an NADA or ANADA
and yearly thereafter. Reports required by this section must contain
data and information for the full reporting period. The 6-month periodic
drug experience reports must be submitted within 30 days following the
end of the 6-month reporting period. The yearly periodic drug experience
reports must be submitted within 90 days of the anniversary date of the
approval of the NADA or ANADA. Any previously submitted information
contained in the report must be identified as such. For yearly (annual)
periodic drug experience reports, the applicant may petition FDA to
change the date of submission or frequency of reporting, and after
approval of such petition, file such reports on the new filing date or
at the new reporting frequency. Also, FDA may require a report at
different times or more frequently. The periodic drug experience report
must contain the following:
(i) Distribution data. (A) Information about the distribution of
each new animal drug product, including information on any distributor-
labeled product. This information must include the total number of
distributed units of each size, strength, or potency (e.g., 100,000
bottles of 100 5-milligram tablets; 50,000 10-milliliter vials of 5-
percent solution). This information must be presented in two categories:
Quantities distributed domestically and quantities exported.
(B) Applicants submitting annual sales and distribution reports for
antimicrobial new animal drug products under Sec. 514.87 have the
option not to report distribution data under paragraph (b)(4)(i)(A) of
this section for the approved applications that include these same
products, but only provided each of the following conditions are met:
(1) Applicants must have submitted complete periodic drug experience
reports under this section for such applications for at least 2 full
years after the date of their initial approval.
(2) Applicants must ensure that the beginning of the reporting
period for the annual periodic drug experience reports for such
applications is January 1. For applications that currently have a
reporting period that begins on a date other than January 1, applicants
must request a change in reporting submission date such that the
reporting period begins on January 1 and ends on December 31, as
described in paragraph (b)(4) of this section.
(3) Applicants that change their reporting submission date must also
submit a special drug experience report, as described in paragraph
(b)(5)(i) of this section, that addresses any gaps in distribution data
caused by the change in date of submission.
(4) Applicants who choose not to report under paragraph (b)(4)(i)(A)
of this section must ensure that full sales and distribution data for
each product approved under such applications are alternatively reported
under Sec. 514.87, including products that are labeled for use only in
nonfood-producing animals.
(ii) Labeling. Applicant and distributor current package labeling,
including package inserts (if any). For large-size package labeling or
large shipping cartons, a representative copy must be submitted (e.g., a
photocopy of pertinent areas of large feed bags). A summary of any
changes in labeling made since the last report (listed by date of
implementation) must be included with the labeling or if there have been
no changes, a statement of such fact must be included with the labeling.
[[Page 115]]
(iii) Nonclinical laboratory studies and clinical data not
previously reported.
(A) Copies of in vitro studies (e.g., mutagenicity) and other
nonclinical laboratory studies conducted by or otherwise obtained by the
applicant.
(B) Copies of published clinical trials of the new animal drug (or
abstracts of them) including clinical trials on safety and
effectiveness, clinical trials on new uses, and reports of clinical
experience pertinent to safety conducted by or otherwise obtained by the
applicant. Review articles, papers, and abstracts in which the drug is
used as a research tool, promotional articles, press clippings, and
papers that do not contain tabulations or summaries of original data are
not required to be reported.
(C) Descriptions of completed clinical trials conducted by or for
the applicant must be submitted no later than 1 year after completion of
research. Supporting information is not to be reported.
(iv) Adverse drug experiences. (A) Product/manufacturing defects and
adverse drug experiences not previously reported under paragraphs (b)(1)
and (2) of this section must be reported individually to FDA in
electronic format as described in paragraph (d)(1) of this section,
unless the applicant obtains a waiver under paragraph (d)(2) of this
section or FDA requests the report in an alternate format.
(B) Reports of adverse drug experiences in the literature must be
noted in the periodic drug experience report. A bibliography of
pertinent references must be included with the report. Upon FDA's
request, the applicant must provide a full text copy of these
publications.
(C) Reports of previously not reported adverse drug experiences that
occur in postapproval studies must be reported individually to FDA in
electronic format as described in paragraph (d)(1) of this section,
unless the applicant obtains a waiver under paragraph (d)(2) of this
section or FDA requests the report in an alternate format.
(v) Summary report of increased frequency of adverse drug
experience. The applicant must periodically review the incidence of
reports of adverse drug experiences to determine if there has been an
increased frequency of serious (expected and unexpected) adverse drug
events. The applicant must evaluate the increased frequency of serious
(expected or unexpected) adverse drug events at least as often as
reporting of periodic drug experience reports. The applicant must report
the increased frequency of serious (expected and unexpected) adverse
drug events in the periodic drug experience report. Summaries of reports
of increased frequency of adverse drug events must be submitted in
narrative form. The summaries must state the time period on which the
increased frequency is based, time period comparisons in determining
increased frequency, references to any reports previously submitted
under paragraphs (b)(1), (2), and (3) and (b)(4)(iv)(A) and (C) of this
section, the method of analysis, and the interpretation of the results.
The summaries must be submitted in a separate section within the
periodic drug experience report.
(5) Other reporting--(i) Special drug experience report. Upon
written request, FDA may require that the applicant submit a report
required under Sec. 514.80 at different times or more frequently than
the timeframes stated in Sec. 514.80.
(ii) Advertisements and promotional labeling. The applicant must
submit at the time of initial dissemination one set of specimens of
mailing pieces and other labeling for prescription and over-the-counter
new animal drugs. For prescription new animal drugs, the applicant must
also submit one set of specimens of any advertisement at the time of
initial publication or broadcast. Mailing pieces and labeling designed
to contain product samples must be complete except that product samples
may be omitted. Each submission of promotional labeling or
advertisements must be accompanied by a completed Form FDA 2301.
(iii) Distributor's statement. At the time of initial distribution
of a new animal drug product by a distributor, the applicant must submit
a special drug experience report accompanied by a completed Form FDA
2301 containing the following:
(A) The distributor's current product labeling.
[[Page 116]]
(1) The distributor's labeling must be identical to that in the
approved NADA/ANADA except for a different and suitable proprietary name
(if used) and the name and address of the distributor. The name and
address of the distributor must be preceded by an appropriate qualifying
phrase as permitted by the regulations such as ``manufactured for'' or
``distributed by.''
(2) Other labeling changes must be the subject of a supplemental
NADA or ANADA as described under Sec. 514.8.
(B) A signed statement by the distributor stating:
(1) The category of the distributor's operations (e.g., wholesale or
retail),
(2) That the distributor will distribute the new animal drug only
under the approved labeling,
(3) That the distributor will promote the product only for use under
the conditions stated in the approved labeling,
(4) That the distributor will adhere to the records and reports
requirements of this section, and
(5) That the distributor is regularly and lawfully engaged in the
distribution or dispensing of prescription products if the product is a
prescription new animal drug.
(c) Multiple applications. Whenever an applicant is required to
submit a periodic drug experience report under the provisions of Sec.
514.80(b)(4) with respect to more than one approved NADA or ANADA for
preparations containing the same new animal drug so that the same
information is required to be reported for more than one application,
the applicant may elect to submit as a part of the report for one such
application (the primary application) all the information common to such
applications in lieu of reporting separately and repetitively on each.
If the applicant elects to do this, the applicant must do the following:
(1) State when a report applies to multiple applications and
identify all related applications for which the report is submitted by
NADA or ANADA number.
(2) Ensure that the primary application contains a list of the NADA
or ANADA numbers of all related applications.
(3) Submit a completed Form FDA 2301 to the primary application and
each related application with reference to the primary application by
NADA/ANADA number and submission date for the complete report of the
common information.
(4) All other information specific to a particular NADA/ANADA must
be included in the report for that particular NADA/ANADA.
(d) Format for submissions--(1) Electronic submissions. Except as
provided in paragraph (d)(2) of this section, reports submitted to FDA
under paragraphs (b)(2)(i) and (ii), (b)(3), and (b)(4)(iv)(A) and (C)
of this section and reports submitted to CVM under paragraph (b)(1) of
this section must be submitted in an electronic format that FDA can
process, review, and archive. Data provided in electronic submissions
must be in conformance with the data elements in Form FDA 1932 and FDA
technical documents describing transmission. As necessary, FDA will
issue updated technical documents on how to provide the electronic
submission (e.g., method of transmission and processing, media, file
formats, preparation, and organization of files). Unless requested by
FDA, paper copies of reports submitted electronically should not be
submitted to FDA.
(2) Waivers. An applicant or nonapplicant may request, in writing, a
temporary waiver of the electronic submission requirements in paragraph
(d)(1) of this section. The initial request may be by telephone or email
to CVM's Division of Veterinary Product Safety, with prompt written
followup submitted as a letter to the application(s). FDA will grant
waivers on a limited basis for good cause shown. If FDA grants a waiver,
the applicant or nonapplicant must comply with the conditions for
reporting specified by FDA upon granting the waiver.
(3) Paper forms. If approved by FDA before use, a computer-generated
equivalent of Form FDA 1932 may be used for reports submitted to the
appropriate FDA District Office or local FDA resident post under
paragraph (b)(1) of this section and to FDA under paragraph (d)(2) of
this section, and a computer-generated equivalent of Form FDA 2301 may
be used for reports
[[Page 117]]
submitted to FDA under paragraph (b)(4) of this section. Form FDA 1932
may be obtained on the FDA website, by telephoning CVM's Division of
Veterinary Product Safety, or by submitting a written request to the
following address: Food and Drug Administration, Center for Veterinary
Medicine, Division of Veterinary Product Safety (HFV-240), 7500 Standish
Pl., Rockville, MD 20855-2764. Form FDA 2301 may be obtained on the FDA
website, by telephoning CVM's Division of Surveillance (HFV-210), or by
submitting a written request to the following address: Food and Drug
Administration, Center for Veterinary Medicine, Division of Surveillance
(HFV-210), 7500 Standish Pl., Rockville, MD 20855-2764.
(e) Records to be maintained. The applicants and nonapplicants must
maintain records and reports of all information required by this section
for a period of 5 years after the date of submission.
(f) Access to records and reports. The applicant and nonapplicant
must, upon request from any authorized FDA officer or employee, at all
reasonable times, permit such officer or employee to have access to copy
and to verify all such required records and reports.
(g) Mailing addresses. Three-day alert reports must be submitted to
the appropriate FDA District Office or local FDA resident post.
Addresses for District Offices and resident posts may be obtained on the
FDA website. Other reports not required to be submitted to FDA in
electronic format must be submitted to the following address: Food and
Drug Administration, Center for Veterinary Medicine, Document Control
Unit (HFV-199), 7500 Standish Pl., Rockville, MD 20855-2764.
(h) Withdrawal of approval. If FDA finds that the applicant has
failed to establish the required records, or has failed to maintain
those records, or failed to make the required reports, or has refused
access to an authorized FDA officer or employee to copy or to verify
such records or reports, FDA may withdraw approval of the application to
which such records or reports relate. If FDA determines that withdrawal
of the approval is necessary, the agency shall give the applicant notice
and opportunity for hearing, as provided in Sec. 514.200, on the
question of whether to withdraw approval of the application.
(i) Disclaimer. Any report or information submitted under this
section and any release of that report or information by FDA will be
without prejudice and does not necessarily reflect a conclusion that the
report or information constitutes an admission that the drug caused or
contributed to an adverse event. A person need not admit, and may deny,
that the report or information constitutes an admission that a drug
caused or contributed to an adverse event.
[68 FR 15365, Mar. 31, 2003, as amended at 81 FR 29141, May 11, 2016; 85
FR 45512, July 29, 2020]
Sec. 514.87 Annual reports for antimicrobial animal drug sales
and distribution.
(a) The applicant for each new animal drug product approved under
section 512 of the Federal Food, Drug, and Cosmetic Act, or
conditionally approved under section 571 of the Federal Food, Drug, and
Cosmetic Act, and containing an antimicrobial active ingredient, must
submit an annual report to FDA on the amount of each such antimicrobial
active ingredient in the drug that is sold or distributed in the
reporting year for use in food-producing animal species, including
information on any distributor-labeled product.
(b) This report must identify the approved or conditionally approved
application and must include the following information for each new
animal drug product described in paragraph (a) of this section:
(1) A listing of each antimicrobial active ingredient contained in
the product;
(2) A description of each product sold or distributed by unit,
including the container size, strength, and dosage form of such product
units;
(3) For each such product, a listing of the target animal species,
indications, and production classes that are specified on the approved
label;
(4) For each such product, the number of units sold or distributed
in the United States (i.e., domestic sales) for each month of the
reporting year; and
[[Page 118]]
(5) For each such product, the number of units sold or distributed
outside the United States (i.e., quantities exported) for each month of
the reporting year.
(c) Each report must also provide a species-specific estimate of the
percentage of each product described in paragraph (b)(2) of this section
that was sold or distributed domestically in the reporting year for use
in any of the following animal species categories, but only for such
species that appear on the approved label: Cattle, swine, chickens,
turkeys. The total of the species-specific percentages reported for each
product must account for 100 percent of its sales and distribution;
therefore, a fifth category of ``other species/unknown'' must also be
reported.
(d) Each report must:
(1) Be submitted not later than March 31 each year;
(2) Cover the period of the preceding calendar year; and
(3) Be submitted using Form FDA 3744, ``Antimicrobial Animal Drug
Distribution Report.''
(e) Sales and distribution data and information reported under this
section will be considered to fall within the exemption for confidential
commercial information established in Sec. 20.61 of this chapter and
will not be publicly disclosed, except that summary reports of such
information aggregated in such a way that does not reveal information
that is not available for public disclosure under this provision will be
prepared by FDA and made available to the public as provided in
paragraph (f) of this section.
(f) FDA will publish an annual summary report of the data and
information it receives under this section for each calendar year by
December 31 of the following year. Such annual reports must include a
summary of sales and distribution data and information by antimicrobial
drug class and may include additional summary data and information as
determined by FDA. In order to protect confidential commercial
information, each individual datum appearing in the summary report must:
(1) Reflect combined product sales and distribution data and
information obtained from three or more distinct sponsors of approved
products that were actively sold or distributed that reporting year, and
(2) Be reported in a manner consistent with protecting both national
security and confidential commercial information.
[81 FR 29141, May 11, 2016]
Sec. 514.100 Evaluation and comment on applications.
(a) After the filed application has been evaluated, the applicant
will be furnished written comment on any apparent deficiencies in the
application.
(b) When the description of the methods used in, and the facilities
and controls used for, the manufacture, processing, and packing of such
new animal drug appears adequate on its face, but it is not feasible to
reach a conclusion as to the safety and effectiveness of the new animal
drug solely from consideration of this description, the applicant may be
notified that an establishment inspection is required to verify their
adequacy.
(c) A request for samples of a new animal drug or any edible tissues
and byproducts of animals treated with such a drug, shall specify the
quantity deemed adequate to permit tests of analytical methods to
determine their adequacy for regulatory purposes. The request should be
made as early in the 180-day period as possible to assure timely
completion. The date used for computing the 180-day limit for the
purposes of section 512(c) of the act shall be moved forward 1 day for
each day after the mailing date of the request until all of the
requested samples are received. If the samples are not received within
90 days after the request, the application will be considered withdrawn
without prejudice.
(d) The information contained in an application may be insufficient
to determine whether a new animal drug is safe or effective in use if it
fails to include (among other things) a statement showing whether such
drug is to be limited to prescription sale and exempt under section
502(f) of the act from the requirement that its labeling bear adequate
directions for lay use. If such drug is to be exempt, the information
may also be insufficient if:
[[Page 119]]
(1) The specimen labeling proposed fails to bear adequate
information for professional use including indications, effects,
dosages, routes, methods, and frequency and duration of administration
and any relevant hazards, contraindications, side effects, and
precautions under which practitioners licensed by law to administer such
drug can use the drug for the purposes for which it is intended,
including all purposes for which it is to be advertised, or represented,
in accordance with Sec. 201.105 of this chapter, and information
concerning hazards, contraindications, side effects, and precautions
relevant with respect to any uses for which such drug is to be
prescribed.
(2) The application fails to show that the labeling and advertising
of such drug will offer the drug for use only under those conditions for
which it is offered in the labeling that is part of the application.
(3) The application fails to show that all labeling that furnishes
or purports to furnish information for professional use of such drug
will contain, in the same language and emphasis, the information for use
including indications, effects, dosages, routes, methods, and frequency
and duration of administration and any relevant warnings, hazards,
contraindications, side effects, and precautions, which is contained in
the labeling that is part of the application in accordance with Sec.
201.105 of this chapter.
(e) The information contained in an application will be considered
insufficient to determine whether a new animal drug is safe and
effective for use when there is a refusal or failure upon written notice
to furnish inspectors authorized by the Food and Drug Administration an
adequate opportunity to inspect the facilities, controls, and records
pertinent to the application.
(f) On the basis of preliminary consideration of an application or
supplemental application containing typewritten or other draft labeling
in lieu of final printed labeling, an applicant may be informed that
such application is approvable when satisfactory final printed labeling
identical in content to such draft copy is submitted.
(g) When an application has been found incomplete on the basis of a
need for the kind of information described in Sec. 514.6, such
application shall be considered withdrawn without prejudice to future
filing on the date of issuance of the letter citing the inadequacies
contained in the application, unless within 30 days the sponsor chooses
to avail himself of the opportunity for hearing as prescribed by Sec.
514.111.
Sec. 514.105 Approval of applications.
(a) The Commissioner shall forward for publication in the Federal
Register a regulation prescribing the conditions under which the new
animal drug may be used, including the name and address of the
applicant; the conditions and indications for use covered by the
application; any tolerance, withdrawal period, or other use
restrictions; any tolerance required for the new animal drug substance
or its metabolites in edible products of food-producing animals; and, if
such new animal drug is intended for use in animal feed, appropriate
purposes and conditions of use (including special labeling requirements)
applicable to any animal feed; and such other information the
Commissioner deems necessary to assure safe and effective use.
(b) He shall notify the applicant by sending him a copy of the
proposed publication as described in paragraph (a)(1) of this section.
[40 FR 13825, Mar. 27, 1975, as amended at 51 FR 7392, Mar. 3, 1986; 64
FR 63203, Nov. 19, 1999]
Sec. 514.106 Approval of supplemental applications.
(a) Within 180 days after a supplement to an approved application is
filed pursuant to Sec. 514.8, the Commissioner shall approve the
supplemental application in accordance with procedures set forth in
Sec. 514.105(a)(1) and (2) if he/she determines that the application
satisfies the requirements of applicable statutory provisions and
regulations.
(b) The Commissioner will assign a supplemental application to its
proper category to ensure processing of the application.
(1) Category I. Supplements that ordinarily do not require a
reevaluation of any of the safety or effectiveness data
[[Page 120]]
in the parent application. Category I supplements include the following:
(i) A corporate change that alters the identity or address of the
sponsor of the new animal drug application (NADA).
(ii) The sale, purchase, or construction of manufacturing
facilities.
(iii) The sale or purchase of an NADA.
(iv) A change in container, container style, shape, size, or
components.
(v) A change in approved labeling (color, style, format, addition,
deletion, or revision of certain statements, e.g., trade name, storage,
expiration dates, etc).
(vi) A change in promotional material for a prescription new animal
drug not exempted by Sec. 514.8(c)(2)(i)(C)(1) through (c)(2)(i)(C)(3).
(vii) Changes in manufacturing processes that do not alter the
method of manufacture or change the final dosage form.
(viii) A change in bulk drug shipments.
(ix) A change in an analytical method or control procedures that do
not alter the approved standards.
(x) A change in an expiration date.
(xi) Addition of an alternate manufacturer, repackager, or relabeler
of the drug product.
(xii) Addition of an alternate supplier of the new drug substance.
(xiii) A change permitted in advance of approval as described under
Sec. 514.8(b)(3).
(2) Category II. Supplements that may require a reevaluation of
certain safety or effectiveness data in the parent application. Category
II supplements include the following:
(i) A change in the active ingredient concentration or composition
of the final product.
(ii) A change in quality, purity, strength, and identity
specifications of the active or inactive ingredients.
(iii) A change in dose (amount of drug administered per dose).
(iv) A change in the treatment regimen (schedule of dosing).
(v) Addition of a new therapeutic claim to the approved uses of the
product.
(vi) Addition of a new or revised animal production claim.
(vii) Addition of a new species.
(viii) A change in the prescription or over-the-counter status of a
drug product.
(ix) A change in statements regarding side effects, warnings,
precautions, and contraindications, except the addition of approved
statements to container, package, and promotional labeling, and
prescription drug advertising.
(x) A change in the drug withdrawal period prior to slaughter or in
the milk discard time.
(xi) A change in the tolerance for drug residues.
(xii) A change in analytical methods for drug residues.
(xiii) A revised method of synthesis or fermentation of the new drug
substance.
(xiv) Updating or changes in the manufacturing process of the new
drug substance and/or final dosage form (other than a change in
equipment that does not alter the method of manufacture of a new animal
drug, or a change from one commercial batch size to another without any
change in manufacturing procedure), or changes in the methods,
facilities, or controls used for the manufacture, processing, packaging,
or holding of the new animal drug (other than use of an establishment
not covered by the approval that is in effect) that give increased
assurance that the drug will have the characteristics of identity,
strength, quality, and purity which it purports or is represented to
possess.
[55 FR 46052, Nov. 1, 1990; 55 FR 49973, Dec. 3, 1990; 56 FR 12422, Mar.
25, 1991, as amended at 71 FR 74785, Dec. 13, 2006]
Sec. 514.110 Reasons for refusing to file applications.
(a) The date of receipt of an application for a new animal drug
shall be the date on which the application shall be deemed to be filed.
(b) An application for a new animal drug shall not be considered
acceptable for filing for any of the following reasons:
(1) It does not contain complete and accurate English translations
of any pertinent part in a foreign language.
(2) Fewer than three copies are submitted.
[[Page 121]]
(3) It is incomplete on its face in that it is not properly
organized and indexed.
(4) On its face the information concerning required matter is so
inadequate that the application is clearly not approvable.
(5) The new animal drug is to be manufactured, prepared, propagated,
compounded, or processed in whole or in part in any State in an
establishment that has not been registered or exempted from registration
under the provisions of section 510 of the act.
(6) The sponsor does not reside or maintain a place of business
within the United States and the application has not been countersigned
by an attorney, agent, or other representative of the applicant, which
representative resides in the United States and has been duly authorized
to act on behalf of the applicant and to receive communications on all
matters pertaining to the application.
(7) The new animal drug is a drug subject to licensing under the
animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21
U.S.C. 151 et seq. ). Such applications will be referred to the U.S.
Department of Agriculture for action.
(8) It fails to include, with respect to each nonclinical laboratory
study contained in the application, either a statement that the study
was conducted in compliance with the good laboratory practice
regulations set forth in part 58 of this chapter, or, if the study was
not conducted in compliance with such regulations, a brief statement of
the reasons for the noncompliance.
(9) [Reserved]
(10) The applicant fails to submit a complete environmental
assessment under Sec. 25.40 of this chapter or fails to provide
sufficient information to establish that the requested action is subject
to categorical exclusion under Sec. 25.30 or Sec. 25.33 of this
chapter.
(c) If an application is determined not to be acceptable for filing,
the applicant shall be notified within 30 days of receipt of the
application and shall be given the reasons therefore.
(d) If the applicant disputes the findings that his application is
not acceptable for filing, he may make written request that the
application be filed over protest, in which case it will be filed as of
the day originally received.
[40 FR 13825, Mar. 27, 1975, as amended at 50 FR 7517, Feb. 22, 1985; 50
FR 16668, Apr. 26, 1985; 62 FR 40600, July 29, 1997]
Sec. 514.111 Refusal to approve an application.
(a) The Commissioner shall, within 180 days after the filing of the
application, inform the applicant in writing of his intention to issue a
notice of opportunity for a hearing on a proposal to refuse to approve
the application, if the Commissioner determines upon the basis of the
application, or upon the basis of other information before him with
respect to a new animal drug, that:
(1) The reports of investigations required to be submitted pursuant
to section 512(b) of the act do not include adequate tests by all
methods reasonably applicable to show whether or not such drug is safe
for use under the conditions prescribed, recommended, or suggested in
the proposed labeling thereof; or
(2) The results of such tests show that such drug is unsafe for use
under such conditions or do not show that such drug is safe for use
under such conditions; or
(3) The methods used in and the facilities and controls used for the
manufacture, processing, and packing of such drug are inadequate to
preserve its identity, strength, quality, and purity; or
(4) Upon the basis of the information submitted to the Food and Drug
Administration as part of the application, or upon the basis of any
other information before it with respect to such drug, it has
insufficient information to determine whether such drug is safe for use
under such conditions. In making this determination the Commissioner
shall consider, among other relevant factors:
(i) The probable consumption of such drug and of any substance
formed in or on food because of the use of such drug;
(ii) The cumulative effect on man or animal of such drug, taking
into account any chemically or pharmacologically related substances;
[[Page 122]]
(iii) Safety factors which, in the opinion of experts qualified by
scientific training and experience to evaluate the safety of such drugs,
are appropriate for the use of animal experimentation data; and
(iv) Whether the conditions of use prescribed, recommended, or
suggested in the proposed labeling are reasonably certain to be followed
in practice; or
(5) Evaluated on the basis of information submitted as part of the
application and any other information before the Food and Drug
Administration with respect to such drug, there is lack of substantial
evidence as defined in Sec. 514.4.
(6) Failure to include an appropriate proposed tolerance for
residues in edible products derived from animals or a withdrawal period
or other restrictions for use of such drug if any tolerance or
withdrawal period or other restrictions for use are required in order to
assure that the edible products derived from animals treated with such
drug will be safe.
(7) Based on a fair evaluation of all material facts, the labeling
is false or misleading in any particular; or
(8) Such drug induces cancer when ingested by man or animal or,
after appropriate tests for evaluation of the safety of such drug,
induces cancer in man or animal, except that this subparagraph shall not
apply with respect to such drug if the Commissioner finds that, under
the conditions of use specified in proposed labeling and reasonably
certain to be followed in practice:
(i) Such drug will not adversely affect the animal for which it is
intended; and
(ii) No residue of such drug will be found (by methods of
examination prescribed or approved by the Commissioner by regulations)
in any edible portion of such animal after slaughter or in any food
yielded by, or derived from the living animals.
(9) The applicant fails to submit an adequate environmental
assessment under Sec. 25.40 of this chapter or fails to provide
sufficient information to establish that the requested action is subject
to categorical exclusion under Sec. 25.30 or Sec. 25.33 of this
chapter.
(10) The drug fails to satisfy the requirements of subpart E of part
500 of this chapter.
(11) Any nonclinical laboratory study that is described in the
application and that is essential to show that the drug is safe for use
under the conditions prescribed, recommended, or suggested in its
proposed labeling, was not conducted in compliance with the good
laboratory practice regulations as set forth in part 58 of this chapter
and no reason for the noncompliance is provided or, if it is, the
differences between the practices used in conducting the study and the
good laboratory practice regulations do not support the validity of the
study.
(12) The drug will be produced in whole or in part in an
establishment that is not registered and not exempt from registration
under section 510 of the Federal Food, Drug, and Cosmetic Act and part
207 of this chapter.
(b) The Commissioner, as provided in Sec. 514.200 of this chapter,
shall expeditiously notify the applicant of an opportunity for a hearing
on the question of whether such application is approvable, unless by the
30th day following the date of issuance of the letter informing the
applicant of the intention to issue a notice of opportunity for a
hearing the applicant:
(1) Withdraws the application; or
(2) Waives the opportunity for a hearing; or
(3) Agrees with the Commissioner on an additional period to precede
issuance of such notice of hearing.
[40 FR 13825, Mar. 27, 1975, as amended at 43 FR 22675, May 26, 1978; 44
FR 16007, Mar. 16, 1979; 50 FR 7517, Feb. 22, 1985; 50 FR 16668, Apr.
26, 1985; 52 FR 49588, Dec. 31, 1987; 54 FR 18280, Apr. 28, 1989; 62 FR
40600, July 29, 1997; 63 FR 10770, Mar. 5, 1998; 64 FR 40757, July 28,
1999; 64 FR 63204, Nov. 19, 1999; 81 FR 60221, Aug. 31, 2016]
Sec. 514.115 Withdrawal of approval of applications.
(a) The Secretary may suspend approval of an application approved
pursuant to section 512(c) of the act and give the applicant prompt
notice of his action and afford the applicant the opportunity for an
expedited hearing on a
[[Page 123]]
finding that there is an imminent hazard to the health of man or of the
animals for which such new animal drug or animal feed is intended.
(b) The Commissioner shall notify in writing the person holding an
application approved pursuant to section 512(c) of the act and afford an
opportunity for a hearing on a proposal to withdraw approval of such
application if he finds:
(1) That the application contains any untrue statement of a material
fact; or
(2) That the applicant has made any changes from the standpoint of
safety or effectiveness beyond the variations provided for in the
application unless he has supplemented the application by filing with
the Secretary adequate information respecting all such changes and
unless there is in effect an approval of the supplemental application,
or such changes are those for which written authorization or approval is
not required as provided for in Sec. 514.8. The supplemental
application shall be treated in the same manner as the original
application.
(3) That in the case of an application for use of a new animal drug
approved or deemed approved pursuant to section 512(c) of the act:
(i) Experience or scientific data show that such drug is unsafe for
use under the conditions of use upon the basis of which the application
was approved; or
(ii) New evidence not contained in such application or not available
to the Secretary until after such application was approved, or tests by
new methods, or tests by methods not deemed reasonably applicable when
such application was approved, evaluated together with the evidence
available to the Secretary when the application was approved, shows that
such drug is not shown to be safe for use under the conditions of use
upon the basis of which the application was approved or that section 512
(d)(1)(H) of the act applies to such drug; or
(iii) On the basis of new information before him with respect to
such drug, evaluated together with the evidence available to him when
the application was approved, there is a lack of substantial evidence
that such drug will have the effect it purports or is represented to
have under the conditions of use prescribed, recommended, or suggested
in the labeling thereof.
(4) That any nonclinical laboratory study that is described in the
application and that is essential to show that the drug is safe for use
under the conditions prescribed, recommended, or suggested in its
proposed labeling, was not conducted in compliance with the good
laboratory practice regulations as set forth in part 58 of this chapter
and no reason for the noncompliance is provided or, if it is, the
differences between the practices used in conducting the study and the
good laboratory practice regulations do not support the validity of the
study.
(c) The Commissioner may notify in writing the person holding an
application approved pursuant to section 512(c) of the act and afford an
opportunity for a hearing on a proposal to withdraw approval of such
application if he finds:
(1) That the applicant has failed to establish a system for
maintaining required records, or has repeatedly or deliberately failed
to maintain such records or to make required reports in accordance with
a regulation or order under section 512(l)(1) of the act, or the
applicant has refused to permit access to, or copying, or verification
of, such records as required by section 512(l)(2) of the act; or
(2) That on the basis of new information before him evaluated
together with the evidence before him when the application was approved,
the methods used in, or the facilities and controls used for, the
manufacture, processing, and packing of such drug or animal feed are
inadequate to assure and preserve its identity, strength, quality, and
purity and were not made adequate within a reasonable time after receipt
of written notice from the Secretary specifying the matter complained
of; or
(3) That on the basis of new information before him, evaluated
together with the evidence before him when the application was approved,
the labeling of such drug, based on a fair evaluation of all material
facts, is false or misleading in any particular and was not corrected
within a reasonable time after receipt of written notice from the
Secretary specifying the matter complained of.
[[Page 124]]
(d) Approval of an application pursuant to section 512(c) of the act
will be withdrawn on the basis of a request for its withdrawal submitted
in writing by a person holding an approved new animal drug application
on the grounds that the drug subject to such application is no longer
being marketed and information is included in support of this finding,
provided none of the conditions cited in paragraphs (a), (b), and (c) of
this section pertain to the subject drug. A written request for such
withdrawal shall be construed as a waiver of the opportunity for a
hearing as otherwise provided for in this section. Withdrawal of
approval of an application under the provisions of this paragraph shall
be without prejudice.
(e) On the basis of the withdrawal of approval of an application for
a new animal drug approved pursuant to section 512(c) of the act, the
regulation published pursuant to section 512(i) of the act covering the
conditions of use of such drug as provided for in the application shall
be revoked.
[40 FR 13825, Mar. 27, 1975, as amended at 50 FR 7517, Feb. 22, 1985; 64
FR 63204, Nov. 19, 1999]
Sec. 514.116 Notice of withdrawal of approval of application.
When an approval of an application submitted pursuant to section 512
of the act is withdrawn by the Commissioner, he will give appropriate
public notice of such action by publication in the Federal Register.
Sec. 514.117 Adequate and well-controlled studies.
(a) Purpose. The primary purpose of conducting adequate and well-
controlled studies of a new animal drug is to distinguish the effect of
the new animal drug from other influences, such as spontaneous change in
the course of the disease, normal animal production performance, or
biased observation. One or more adequate and well-controlled studies are
required to establish, by substantial evidence, that a new animal drug
is effective. The characteristics described in paragraph (b) of this
section have been developed over a period of years and are generally
recognized as the essentials of an adequate and well-controlled study.
Well controlled, as used in the phrase adequate and well controlled,
emphasizes an important aspect of adequacy. The Food and Drug
Administration (FDA) considers these characteristics in determining
whether a study is adequate and well controlled for purposes of section
512 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C.
360b). Adequate and well-controlled studies, in addition to providing a
basis for determining whether a new animal drug is effective, may also
be relied upon to support target animal safety. The report of an
adequate and well-controlled study should provide sufficient details of
study design, conduct, and analysis to allow critical evaluation and a
determination of whether the characteristics of an adequate and well-
controlled study are present.
(b) Characteristics. An adequate and well-controlled study has the
following characteristics:
(1) The protocol for the study (protocol) and the report of the
study results (study report) must include a clear statement of the study
objective(s).
(2) The study is conducted in accordance with an appropriate
standard of conduct that addresses, among other issues, study conduct,
study personnel, study facilities, and study documentation. The protocol
contains a statement acknowledging the applicability of, and intention
to follow, a standard of conduct acceptable to FDA. The study report
contains a statement describing adherence to the standard.
(3) The study is conducted with a new animal drug that is produced
in accordance with appropriate manufacturing practices, which include,
but are not necessarily limited to, the manufacture, processing,
packaging, holding, and labeling of the new animal drug such that the
critical characteristics of identity, strength, quality, purity, and
physical form of the new animal drug are known, recorded, and
reproducible, to permit meaningful evaluations of and comparisons with
other studies conducted with the new animal drug. The physical form of a
new animal drug includes the formulation and physical characterization
(including delivery systems thereof, if any) of the new animal drug as
presented to the
[[Page 125]]
animal. The protocol and study report must include an identification
number which can be correlated with the specific formulation and
production process used to manufacture the new animal drug used in the
study.
(4) The study uses a design that permits a valid comparison with one
or more controls to provide a quantitative evaluation of drug effects.
The protocol and the study report must describe the precise nature of
the study design, e.g., duration of treatment periods, whether
treatments are parallel, sequential, or crossover, and the determination
of sample size. Within the broad range of studies conducted to support a
determination of the effectiveness of a new animal drug, certain of the
controls listed below would be appropriate and preferred depending on
the study conducted:
(i) Placebo concurrent control. The new animal drug is compared with
an inactive preparation designed to resemble the new animal drug as far
as possible.
(ii) Untreated concurrent control. The new animal drug is compared
with the absence of any treatment. The use of this control may be
appropriate when objective measurements of effectiveness, not subject to
observer bias, are available.
(iii) Active treatment concurrent control. The new animal drug is
compared with known effective therapy. The use of this control is
appropriate when the use of a placebo control or of an untreated
concurrent control would unreasonably compromise the welfare of the
animals. Similarity of the new animal drug and the active control drug
can mean either that both drugs were effective or that neither was
effective. The study report should assess the ability of the study to
have detected a difference between treatments. The evaluation of the
study should explain why the new animal drugs should be considered
effective in the study, for example, by reference to results in previous
placebo-controlled studies of the active control.
(iv) Historical control. The results of treatment with the new
animal drug are quantitatively compared with experience historically
derived from the adequately documented natural history of the disease or
condition, or with a regimen (therapeutic, diagnostic, prophylactic)
whose effectiveness is established, in comparable animals. Because
historical control populations usually cannot be as well assessed with
respect to pertinent variables as can concurrent control populations,
historical control designs are usually reserved for special
circumstances. Examples include studies in which the effect of the new
animal drug is self-evident or studies of diseases with high and
predictable mortality, or signs and symptoms of predictable duration or
severity, or, in the case of prophylaxis, predictable morbidity.
(5) The study uses a method of selecting animals that provides
adequate assurances that the animals are suitable for the purposes of
the study. For example, the animals can reasonably be expected to have
animal production characteristics typical of the class(es) of animals
for which the new animal drug is intended, there is adequate assurance
that the animals have the disease or condition being studied, or, in the
case of prophylactic agents, evidence of susceptibility and exposure to
the condition against which prophylaxis is desired has been provided.
The protocol and the study report describe the method of selecting
animals for the study.
(6) The study uses a method to assign a treatment or a control to
each experimental unit of animals that is random and minimizes bias.
Experimental units of animals are groups of animals that are comparable
with respect to pertinent variables such as age, sex, class of animal,
severity of disease, duration of disease, dietary regimen, level of
animal production, and use of drugs or therapy other than the new animal
drug. The protocol and the study report describe the method of
assignment of animals to an experimental unit to account for pertinent
variables and method of assignment of a treatment or a control to the
experimental units. When the effect of such variables is accounted for
by an appropriate design, and when, within the same animal, effects due
to the test drug can be obtained free of the effects of such variables,
the same animal may be used for both the test drug and the
[[Page 126]]
control using the controls set forth in paragraph (b)(4) of this
section.
(7) The study uses methods to minimize bias on the part of observers
and analysts of the data that are adequate to prevent undue influences
on the results and interpretation of the study data. The protocol and
study report explain the methods of observation and recording of the
animal response variables and document the methods, such as ``blinding''
or ``masking,'' used in the study for excluding or minimizing bias in
the observations.
(8) The study uses methods to assess animal response that are well
defined and reliable. The protocol and study report describe the methods
for conducting the study, including any appropriate analytical and
statistical methods, used to collect and analyze the data resulting from
the conduct of the study, describe the criteria used to assess response,
and, when appropriate, justify the selection of the methods to assess
animal response.
(9) There is an analysis and evaluation of the results of the study
in accord with the protocol adequate to assess the effects of the new
animal drug. The study report evaluates the methods used to conduct, and
presents and evaluates the results of, the study as to their adequacy to
assess the effects of the new animal drug. This evaluation of the
results of the study assesses, among other items, the comparability of
treatment and control groups with respect to pertinent variables and the
effects of any interim analyses performed.
(c) Field studies. (1) Field conditions as used in this section
refers to conditions which closely approximate the conditions under
which the new animal drug, if approved, is intended to be applied or
administered.
(2) Studies of a new animal drug conducted under field conditions
shall, consistent with generally recognized scientific principles and
procedures, use an appropriate control that permits comparison, employ
procedures to minimize bias, and have the characteristics generally
described in paragraph (b) of this section. However, because field
studies are conducted under field conditions, it is recognized that the
level of control over some study conditions need not or should not be
the same as the level of control in laboratory studies. While not all
conditions relating to a field study need to be or should be controlled,
observations of the conditions under which the new animal drug is tested
shall be recorded in sufficient detail to permit evaluation of the
study. Adequate and well-controlled field studies shall balance the need
to control study conditions with the need to observe the true effect of
the new animal drug under closely approximated actual use conditions.
(d) Waiver. The Director of the Center for Veterinary Medicine (the
Director) may, on the Director's own initiative or on the petition of an
interested person, waive in whole or in part any of the criteria in
paragraph (b) of this section with respect to a specific study. A
petition for a waiver is required to set forth clearly and concisely the
specific criteria from which waiver is sought, why the criteria are not
reasonably applicable to the particular study, what alternative
procedures, if any, are to be, or have been employed, and what results
have been obtained. The petition is also required to state why the
studies so conducted will yield, or have yielded, substantial evidence
of effectiveness, notwithstanding nonconformance with the criteria for
which waiver is requested.
(e) Uncontrolled studies. Uncontrolled studies or partially
controlled studies are not acceptable as the sole basis for the approval
of claims of effectiveness or target animal safety. Such studies,
carefully conducted and documented, may provide corroborative support of
adequate and well-controlled studies regarding effectiveness and may
yield valuable data regarding safety of the new animal drug. Such
studies will be considered on their merits in light of the
characteristics listed here. Isolated case reports, random experience,
and reports lacking the details which permit scientific evaluation will
not be considered.
[63 FR 10770, Mar. 5, 1998]
[[Page 127]]
Sec. 514.120 Revocation of order refusing to approve an application
or suspending or withdrawing approval of an application.
The Commissioner, upon his own initiative or upon request of an
applicant stating reasonable grounds therefor and if he finds that the
facts so require, may issue an order approving an application that
previously has had its approval refused, suspended, or withdrawn.
Sec. 514.121 Service of notices and orders.
All notices and orders under this subchapter E and section 512 of
the act pertaining to new animal drug applications shall be served:
(a) In person by any officer or employee of the Department
designated by the Commissioner; or
(b) By mailing the order by certified mail addressed to the
applicant or respondent at his last known address in the records of the
Food and Drug Administration.
Subpart C_Hearing Procedures
Sec. 514.200 Notice of opportunity for hearing; notice of participation
and requests for hearing; grant or denial of hearing.
(a) The notice to the applicant of opportunity for a hearing on a
proposal by the Commissioner to refuse to approve an application or to
withdraw the approval of an application will be published in the Federal
Register together with an explanation of the grounds for the proposed
action. The notice will describe how to request a hearing. An applicant
has 30 days after publication of the notice to request a hearing.
(b) If the applicant fails to request a hearing within the 30-day
timeframe, the Commissioner, without further notice, will publish a
final order denying or withdrawing approval of the application.
(c) If the applicant desires to request a hearing:
(1) Within 30 days after publication of the notice of opportunity
for hearing, the applicant must submit to the Division of Dockets
Management written objections and a request for a hearing in accordance
with Sec. Sec. 12.20 and 12.22. This request for a hearing must include
each specific objection to the proposal on which a hearing is requested,
together with a detailed description and analysis of the factual
information (including all relevant clinical and other investigational
data) the applicant will present in support of that objection. A request
for a hearing may not rest upon mere allegations or denials or general
descriptions of positions or contentions, but must set forth specific
reliable evidence showing there is a genuine and substantial issue of
fact that requires a hearing.
(2) If the Commissioner determines upon review of the data and
information submitted in the objections and request for a hearing that a
hearing is not justified because no genuine and substantial issue of
fact precludes the refusal to approve the application or the withdrawal
of approval of the application (for example, the applicant has not
identified any adequate and well-controlled clinical investigations to
support the claims of effectiveness), the Commissioner will enter an
order denying the hearing and stating the final findings and
conclusions.
(3) If the Commissioner determines upon review of the data and
information submitted in the objections and request for a hearing that a
hearing is justified, the Commissioner will publish a notice setting
forth the following:
(i) The regulation or order that is the subject of the hearing;
(ii) A statement specifying any part of the regulation or order that
has been stayed by operation of law or in the Commissioner's discretion;
(iii) The parties to the hearing;
(iv) The specific issues of fact for resolution at the hearing;
(v) The presiding officer, or a statement that the presiding officer
will be designated in a later notice; and
(vi) The date, time, and place of the prehearing conference, or a
statement that the date, time, and place will be announced in a later
notice. However, in the case of a denial of approval, the hearing must
not occur more than 90 days after expiration of the 30-day time period
in which to request a hearing, unless the presiding officer and the
applicant otherwise agree; and in the case
[[Page 128]]
of withdrawal of approval, the hearing will occur as soon as
practicable.
(d) The hearing will be open to the public; however, if the
Commissioner finds that portions of the application which serve as a
basis for the hearing contain information concerning a method or process
entitled to protection as a trade secret, the part of the hearing
involving such portions will not be public, unless the respondent so
specifies in the request for a hearing.
[81 FR 52997, Aug. 11, 2016]
Sec. 514.201 Procedures for hearings.
Hearings relating to new animal drugs under section 512(d) and (e)
of the act shall be governed by part 12 of this chapter.
[64 FR 63204, Nov. 19, 1999]
Subparts D-E [Reserved]
Subpart F_Judicial Review
Sec. 514.235 Judicial review.
(a) The transcript and record shall be certified by the
Commissioner. In any case in which the Commissioner enters an order
without a hearing pursuant to Sec. 314.200(g) of this chapter, the
request(s) for hearing together with the data and information submitted
and the Commissioner's findings and conclusions shall be included in the
record certified by the Commissioner.
(b) Judicial review of an order withdrawing approval of a new drug
application, whether or not a hearing has been held, may be sought by a
manufacturer or distributor of an identical, related, or similar drug
product, as defined in Sec. 310.6 of this chapter, in a United States
court of appeals pursuant to section 505(h) of the act.
[42 FR 4717, Jan. 25, 1977]
PART 515_MEDICATED FEED MILL LICENSE--Table of Contents
Subpart A_Applications
Sec.
515.10 Medicated feed mill license applications.
515.11 Supplemental medicated feed mill license applications.
Subpart B_Administrative Actions on Licenses
515.20 Approval of medicated feed mill license applications.
515.21 Refusal to approve a medicated feed mill license application.
515.22 Suspension and/or revocation of approval of a medicated feed mill
license.
515.23 Voluntary revocation of medicated feed mill license.
515.24 Notice of revocation of a medicated feed mill license.
515.25 Revocation of order refusing to approve a medicated feed mill
license application or suspending or revoking a license.
515.26 Services of notices and orders.
Subpart C_Hearing Procedures
515.30 Contents of notice of opportunity for a hearing.
515.31 Procedures for hearings.
Subpart D_Judicial Review
515.40 Judicial review.
Authority: 21 U.S.C. 360b, 371.
Source: 64 FR 63204, Nov. 19, 1999, unless otherwise noted.
Subpart A_Applications
Sec. 515.10 Medicated feed mill license applications.
(a) Medicated feed mill license applications (Forms FDA 3448) may be
obtained from the Public Health Service, Consolidated Forms and
Publications Distribution Center, Washington Commerce Center, 3222
Hubbard Rd., Landover, MD 20785, or electronically from the Center for
Veterinary Medicine home page at http://www.fda.gov/cvm.
(b) A completed medicated feed mill license must contain the
following information:
(1) The full business name and address of the facility at which the
manufacturing is to take place.
(2) The facility's FDA registration number as required by section
510 of the Federal Food, Drug, and Cosmetic Act (the act).
(3) The name, title, and signature of the responsible individual or
individuals for that facility.
(4) A certification that the animal feeds bearing or containing new
animal drugs are manufactured and labeled in
[[Page 129]]
accordance with the applicable regulations published under section
512(i) of the act or in accordance with the index listing published
under section 572(e)(2) of the act.
(5) A certification that the methods used in, and the facilities and
controls used for, manufacturing, processing, packaging, and holding
such animal feeds conform to current good manufacturing practice as
described in section 501(a)(2)(B) of the act and in part 225 of this
chapter.
(6) A certification that the facility will establish and maintain
all records required by regulation or order issued under sections
512(m)(5)(A) or 504(a)(3)(A) of the act, and will permit access to, or
copying or verification of such records.
(7) A commitment that current approved or index listed Type B and/or
Type C medicated feed labeling for each Type B and/or Type C medicated
feed to be manufactured will be in the possession of the feed
manufacturing facility prior to receiving the Type A medicated article
containing such drug.
(8) A commitment to renew registration every year with FDA as
required in part 207 of this chapter.
(c) Applications must be completed, signed, and submitted to the
Division of Animal Feeds (HFV-220), Center for Veterinary Medicine, Food
and Drug Administration, 7500 Standish Pl., Rockville, MD 20855.
(d) Applications that are facially deficient will be returned to the
applicant. All reasons for the return of the application will be made
known to the applicant.
(e) Upon approval, the original copy of the application will be
signed by an authorized employee of FDA designated by the Commissioner
of Food and Drugs, and a copy will be returned to the applicant.
[64 FR 63204, Nov. 19, 1999, as amended at 72 FR 69121, Dec. 6, 2007; 81
FR 60221, Aug. 31, 2016]
Sec. 515.11 Supplemental medicated feed mill license applications.
(a) After approval of a medicated feed mill license application to
manufacture animal feed, a supplemental application shall be submitted
for a change in ownership and/or a change in mailing address of the
facility site.
(b) Each supplemental application should be accompanied by a fully
completed Form FDA 3448 and include an explanation of the change.
(c) Within 30 working days after a supplemental application has been
filed, if the Commissioner of Food and Drugs determines that the
application provides adequate information respecting the change in
ownership and/or postal address of the facility site, then an authorized
employee of the Food and Drug Administration designated by the
Commissioner shall notify the applicant that it is approved by signing
and mailing to the applicant a copy of the Form FDA 3448. Supplemental
applications that do not provide adequate information shall be returned
to the applicant and all reasons for the return of the application shall
be made known to the applicant.
Subpart B_Administrative Actions on Licenses
Sec. 515.20 Approval of medicated feed mill license applications.
Within 90 days after an application has been filed under Sec.
515.10, if the Commissioner of Food and Drugs (the Commissioner)
determines that none of the grounds for denying approval specified in
section 512(m)(3) of the Federal Food, Drug, and Cosmetic Act (the act)
applies, an authorized employee of the Food and Drug Administration
designated by the Commissioner shall notify the applicant that it is
approved by signing and mailing to the applicant a copy of the Form FDA
3448.
Sec. 515.21 Refusal to approve a medicated feed mill license application.
(a) The Commissioner of Food and Drugs (the Commissioner) shall
within 90 days, or such additional period as may be agreed upon by the
Commissioner and the applicant, after the filing of an application under
Sec. 515.10, inform the applicant in writing of his/her intention to
issue a notice of opportunity for a hearing on a proposal to refuse to
approve the application, if the Commissioner determines upon the basis
of the application, on the basis of a preapproval inspection, or upon
the
[[Page 130]]
basis of any other information before him that:
(1) The application is incomplete, false, or misleading in any
particular; or
(2) The methods used in and the facilities and controls used for the
manufacturing, processing, and packaging of such animal feed are not
adequate to preserve the identity, strength, quality, and purity of the
new animal drug therein; or
(3) The facility manufactures animal feeds bearing or containing new
animal drugs in a manner that does not accord with the specifications
for manufacture or labels animal feeds bearing or containing new animal
drugs in a manner that does not accord with the conditions or
indications of use that are published under section 512(i) or 572(e)(2)
of the act.
(b) The Commissioner, as provided in Sec. 515.30, shall
expeditiously notify the applicant of an opportunity for a hearing on
the question of whether such application is approvable, unless by the
30th day following the date of issuance of the letter informing the
applicant of the intention to issue a notice of opportunity for a
hearing the applicant:
(1) Withdraws the application; or
(2) Waives the opportunity for a hearing; or
(3) Agrees with the Commissioner on an additional period to precede
issuance of such notice of hearing.
[64 FR 63204, Nov. 19, 1999, as amended at 72 FR 69121, Dec. 6, 2007]
Sec. 515.22 Suspension and/or revocation of approval of a medicated
feed mill license.
(a) The Secretary of Health and Human Services may suspend a
medicated feed mill license approved under section 512(m)(2) of the
Federal Food, Drug, and Cosmetic Act (the act) and give the person
holding the medicated feed mill license application prompt notice of
this action and afford the applicant the opportunity for an expedited
hearing on a finding that there is an imminent hazard to the health of
man or of the animals for which such animal feed is intended.
(b) The Commissioner of Food and Drugs (the Commissioner) shall
notify in writing the person holding an application approved under
section 512(m)(2) of the act and afford an opportunity for a hearing on
a proposal to revoke approval of such application if the Commissioner
finds:
(1) That the application contains any untrue statement of a material
fact; or
(2) That the applicant has made any changes that would cause the
application to contain any untrue statements of material fact or that
would affect the safety or effectiveness of the animal feeds
manufactured at the facility unless the applicant has supplemented the
application by filing a supplemental application under Sec. 515.11.
(c) The Commissioner may notify in writing the person holding an
application approved under section 512(m)(2) of the act and afford an
opportunity for a hearing on a proposal to revoke approval of such
application if the Commissioner finds:
(1) That the applicant has failed to establish a system for
maintaining required records, or has repeatedly or deliberately failed
to maintain such records or to make required reports in accordance with
a regulation or order under sections 512(m)(5)(A) or 504(a)(3)(A) of the
act, or the applicant has refused to permit access to, or copying, or
verification of, such records as required by sections 512(m)(5)(B) or
504(a)(3)(B) of the act; or
(2) That on the basis of new information before him, evaluated
together with the evidence before him when such license was issued, the
methods used in, or the facilities and controls used for, the
manufacture, processing, packing, and holding of such animal feed are
inadequate to assure and preserve the identity, strength, quality, and
purity of the new animal drug therein, and were not made adequate within
a reasonable time after receipt of written notice from the Commissioner
specifying the matter complained of; or
(3) That on the basis of new information before him, evaluated
together with the evidence before him when such license was issued, the
labeling of any animal feeds, based on a fair evaluation of all material
facts, is false or misleading in any particular and was not corrected
within a reasonable time after receipt of written notice from the
[[Page 131]]
Commissioner specifying the matter complained of; or
(4) That on the basis of new information before him, evaluated
together with the evidence before him when such license was issued, the
facility has manufactured, processed, packed, or held animal feed
bearing or containing a new animal drug adulterated under section
501(a)(6) of the act, and the facility did not discontinue the
manufacture, processing, packing, or holding of such animal feed within
a reasonable time after receipt of written notice from the Commissioner
specifying the matter complained of.
Sec. 515.23 Voluntary revocation of medicated feed mill license.
A license issued under section 512(m)(2) of the Federal Food, Drug,
and Cosmetic Act (the act) will be revoked on the basis of a request for
its revocation submitted in writing by a responsible individual holding
such license on the grounds that the facility no longer manufactures any
animal feed covered under Sec. 558.4(b) of this chapter. A written
request for such revocation shall be construed as a waiver of the
opportunity for a hearing as otherwise provided for in this section.
Revocation of approval of a medicated feed mill license under the
provisions of this paragraph shall be without prejudice.
Sec. 515.24 Notice of revocation of a medicated feed mill license.
When a license approved under section 512 of the Federal Food, Drug,
and Cosmetic Act (the act) is revoked by the Commissioner of Food and
Drugs (the Commissioner), the Commissioner will give appropriate public
notice of such action by publication in the Federal Register.
Sec. 515.25 Revocation of order refusing to approve a medicated
feed mill license application or suspending or revoking a license.
The Commissioner of Food and Drugs (the Commissioner), upon his/her
own initiative or upon request of an applicant stating reasonable
grounds therefor and if the Commissioner finds that the facts so
require, may issue an order approving a medicated feed mill license
application that previously has had its approval refused, suspended, or
revoked.
Sec. 515.26 Services of notices and orders.
All notices and orders under this part 515 and section 512 of the
Federal Food, Drug, and Cosmetic Act (the act) pertaining to medicated
feed mill licenses shall be served:
(a) In person by any officer or employee of the Department of Health
and Human Services designated by the Commissioner of Food and Drugs; or
(b) By mailing the order by certified mail addressed to the
applicant or respondent at the applicant or respondent's last known
address in the records of the Food and Drug Administration.
Subpart C_Hearing Procedures
Sec. 515.30 Contents of notice of opportunity for a hearing.
(a) The notice to the applicant of opportunity for a hearing on a
proposal by the Commissioner of Food and Drugs (the Commissioner) to
refuse to approve a medicated feed mill license application or to revoke
the approval of a medicated feed mill license will specify the grounds
upon which the Commissioner proposes to issue this order. On request of
the applicant, the Commissioner will explain the reasons for the action.
The notice of opportunity for a hearing will be published in the Federal
Register and will specify that the applicant has 30 days after issuance
of the notice within which the Commissioner is required to file a
written appearance electing whether:
(1) To avail himself of the opportunity for a hearing; or
(2) Not to avail himself of the opportunity for a hearing.
(b) If the applicant fails to file a written appearance in answer to
the notice of opportunity for hearing, this failure will be construed as
an election not to avail himself of the opportunity for the hearing, and
the Commissioner without further notice may enter a final order.
(c) If the applicant elects to avail himself of the opportunity for
a hearing, the applicant is required to file a written appearance
requesting the
[[Page 132]]
hearing within 30 days after the publication of the notice, giving the
reason why the application should not be refused or the medicated feed
mill license should not be revoked, together with a well-organized and
full-factual analysis of the information the applicant is prepared to
prove in support of his opposition to the Commissioner's proposal. A
request for a hearing may not rest upon mere allegations or denials, but
must set forth specific facts showing there is a genuine and substantial
issue of fact that requires a hearing. When it clearly appears from the
information in the application and from the reasons and factual analysis
in the request for the hearing that no genuine and substantial issue of
fact precludes the refusal to approve the application or the revocation
of approval of the application, the Commissioner will enter an order on
this information, stating his/her findings and conclusions. If a hearing
is requested and is justified by the applicant's response to the notice
of opportunity for a hearing, the issues will be defined, an
Administrative Law Judge will be named, and the Judge shall issue a
written notice of the time and place at which the hearing will commence.
In the case of denial of approval, such time shall be not more than 90
days after the expiration of such 30 days unless the Administrative Law
Judge and the applicant otherwise agree; and, in the case of withdrawal
of approval, such time shall be as soon as practicable.
(d) The hearing will be open to the public; however, if the
Commissioner finds that portions of the application which serve as a
basis for the hearing contain information concerning a method or process
entitled to protection as a trade secret, the part of the hearing
involving such portions will not be public, unless the respondent so
specifies in the appearance.
Sec. 515.31 Procedures for hearings.
Hearings relating to new animal drugs under section 512(m)(3) and
(m)(4) of the Federal Food, Drug, and Cosmetic Act (the act) shall be
governed by part 12 of this chapter.
Subpart D_Judicial Review
Sec. 515.40 Judicial review.
The transcript and record shall be certified by the Commissioner of
Food and Drugs (the Commissioner). In any case in which the Commissioner
enters an order without a hearing under Sec. 314.200(g) of this
chapter, the request(s) for hearing together with the data and
information submitted and the Commissioner's findings and conclusions
shall be included in the record certified by the Commissioner.
PART 516_NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES--Table of Contents
Subpart A_General Provisions
Sec.
516.1 Scope.
516.2 Purpose.
516.3 Definitions.
Subpart B_Designation of a Minor Use or Minor Species New Animal Drug
516.11 Scope of this subpart.
516.12 Purpose.
516.13 Definitions.
516.14 Submission of requests for designation.
516.16 Eligibility to request designation.
516.20 Content and format of a request for MUMS-drug designation.
516.21 Documentation of minor use status.
516.22 Permanent-resident U.S. agent for foreign sponsor.
516.23 Timing of requests for MUMS-drug designation.
516.24 Granting MUMS-drug designation.
516.25 Refusal to grant MUMS-drug designation.
516.26 Amendment to MUMS-drug designation.
516.27 Change in sponsorship.
516.28 Publication of MUMS-drug designations.
516.29 Termination of MUMS-drug designation.
516.30 Annual reports for a MUMS-designated drug.
516.31 Scope of MUMS-drug exclusive marketing rights.
516.34 FDA recognition of exclusive marketing rights.
516.36 Insufficient quantities of MUMS-designated drugs.
[[Page 133]]
516.52 Availability for public disclosure of data and information in
requests.
Subpart C_Index of Legally Marketed Unapproved New Animal Drugs for
Minor Species
516.111 Scope of this subpart.
516.115 Definitions.
516.117 Submission of correspondence under this subpart.
516.119 Permanent-resident U.S. agent for foreign requestors and
holders.
516.121 Meetings.
516.123 Informal conferences regarding agency administrative actions.
516.125 Investigational use of minor species new animal drugs to support
indexing.
516.129 Content and format of a request for determination of eligibility
for indexing.
516.131 Refuse to file a request for determination of eligibility for
indexing.
516.133 Denying a request for determination of eligibility for indexing.
516.135 Granting a request for determination of eligibility for
indexing.
516.137 Notification of decision regarding eligibility for indexing.
516.141 Qualified expert panels.
516.143 Written report.
516.145 Content and format of a request for addition to the index.
516.147 Refuse to file a request for addition to the index.
516.149 Denying a request for addition to the index.
516.151 Granting a request for addition to the index.
516.153 Notification of decision regarding index listing.
516.155 Labeling of indexed drugs.
516.157 Publication of the index and content of an index listing.
516.161 Modifications to indexed drugs.
516.163 Change in ownership of an index file.
516.165 Records and reports.
516.167 Removal from the index.
516.171 Confidentiality of data and information in an index file.
516.498 Crofelemer.
Subpart D [Reserved]
Subpart E_Conditionally Approved New Animal Drugs For Minor Use and
Minor Species
516.812 Enrofloxacin.
516.1684 Paclitaxel.
516.1858 Potassium bromide.
516.2980 Verdinexor.
Authority: 21 U.S.C. 360ccc-1, 360ccc-2, 371.
Source: 72 FR 41017, July 26, 2007, unless otherwise noted.
Subpart A_General Provisions
Sec. 516.1 Scope.
(a) This part implements section 573 of the Federal Food, Drug, and
Cosmetic Act (the act) (21 U.S.C. 360ccc-2) and contains the following
subparts:
(1) Subpart A--General Provisions.
(2) Subpart B--Designation of a Minor Use or Minor Species New
Animal Drug.
(3) Subpart C [Reserved]
(4) Subpart D [Reserved]
(b) References in this part to regulatory sections of the Code of
Federal Regulations are to Chapter I of Title 21, unless otherwise
noted.
Sec. 516.2 Purpose.
This part establishes standards and procedures for implementing
section 573 of the act, including designation of minor use or minor
species new animal drugs and associated exclusive marketing rights.
Sec. 516.3 Definitions.
(a) The definitions and interpretations contained in section 201 of
the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321) apply
to those terms when used in this part.
(b) The following definitions of terms apply to all subparts of part
516:
Active moiety means the molecule or ion, excluding those appended
portions of the molecule that cause the drug to be an ester, salt
(including a salt with hydrogen or coordination bonds), or other
noncovalent derivative (such as a complex, chelate, or clathrate) of the
molecule, responsible for the pharmacological action of the drug
substance.
Functionally superior means that a drug has been shown to provide a
significant therapeutic or physiologic advantage over that provided by a
conditionally-approved or approved MUMS drug, that is otherwise the same
drug, in one or more of the following ways:
(i) The drug has been shown to be more effective, as assessed by
effect on a clinically meaningful endpoint in adequate and well-
controlled clinical trials, than a conditionally approved or approved
MUMS drug, that is otherwise the same drug. Generally, this would
represent the same kind of evidence needed to support a comparative
[[Page 134]]
effectiveness claim for two different drugs; in most cases, direct
comparative clinical trials will be necessary; or
(ii) The drug has been shown to be safer than a conditionally-
approved or approved MUMS drug, that is otherwise the same drug, in a
substantial portion of the target population, for example, by the
elimination of an ingredient or contaminant that is associated with
relatively frequent adverse effects. In some cases, direct comparative
clinical trials will be necessary.
Infrequently, as used in the minor use definition, means a disease
or condition that is uncommon or that occurs only sporadically on an
annualized basis.
Limited geographical areas, as used in the minor use definition,
means regions of the United States distinguished by physical, chemical,
or biological factors that limit the distribution of a disease or
condition.
Major species means cattle, horses, swine, chickens, turkeys, dogs,
and cats.
Minor species means animals, other than humans, that are not major
species.
Minor use means the intended use of a drug in a major species for an
indication that occurs infrequently and in only a small number of
animals or in limited geographical areas and in only a small number of
animals annually.
MUMS drug means a new animal drug, as defined in section 201 of the
act, intended for a minor use or for use in a minor species.
Same dosage form means the same as one of the dosage form categories
specified in the following parts of this chapter:
(i) Part 520: Oral dosage form new animal drugs (excluding use in
animal feeds as specified in part 558 of this chapter).
(ii) Part 522: Implantation or injectable dosage form new animal
drugs.
(iii) Part 524: Ophthalmic and topical dosage form new animal drugs.
(iv) Part 526: Intramammary dosage forms.
(v) Part 529: Certain other dosage form new animal drugs.
(vi) Part 558: New animal drugs for use in animal feeds.
Same drug means a MUMS drug for which designation, indexing, or
conditional approval is sought that meets the following criteria:
(i) If it is a MUMS drug composed of small molecules and contains
the same active moiety as a prior designated, conditionally-approved, or
approved MUMS drug, even if the particular ester or salt (including a
salt with hydrogen or coordination bonds) or other noncovalent
derivative such as a complex, chelate or clathrate is not the same, it
is considered the same drug; except that, if the prior MUMS drug is
conditionally approved or approved and the second MUMS drug is shown to
be functionally superior to the conditionally approved or approved MUMS
drug for the same intended use, it is not considered the same drug.
(ii) If it is a MUMS drug composed of large molecules
(macromolecules) and contains the same principal molecular structural
features (but not necessarily all of the same structural features) as a
prior designated, conditionally approved, or approved MUMS drug, it is
considered the same drug; except that, if the prior MUMS drug is
conditionally approved or approved and the second MUMS drug is shown to
be functionally superior to the conditionally approved or approved MUMS
drug for the same intended use, it is not considered the same drug. This
criterion will be applied as follows to different kinds of
macromolecules:
(A) Two protein drugs would be considered the same if the only
differences in structure between them were due to post-translational
events or infidelity of translation or transcription or were minor
differences in amino acid sequence; other potentially important
differences, such as different glycosylation patterns or different
tertiary structures, would not cause the drugs to be considered
different unless the subsequent drug is shown to be functionally
superior.
(B) Two polysaccharide drugs would be considered the same if they
had identical saccharide repeating units, even if the number of units
were to vary and even if there were postpolymerization modifications,
unless the subsequent drug is shown to be functionally superior.
[[Page 135]]
(C) Two polynucleotide drugs consisting of two or more distinct
nucleotides would be considered the same if they had an identical
sequence of purine and pyrimidine bases (or their derivatives) bound to
an identical sugar backbone (ribose, deoxyribose, or modifications of
these sugars), unless the subsequent drug is shown to be functionally
superior.
(D) Closely related, complex partly definable drugs with similar
pharmacologic intent would be considered the same unless the subsequent
drug is shown to be functionally superior.
Same intended use means an intended use of a MUMS drug, for which
designation, indexing, or conditional approval is sought, that is
determined to be the same as (or not different from) a previously
designated, conditionally approved, or approved intended use of a MUMS
drug. Same intended use is established by comparing two intended uses
and not by simply comparing the specific language by means of which the
intent is established in labeling in accordance with the following
criteria:
(i) Two intended uses are considered the same if one of the intended
uses falls completely within the scope of the other.
(ii) For intended uses associated with diseases or conditions with
multiple causative organisms, two intended uses are not considered the
same when they involve different causative organisms or different
subsets of causative organisms of that disease or condition when the
causative organisms involved can reliably be shown to be clinically
significant causes of the disease or condition.
(iii) Two intended uses of a drug are not considered the same if
they involve different intended species or different definable
subpopulations (including ``production classes'') of a species.
Small number of animals means equal to or less than 50,000 horses;
70,000 dogs; 120,000 cats; 310,000 cattle; 1,450,000 pigs; 14,000,000
turkeys; and 72,000,000 chickens.
Sponsor means the person requesting designation for a MUMS drug who
must be the real party in interest of the development and the intended
or actual production and sales of such drug (in this context, the
sponsor may be an individual, partnership, organization, or
association). Sponsor also means the person responsible for an
investigation of a new animal drug (in this context, the sponsor may be
an individual, partnership, corporation, or Government agency or may be
a manufacturer, scientific institution, or an investigator regularly and
lawfully engaged in the investigation of new animal drugs). Sponsor also
means the person submitting or receiving approval for a new animal drug
application (in this context, the sponsor may be an individual,
partnership, organization, or association). In all contexts, the sponsor
is responsible for compliance with applicable provisions of the act and
regulations.
[72 FR 41017, July 26, 2007, as amended at 74 FR 43050, Aug. 25, 2009;
75 FR 69588, Nov. 15, 2010]
Subpart B_Designation of a Minor Use or Minor Species New Animal Drug
Sec. 516.11 Scope of this subpart.
This subpart implements section 573 of the act. Specifically, this
subpart sets forth the procedures and requirements for submissions to
FDA of requests for designation of a new animal drug for a minor use or
a minor species.
Sec. 516.12 Purpose.
This subpart establishes standards and procedures for determining
eligibility for designation and the associated incentives and benefits
described in section 573 of the act, including a 7-year period of
exclusive marketing rights.
Sec. 516.13 Definitions.
The following definitions of terms apply only in the context of
subpart B of this part:
Director means the Director of the Office of Minor Use and Minor
Species Animal Drug Development of the FDA Center for Veterinary
Medicine.
Intended use means the intended treatment, control or prevention of
a disease or condition, or the intention to affect the structure or
function of
[[Page 136]]
the body of animals within an identified species, subpopulation of a
species, or collection of species.
MUMS-designated drug means a new animal drug, as defined in section
201 of the act, intended for a minor use or for use in a minor species
that has been designated under section 573 of the act.
MUMS-drug exclusive marketing rights or exclusive marketing rights
means that, effective on the date of FDA conditional approval or
approval as stated in the approval letter of an application for a MUMS-
designated drug, no conditional approval or approval will be given to a
subsequent application for the same drug, in the same dosage form, for
the same intended use for 7 years, except as otherwise provided by law
or in this subpart.
Sec. 516.14 Submission of requests for designation.
All correspondence relating to a request for designation of a MUMS
drug must be addressed to the Director of the Office of Minor Use and
Minor Species Animal Drug Development. Submissions not including all
elements specified in Sec. 516.20 will be returned to the sponsor
without review.
Sec. 516.16 Eligibility to request designation.
The person requesting designation must be the sponsor and the real
party in interest of the development and the intended or actual
production and sales of the drug or the permanent-resident U.S. agent
for such a sponsor.
Sec. 516.20 Content and format of a request for MUMS-drug designation.
(a) A sponsor that submits a request for designation of a new animal
drug intended for a minor use or minor species must submit each request
in the form and containing the information required in paragraph (b) of
this section. While a request for designation may involve multiple
intended uses, each request for designation must constitute a separate
submission. A sponsor may request MUMS-drug designation of a previously
unapproved drug, or a new intended use or dosage form for an already
conditionally approved or approved drug. Only one sponsor may receive
MUMS-drug designation of the same drug, in the same dosage form, for the
same intended use.
(b) A sponsor must submit two copies of a completed, dated, and
signed request for designation that contains the following information:
(1) A request for designation of a new animal drug for a minor use
or use in a minor species, which must be specific.
(2) The name and address of the sponsor; the name of the sponsor's
primary contact person and/or permanent-resident U.S. agent including
title, address, and telephone number; the established name (and
proprietary name, if any) of the active pharmaceutical ingredient of the
drug; and the name and address of the source of the active
pharmaceutical ingredient of the drug.
(3) A description of the proposed intended use for which the drug is
being or will be investigated.
(4) A description of the drug and dosage form.
(5) A discussion of the scientific rationale for the intended use of
the drug; specific reference, including date(s) of submission, to all
data from nonclinical laboratory studies, clinical investigations,
copies of pertinent unpublished and published papers, and other relevant
data that are available to the sponsor, whether positive, negative, or
inconclusive.
(6) A specific description of the product development plan for the
drug, its dosage form, and its intended use.
(7) If the drug is intended for a minor use in a major species,
documentation in accordance with Sec. 516.21, with appended
authoritative references, to demonstrate that such use is a minor use.
(8) A statement that the sponsor submitting the request is the real
party in interest of the development and the intended or actual
production and sales of the product.
(9) A statement that the sponsor acknowledges that, upon granting a
request for MUMS designation, FDA will make information regarding the
designation publicly available as specified in Sec. 516.28.
[72 FR 41017, July 26, 2007, as amended at 75 FR 69588, Nov. 15, 2010;
77 FR 18685, Mar. 28, 2012]
[[Page 137]]
Sec. 516.21 Documentation of minor use status.
So that FDA can determine whether a drug qualifies for MUMS-drug
designation as a minor use in a major species under section 573 of the
act, the sponsor shall include in its request to FDA for MUMS-drug
designation under Sec. 516.20 documentation demonstrating that the use
is limited to a small number of animals (annualized). This documentation
must include the following information:
(a) The estimated total number of animals to which the drug could
potentially be administered on an annual basis for the treatment,
control, or prevention of the disease or condition for which the drug is
being developed, including animals administered the drug as part of herd
or flock treatment, together with a list of the sources (including dates
of information provided and literature citations) for the estimate.
(b) The estimated total number of animals referred to in paragraph
(a) of this section may be further reduced to only a subset of the
estimated total number of animals if administration of the drug is only
medically justified for this subset. To establish this, requestors must
demonstrate that administration of the drug to animals subject to the
disease or condition for which the drug is being developed other than
the subset is not medically justified. The sponsor must also include a
list of the sources (including dates of information provided and
literature citations) for the justification that administration of the
drug to animals other than the targeted subset is medically
inappropriate.
[72 FR 41017, July 26, 2007, as amended at 74 FR 43050, Aug. 25, 2009]
Sec. 516.22 Permanent-resident U.S. agent for foreign sponsor.
Every foreign sponsor that seeks MUMS-drug designation shall name a
permanent resident of the United States as the sponsor's agent upon whom
service of all processes, notices, orders, decisions, requirements, and
other communications may be made on behalf of the sponsor. Notifications
of changes in such agents or changes of address of agents should
preferably be provided in advance, but not later than 60 days after the
effective date of such changes. The permanent-resident U.S. agent may be
an individual, firm, or domestic corporation and may represent any
number of sponsors. The name and address of the permanent-resident U.S.
agent shall be provided to the Director of the Office of Minor Use and
Minor Species Animal Drug Development.
Sec. 516.23 Timing of requests for MUMS-drug designation.
A sponsor may request MUMS-drug designation at any time in the drug
development process prior to the submission of an application for either
conditional approval or approval of the MUMS drug for which designation
is being requested.
Sec. 516.24 Granting MUMS-drug designation.
(a) FDA may grant the request for MUMS-drug designation if none of
the reasons described in Sec. 516.25 for refusal to grant such a
request apply.
(b) When a request for MUMS-drug designation is granted, FDA will
notify the sponsor in writing and will give public notice of the MUMS-
drug designation in accordance with Sec. 516.28.
Sec. 516.25 Refusal to grant MUMS-drug designation.
(a) FDA will refuse to grant a request for MUMS-drug designation if
any of the following reasons apply:
(1) The drug is not intended for use in a minor species or FDA
determines that there is insufficient evidence to demonstrate that the
drug is intended for a minor use in a major species.
(2) The drug is the same drug in the same dosage form for the same
intended use as one that already has a MUMS-drug designation but has not
yet been conditionally approved or approved.
(3) The drug is the same drug in the same dosage form for the same
intended use as one that is already conditionally approved or approved.
A drug that FDA has found to be functionally superior is not considered
the same drug as an already conditionally approved or approved drug even
if it is
[[Page 138]]
otherwise the same drug in the same dosage form for the same intended
use.
(4) The sponsor has failed to provide:
(i) A credible scientific rationale in support of the intended use,
(ii) Sufficient information about the product development plan for
the drug, its dosage form, and its intended use to establish that
adherence to the plan can lead to successful drug development in a
timely manner, and
(iii) Any other information required under Sec. 516.20.
(b) FDA may refuse to grant a request for MUMS-drug designation if
the request for designation contains an untrue statement of material
fact or omits material information.
Sec. 516.26 Amendment to MUMS-drug designation.
(a) At any time prior to conditional approval or approval of an
application for a MUMS-designated drug, the sponsor may apply for an
amendment to the designated intended use if the proposed change is due
to new and unexpected findings in research on the drug, information
arising from FDA recommendations, or other unforeseen developments.
(b) FDA will grant the amendment if it finds:
(1) That the initial designation request was made in good faith;
(2) That the amendment is intended to make the MUMS-drug designated
intended use conform to the results of new and unexpected findings in
research on the drug, information arising from FDA recommendations, or
other unforeseen developments; and
(3) In the case of a minor use, that as of the date of the
submission of the amendment request, the amendment would not result in
the intended use of the drug no longer being considered a minor use.
Sec. 516.27 Change in sponsorship.
(a) A sponsor may transfer sponsorship of a MUMS-designated drug to
another person. A change of sponsorship will also transfer the
designation status of the drug which will remain in effect for the new
sponsor subject to the same conditions applicable to the former sponsor
provided that at the time of a potential transfer, the new and former
sponsors submit the following information in writing and obtain
permission from FDA:
(1) The former sponsor shall submit a letter to FDA that documents
the transfer of sponsorship of the MUMS-designated drug. This letter
shall specify the date of the transfer. The former sponsor shall also
certify in writing to FDA that a complete copy of the request for MUMS-
drug designation, including any amendments to the request, and
correspondence relevant to the MUMS-drug designation, has been provided
to the new sponsor.
(2) The new sponsor shall submit a letter or other document
containing the following information:
(i) A statement accepting the MUMS-drug designated file or
application;
(ii) The date that the change in sponsorship is intended to be
effective;
(iii) A statement that the new sponsor has a complete copy of the
request for MUMS-drug designation, including any amendments to the
request and any correspondence relevant to the MUMS-drug designation;
(iv) A statement that the new sponsor understands and accepts the
responsibilities of a sponsor of a MUMS-designated drug established
elsewhere in this subpart;
(v) The name and address of a new primary contact person or
permanent resident U.S. agent; and
(vi) Evidence that the new sponsor is capable of actively pursuing
approval with due diligence.
(b) No sponsor may relieve itself of responsibilities under the act
or under this subpart by assigning rights to another person without:
(1) Assuring that the new sponsor will carry out such
responsibilities; and
(2) Obtaining prior permission from FDA.
Sec. 516.28 Publication of MUMS-drug designations.
FDA will periodically update a publicly available list of MUMS-
designated drugs. This list will be placed on file at the FDA Division
of Dockets Management, and will contain the following information for
each MUMS-designated drug:
[[Page 139]]
(a) The name and address of the sponsor;
(b) The established name and trade name, if any, of the drug;
(c) The dosage form of the drug;
(d) The species and the proposed intended use for which MUMS-drug
designation was granted; and
(e) The date designation was granted.
Sec. 516.29 Termination of MUMS-drug designation.
(a) The sponsor of a MUMS-designated drug must notify FDA of any
decision to discontinue active pursuit of conditional approval or
approval of such MUMS drug. FDA must terminate the designation upon such
notification.
(b) A conditionally-approved or approved MUMS-designated drug
sponsor must notify FDA at least 1 year before it intends to discontinue
the manufacture of such MUMS drug. FDA must terminate designation upon
such notification.
(c) MUMS designation shall terminate upon the expiration of any
applicable period of exclusive marketing rights under this subpart.
(d) FDA may terminate designation if it independently determines
that the sponsor is not actively pursuing conditional approval or
approval with due diligence. At a minimum, due diligence must be
demonstrated by:
(1) Submission of annual progress reports in a timely manner in
accordance with Sec. 516.30 that demonstrate that the sponsor is
progressing in accordance with the drug development plan submitted to
the agency under Sec. 516.20 and
(2) Compliance with all applicable requirements of part 511 of this
chapter.
(e) Designation of a conditionally approved or approved MUMS-
designated drug and the associated exclusive marketing rights may be
terminated if the sponsor is unable to provide sufficient quantities of
the drug to meet the needs for which it is designated.
(f) FDA may also terminate MUMS-drug designation for any drug if the
agency finds that:
(1) The request for designation contained an untrue statement of
material fact; or
(2) The request for designation omitted material information
required by this subpart; or
(3) FDA subsequently finds that the drug in fact had not been
eligible for MUMS-drug designation at the time of submission of the
request;
(4) The same drug, in the same dosage form, for the same intended
use becomes conditionally approved or approved for another sponsor; or
(5) FDA withdraws the conditional approval or approval of the
application for the new animal drug.
(g) For a conditionally approved or approved drug, termination of
MUMS-drug designation also terminates the sponsor's exclusive marketing
rights for the drug but does not withdraw the conditional approval or
approval of the drug's application.
(h) Where a drug has been MUMS-designated for a minor use in a major
species, its designation will not be terminated on the grounds that the
number of animals to which the drug could potentially be administered on
an annual basis for the treatment, control, or prevention of the disease
or condition for which the drug is being developed, including animals
administered the drug as part of herd or flock treatment, subsequently
increases.
(i) When a MUMS-drug designation is terminated, FDA will notify the
sponsor in writing and will give public notice of the termination of the
MUMS-drug designation.
Sec. 516.30 Annual reports for a MUMS-designated drug.
Within 14 months after the date on which a MUMS drug is granted
designation and annually thereafter until approval, the sponsor of a
MUMS-designated drug shall submit a brief progress report on the drug to
the investigational new animal drug file addressed to the Director of
the Office of Minor Use and Minor Species Animal Drug Development that
includes the following information:
(a) A short account of the progress of drug development including a
description of studies initiated, ongoing, and completed, and a short
summary of the status or results of such studies;
(b) A description of the investigational plan for the coming year,
as well as any anticipated difficulties in development, testing, and
marketing; and
[[Page 140]]
(c) A brief discussion of any changes that may affect the MUMS-
designated drug status of the product. For example, situations in which
testing data demonstrate that the proposed intended use is inappropriate
due to unexpected issues of safety or effectiveness.
Sec. 516.31 Scope of MUMS-drug exclusive marketing rights.
(a) After conditional approval or approval of an application for a
MUMS-designated drug in the dosage form and for the intended use for
which MUMS-drug designation has been granted, FDA will not conditionally
approve or approve another application or abbreviated application for
the same drug in the same dosage form for the same intended use before
the expiration of 7 years after the date of conditional approval or
approval as stated in the approval letter from FDA, except that such an
application can be conditionally approved or approved sooner if, and at
such time as, any of the following occurs:
(1) FDA terminates the MUMS-drug designation and associated
exclusive marketing rights under Sec. 516.29; or
(2) FDA withdraws the conditional approval or approval of the
application for the drug for any reason; or
(3) The sponsor with exclusive marketing rights provides written
consent to FDA to conditionally approve or approve another application
before the expiration of 7 years; or
(4) The sponsor fails to assure a sufficient quantity of the drug in
accordance with section 573 of the act and Sec. 516.36.
(b) If an application for a MUMS drug cannot be approved until the
expiration of the period of exclusive marketing of a MUMS-designated
drug, FDA will so notify the sponsor in writing.
Sec. 516.34 FDA recognition of exclusive marketing rights.
(a) FDA will send the sponsor (or the permanent-resident U.S. agent,
if applicable) timely written notice recognizing exclusive marketing
rights when an application for a MUMS-designated drug has been
conditionally approved or approved. The written notice will inform the
sponsor of the requirements for maintaining MUMS-designated drug
exclusive marketing rights for the full 7-year term. This notice will
generally be contained in the letter conditionally approving or
approving the application.
(b) When an application is conditionally approved or approved for a
MUMS-designated drug that qualifies for exclusive marketing rights, FDA
will publish this information in the Federal Register at the time of the
conditional approval or approval. This notice will generally be
contained in the notice of conditional approval or approval of the
application.
Sec. 516.36 Insufficient quantities of MUMS-designated drugs.
(a) Under section 573 of the act, whenever FDA has reason to believe
that sufficient quantities of a conditionally-approved or approved,
MUMS-designated drug to meet the needs for which the drug was designated
cannot be assured by the sponsor, FDA will so notify the sponsor of this
possible insufficiency and will offer the sponsor the following options,
one of which must be exercised by a time that FDA specifies:
(1) Provide FDA information and data regarding how the sponsor can
assure the availability of sufficient quantities of the MUMS-designated
drug within a reasonable time to meet the needs for which the drug was
designated; or
(2) Provide FDA in writing the sponsor's consent for the conditional
approval or approval of other applications for the same drug before the
expiration of the 7-year period of exclusive marketing rights.
(b) If, within the time that FDA specifies, the sponsor fails to
consent to the conditional approval or approval of other applications
and if FDA finds that the sponsor has not shown that it can assure the
availability of sufficient quantities of the MUMS-designated drug to
meet the needs for which the drug was designated, FDA will issue a
written order terminating designation of the MUMS drug and the
associated exclusive marketing rights. This order will state FDA's
findings and conclusions and will constitute final agency
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action. An order terminating designation and associated exclusive
marketing rights may issue whether or not there are other sponsors that
can assure the availability of alternative sources of supply. Such an
order will not withdraw the conditional approval or approval of an
application. Once terminated under this section, neither designation,
nor exclusive marketing rights may be reinstated.
Sec. 516.52 Availability for public disclosure of data
and information in requests.
(a) FDA will not publicly disclose the existence of a request for
MUMS-drug designation under section 573 of the act prior to final FDA
action on the request unless the existence of the request has been
previously publicly disclosed or acknowledged.
(b) Whether or not the existence of a pending request for
designation has been publicly disclosed or acknowledged, no data or
information in the request are available for public disclosure prior to
final FDA action on the request.
(c) Except as provided in paragraph (d) of this section, upon final
FDA action on a request for designation, the public availability of data
and information in the request will be determined in accordance with
part 20 of this chapter and other applicable statutes and regulations.
(d) In accordance with Sec. 516.28, FDA will make a cumulative list
of all MUMS-drug designations available to the public and update such
list periodically. In accordance with Sec. 516.29, FDA will give public
notice of the termination of all MUMS-drug designations.
Subpart C_Index of Legally Marketed Unapproved New Animal Drugs for
Minor Species
Source: 72 FR 69121, Dec. 6, 2007, unless otherwise noted.
Sec. 516.111 Scope of this subpart.
This subpart implements section 572 of the act and provides
standards and procedures to establish an index of legally marketed
unapproved new animal drugs. This subpart applies only to minor species
and not to minor use in major species. This index is only available for
new animal drugs intended for use in a minor species for which there is
a reasonable certainty that the animal or edible products from the
animal will not be consumed by humans or food-producing animals and for
new animal drugs intended for use only in a hatchery, tank, pond, or
other similar contained man-made structure in an early, nonfood life
stage of a food-producing minor species, where safety for humans is
demonstrated in accordance with the standard of section 512(d) of the
act (including, for an antimicrobial new animal drug, with respect to
antimicrobial resistance). The index shall not include a new animal drug
that is contained in, or a product of, a transgenic animal. Among its
topics, this subpart sets forth the standards and procedures for:
(a) Investigational exemptions for indexing purposes;
(b) Submissions to FDA of requests for determination of eligibility
of a new animal drug for indexing;
(c) Establishment and operation of expert panels;
(d) Submissions to FDA of requests for addition of a new animal drug
to the index;
(e) Modifications to index listings;
(f) Publication of the index; and
(g) Records and reports.
Sec. 516.115 Definitions.
(a) The following definitions of terms apply only in the context of
subpart C of this part:
Director OMUMS means the Director of the Office of Minor Use and
Minor Species Animal Drug Development of the FDA Center for Veterinary
Medicine.
Holder means the requestor of an index listing after the request is
granted and the new animal drug is added to the index.
Index means FDA's list of legally marketed unapproved new animal
drugs for minor species.
Intended use has the same meaning as that given in Sec. 516.13 of
this chapter.
Qualified expert panel means a panel that is composed of experts
qualified by scientific training and experience to evaluate the target
animal safety and
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effectiveness of a new animal drug under consideration for indexing.
Requestor means the person making a request for determination of
eligibility for indexing or a request for addition to the index.
Transgenic animal means an animal whose genome contains a nucleotide
sequence that has been intentionally modified in vitro, and the progeny
of such an animal, provided that the term `transgenic animal' does not
include an animal of which the nucleotide sequence of the genome has
been modified solely by selective breeding.
(b) The definitions of the following terms are given in Sec. 514.3
of this chapter:
Adverse drug experience.
Product defect/manufacturing defect.
Serious adverse drug experience.
Unexpected adverse drug experience.
(c) The definitions of the following terms are given in Sec. 516.3
of this chapter:
Same dosage form.
Same drug.
Same intended use.
Sec. 516.117 Submission of correspondence under this subpart.
Unless directed otherwise by FDA, all correspondence relating to any
aspect of the new animal drug indexing process described in this subpart
must be addressed to the Director, OMUMS. The initial correspondence for
a particular index listing should include the name and address of the
authorized contact person. Notifications of changes in such person or
changes of address of such person should be provided in a timely manner.
Sec. 516.119 Permanent-resident U.S. agent for foreign requestors
and holders.
Every foreign requestor and holder shall name a permanent resident
of the United States as their agent upon whom service of all processes,
notices, orders, decisions, requirements, and other communications may
be made on behalf of the requestor or holder. Notifications of changes
in such agents or changes of address of agents should preferably be
provided in advance, but not later than 60 days after the effective date
of such changes. The permanent resident U.S. agent may be an individual,
firm, or domestic corporation and may represent any number of requestors
or holders. The name and address of the permanent-resident U.S. agent
shall be submitted to the Director, OMUMS, and included in the index
file.
Sec. 516.121 Meetings.
(a) A requestor or potential requestor is entitled to one or more
meetings to discuss the requirements for indexing a new animal drug.
(b) Requests for such meetings should be in writing, be addressed to
the Director, OMUMS, specify the participants attending on behalf of the
requestor or potential requestor, and contain a proposed agenda for the
meeting.
(c) Within 30 days of receiving a request for a meeting, FDA will
attempt to schedule the meeting at a time agreeable to both FDA and the
person making the request.
Sec. 516.123 Informal conferences regarding agency administrative actions.
(a) Should FDA make an initial decision denying a request for
determination of eligibility for indexing, terminating an
investigational exemption, determining that a qualified expert panel
does not meet the selection criteria, denying a request for addition to
the index, or removing a new animal drug from the index, FDA will give
written notice that specifies the grounds for the initial decision and
provides an opportunity for an informal conference for review of the
decision.
(b) The written notice will include information for scheduling the
informal conference and state that a written request for a conference
must be made within 60 days of the date FDA sends its notice.
(c) Within 45 days of receiving a request for an informal
conference, FDA will schedule and hold the informal conference at a time
agreeable to both FDA and the person making the request.
(d) Such an informal conference will be conducted by a presiding
officer who will be the Director of the Center for
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Veterinary Medicine or his or her designee, excluding the Director of
the Office of Minor Use and Minor Species Animal Drug Development and
other persons significantly involved in the initial decision.
(e) The person requesting an informal conference must provide a
written response to FDA's initial decision at least 2 weeks prior to the
date of the scheduled meeting. Generally, this written response would be
attached to the request for an informal conference. At the option of the
person requesting an informal conference, such written response to FDA's
initial decision may act in lieu of a face-to-face meeting. In this
case, the informal conference will consist of a review by the presiding
officer of the submitted written response.
(f) The purpose of an informal conference is to discuss scientific
and factual issues. It will involve a discussion of FDA's initial
decision and any written response to that decision.
(g) Internal agency review of a decision must be based on the
information in the administrative file. If the person requesting an
informal conference presents new information not in the file, the matter
will be returned to the appropriate lower level in the agency for
reevaluation based on the new information.
(h) Informal conferences under this part are not subject to the
separation of functions rules in Sec. 10.55 of this chapter.
(i) The rules of evidence do not apply to informal conferences. No
motions or objections relating to the admissibility of information and
views will be made or considered, but any party to the conference may
comment upon or rebut all such data, information and views.
(j) [Reserved]
(k) The presiding officer will prepare a written report regarding
the subject of the informal conference that states and describes the
basis for his or her findings. Whenever time permits, the parties to the
informal conference will have 30 days to review and comment on the
report.
(l) The administrative record of the informal conference will
consist of:
(1) The notice providing an opportunity for an informal conference
and the written response to the notice.
(2) All written information and views submitted to the presiding
officer at the conference or, at the discretion of the presiding
officer, thereafter.
(3) The presiding officer's written report.
(4) All correspondence and memoranda of any and all meetings between
the participants and the presiding officer.
(m) The administrative record of the informal conference is closed
to the submission of information at the close of the conference, unless
the presiding officer specifically permits additional time for further
submission.
(n) The administrative record of the informal conference specified
herein constitutes the exclusive record for decision.
Sec. 516.125 Investigational use of minor species new animal drugs
to support indexing.
(a) The investigational use of a new animal drug or animal feed
bearing or containing a new animal drug intended solely for
investigational use in minor species shall meet the requirements of part
511 of this chapter if the investigational use is for the purpose of:
(1) Demonstrating human food safety under section 572(a)(1)(B) of
the act;
(2) Demonstrating safety with respect to individuals exposed to the
new animal drug through its manufacture and use under section
572(c)(1)(F) of the act;
(3) Conducting an environmental assessment under section
572(c)(1)(E) of the act; or
(4) Obtaining approval of a new animal drug application or
abbreviated new animal drug application under section 512(b) of the act.
(b) Correspondence and information associated with investigations
described in paragraph (a) of this section shall not be sent to the
Director, OMUMS, but shall be submitted to FDA in accordance with the
provisions of part 511 of this chapter.
(c) The investigational use of a new animal drug or animal feed
bearing or containing a new animal drug intended solely for
investigational use in minor
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species, other than for an investigational use described in paragraph
(a) of this section, shall meet the requirements of this section. For
such investigations, all provisions of part 511 of this chapter apply
with the following modifications:
(1) Under Sec. 511.1(a)(1) of this chapter, the label statement is
as follows:
``Caution. Contains a new animal drug for investigational use only
in laboratory animals or for tests in vitro in support of index listing.
Not for use in humans.''
(2) Under Sec. 511.1(b)(1) of this chapter, the label statement is
as follows:
``Caution. Contains a new animal drug for use only in
investigational animals in clinical trials in support of index listing.
Not for use in humans. Edible products of investigational animals are
not to be used for food for humans or other animals unless authorization
has been granted by the U.S. Food and Drug Administration or by the U.S.
Department of Agriculture.''
(3) Under Sec. 511.1(b)(4) of this chapter, the notice is titled
``Notice of Claimed Investigational Exemption for a New Animal Drug for
Index Listing'' and is submitted in duplicate to the Director, OMUMS.
(4) Under Sec. 511.1(c)(3) of this chapter, if an investigator is
determined to be ineligible to receive new animal drugs, each ``Notice
of Claimed Investigational Exemption for a New Animal Drug for Index
Listing'' and each request for indexing shall be examined with respect
to the reliability of information submitted by the investigator.
(5) Under Sec. 511.1(c)(4) and (d)(2) of this chapter, with respect
to termination of exemptions, the sponsor of an investigation shall not
be granted an opportunity for a regulatory hearing before FDA pursuant
to part 16 of this chapter. Instead, the sponsor shall have an
opportunity for an informal conference as described in Sec. 516.123.
(6) Under Sec. 511.1(c)(5) of this chapter, if the Commissioner of
Food and Drugs determines, after the unreliable data submitted by the
investigator are eliminated from consideration, that the data remaining
are such that a request for addition to the index would have been
denied, FDA will remove the new animal drug from the index in accordance
with Sec. 516.167.
(d) The investigational use of a new animal drug or animal feed
bearing or containing a new animal drug subject to paragraph (c) of this
section shall not be subject to the good laboratory practice
requirements in part 58 of this chapter.
(e) Correspondence and information associated with investigations
described in paragraph (c) of this section shall be sent to the
Director, OMUMS, in accordance with the provisions of this section.
Sec. 516.129 Content and format of a request for determination
of eligibility for indexing.
(a) Each request for determination of eligibility:
(1) May involve only one drug (or one combination of drugs) in one
dosage form;
(2) May not involve a new animal drug that is contained in or a
product of a transgenic animal;
(3) May not involve the same drug in the same dosage form for the
same intended use as a drug that is already approved or conditionally
approved; and
(4) Must be submitted separately.
(b) A request for determination of eligibility for indexing may
involve multiple intended uses and/or multiple minor species. However,
if a request for determination of eligibility for indexing that contains
multiple intended uses and/or multiple minor species cannot be granted
in any part, the entire request will be denied.
(c) A requestor must submit two copies of a dated request signed by
the authorized contact person for determination of eligibility for
indexing that contains the following:
(1) Identification of the minor species or groups of minor species
for which the new animal drug is intended;
(2) Information regarding drug components and composition;
(3) A statement of the intended use(s) of the new animal drug in the
identified minor species or groups of minor species;
(4) A statement of the proposed conditions of use associated with
the stated intended use(s) of the new animal drug, including the
proposed dosage,
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route of administration, contraindications, warnings, and any other
significant limitations associated with the intended use(s) of the new
animal drug;
(5) A brief discussion of the need for the new animal drug for the
intended use(s);
(6) An estimate of the anticipated annual distribution of the new
animal drug, in terms of the total quantity of active ingredient, after
indexing;
(7) Information to establish that the new animal drug is intended
for use:
(i) In a minor species for which there is a reasonable certainty
that the animal or edible products from the animal will not be consumed
by humans or food-producing animals; or
(ii) In a hatchery, tank, pond, or other similar contained man-made
structure in (which includes on) an early, non-food life stage of a
food-producing minor species, and information to demonstrate food safety
in accordance with the standards of section 512(d) of the act and Sec.
514.111 of this chapter (including, for an antimicrobial new animal
drug, with respect to antimicrobial resistance);
(8) A description of the methods used in, and the facilities and
controls used for, the manufacture, processing and packing of the new
animal drug sufficient to demonstrate that the requestor has established
appropriate specifications for the manufacture and control of the new
animal drug and that the requestor has an understanding of current good
manufacturing practices;
(9) Either a claim for categorical exclusion under Sec. 25.30 or
Sec. 25.33 of this chapter or an environmental assessment under Sec.
25.40 of this chapter;
(10) Information sufficient to support the conclusion that the new
animal drug is safe under section 512(d) of the act with respect to
individuals exposed to the new animal drug through its manufacture and
use; and
(11) The name and address of the contact person or permanent-
resident U.S. agent.
Sec. 516.131 Refuse to file a request for determination
of eligibility for indexing.
(a) If a request for determination of eligibility for indexing
contains all of the information required by Sec. 516.129, FDA shall
file it, and the filing date shall be the date FDA receives the request.
(b) If a request for a determination of eligibility lacks any of the
information required by Sec. 516.129, FDA will not file it, but will
inform the requestor in writing within 30 days of receiving the request
as to what information is lacking.