[Title 21 CFR ]
[Code of Federal Regulations (annual edition) - April 1, 2015 Edition]
[From the U.S. Government Publishing Office]
[[Page i]]
Title 21
Food and Drugs
________________________
Parts 500 to 599
Revised as of April 1, 2015
Containing a codification of documents of general
applicability and future effect
As of April 1, 2015
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........................ 541
Alphabetical List of Agencies Appearing in the CFR...... 561
List of CFR Sections Affected........................... 571
[[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
regulation. Each title is divided into chapters which usually bear the
name of the issuing agency. Each chapter is further subdivided into
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
The contents of the Federal Register are required to be judicially
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HOW TO USE THE CODE OF FEDERAL REGULATIONS
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To determine whether a Code volume has been amended since its
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EFFECTIVE AND EXPIRATION DATES
Each volume of the Code contains amendments published in the Federal
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OMB CONTROL NUMBERS
The Paperwork Reduction Act of 1980 (Pub. L. 96-511) requires
Federal agencies to display an OMB control number with their information
collection request.
[[Page vi]]
Many agencies have begun publishing numerous OMB control numbers as
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PAST PROVISIONS OF THE CODE
Provisions of the Code that are no longer in force and effect as of
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for 1949-1963, 1964-1972, 1973-1985, and 1986-2000.
``[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
necessary to afford fairness and uniformity in the administrative
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(c) The incorporating document is drafted and submitted for
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What if the material incorporated by reference cannot be found? If
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alphabetical list of agencies publishing in the CFR are also included in
this volume.
[[Page vii]]
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Amy P. Bunk,
Acting Director,
Office of the Federal Register.
April 1, 2015.
[[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, 2015.
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............................ 32
509 Unavoidable contaminants in animal food and
food-packaging material................. 34
510 New animal drugs............................ 38
511 New animal drugs for investigational use.... 48
514 New animal drug applications................ 53
515 Medicated feed mill license................. 88
516 New animal drugs for minor use and minor
species................................. 93
520 Oral dosage form new animal drugs........... 117
522 Implantation or injectable dosage form new
animal drugs............................ 230
524 Ophthalmic and topical dosage form new
animal drugs............................ 310
526 Intramammary dosage form new animal drugs... 334
528 New animal drugs in genetically engineered
animals................................. 340
529 Certain other dosage form new animal drugs.. 340
530 Extralabel drug use in animals.............. 347
556 Tolerances for residues of new animal drugs
in food................................. 353
558 New animal drugs for use in animal feeds.... 367
564
[Reserved]
570 Food additives.............................. 472
571 Food additive petitions..................... 480
573 Food additives permitted in feed and
drinking water of animals............... 485
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579 Irradiation in the production, processing,
and handling of animal feed and pet food 505
582 Substances generally recognized as safe..... 506
584 Food substances affirmed as generally
recognized as safe in feed and drinking
water of animals........................ 531
589 Substances prohibited from use in animal
food or feed............................ 532
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.
The provisions of part 113 of this chapter shall apply to the
manufacture, processing or packing of low-acid foods in hermetically
sealed containers, and intended for use as food for animals.
[61 FR 37681, July 19, 1996]
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
assistance in the diagnosis, treatment, and control of parasitism.
[[Page 6]]
(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. 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 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 act for risks other than cancer.
(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]
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.
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 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
[[Page 13]]
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.
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]
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 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
[[Page 14]]
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.
(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]
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, and color additive petitions 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:
(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.
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 as determined by a
method entitled ``Method of Analysis: N-methyl-2-pyrrolidone,''
September 26, 2011, Center for Veterinary Medicine, Food and Drug
Administration, which is incorporated by reference with the approval of
the Director of the Federal Register under 5 U.S.C. 522(a) and 1 CFR
part 51. You may obtain a copy of the method from the Communications
Staff (HFV-
[[Page 15]]
12), Center for Veterinary Medicine, Food and Drug Administration, 7519
Standish Pl., Rockville, MD 20855, 240-276-9120; or go to http://
www.fda.gov/AboutFDA/CentersOffices/OfficeofFoods/CVM/
CVMFOIAElectronicReadingRoom/default.htm. You may inspect a copy at the
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, (301) 827-6860,
between 9 a.m. and 4 p.m., Monday through Friday or at the National
Archives and Records Administration (NARA). For information on the
availability of this material at NARA, call (202) 741-6030, or go to:
http://www.archives.gov/federal-register/cfr/ibr-locations.html.
(b) Related conditions of use. See Sec. Sec. 522.814 and 522.955 of
this chapter.
[76 FR 72618, Nov. 25, 2011, as amended at 77 FR 9528, Feb. 17, 2012]
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.
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
[[Page 16]]
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 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.
[[Page 17]]
(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,
(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
[[Page 18]]
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:
(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,
[[Page 19]]
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 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
[[Page 20]]
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, 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.
[[Page 21]]
(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.
(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
[[Page 22]]
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.
(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.
[[Page 23]]
(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:
(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
[[Page 24]]
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 (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:
[[Page 25]]
(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 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
[[Page 26]]
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.
(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
[[Page 27]]
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 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
[[Page 28]]
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.
(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
[[Page 29]]
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.
(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).
[[Page 30]]
(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).
(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
[[Page 31]]
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
(except the requirement that food falling below the applicable standard
of fill of container shall bear the general statement of substandard
fill specified in Sec. 564.14(b) of this chapter), the mislabeled food
product, including any food product that fails to bear the general
statement of substandard fill specified in Sec. 564.14(b) of this
chapter, 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 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]
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
[[Page 32]]
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.
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
[[Page 33]]
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.
(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]
[[Page 34]]
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.
(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
[[Page 35]]
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.
(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
[[Page 36]]
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]
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:
[[Page 37]]
(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 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
[[Page 38]]
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 [Reserved]
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,
[[Page 39]]
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 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.
[[Page 40]]
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]
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
[[Page 41]]
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 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
[[Page 42]]
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 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 [Reserved]
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
[[Page 43]]
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, 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.
[[Page 44]]
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 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.
[[Page 45]]
(c) The names, addresses, and drug labeler codes of sponsors of
approved new animal drug applications are as follows:
(1) Alphabetical Listing of Sponsors
------------------------------------------------------------------------
Drug labeler
Firm name and address code
------------------------------------------------------------------------
A & G Pharmaceuticals, Inc., 1030 West Commodore Blvd., 057699
Jackson, NJ 08527......................................
AB Science, 3 Avenue George V, 75008 Paris, France...... 052913
Abbott Laboratories, North Chicago, IL 60064............ 000044
Accord Healthcare, Inc., 1009 Slater Rd., suite 210-B, 016729
Durham, NC 27703.......................................
ADM Alliance Nutrition, Inc., 1000 North 30th St., 012286
Quincy, 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.............................
Alaco, Inc., 1500 North Wilmot Rd., suite 290-C, Tucson, 064146
AZ 85712...............................................
American Pharmaceuticals and Cosmetics, Inc., 1401 Joel 065531
East Rd., Fort Worth, TX 76140.........................
Anika Therapeutics Inc., 236 West Cummings Park, Woburn, 060865
MA 01801...............................................
Ark Sciences, Inc., 1101 East 33rd St., suite B304, 076175
Baltimore, MD 21218....................................
Aurora Pharmaceutical, LLC, 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
Baxter Healthcare Corp., One Baxter Pkwy., Deerfield, IL 010019
60015..................................................
Bayer HealthCare LLC, Animal Health Division, P.O. Box 000859
390, Shawnee Mission, KS 66201.........................
Belcher Pharmaceuticals, LLC, 6911 Bryan Dairy Rd., 062250
Largo, FL 33777........................................
Boehringer Ingelheim Vetmedica, Inc., 2621 North Belt 000010
Highway, St. Joseph, MO 64506-2002.....................
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.................................
ConAgra Pet Products Co., 3902 Leavenworth St., Omaha, 021091
NE 68105...............................................
Contemporary Products, Inc., 3788 Elm Springs Rd., 055462
Springdale, AR 72764-6067..............................
Cooperative Research Farms, Box 69, Charlotteville, NY 051267
12036..................................................
Cross Vetpharm Group Ltd., Broomhill Rd., Tallaght, 061623
Dublin 24, Ireland.....................................
Dechra, Ltd., Snaygill Industrial Estate, Keighley Rd., 043264
Skipton, North Yorkshire, BD23 2RW, United Kingdom.....
ECO LLC, 344 Nassau St., Princeton, NJ 08540............ 066916
Elanco Animal Health, A Division of Eli Lilly & Co., 000986
Lilly Corporate Center, Indianapolis, IN 46285.........
Farnam Companies, Inc., 301 West Osborn, Phoenix, AZ 017135
85013-3928.............................................
First Priority, Inc., 1590 Todd Farm Dr., Elgin, IL 058829
60123..................................................
Fleming Laboratories, Inc., P.O. Box 34384, Charlotte, 015565
NC 28234...............................................
Fougera Pharmaceuticals, Inc., P.O. Box 2006, 60 Baylis 025463
Rd., Melville, NY 11747................................
G. C. Hanford Manufacturing Co., P.O. Box 1017, 010515
Syracuse, NY 13201.....................................
GTC Biotherapeutics, Inc., 175 Crossing Blvd., 042976
Framingham, MA 01702...................................
Halocarbon Products Corp., 887 Kinderkamack Rd., River 012164
Edge, NJ 07661.........................................
Happy Jack, Inc., Snow Hill, NC 28580................... 023851
Heska Corp., 1825 Sharp Point Dr., Fort Collins, CO 063604
80525..................................................
Hikma International Pharmaceuticals LLC, P.O. Box 059115
182400, Bayader Wadi Seer, Amman, Jordan 11118.........
Hospira, Inc., 275 North Field Dr., Lake Forest, IL 000409
60045..................................................
HQ Specialty Pharma Corp., 120 Rte. 17 North, Suite 130, 042791
Paramus, NJ 07652......................................
Huvepharma AD, 5th Floor, 3A Nikolay Haytov Str., 1113 016592
Sofia, Bulgaria........................................
IDEXX Pharmaceuticals, Inc., 7009 Albert Pick Rd., 065274
Greensboro, NC 27409...................................
IMPAX Laboratories, Inc., 30831 Huntwood Ave., Hayward, 000115
CA 94544...............................................
International Nutrition, Inc., 7706 `I' Plaza, Omaha, NE 043733
68127..................................................
Intervet, Inc., 556 Morris Ave., Summit, NJ 07901....... 000061
JBS United Animal Health II LLC, 322 S. Main St., 051233
Sheridan, IN 46069.....................................
Jurox Pty. Ltd., 85 Gardiner St., Rutherford, NSW 2320, 049480
Australia..............................................
Lloyd, Inc., 604 W. Thomas Ave., Shenandoah, IA 51601... 061690
Luitpold Pharmaceuticals, Inc., Animal Health Division, 010797
Shirley, NY 11967......................................
Med-Pharmex, Inc., 2727 Thompson Creek Rd., Pomona, CA 054925
91767-1861.............................................
Medicis Dermatologics, Inc., 8125 North Hayden Rd., 099207
Scottsdale, AZ 85258...................................
Merial Ltd., 3239 Satellite Blvd., Bldg. 500, Duluth, GA 050604
30096-4640.............................................
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
Nexcyon Pharmaceuticals, Inc., 644 West Washington Ave., 050929
Madison, WI 53719......................................
Norbrook Laboratories, Ltd., Station Works, Newry BT35 055529
6JP, Northern Ireland..................................
Novartis Animal Health US, Inc., 3200 Northline Ave., 058198
suite 300, Greensboro, NC 27408........................
NutriBasics Co., North Highway 71, P.O. Box 1014, 053740
WIllmar, MN 56201......................................
Oasmia Pharmaceutical AB, Vallongatan 1, 75228 Uppsala, 052818
Sweden.................................................
Orion Corp., Orionintie 1, 02200 Espoo, Finland......... 052483
OPK Biotech, LLC, 11 and 39 Hurley St., Cambridge, MA 063075
02141..................................................
OXIS International, Inc., 6040 N. Cutter Circle, Suite 024991
317, Portland, OR 97217-3935...........................
Paladin Labs (USA), Inc., 160 Greentree Dr., suite 101, 046129
Dover, DE 19904........................................
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..................................................
[[Page 46]]
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 LLC, 161 North Franklin Turnpike, suite 2C, 069254
Ramsey, NJ 07446.......................................
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 Healthcare Ltd., Piramal Tower, Ganpatrao Kadam 065085
Marg, Lower Parel, Mumbai - 400 013, India.............
Planalquimica Industrial Ltda., Rua das Magnolias nr. 060728
2405, Jardim das Bandeiras, CEP 13053-120, Campinas,
Sao Paulo, Brazil......................................
Purina Animal Nutrition LLC, 1080 County Road F West, 017800
Shoreview, MN 55126-2910...............................
Putney, Inc., One Monument Sq., Suite 400, Portland, ME 026637
04101..................................................
Quo Vademus, LLC, 277 Faison McGowan Rd., Kenansville, 076475
NC 28349...............................................
Ridley Block Operations Inc., 424 North Riverfront Dr., 068287
P.O. Box 8500, Mankato, MN 56002-8500..................
Ridley U.S. Holdings, Inc., 424 North Riverfront Dr., 067949
P.O. Box 8500, Mankato, MN 56002-8500..................
RSR Laboratories, Inc., 501 Fifth St., Bristol, TN 37620 058670
Seeco Inc., Box 1014, North Highway 71, Willmar, MN 011749
56201..................................................
Sioux Biochemical, Inc., 204 Third St. NW., Sioux 063112
Center, IA 51250.......................................
SmartVet USA, Inc., 22201 West Innovation Dr., Suite 086001
170A, Olathe, KS 66061-1304............................
Sogeval S.A., 200 Avenue de Mayenne, 53000 Laval, France 059120
Southern Micro-Blenders, Inc., 3801 North Hawthorne St., 049685
Chattanooga, TN 37406..................................
Sparhawk Laboratories, Inc., 12340 Santa Fe Trail Dr., 058005
Lenexa, KS 66215.......................................
Squire Laboratories, Inc., 100 Mill St., Revere, MA 017153
02151..................................................
Strategic Veterinary Pharmaceuticals, Inc., 100 NW. 054628
Airport Rd., St. Joseph, MO 64503......................
Summit Hill Laboratories, P.O. Box 535, Navesink, NJ 037990
07752..................................................
Superior Equine Pharmaceuticals, Inc., Pleasant Grove, 027053
UT 84062...............................................
Taro Pharmaceuticals U.S.A., Inc., 3 Skyline Dr., 051672
Hawthorne, NY 10532....................................
Teva Canada Ltd., 30 Novopharm Ct., Toronto, Ontario, 043806
Canada M1B 2K9.........................................
Therio, Inc., 8801 Anderson Ave., Manhattan, KS 66503... 052923
Thorn Bioscience LLC, 1044 East Chestnut St., 051330
Louisville, KY 40204...................................
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., 3200 Meacham Blvd., Ft. Worth, TX 76137 051311
Walco International, Inc., 15 West Putnam, Porterville, 049185
CA 93257
Watson Laboratories, Inc., 311 Bonnie Circle, Corona, CA 000402
92880..................................................
Wellmark International, 1501 East Woodfield Rd., suite 011536
200 West, Schaumburg, IL 60173.........................
Western Chemical, Inc., 1269 Lattimore Rd., Ferndale, WA 050378
98248..................................................
Wildlife Laboratories, Inc., 1401 Duff Dr., Suite 600, 053923
Fort Collins, CO 80524.................................
Zoetis Inc., 333 Portage St., Kalamazoo, MI 49007....... 054771
------------------------------------------------------------------------
(2) Numerical Listing of Sponsors
------------------------------------------------------------------------
Drug labeler
code Firm name and address
------------------------------------------------------------------------
000010 Boehringer Ingelheim Vetmedica, Inc., 2621 North Belt
Highway, St. Joseph, MO 64506-2002.
000044 Abbott Laboratories, North Chicago, IL 60064.
000061 Intervet, Inc., 556 Morris Ave., Summit, NJ 07901.
000115 IMPAX Laboratories, Inc., 30831 Huntwood Ave., Hayward,
CA 94544.
000402 Watson Laboratories, Inc., 311 Bonnie Circle, Corona, CA
92880.
000409 Hospira Inc., 275 North Field Dr., Lake Forest, IL
60045.
000859 Bayer HealthCare LLC, Animal Health Division, P.O. Box
390, Shawnee Mission, KS 66201.
000986 Elanco Animal Health, A Division of Eli Lilly & Co.,
Lilly Corporate Center, Indianapolis, IN 46285.
010019 Baxter Healthcare Corp., One Baxter Pkwy., Deerfield, IL
60015.
010515 G. C. Hanford Manufacturing Co., P.O. Box 1017,
Syracuse, NY 13201.
010797 Luitpold Pharmaceuticals, Inc., Animal Health Division,
Shirley, NY 11967.
011536 Wellmark International, 1501 East Woodfield Rd., suite
200 West, Schaumburg, IL 60173.
012164 Halocarbon Products Corp., 887 Kinderkamack Rd., River
Edge, NJ 07661.
012286 ADM Alliance 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.
015565 Fleming Laboratories, Inc., P.O. Box 34384, Charlotte,
NC 28234.
016592 Huvepharma AD, 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.
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, 1080 County Road F West,
Shoreview, MN 55126-2910.
021091 ConAgra Pet Products Co., 3902 Leavenworth St., Omaha,
NE 68105.
[[Page 47]]
023851 Happy Jack, Inc., Snow Hill, NC 28580.
024991 OXIS International, Inc., 6040 N. Cutter Circle, Suite
317 Portland, OR 97217-3935.
025463 Fougera Pharmaceuticals, Inc., P.O. Box 2006, 60 Baylis
Rd., Melville, NY 11747.
026637 Putney, Inc., One Monument Sq., Suite 400, Portland, ME
04101.
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.
043733 International Nutrition, Inc., 7706 `I' Plaza, Omaha, NE
68127.
043806 Teva Canada Ltd., 30 Novopharm Ct., Toronto, Ontario,
Canada M1B 2K9.
046129 Paladin Labs (USA), Inc., 160 Greentree Dr., suite 101,
Dover, DE 19904.
049185 Walco International, Inc., 15 West Putnam, Porterville,
CA 93257.
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 Western Chemical, Inc., 1269 Lattimore Rd., Ferndale, WA
98248.
050604 Merial Ltd., 3239 Satellite Blvd., Bldg. 500, Duluth, GA
30096-4640.
050929 Nexcyon Pharmaceuticals, Inc., 644 West Washington Ave.,
Madison, WI 53719.
051072 Aurora Pharmaceutical, LLC, 1196 Highway 3 South,
Northfield, MN 55057-3009.
051079 Mylan Institutional, Inc., 12720 Dairy Ashford Rd.,
Sugar Land, TX 77478.
051233 JBS United Animal Health II LLC, 322 S. Main St.,
Sheridan, IN 46069.
051267 Cooperative Research Farms, Box 69, Charlotteville, NY
12036.
051311 Virbac AH, Inc., 3200 Meacham Blvd., Ft. Worth, TX
76137.
051330 Thorn Bioscience LLC, 1044 East Chestnut St.,
Louisville, KY 40204.
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.
052913 AB Science, 3 Avenue George V, 75008 Paris, France.
052923 Therio, Inc., 8801 Anderson Ave., Manhattan, KS 66503.
053923 Wildlife Laboratories, Inc., 1401 Duff Dr., Suite 600,
Fort Collins, CO 80524.
054628 Strategic Veterinary Pharmaceuticals, Inc., 100 NW.
Airport Rd., St. Joseph, MO 64503.
054771 Zoetis Inc., 333 Portage St., Kalamazoo, MI 49007.
054925 Med-Pharmex, Inc., 2727 Thompson Creek Rd., Pomona, CA
91767-1861.
055246 Pegasus Laboratories, Inc., 8809 Ely Rd., Pensacola, FL
32514.
055462 Contemporary Products, Inc., 3788 Elm Springs Rd.,
Springdale, AR 72764-6067.
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 Novartis Animal Health US, Inc., 3200 Northline Ave.,
suite 300, Greensboro, NC 27408.
058670 RSR Laboratories, Inc., 501 Fifth St., Bristol, TN
37620.
058829 First Priority, Inc., 1590 Todd Farm Dr., Elgin, IL
60123.
059051 Neogen Corp., 944 Nandino Blvd., Lexington, KY 40511.
059115 Hikma International Pharmaceuticals LLC, P.O. Box
182400, Bayader Wadi Seer, Amman, Jordan 11118.
059120 Sogeval S.A., 200 Avenue de Mayenne, 53000 Laval,
France.
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.
061623 Cross Vetpharm Group Ltd., Broomhill Rd., Tallaght,
Dublin 24, 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 OPK Biotech, LLC, 11 and 39 Hurley St., Cambridge, MA
02141.
063112 Sioux Biochemical, Inc., 204 Third St. NW., Sioux
Center, IA 51250.
063286 Mylan Institutional, LLC, 4901 Hiawatha Dr., Rockford,
IL 61103.
063604 Heska Corp., 1825 Sharp Point Dr., Fort Collins, CO
80525.
064146 Alaco, Inc., 1500 North Wilmot Rd., suite 290-C, Tucson,
AZ 85712.
065085 Piramal Healthcare Ltd., Piramal Tower, Ganpatrao Kadam
Marg, Lower Parel, Mumbai - 400 013, India.
065274 IDEXX Pharmaceuticals, Inc., 7009 Albert Pick Rd.,
Greensboro, NC 27409.
065531 American Pharmaceuticals and Cosmetics, Inc., 1401 Joel
East Rd., Fort Worth, TX 76140.
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 U.S. Holdings, Inc., 424 N. Riverfront Dr., P.O.
Box 8500, Mankato, MN 56002-8500.
[[Page 48]]
068287 Ridley Block Operations Inc., 424 North Riverfront Dr.,
P.O. Box 8500, Mankato, MN 56002-8500.
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.
069254 Pharmgate LLC, 161 North Franklin Turnpike, suite 2C,
Ramsey, NJ 07446
076175 Ark Sciences, Inc., 1101 East 33rd St., suite B304,
Baltimore, MD 21218.
076475 Quo Vademus, LLC, 277 Faison McGowan Rd., Kenansville,
NC 28349.
086001 SmartVet USA, Inc., 22201 West Innovation Dr., Suite
170A, Olathe, KS 66061-1304.
086009 Axcentive SARL, Chemin de Champouse, Quartier Violesi,
13320 Bouc Bel Air, France.
099207 Medicis Dermatologics, Inc., 8125 North Hayden Rd.,
Scottsdale, AZ 85258.
------------------------------------------------------------------------
[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.fdsys.gov.
2. At 72 FR 36595, July 5, 2007, Sec. 510.600, in the table in
paragraph (c)(2), was amended by removing the entry for ``062749'';
however, the amendment could not be incorporated because the entry does
not exist.
3. 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''
doesn't exist.
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 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 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
[[Page 49]]
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. 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
[[Page 50]]
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.
(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,
[[Page 51]]
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 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 any clinical investigation that supports an
application for a research or marketing permit for products regulated by
FDA.
(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 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.
(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
[[Page 52]]
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, solely in
compliance with the applicable provisions of this chapter.
(d) Termination of exemption. If the Commissioner finds that:
(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]
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
[[Page 53]]
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 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.
514.100 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 Contents of notice of opportunity for a 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, 356a, 360b, 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
[[Page 54]]
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.
(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
[[Page 55]]
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:
(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
[[Page 56]]
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, 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,
[[Page 57]]
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 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
[[Page 58]]
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 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,
[[Page 59]]
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 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 the format described under Sec.
558.6(a)(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
[[Page 60]]
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 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.fdsys.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.
[[Page 61]]
(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.
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
[[Page 62]]
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 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
[[Page 63]]
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 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
[[Page 64]]
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
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
[[Page 65]]
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
(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.
[[Page 66]]
(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.
(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;
[[Page 67]]
(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),
(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.''
[[Page 68]]
(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
(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)
[[Page 69]]
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 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
[[Page 70]]
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;
(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
[[Page 71]]
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.
(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
[[Page 72]]
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.
(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:
[[Page 73]]
(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 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., forms to be submitted,
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?
------------------------------------------------------------------------
[[Page 74]]
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?
------------------------------------------------------------------------
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 forms do I need? 514.80(d) Reporting forms.
What are Forms FDA 1932 and 2301?
How can I get them?
Can I use computer-generated
equivalents?
------------------------------------------------------------------------
How long must I maintain Form FDA 1932 514.80(e) Records to be
and records and reports of other maintained.
required information, i.e., how long do
I need to maintain this information?
------------------------------------------------------------------------
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?
------------------------------------------------------------------------
How do I obtain Forms FDA 1932 and 2301? 514.80(g) Mailing addresses.
Where do I mail FDA's required forms,
records, and reports?
------------------------------------------------------------------------
[[Page 75]]
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 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.''
(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 on Form FDA 1932, and its mailing cover must be plainly marked
``15-Day NADA/ANADA Alert Report.''
(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
[[Page 76]]
report must be submitted on Form FDA 1932, and its mailing cover must be
plainly marked ``15-Day NADA/ANADA Alert Report Followup.'' 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 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
should submit the report on Form FDA 1932 within 15 working days of
first receiving the information.
(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 60 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. 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.
(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.
(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.
[[Page 77]]
(iv) Adverse drug experiences. (A) Product/manufacturing defects and
adverse drug experiences not previously reported under Sec.
514.80(b)(1) and (b)(2) must be reported individually on Form FDA 1932.
(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 separately from other
experiences in the periodic drug experience report and clearly marked or
highlighted.
(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 previously submitted Form FDA
1932, 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.
(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
[[Page 78]]
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) Reporting forms. Applicant must report adverse drug experiences
and product/manufacturing defects on Form FDA 1932, ``Veterinary Adverse
Drug Reaction, Lack of Effectiveness, Product Defect Report.'' Periodic
drug experience reports and special drug experience reports must be
accompanied by a completed Form FDA 2301 ``Transmittal of Periodic
Reports and Promotional Material for New Animal Drugs,'' in accordance
with directions provided on the forms. Computer-generated equivalents of
Form FDA 1932 or Form FDA 2301, approved by FDA before use, may be used.
Form FDA 1932 and Form FDA 2301 may be obtained on the Internet at
http://www.fda.gov/cvm/forms/forms.html, by telephoning the 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. Completed 15-day alert reports, periodic drug
experience reports, and special drug experience reports 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. 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 from
the Internet at http://www.fda.gov (click on ``Contact FDA,'' then ``FDA
Field Offices'').
(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
[[Page 79]]
drug caused or contributed to an adverse event.
[68 FR 15365, Mar. 31, 2003]
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:
(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
[[Page 80]]
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 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,
[[Page 81]]
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; 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.
(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]
[[Page 82]]
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;
(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
[[Page 83]]
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.
(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]
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 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.
[[Page 84]]
(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.
(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
[[Page 85]]
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 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.
[[Page 86]]
(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 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
[[Page 87]]
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]
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 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 to refuse to approve an application or to
withdraw the approval of an application will specify the grounds upon
which he proposes to issue his order. On request of the applicant, the
Commissioner will explain the reasons for his 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 he 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, his 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, he is required to file a written appearance requesting the
hearing within 30 days after the publication of the notice, giving the
reason why the application should not be refused or should not be
withdrawn, together with a well-organized and full-factual analysis of
the clinical and other investigational data he 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 data in
the application and from the reasons and a factual analysis in the
request for the hearing that no genuine and substantial issue
[[Page 88]]
of fact precludes the refusal to approve the application or the
withdrawal of approval of the application (for example, no adequate and
well-controlled clinical investigations to support the claims of
effectiveness have been identified), the Commissioner will enter an
order on this data, stating his 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 he 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 his appearance.
[40 FR 13825, Mar. 27, 1975, as amended at 43 FR 1941, Jan. 13, 1978]
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.
[[Page 89]]
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 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 Sec. Sec. 207.20 and 207.21 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]
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.
[[Page 90]]
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 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:
[[Page 91]]
(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
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.
[[Page 92]]
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 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.
[[Page 93]]
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.
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.
Subpart D [Reserved]
Subpart E_Conditionally Approved New Animal Drugs For Minor Use and
Minor Species
516.1318 xMasitinib.
516.1684 Paclitaxel.
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
[[Page 94]]
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
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.
[[Page 95]]
(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.
(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,
[[Page 96]]
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 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
[[Page 97]]
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]
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.
[[Page 98]]
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 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
[[Page 99]]
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:
(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
[[Page 100]]
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
(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
[[Page 101]]
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 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
[[Page 102]]
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 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.
[[Page 103]]
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 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
[[Page 104]]
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 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
[[Page 105]]
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, 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.
[[Page 106]]
Sec. 516.133 Denying a request for determination of eligibility for
indexing.
(a) FDA will deny a request for determination of eligibility for
indexing if it determines upon the basis of the request evaluated
together with any other information before it with respect to the new
animal drug that:
(1) The same drug in the same dosage form for the same intended use
is already approved or conditionally approved;
(2) There is insufficient information to demonstrate 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 there is insufficient evidence to
demonstrate safety for humans in accordance with the standard 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);
(3) The new animal drug is contained in or is a product of a
transgenic animal;
(4) There is insufficient information 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;
(5) The requester 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;
(6) There is insufficient information to determine that the new
animal drug is safe with respect to individuals exposed to the new
animal drug through its manufacture or use; or
(7) The request for determination of eligibility for indexing fails
to contain any other information required under the provisions of Sec.
516.129.
(b) FDA may deny a request for determination of eligibility for
indexing if it contains any untrue statement of a material fact or omits
material information.
(c) When a request for determination of eligibility for indexing is
denied, FDA will notify the requestor in accordance with Sec. 516.137.
Sec. 516.135 Granting a request for determination of eligibility for
indexing.
(a) FDA will grant the request for determination of eligibility for
indexing if none of the reasons described in Sec. 516.133 for denying
such a request applies.
(b) When a request for determination of eligibility for indexing is
granted, FDA will notify the requestor in accordance with Sec. 516.137.
Sec. 516.137 Notification of decision regarding eligibility for indexing.
(a) Within 90 days after the filing of a request for a determination
of eligibility for indexing based on Sec. 516.129(c)(7)(i), or 180 days
for a request based on Sec. 516.129(c)(7)(ii), FDA shall grant or deny
the request, and notify the requestor of FDA's decision in writing.
(b) If FDA denies the request, FDA shall provide due notice and an
opportunity for an informal conference as described in Sec. 516.123
regarding its decision. A decision of FDA to deny a request for
determination of eligibility for indexing following an informal
conference shall constitute final agency action subject to judicial
review.
Sec. 516.141 Qualified expert panels.
(a) Establishment of a qualified expert panel. Establishing a
qualified expert panel is the first step in the process of requesting
the addition of a new animal drug to the index. A qualified expert panel
may not be established until FDA has determined that the new animal drug
is eligible for indexing. The requestor must choose members for the
qualified expert panel in accordance with selection criteria listed in
paragraph (b) of this section and submit information about these
proposed members to FDA. FDA must determine whether the proposed
qualified expert panel meets the selection criteria prior
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to the panel beginning its work. Qualified expert panels operate
external to FDA and are not subject to the Federal Advisory Committee
Act, as amended, 5 U.S.C. App.
(b) Criteria for the selection of a qualified expert panel. (1) A
qualified expert panel member must be an expert qualified by training
and experience to evaluate a significant aspect of target animal safety
or effectiveness of the new animal drug under consideration.
(2) A qualified expert panel member must certify that he or she has
a working knowledge of section 572 of the act (the indexing provisions
of the statute) and this subpart, and that he or she has also read and
understood a clear written statement provided by the requestor stating
his or her duties and responsibilities with respect to reviewing the new
animal drug proposed for addition to the index.
(3) A qualified expert panel member may not be an FDA employee.
(4) A qualified expert panel must have at least three members.
(5) A qualified expert panel must have members with a range of
expertise such that the panel, as a whole, is qualified by training and
experience to evaluate the target animal safety and effectiveness of the
new animal drug under consideration.
(6) Unless FDA makes a determination to allow participation
notwithstanding an otherwise disqualifying financial interest, a
qualified expert panel member must not have a conflict of interest or
the appearance of a conflict of interest, as described in paragraph (g)
of this section.
(c) Requestor responsibilities. (1) The requestor must:
(i) Choose members for the qualified expert panel in accordance with
selection criteria listed in paragraph (b) of this section.
(ii) Provide each potential expert panel member a copy of section
572 of the act (the indexing provisions of the statute) and this subpart
and obtain certification that he or she has a working knowledge of the
information.
(iii) Provide each potential expert panel member a written statement
describing the purpose and scope of his or her participation on the
qualified expert panel and obtain certification that he or she has read
and understood the information. The written statement should describe
the duties and responsibilities of qualified expert panels and their
members established by paragraphs (e) and (f) of this section, including
the need to prepare a written report under Sec. 516.143.
(iv) Obtain information from each potential expert panel member
demonstrating that he or she is qualified by training and experience to
evaluate the target animal safety and effectiveness of the new animal
drug under consideration. This information can be obtained from a
comprehensive curriculum vitae or similar document.
(v) Notify each potential expert panel member that he or she must
submit information relating to potential conflict of interest directly
to FDA in a timely manner, as required in paragraph (e)(6) of this
section.
(2) The requestor must submit, in writing, the names and addresses
of the proposed qualified expert panel members and sufficient
information about each proposed member for FDA to determine whether the
panel meets the selection criteria listed in paragraphs (b)(1) through
(b)(5) of this section.
(3) After FDA has determined that the qualified expert panel meets
the selection criteria, the requestor must provide to the panel all
information known by the requestor that is relevant to a determination
of the target animal safety and the effectiveness of the new animal drug
at issue. In addition, the requestor must notify FDA of the name of the
qualified expert panel leader.
(4) The requestor must immediately notify FDA if it believes a
qualified expert panel member no longer meets the selection criteria
listed in paragraph (b) of this section or is otherwise not in
compliance with the requirements of this section.
(5) If a qualified expert panel member cannot complete the review
for which he or she was selected, the requestor must either choose a
replacement or justify the continued work of the panel in the absence of
the lost panelist. In either case, the requestor must submit sufficient
information for FDA to determine whether the proposed revised
[[Page 108]]
qualified expert panel meets the selection criteria listed in paragraphs
(b)(1) through (b)(5) of this section.
(6) The requestor must keep copies of all information provided to,
or received from, qualified expert panel members, including the written
report, for 2 years after the completion of the report, or the product
is added to the index, whichever occurs later, and make them available
to a duly authorized employee of the agency at all reasonable times.
(d) FDA responsibilities. (1) FDA will determine whether the
requestor's proposed qualified expert panel meets the selection criteria
listed in paragraph (b) of this section. FDA will expeditiously inform
the requestor, in writing, of its determination. If FDA determines that
the qualified expert panel does not meet the selection criteria, FDA
will provide due notice and an opportunity for an informal conference as
described in Sec. 516.123. A determination by FDA that a proposed
qualified expert panel does not meet the selection criteria following an
informal conference shall constitute final agency action subject to
judicial review.
(2) If FDA determines that a qualified expert panel no longer meets
the selection criteria listed in paragraph (b) of this section or that
the panel or its members are not in compliance with the requirements of
this section, the agency will expeditiously inform the requestor, in
writing, of this determination and provide due notice and an opportunity
for an informal conference as described in Sec. 516.123. A
determination by FDA, following an informal conference, that a qualified
expert panel no longer meets the selection criteria listed in paragraph
(b) of this section or that the panel or its members are not in
compliance with the requirements of this section shall constitute final
agency action subject to judicial review.
(e) Responsibilities of a qualified expert panel member. A qualified
expert panel member must do the following:
(1) Continue to meet all selection criteria described in paragraph
(b) of this section.
(2) Act in accordance with generally accepted professional and
ethical business practices.
(3) Review all information relevant to a determination of the target
animal safety and effectiveness of the new animal drug provided by the
requestor. The panel should also consider all relevant information
otherwise known by the panel members, including anecdotal information.
(4) Participate in the preparation of the written report of the
findings of the qualified expert panel, described in Sec. 516.143.
(5) Sign, or otherwise approve in writing, the written report. Such
signature or other written approval will serve as certification that the
written report meets the requirements of the written report in Sec.
516.143.
(6) Provide the information relating to potential conflict of
interest described in paragraph (g) of this section to FDA for its
consideration. Such information should be submitted directly to the
Director, OMUMS, when notified by the requestor.
(7) Immediately notify the requestor and FDA of any change in
conflict of interest status.
(8) Certify at the time of submission of the written report that
there has been no change in conflict of interest status, or identify and
document to FDA any such change.
(f) Additional responsibilities of a qualified expert panel leader.
(1) The qualified expert panel leader must ensure that the activities of
the panel are performed efficiently and in accordance with generally
accepted professional and ethical business practices.
(2) The qualified expert panel leader serves as the principal point
of contact between representatives of the agency and the panel.
(3) The qualified expert panel leader is responsible for submitting
the written report and all notes or minutes relating to panel
deliberations to the requestor.
(4) The qualified expert panel leader must maintain a copy of the
written report and all notes or minutes relating to panel deliberations
that are submitted to the requestor for 2 years after the report is
submitted. Such records must be made available to a duly authorized
employee of the agency for inspection at all reasonable times.
[[Page 109]]
(g) Prevention of conflicts of interest. (1) For the purposes of
this subpart, FDA will consider a conflict of interest to be any
financial or other interest that could impair a person's objectivity in
serving on the qualified expert panel or could create an unfair
competitive advantage for a person or organization.
(2) Factors relevant to whether there is a conflict of interest or
the appearance of a conflict of interest include whether the qualified
expert panel member, their spouse, their minor children, their general
partners, or any organizations in which they serve as an officer,
director, trustee, general partner or employee:
(i) Is currently receiving or seeking funding from the requestor
through a contract or research grant (either directly or indirectly
through another entity, such as a university).
(ii) Has any employment, contractual, or other financial arrangement
with the requestor other than receiving a reasonable fee for serving as
a member of the qualified expert panel.
(iii) Has any ownership or financial interest in any drug, drug
manufacturer, or drug distributor which will benefit from either a
favorable or unfavorable evaluation or opinion.
(iv) Has any ownership or financial interest in the new animal drug
being reviewed by the qualified expert panel.
(v) Has participated in the design, manufacture, or distribution of
any drug that will benefit from either a favorable or unfavorable
opinion of the qualified expert panel.
(vi) Has provided within 1 year any consultative services regarding
the new animal drug being reviewed by the qualified expert panel.
(vii) Has entered into an agreement in which fees charged or
accepted are contingent upon the panel member making a favorable
evaluation or opinion.
(viii) Receives payment for services related to preparing
information the requestor presents to the qualified expert panel, other
than for services related to the written report described in Sec.
516.143.
(3) To permit FDA to make a decision regarding potential conflict of
interest, a potential qualified expert panel member must submit to the
Director, OMUMS, the following information relating to themselves, their
spouse, their minor children, their general partners, or any
organizations in which they serve as an officer, director, trustee,
general partner or employee, regarding the following issues to the
extent that they are, in any way, relevant to the subject of the review
of the qualified expert panel:
(i) Investments (for example, stocks, bonds, retirement plans,
trusts, partnerships, sector funds, etc.), including for each the
following: Name of the firm, type of investment, owner (self, spouse,
etc.), number of shares / current value.
(ii) Employment (full or part time, current or under negotiation),
including for each the following: Name of the firm, relationship (self,
spouse, etc.), position in firm, date employment or negotiation began.
(iii) Consultant/advisor (current or under negotiation), including
for each the following: Name of the firm, topic/issue, amount received,
date initiated.
(iv) Contracts, grants, Cooperation Research and Development
Agreement (CRADAs) (current or under negotiation), including for each
the following: Type of agreement, product under study and indications,
amount of remuneration (institution/self), time period, sponsor
(government, firm, institution, individual), role of the person (site
investigator, principal investigator, co-investigator, partner, no
involvement, other), awardee.
(v) Patents/royalties/trademarks, including for each the following:
Description, name of firm involved, income received.
(vi) Expert witness (last 12 months or under negotiation), including
for each the following: For or against, name of firm, issue, amount
received.
(vii) Speaking/writing (last 12 months or under negotiation),
including for each the following: Firm, topic/issue, amount received
(honorarium/travel), date.
(viii) Whether the potential qualified expert panel member, their
spouse, their minor children, their general partners or any
organizations in which they serve as an officer, director, trustee,
general partner or employee, have
[[Page 110]]
had, at any time in the past, involvement of the kind noted in paragraph
(g)(3)(i) through (g)(3)(vii) of this section with respect to the animal
drug that is the subject of the qualified expert panel review.
(ix) Whether there are any other involvements (other kinds of
relationships) that would give the appearance of a conflict of interest
which have not been described in paragraph (g)(3)(i) through
(g)(3)(viii) of this section.
(x) In all cases, a response of ``no,'' ``none,'' or ``not
applicable'' is satisfactory when there is no relevant information to
submit.
(xi) A certification statement signed by the potential qualified
expert panel member to the effect that all information submitted is true
and complete to the best of their knowledge, that they have read and
understood their obligations as an expert panel member, and that they
will notify FDA and the requestor of any change in their conflict of
interest status.
(4) The fact that a qualified expert panel member receives a
reasonable fee for services as a member of the qualified expert panel,
provided that the fee is no more than commensurate with the value of the
time that the member devotes to the review process, does not constitute
a conflict of interest or the appearance of a conflict of interest.
Sec. 516.143 Written report.
The written report required in Sec. 516.145(b)(3) shall:
(a) Be written in English by a qualified expert panel meeting the
requirements of Sec. 516.141;
(b) Describe the panel's evaluation of all available target animal
safety and effectiveness information relevant to the proposed use of the
new animal drug, including anecdotal information;
(c) For all information considered, including anecdotal information,
include either a citation to published literature or a summary of the
information;
(d) State the panel's opinion regarding whether the benefits of
using the new animal drug for the proposed use in a minor species
outweigh its risks to the target animal, taking into account the harm
being caused by the absence of an approved or conditionally-approved new
animal drug for the minor species in question;
(e) Be signed, or otherwise approved in writing, by all panel
members, in accordance with Sec. 516.141; and
(f) If the panel unanimously concludes that the benefits of using
the new animal drug for the proposed use in a minor species outweigh its
risks to the target animal, taking into account the harm being caused by
the absence of an approved or conditionally-approved new animal drug for
the minor species in question, the written report shall:
(1) Provide draft labeling that includes all conditions of use and
limitations of use of the new animal drug deemed necessary by the panel
to assure that the benefits of use of the new animal drug outweigh the
risks, or provide narrative information from which such labeling can be
written by the requestor; and
(2) Include a recommendation regarding whether the new animal drug
should be limited to use under the professional supervision of a
licensed veterinarian.
Sec. 516.145 Content and format of a request for addition to the index.
(a) A requestor may request addition of a new animal drug to the
index only after the new animal drug has been granted eligibility for
indexing.
(b) A requestor shall submit two copies of a dated request signed by
the authorized contact for addition of a new animal drug to the index
that contains the following:
(1) A copy of FDA's determination of eligibility issued under Sec.
516.137;
(2) A copy of FDA's written determination that the proposed
qualified expert panel meets the selection criteria provided for in
Sec. 516.141(b);
(3) A written report that meets the requirements of Sec. 516.143;
(4) A proposed index entry that contains the information described
in Sec. 516.157;
(5) Proposed labeling, including representative labeling proposed to
be used for Type B and Type C medicated feeds if the drug is intended
for use in the manufacture of medicated feeds;
(6) Anticipated annual distribution of the new animal drug, in terms
of the
[[Page 111]]
total quantity of active ingredient, after indexing;
(7) A written commitment to manufacture the new animal drug and
animal feeds bearing or containing such new animal drug according to
current good manufacturing practices;
(8) A written commitment to label, distribute, and promote the new
animal drug only in accordance with the index entry;
(9) The name and address of the contact person or permanent-resident
U.S. agent; and
(10) A draft Freedom of Information summary which includes the
following information:
(i) A general information section that contains the name and address
of the requestor and a description of the drug, route of administration,
indications, and recommended dosage.
(ii) A list of the names and affiliations of the members of the
qualified expert panel, not including their addresses or other contact
information.
(iii) A summary of the findings of the qualified expert panel
concerning the target animal safety and effectiveness of the drug.
(iv) Citations of all publicly-available literature considered by
the qualified expert panel.
(v) For an early life stage of a food-producing minor species
animal, a human food safety summary.
(c) Upon specific request by FDA, the requestor shall submit the
information described in Sec. 516.141 that it submitted to the
qualified expert panel. Any such information not in English should be
accompanied by an English translation.
Sec. 516.147 Refuse to file a request for addition to the index.
(a) If a request for addition to the index contains all of the
information required by Sec. 516.145(b), FDA shall file it, and the
filing date shall be the date FDA receives the request.
(b) If a request for addition to the index lacks any of the
information required by Sec. 516.145, 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.
Sec. 516.149 Denying a request for addition to the index.
(a) FDA will deny a request for addition to the index if it finds
the following:
(1) The same drug in the same dosage form for the same intended use
is already approved or conditionally approved;
(2) On the basis of new information, the new animal drug no longer
meets the conditions for eligibility for indexing;
(3) The request for indexing fails to contain information required
under the provisions of Sec. 516.145;
(4) The qualified expert panel fails to meet any of the selection
criteria listed in Sec. 516.141(b);
(5) The written report of the qualified expert panel and other
information available to FDA is insufficient to permit FDA to determine
that the benefits of using the new animal drug for the proposed use in a
minor species outweigh its risks to the target animal, taking into
account the harm caused by the absence of an approved or conditionally-
approved new animal drug for the minor species in question;
(6) On the basis of the report of the qualified expert panel and
other information available to FDA, the benefits of using the new animal
drug for the proposed use in a minor species do not outweigh its risks
to the target animal, taking into account the harm caused by the absence
of an approved or conditionally-approved new animal drug for the minor
species in question; or
(7) The request contains any untrue statement of a material fact or
omits material information.
(b) When a request for addition to the index is denied, FDA will
notify the requestor in accordance with Sec. 516.153.
Sec. 516.151 Granting a request for addition to the index.
(a) FDA will grant the request for addition of a new animal drug to
the index if none of the reasons described in Sec. 516.149 for denying
such a request applies.
(b) When a request for addition of a new animal drug to the index is
granted, FDA will notify the requestor in accordance with Sec. 516.153.
[[Page 112]]
Sec. 516.153 Notification of decision regarding index listing.
(a) Within 180 days after the filing of a request for addition of a
new animal drug to the index, FDA shall grant or deny the request and
notify the requestor of FDA's decision in writing.
(b) If FDA denies the request for addition of a new animal drug to
the index, FDA shall provide due notice and an opportunity for an
informal conference as described in Sec. 516.123. A decision of FDA to
deny a request to index a new animal drug following an informal
conference shall constitute final agency action subject to judicial
review.
Sec. 516.155 Labeling of indexed drugs.
(a) The labeling of an indexed drug that is found to be eligible for
indexing under Sec. 516.129(c)(7)(i) shall state, prominently and
conspicuously: ``NOT APPROVED BY FDA.--Legally marketed as an FDA
indexed product. Extra-label use is prohibited.'' ``This product is not
to be used in animals intended for use as food for humans or other
animals.''
(b) The labeling of an indexed drug that was found to be eligible
for indexing for use in an early, non-food life stage of a food-
producing minor species animal, under Sec. 516.129(c)(7)(ii), shall
state, prominently and conspicuously: ``NOT APPROVED BY FDA.--Legally
marketed as an FDA indexed product. Extra-label use is prohibited.''
(c) The labeling of an indexed drug shall contain such other
information as may be prescribed in the index listing.
Sec. 516.157 Publication of the index and content of an index listing.
(a) FDA will make the list of indexed drugs available through the
FDA Web site at http://www.fda.gov. A printed copy can be obtained by
writing to the Freedom of Information Staff or by visiting FDA's Freedom
of Information Staff's Public Reading Room at the address listed on the
Agency's Web site at http://www.fda.gov.
(b) The list will contain the following information for each indexed
drug:
(1) The name and address of the person who holds the index listing;
(2) The name of the drug and the intended use and conditions of use
for which it is indexed;
(3) Product labeling; and
(4) Conditions and any limitations that FDA deems necessary
regarding use of the drug.
[72 FR 69121, Dec. 6, 2007; 76 FR 31470, June 1, 2011, as amended at 79
FR 68115, Nov. 14, 2014]
Sec. 516.161 Modifications to indexed drugs.
(a) After a drug is listed in the index, certain modifications to
the index listing may be requested. Any modification of an index listing
may not cause an indexed drug to be a different drug (or different
combination of drugs) or a different dosage form. If such modification
is requested, FDA will notify the holder that a new index listing is
required for the new drug or dosage form.
(b) Modifications to the indexed drug will fall under one of three
categories and must be submitted as follows:
(1) Urgent changes. (i) The following modifications to an indexed
drug or its labeling should be made as soon as possible, and a request
to modify the indexed drug should be concurrently submitted:
(A) The addition to package labeling, promotional labeling, or
prescription drug advertising of additional warning, contraindication,
side effect, or cautionary information.
(B) The deletion from package labeling, promotional labeling, and
drug advertising of false, misleading, or unsupported indications for
use or claims for effectiveness.
(C) Changes in manufacturing methods or controls required to correct
product or manufacturing defects that may result in serious adverse drug
events.
(ii) The modifications described in paragraph (b)(1)(i) of this
section must be submitted to the Director, OMUMS, in the form of a
request for modification of an indexed drug, and must contain sufficient
information to permit FDA to determine the need for the modification and
whether the modification appropriately addresses the need.
(iii) FDA will take no action against an indexed drug or index
holder solely because modifications of the kinds described in paragraph
(b)(1)(i) of this section are placed into effect by the
[[Page 113]]
holder prior to receipt of a written notice granting the request if all
the following conditions are met:
(A) A request to modify the indexed drug providing a full
explanation of the basis for the modifications has been submitted,
plainly marked on the mailing cover and on the request as follows:
``Special indexing request-- modifications being effected;''
(B) The holder specifically informs FDA of the date on which such
modifications are to be effected and submits two printed copies of any
revised labeling to be placed in use, and
(C) All promotional labeling and all drug advertising are promptly
revised consistent with modifications made in the labeling on or within
the indexed drug package.
(2) Significant changes. (i) The following modifications to an
indexed drug or its labeling may be made only after a request has been
submitted to and subsequently granted by FDA:
(A) Addition of an intended use.
(B) Addition of a species.
(C) Addition or alteration of an active ingredient.
(D) Alteration of the concentration of an active ingredient.
(E) Alteration of dose or dosage regimen.
(F) Alteration of prescription or over-the-counter status.
(ii) Each modification described in paragraph (b)(2)(i) of this
section must go through the same review process as an original index
listing and is subject to the same standards for review.
(iii) Each submission of a request for a modification described in
paragraph (b)(2)(i) of this section should contain only one type of
modification unless one modification is actually necessitated by
another, such as a modification of dose necessitated by a modification
of the concentration of an active ingredient. Submissions relating to
addition of an intended use for an existing species or addition of a
species should be submitted separately, but each such submission may
include multiple additional intended uses and/or multiple additional
species.
(3) Minor changes. All modifications other than those described in
paragraphs (b)(1) and (b)(2) of this section including, but not limited
to, formulation, labeling, and manufacturing methods and controls (at
the same level of detail that these were described in the request for
determination of eligibility for indexing) must be submitted as part of
the annual indexed drug experience report or as otherwise required by
Sec. 516.165.
(c) When changes affect the index listing, it will be updated
accordingly.
Sec. 516.163 Change in ownership of an index file.
(a) A holder may transfer ownership of a drug's index file to
another person.
(1) The former owner shall submit in writing to FDA a statement that
all rights in the index file have been transferred, giving the name and
address of the new owner and the date of the transfer. The former owner
shall also certify that a complete copy of the following, to the extent
that they exist at the time of the transfer of ownership, has been
provided to the new owner:
(i) The request for determination of eligibility;
(ii) The request for addition to the index;
(iii) Any modifications to the index listing;
(iv) Any records and reports under Sec. 516.165; and
(v) All correspondence with FDA relevant to the indexed drug and its
index listing.
(2) The new owner shall submit the following information in writing
to FDA:
(i) The date that the change in ownership is effective;
(ii) A statement that the new owner has a complete copy of all
documents listed in paragraph (a)(1) of this section to the extent that
they exist at the time of the transfer of ownership;
(iii) A statement that the new owner understands and accepts the
responsibilities of a holder of an indexed drug;
(iv) The name and address of a new primary contact person or
permanent-resident U.S. agent; and
(v) A list of labeling changes associated with the change of
ownership (e.g., a new trade name) as draft labeling, with complete
final printed labeling to be submitted in the indexed drug annual report
in accordance with Sec. Sec. 516.161 and 516.165.
[[Page 114]]
(b) Upon receiving the necessary information to support a change of
ownership of a drug's index file, FDA will update its publicly-available
listing in accordance with Sec. 516.157.
Sec. 516.165 Records and reports.
(a) Scope and purpose. (1) The recordkeeping and reporting
requirements of this section apply to all holders of indexed drugs,
including indexed drugs intended for use in medicated feeds.
(2) A holder is not required to report information under this
section if the holder has reported the same information under Sec.
514.80 of this chapter.
(3) 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.
(4) FDA will review the records and reports required in this section
to determine, or facilitate a determination, whether there may be
grounds for removing a drug from the index under section 572(f) of the
act.
(b) Recordkeeping requirements. (1) Each holder of an indexed drug
must establish and maintain complete files containing full records of
all information pertinent to the safety or effectiveness of the indexed
drug. Such records must include information from foreign and domestic
sources.
(2) The holder 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 records.
(c) Reporting requirements--(1) Three-day indexed drug field alert
report. The holder must inform the appropriate FDA District Office or
local FDA resident post of any product or manufacturing defects that may
result in serious adverse drug events within 3 working days of first
becoming aware that such a defect may exist. The holder may initially
provide this information by telephone or other electronic communication
means, with prompt written followup. The mailing cover must be plainly
marked ``3-Day Indexed Drug Field Alert Report.''
(2) Fifteen-day indexed drug alert report. The holder must submit a
report on each serious, unexpected adverse drug event, regardless of the
source of the information. The holder must submit the report within 15
working days of first receiving the information. The mailing cover must
be plainly marked ``15-Day Indexed Drug Alert Report.''
(3) Annual indexed drug experience report. The holder must submit
this report every year on the anniversary date of the letter granting
the request for addition of the new animal drug to the index, or within
60 days thereafter. The report must contain data and information for the
full reporting period. Any previously submitted information contained in
the report must be identified as such. The holder may ask FDA to change
the date of submission and, after approval of such request, file such
reports by the new filing date. The report must contain the following:
(i) The 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) distributed during the
reporting period. This information must be presented in two categories:
Quantities distributed domestically and quantities exported. This
information must include any distributor-labeled product.
(ii) If the labeling has changed since the last report, include a
summary of those changes and the holder's and distributor's current
package labeling, including any package inserts. For large-size package
labeling or large shipping cartons, submit a representative copy (e.g.,
a photocopy of pertinent areas of large feed bags). If the labeling has
not changed since the last report, include a statement of such fact.
(iii) A summary of any changes made during the reporting period in
the methods used in, and facilities and controls used for, manufacture,
processing, and packing. This information must be presented in the same
level of detail that it was presented in the request for determination
of eligibility for indexing. Do not include changes that have already
been submitted under Sec. 516.161.
(iv) Nonclinical laboratory studies and clinical data not previously
reported under this section.
(v) Adverse drug experiences not previously reported under this
section.
[[Page 115]]
(vi) Any other information pertinent to safety or effectiveness of
the indexed drug not previously reported under this section.
(4) Distributor's statement. At the time of initial distribution of
an indexed drug by a distributor, the holder must submit a report
containing the following:
(i) The distributor's current product labeling. This must be
identical to that in the index listing 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 such as ``manufactured for'' or
``distributed by.''
(ii) A signed statement by the distributor stating:
(A) The category of the distributor's operations (e.g., wholesale or
retail);
(B) That the distributor will distribute the drug only under the
indexed drug labeling;
(C) That the distributor will promote the indexed drug only for use
under the conditions stated in the index listing; and
(D) If the indexed drug is a prescription new animal drug, that the
distributor is regularly and lawfully engaged in the distribution or
dispensing of prescription products.
(5) Other reporting. FDA may by order require that a holder submit
information in addition to that required by this section or that the
holder submit the same information but at different times or reporting
periods.
Sec. 516.167 Removal from the index.
(a) After due notice to the holder of the index listing and an
opportunity for an informal conference as described in Sec. 516.123,
FDA shall remove a new animal drug from the index if FDA finds that:
(1) The same drug in the same dosage form for the same intended use
has been approved or conditionally approved;
(2) The expert panel failed to meet the requirements in Sec.
516.141;
(3) On the basis of new information before FDA, evaluated together
with the evidence available to FDA when the new animal drug was listed
in the index, the benefits of using the new animal drug for the indexed
use do not outweigh its risks to the target animal, taking into account
the harm caused by the absence of an approved or conditionally-approved
new animal drug for the minor species in question;
(4) Any of the conditions in Sec. 516.133(a)(2), (5), or (6) are
present;
(5) The manufacture of the new animal drug is not in accordance with
current good manufacturing practices;
(6) The labeling, distribution, or promotion of the new animal drug
is not in accordance with the index listing;
(7) The conditions and limitations of use associated with the index
listing have not been followed; or
(8) Any information used to support the request for addition to the
index contains any untrue statement of material fact.
(b) The agency may partially remove an indexing listing if, in the
opinion of the agency, such partial removal would satisfactorily resolve
a safety or effectiveness issue otherwise warranting removal of the
listing under section 572(f)(1)(B) of the act.
(c) FDA may immediately suspend a new animal drug from the index if
FDA determines that there is a reasonable probability that the use of
the drug would present a risk to the health of humans or other animals.
The agency will subsequently provide due notice and an opportunity for
an informal conference as described in Sec. 516.123.
(d) A decision of FDA to remove a new animal drug from the index
following an informal conference, if any, shall constitute final agency
action subject to judicial review.
Sec. 516.171 Confidentiality of data and information in an index file.
(a) For purposes of this section, the index file includes all data
and information submitted to or incorporated by reference into the index
file, such as data and information related to investigational use
exemptions under Sec. 516.125, requests for determination of
eligibility for indexing, requests for addition to the index,
modifications to indexed drugs, changes in ownership, reports submitted
under Sec. 516.165, and master files. The availability for public
disclosure of any record in the index
[[Page 116]]
file shall be handled in accordance with the provisions of this section.
(b) The existence of an index file will not be disclosed by FDA
before an index listing has been made public by FDA, unless it has
previously been publicly disclosed or acknowledged by the requestor.
(c) If the existence of an index file has not been publicly
disclosed or acknowledged, no data or information in the index file are
available for public disclosure.
(d) If the existence of an index file has been publicly disclosed or
acknowledged before an index listing has been made public by FDA, no
data or information contained in the file will be available for public
disclosure before such index listing is made public, but the agency may,
at its discretion, disclose a brief summary of such selected portions of
the safety and effectiveness data as are appropriate for public
consideration of a specific pending issue, e.g., 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 FDA sends a written notice to the requestor granting a
request for addition to the index, the following data and information in
the index file are 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 index
file. Such summaries do not constitute the full information described
under section 572(c) and (d) of the act on which the safety or
effectiveness of the drug may be determined. Such summaries will be
based on the draft Freedom of Information summary submitted under Sec.
516.145, which will be reviewed and, where appropriate, revised by FDA.
(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
the following:
(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 veterinarian.
(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 index file, in accordance with the provisions of part 20
of this chapter.
(f) The following data and information in an index 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.
(g) Subject to the disclosure provisions of this section, the agency
shall regard the contents of an index file as confidential information
unless specifically notified in writing by the holder of the right to
disclose, to reference, or otherwise utilize such information on behalf
of another named person.
[[Page 117]]
(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.
(i) Safety and effectiveness data and information that have not been
previously disclosed to the public are available for public disclosure
at the time any of the following events occurs unless extraordinary
circumstances are shown:
(1) No work is being or will be undertaken to have the drug indexed
in accordance with the request.
(2) A final determination is made that the drug cannot be indexed
and all legal appeals have been exhausted.
(3) The drug has been removed from the index and all legal appeals
have been exhausted.
(4) A final determination has been made that the animal drug is not
a new animal drug.
Subpart D [Reserved]
Subpart E_Conditionally Approved New Animal Drugs For Minor Use and
Minor Species
Source: 72 FR 57200, Oct. 9, 2007, unless otherwise noted.
Sec. 516.1318 Masitinib.
(a) Specifications. Each tablet contains 50 or 150 milligrams (mg)
masitinib mesylate.
(b) Sponsor. See No. 052913 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs (1) Amount. 12.5 mg/kilograms (5.7 mg/
lb) of body weight daily.
(2) Indications for use. For the treatment of nonresectable Grade II
or III cutaneous mast cell tumors in dogs that have not previously
received radiotherapy and/or chemotherapy except corticosteroids.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian. It is a violation of Federal law to
use this product other than as directed in the labeling.
[76 FR 6327, Feb. 4, 2011, as amended at 77 FR 35837, June 15, 2012]
Sec. 516.1684 Paclitaxel.
(a) Specifications. Each vial of powder contains 60 milligrams (mg)
paclitaxel. Each milliliter of constituted solution contains 1 mg
paclitaxel.
(b) Sponsor. See No. 052818 in 510.600(c) of this chapter.
(c) Conditions of use in dogs--(1) Amount. Administer 150 mg per
square meter of body surface area intravenously over 15 to 30 minutes,
once every 3 weeks, for up to 4 doses.
(2) Indications for use. For the treatment of nonresectable stage
III, IV, or V mammary carcinoma in dogs that have not received previous
chemotherapy or radiotherapy. For the treatment of resectable and
nonresectable squamous cell carcinoma in dogs that have not received
previous chemotherapy or radiotherapy.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian. It is a violation of Federal law to
use this product other than as directed in the labeling.
[79 FR 18158, Apr. 1, 2014]
PART 520_ORAL DOSAGE FORM NEW ANIMAL DRUGS--Table of Contents
Sec.
520.23 Acepromazine.
520.28 Acetazolamide.
520.38 Albendazole oral dosage forms.
520.38a Albendazole suspension.
520.38b Albendazole paste.
520.43 Afoxolaner.
520.48 Altrenogest.
520.62 Aminopentamide.
520.82 Aminopropazine oral dosage forms.
520.82a Aminopropazine.
520.82b Aminopropazine and neomycin.
520.88 Amoxicillin oral dosage forms.
520.88a Amoxicillin trihydrate film-coated tablets.
520.88b Amoxicillin trihydrate for oral suspension.
520.88c Amoxicillin trihydrate oral suspension.
520.88d Amoxicillin trihydrate soluble powder.
520.88e Amoxicillin trihydrate boluses.
520.88f Amoxicillin trihydrate tablets.
520.88g Amoxicillin trihydrate and clavulanate potassium film-coated
tablets.
520.88h Amoxicillin trihydrate and clavulanate potassium for oral
suspension.
520.90 Ampicillin oral dosage forms.
[[Page 118]]
520.90a [Reserved]
520.90b Ampicillin tablets.
520.90c Ampicillin capsules.
520.90d Ampicillin for oral suspension.
520.90e Ampicillin for soluble powder.
520.90f Ampicillin boluses.
520.100 Amprolium.
520.110 Apramycin sulfate soluble powder.
520.154 Bacitracin oral dosage forms.
520.154a Bacitracin methylene disalicylate.
520.154b Bacitracin methylene disalicylate and streptomycin sulfate
powder.
520.154c Bacitracin zinc soluble powder.
520.222 Bunamidine hydrochloride.
520.246 Butorphanol tablets.
520.260 n-Butyl chloride.
520.300 Cambendazole oral dosage forms.
520.300a Cambendazole suspension.
520.300b Cambendazole pellets.
520.300c Cambendazole paste.
520.301 Caramiphen ethanedisulfonate and ammonium chloride tablets.
520.302 Carnidazole tablets.
520.304 Carprofen.
520.314 Cefadroxil.
520.370 Cefpodoxime tablets.
520.376 Cephalexin.
520.390 Chloramphenicol oral dosage forms.
520.390a Chloramphenicol tablets.
520.390b Chloramphenicol capsules.
520.390c Chloramphenicol palmitate oral suspension.
520.420 Chlorothiazide tablets and boluses.
520.434 Chlorphenesin carbamate tablets.
520.441 Chlortetracycline powder.
520.443 Chlortetracycline tablets and boluses.
520.445 Chlortetracycline and sulfamethazine powder.
520.446 Clindamycin capsules and tablets.
520.447 Clindamycin solution.
520.452 Clenbuterol syrup.
520.455 Clomipramine tablets.
520.462 Clorsulon drench.
520.522 Cyclosporine.
520.530 Cythioate oral liquid.
520.531 Cythioate tablets.
520.534 Decoquinate.
520.538 Deracoxib.
520.540 Dexamethasone oral dosage forms.
520.540a Dexamethasone powder.
520.540b Dexamethasone tablets and boluses.
520.540c Dexamethasone chewable tablets.
520.563 Dexamethasone chewable tablets.
520.580 Dichlorophene and toluene.
520.581 Dichlorophene tablets.
520.600 Dichlorvos.
520.606 Diclazuril.
520.608 Dicloxacillin.
520.620 Diethylcarbamazine oral dosage forms.
520.622 Diethylcarbamazine citrate oral dosage forms.
520.622a Diethylcarbamazine citrate tablets.
520.622b Diethylcarbamazine citrate syrup.
520.622c Diethylcarbamazine citrate chew- able tablets.
520.623 Diethylcarbamazine and oxibendazole chewable tablets.
520.645 Difloxacin.
520.666 Dirlotapide.
520.763 Dithiazanine oral dosage forms.
520.763a Dithiazanine tablets.
520.763b Dithiazanine powder.
520.763c Dithiazanine iodide and piperazine citrate suspension.
520.766 Domperidone.
520.784 Doxylamine.
520.804 Enalapril.
520.812 Enrofloxacin.
520.816 Epsiprantel.
520.823 Erythromycin.
520.852 Estriol.
520.863 Ethylisobutrazine.
520.870 Etodolac.
520.903 Febantel oral dosage forms.
520.903a Febantel paste.
520.903b Febantel suspension.
520.903c [Reserved]
520.903d Febantel and praziquantel paste.
520.903e Febantel tablets.
520.905 Fenbendazole oral dosage forms.
520.905a Fenbendazole suspension.
520.905b Fenbendazole granules.
520.905c Fenbendazole paste.
520.905d Fenbendazole powder.
520.905e Fenbendazole blocks.
520.928 Firocoxib tablets.
520.930 Firocoxib paste.
520.955 Florfenicol.
520.960 Flumethasone.
520.970 Flunixin.
520.980 Fluoxetine.
520.998 Fluralaner.
520.1010 Furosemide.
520.1044 Gentamicin sulfate oral dosage forms.
520.1044a Gentamicin sulfate oral solution.
520.1044b Gentamicin sulfate pig pump oral solution.
520.1044c Gentamicin sulfate powder.
520.1060 Glucose and glycine.
520.1100 Griseofulvin.
520.1120 Haloxon oral dosage forms.
520.1120a Haloxon drench.
520.1120b Haloxon boluses.
520.1130 Hetacillin.
520.1157 Iodinated casein.
520.1158 Iodochlorhydroxyquin.
520.1182 Iron dextran suspension.
520.1192 Ivermectin paste.
520.1193 Ivermectin tablets and chewables.
520.1194 Ivermectin meal.
520.1195 Ivermectin liquid.
520.1196 Ivermectin and pyrantel tablets.
520.1197 Ivermectin sustained-release bolus.
520.1198 Ivermectin and praziquantel paste.
520.1199 Ivermectin, pyrantel, and praziquantel tablets.
520.1200 Ivermectin, fenbendazole, and praziquantel tablets.
[[Page 119]]
520.1204 Kanamycin, bismuth subcarbonate, activated attapulgite.
520.1242 Levamisole.
520.1242a Levamisole powder.
520.1242b Levamisole boluses or oblets.
520.1242c Levamisole and piperazine.
520.1242d Levamisole resinate.
520.1242e Levamisole hydrochloride effervescent tablets.
520.1242f Levamisole gel.
520.1242g Levamisole resinate and famphur paste.
520.1263 Lincomycin.
520.1263a Lincomycin tablets and syrup.
520.1263b [Reserved]
520.1263c Lincomycin powder.
520.1265 Lincomycin and spectinomycin powder.
520.1284 Liothyronine.
520.1288 Lufenuron tablets.
520.1289 Lufenuron suspension.
520.1310 Marbofloxacin.
520.1315 Maropitant.
520.1320 Mebendazole.
520.1326 Mebendazole and trichlorfon oral dosage forms.
520.1326a Mebendazole and trichlorfon powder.
520.1326b Mebendazole and trichlorfon paste.
520.1330 Meclofenamic acid granules.
520.1331 Meclofenamic acid tablets.
520.1341 Megestrol.
520.1367 Meloxicam.
520.1372 Methimazole.
520.1380 Methocarbamol.
520.1408 Methylprednisolone.
520.1409 Methylprednisolone and aspirin.
520.1422 Metoserpate hydrochloride.
520.1430 Megestrol acetate tablets.
520.1441 Milbemycin oxime.
520.1443 Milbemycin oxime and lufenuron.
520.1445 Milbemycin oxime and praziquantel.
520.1447 Milbemycin oxime, lufenuron, and praziquantel tablets.
520.1450 Morantel tartrate oral dosage forms.
520.1450a Morantel tartrate bolus.
520.1450b Morantel tartrate cartridge.
520.1450c Morantel tartrate sustained-release trilaminate cylinder/
sheet.
520.1451 Moxidectin tablets.
520.1452 Moxidectin gel.
520.1453 Moxidectin and praziquantel gel.
520.1454 Moxidectin solution.
520.1468 Naproxen.
520.1484 Neomycin.
520.1510 Nitenpyram tablets.
520.1604 Oclacitinib.
520.1615 Omeprazole.
520.1616 Orbifloxacin tablets..
520.1618 Orbifloxacin suspension.
520.1628 Oxfendazole powder and pellets.
520.1629 Oxfendazole paste.
520.1630 Oxfendazole suspension.
520.1631 Oxfendazole and trichlorfon paste.
520.1638 Oxibendazole.
520.1660 Oxytetracycline.
520.1660a Oxytetracycline and carbomycin in combination.
520.1660b Oxytetracycline hydrochloride capsules.
520.1660c Oxytetracycline hydrochloride tablets/boluses.
520.1660d Oxytetracycline powder.
520.1696 Penicillin.
520.1696a [Reserved]
520.1696b Penicillin G powder.
520.1696c Penicillin V powder.
520.1696d Penicillin V tablets.
520.1705 Pergolide.
520.1720 Phenylbutazone oral dosage forms.
520.1720a Phenylbutazone tablets and boluses.
520.1720b Phenylbutazone granules.
520.1720c Phenylbutazone paste.
520.1720d Phenylbutazone gel.
520.1720e Phenylbutazone powder.
520.1760 Phenylpropanolamine.
520.1780 Pimobendan.
520.1802 Piperazine-carbon disulfide complex oral dosage forms.
520.1802a Piperazine-carbon disulfide complex suspension.
520.1802b Piperazine-carbon disulfide complex boluses.
520.1802c Piperazine-carbon disulfide complex with phenothiazine
suspension.
520.1803 Piperazine citrate capsules.
520.1804 Piperazine phosphate capsules.
520.1805 Piperazine phosphate with thenium closylate tablets.
520.1806 Piperazine suspension.
520.1807 Piperazine.
520.1840 Poloxalene.
520.1846 Polyoxyethylene (23) lauryl ether blocks.
520.1855 Ponazuril.
520.1860 Pradofloxacin.
520.1870 Praziquantel tablets.
520.1871 Praziquantel and pyrantel.
520.1872 Praziquantel, pyrantel pamoate, and febantel tablets.
520.1880 Prednisolone.
520.1900 Primidone.
520.1920 Prochlorperazine and isopropamide.
520.1921 Prochlorperazine, isopropamide, and neomycin.
520.1962 Promazine.
520.2002 Propiopromazine.
520.2041 Pyrantel pamoate chewable tablets.
520.2042 Pyrantel pamoate tablets.
520.2043 Pyrantel pamoate suspension.
520.2044 Pyrantel pamoate paste.
520.2045 Pyrantel tartrate powder.
520.2046 Pyrantel tartrate pellets.
520.2075 Robenacoxib.
520.2098 Selegiline.
520.2100 Selenium and vitamin E.
520.2123 Spectinomycin oral dosage forms.
520.2123a Spectinomycin tablets.
520.2123b Spectinomycin powder.
520.2123c Spectinomycin solution.
520.2130 Spinosad.
[[Page 120]]
520.2134 Spinosad and milbemycin.
520.2150 Stanozolol.
520.2158 Streptomycin.
520.2170 Sulfabromomethazine.
520.2184 Sulfachloropyrazine.
520.2200 Sulfachlorpyridazine.
520.2215 Sulfadiazine/pyrimethamine suspension.
520.2218 Sulfamerazine, sulfamethazine, and sulfaquinoxaline powder.
520.2220 Sulfadimethoxine oral dosage forms.
520.2220a Sulfadimethoxine solution and soluble powder.
520.2220b Sulfadimethoxine suspension.
520.2220c Sulfadimethoxine tablet.
520.2220d Sulfadimethoxine bolus.
520.2220e Sulfadimethoxine extended-release bolus.
520.2220f Sulfadimethoxine and ormetoprim tablet.
520.2240 Sulfaethoxypyridazine.
520.2240a Sulfaethoxypyridazine solution.
520.2240b Sulfaethoxypyridazine tablets.
520.2260 Sulfamethazine oral dosage forms.
520.2260a Sulfamethazine oblet, tablet, and bolus.
520.2260b Sulfamethazine sustained-release boluses.
520.2260c Sulfamethazine sustained-release tablets.
520.2261 Sulfamethazine sodium oral dosage forms.
520.2261a Sulfamethazine solution.
520.2261b Sulfamethazine powder.
520.2280 Sulfamethizole and methenamine.
520.2325 Sulfaquinoxaline oral dosage forms.
520.2325a Sulfaquinoxaline powder and solution.
520.2325b Sulfaquinoxaline drench.
520.2330 Sulfisoxazole tablets.
520.2340 Tepoxalin.
520.2345 Tetracycline.
520.2345a Tetracycline capsules.
520.2345b Tetracycline tablets.
520.2345c Tetracycline boluses.
520.2345d Tetracycline powder.
520.2345e Tetracycline solution.
520.2345f Tetracycline phosphate complex and sodium novobiocin capsules.
520.2345g Tetracycline hydrochloride and sodium novobiocin tablets.
520.2345h Tetracycline hydrochloride, sodium novobiocin, and
prednisolone tablets.
520.2362 Thenium closylate.
520.2380 Thiabendazole oral dosage forms.
520.2380a Thiabendazole top dressing and mineral protein block.
520.2380b Thiabendazole drench or paste.
520.2380c Thiabendazole bolus.
520.2380d Thiabendazole and piperazine citrate.
520.2380e Thiabendazole and trichlorfon.
520.2380f Thiabendazole and piperazine phosphate.
520.2455 Tiamulin.
520.2471 Tilmicosin.
520.2473 Tioxidazole oral dosage forms.
520.2473a Tioxidazole granules.
520.2473b Tioxidazole paste.
520.2475 Toceranib.
520.2481 Triamcinolone acetonide tablets.
520.2482 Triamcinolone acetonide oral powder.
520.2483 Triamcinolone.
520.2520 Trichlorfon oral dosage forms.
520.2520a Trichlorfon and atropine.
520.2520b Trichlorofon boluses.
520.2520c Trichlorofon granules.
520.2520d Trichlorfon, phenothiazine, and piperazine dihydrochloride
powder.
520.2582 Triflupromazine.
520.2598 Trilostane.
520.2604 Trimeprazine and prednisolone tablets.
520.2605 Trimeprazine and prednisolone capsules.
520.2610 Trimethoprim and sulfadiazine tablets.
520.2611 Trimethoprim and sulfadiazine paste.
520.2612 Trimethoprim and sulfadiazine suspension.
520.2613 Trimethoprim and sulfadiazine powder.
520.2640 Tylosin.
520.2645 Tylvalosin.
Authority: 21 U.S.C. 360b.
Source: 40 FR 13838, Mar. 27, 1975, unless otherwise noted.
Sec. 520.23 Acepromazine.
(a) Specifications. Each tablet contains 5, 10, or 25 milligrams
(mg) acepromazine maleate.
(b) Sponsors. See No. 000010 in Sec. 510.600(c) of this chapter.
(c) Conditions of use(1) Dogs--(i) Amount. 0.25 to 1.0 mg per pound
(/lb) body weight orally.
(ii) Indications for use. As an aid in tranquilization and as a
preanesthetic agent.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(2) Cats--(i) Amount. 0.5 to 1.0 mg/lb body weight orally.
(ii) Indications for use. As a tranquilizer.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
[75 FR 10165, Mar. 5, 2010]
Sec. 520.28 Acetazolamide.
(a) Specifications. A powder containing acetazolamide sodium, USP
[[Page 121]]
equivalent to 25 percent acetazolamide activity.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs--(1) Amount. Administer orally at a
dosage of 5 to 15 milligrams per pound of body weight daily.
(2) Indications for use. As an aid in the treatment of mild
congestive heart failure and for rapid reduction of intraocular
pressure.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[79 FR 28816, May 20, 2014]
Sec. 520.38 Albendazole oral dosage forms.
Sec. 520.38a Albendazole suspension.
(a) Specifications. Each milliliter of suspension contains 45.5
milligrams (mg) (4.55 percent) or 113.6 mg (11.36 percent) albendazole.
(b) Sponsor. See No. 054771 in Sec. 510.600 of this chapter.
(c) Related tolerances. See Sec. 556.34 of this chapter.
(d) Special considerations. See Sec. 500.25 of this chapter.
(e) Conditions of use--(1) Cattle. Administer 11.36 percent
suspension:
(i) Amount. 4.54 mg/pound (lb) body weight (10 mg/kilogram (kg)) as
a single oral dose using dosing gun or dosing syringe.
(ii) Indications for use. For removal and control of adult liver
flukes (Fasciola hepatica); heads and segments of tapeworms (Moniezia
benedeni and M. expansa); adult and 4th stage larvae of stomach worms
(brown stomach worms including 4th stage inhibited larvae (Ostertagia
ostertagi), barberpole worm (Haemonchus contortus and H. placei), small
stomach worm (Trichostrongylus axei)); adult and 4th stage larvae of
intestinal worms (thread-necked intestinal worm (Nematodirus spathiger
and N. helvetianus), small intestinal worm (Cooperia punctata and C.
oncophora)); adult stages of intestinal worms (hookworm (Bunostomum
phlebotomum), bankrupt worm (Trichostrongylus colubriformis), nodular
worm (Oesophagostomum radiatum)); adult and 4th stage larvae of
lungworms (Dictyocaulus viviparus).
(iii) Limitations. Do not slaughter within 27 days of last
treatment. Do not use in female dairy cattle of breeding age: Do not
administer to female cattle during first 45 days of pregnancy or for 45
days after removal of bulls.
(2) Sheep. Administer 4.45 or 11.36 percent suspension:
(i) Amount. 3.4 mg/lb body weight (7.5 mg/kg) as a single oral dose
using dosing gun or dosing syringe.
(ii) Indications for use. For removal and control of adult liver
flukes (Fasciola hepatica and Fascioloides magna); heads and segments of
common tapeworms (Moniezia expansa) and fringed tapeworm (Thysanosoma
actinioides); adult and fourth stage larvae of stomach worms (brown
stomach worm (Ostertagia circumcinta and Marshallagia marshalli),
barberpole worm (Haemonchus contortus), small stomach worm
(Trichostrongylus axei)); adult and fourth stage larvae of intestinal
worms (thread-necked intestinal worm (Nematodirus spathiger and N.
filicollis), Cooper's worm (Cooperia oncophora), bankrupt worm
(Trichostrongylus colubriformis), nodular worm (Oesophagostomum
columbianum), and large-mouth bowel worm (Chabertia ovina)); adult and
larval stages of lungworms (Dictyocaulus filaria).
(iii) Limitations. Do not slaughter within 7 days of last treatment.
Do not administer to ewes during first 30 days of pregnancy or for 30
days after removal of rams.
(3) Goats. Administer 11.36 percent suspension:
(i) Amount. 4.54 mg/lb body weight (10 mg/kg) as a single oral dose
using dosing gun or dosing syringe.
(ii) Indications for use. For the treatment of adult liver flukes
(Fasciola hepatica) in nonlactating goats.
(iii) Limitations. Do not slaughter within 7 days of last treatment.
Do not administer to does during the first 30 days of pregnancy or for
30 days after removal of bucks.
[73 FR 11027, Feb. 29, 2008. Redesignated at 78 FR 66264, Nov. 5, 2013,
as amended at 79 FR 28816, May 20, 2014]
Sec. 520.38b Albendazole paste.
(a) Specifications. The product contains 30 percent albendazole.
[[Page 122]]
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.34 of this chapter.
(d) Conditions of use in cattle--(1) Amount. Equivalent to 4.54
milligrams per 1 pound of body weight (10 milligrams per kilogram).
(2) Indications for use. For removal and control of the following
internal parasites of cattle: adult liver flukes (Fasciola hepatica);
heads and segments of tapeworms (Moniezia benedeni, M. expansa); adult
and 4th stage larvae of stomach worms (brown stomach worms including 4th
stage inhibited larvae (Ostertagia ostertagi); barberpole worm
(Haemonchus contortus, H. placei); small stomach worm (Trichostrongylus
axei)); adult and 4th stages larvae of intestinal worms (thread-necked
intestinal worm (Nematodirus spathiger, N. helvetianus); small
intestinal worm (Cooperia punctata and C. oncophora)); adult stages of
intestinal worms (hookworm (Bunostomum phlebotmum); bankrupt worm
(Trichostrongylus colubriformis), nodular worm (Oesophagostomum
radiatum)); adult and 4th stage larvae of lungworms (Dictyocaulus
viviparus).
(3) Limitations. Administer as a single oral dose. Do not slaughter
within 27 days of last treatment. Do not use in female dairy cattle of
breeding age. Do not administer to female cattle during first 45 days of
pregnancy or for 45 days after removal of bulls. Consult your
veterinarian for assistance in the diagnosis, treatment, and control of
parasitism.
[54 FR 51385, Dec. 15, 1989, as amended at 56 FR 50653, Oct. 8, 1991; 60
FR 55658, Nov. 2, 1995. Redesignated at 78 FR 66264, Nov. 5, 2013, as
amended at 79 FR 28816, May 20, 2014]
Sec. 520.43 Afoxolaner.
(a) Specifications. Each chewable tablet contains 11.3, 28.3, 68, or
136 milligrams (mg) afoxolaner.
(b) Sponsor. See No. 050604 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Amount. Administer orally once a month at
a minimum dosage of 1.14 mg/pound (lb) (2.5 mg/kilogram (kg)).
(2) Indications for use. Kills adult fleas; for the treatment and
prevention of flea infestations (Ctenocephalides felis); and for the
treatment and control of black-legged tick (Ixodes scapularis), American
Dog tick (Dermacentor variabilis), and lone star tick (Amblyomma
americanum) infestations in dogs and puppies 8 weeks of age and older,
weighing 4 lb of body weight or greater, for 1 month.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[78 FR 66264, Nov. 5, 2013, as amended at 79 FR 37619, July 2, 2014]
Sec. 520.48 Altrenogest.
(a) Specifications. Each milliliter (mL) of solution contains 2.2
milligrams (mg) altrenogest.
(b) Sponsors. See sponsor listings in Sec. 510.600(c) of this
chapter:
(1) No. 000061 for use as in paragraph (d) of this section.
(2) No. 013744 for use as in paragraph (d)(1) of this section.
(c) Tolerances. See Sec. 556.36 of this chapter.
(d) Conditions of use--(1) Horses--(i) Amount. 1.0 mL per 110 pounds
body weight (0.044 mg/kg) daily for 15 consecutive days.
(ii) Indications for use. For suppression of estrus in mares.
(iii) Limitations. Do not use in horses intended for human
consumption. Federal law restricts this drug to use by or on the order
of a licensed veterinarian.
(2) Swine--(i) Amount. Administer 6.8 mL (15 mg altrenogest) per
gilt once daily for 14 consecutive days by top-dressing on a portion of
each gilt's daily feed.
(ii) Indications for use. For synchronization of estrus in sexually
mature gilts that have had at least one estrous cycle.
(iii) Limitations. Do not use in gilts having a previous or current
history of uterine inflammation (i.e., acute, subacute or chronic
endometritis). Gilts must not be slaughtered for human consumption for
21 days after the last treatment.
[66 FR 47960, Sept. 17, 2001, as amended at 68 FR 62006, Oct. 31, 2003;
72 FR 9455, Feb. 21, 2008; 74 FR 61516, Nov. 25, 2009; 77 FR 32012, May
31, 2012]
[[Page 123]]
Sec. 520.62 Aminopentamide.
(a) Specifications. Each tablet contains 0.2 milligram (mg)
aminopentamide hydrogen sulphate.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs and cats--(1) Amount. Administer
orally every 8 to 12 hours as follows: For animals weighing up to 10
pounds (lbs): 0.1 mg; for animals weighing 11 to 20 lbs: 0.2 mg; for
animals weighing 21 to 50 lbs: 0.3 mg; for animals weighing 51 to 100
lbs: 0.4 mg; for animal weighing over 100 lbs: 0.5 mg. Dosage may be
gradually increased up to a maximum of five times the suggested dosage.
Oral administration of tablets may be preceded by subcutaneous or
intramuscular use of the injectable form of the drug.
(2) Indications for use. For the treatment of vomiting and/or
diarrhea, nausea, acute abdominal visceral spasm, pylorospasm, or
hypertrophic gastritis.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[79 FR 28816, May 20, 2014]
Sec. 520.82 Aminopropazine oral dosage forms.
Sec. 520.82a Aminopropazine.
(a) Specifications. Each tablet contains aminopropazine fumarate
equivalent to 25 percent aminopropazine base.
(b) Sponsor. See No. 000061 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs and cats--(1) Amount. Administer
orally at a dosage of 1 to 2 milligrams per pound of body weight,
repeated every 12 hours as indicated.
(2) Indications for use. For reducing excessive smooth muscle
contractions, such as occur in urethral spasms associated with
urolithiasis.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[79 FR 28816, May 20, 2014]
Sec. 520.82b Aminopropazine and neomycin.
(a) Specifications. Each tablet contains aminopropazine fumarate
equivalent to 25 percent aminopropazine base and neomycin sulfate
equivalent to 50 milligrams (mg) of neomycin base.
(b) Sponsor. See No. 000061 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs--(1) Amount. Administer orally at a
dosage of 1 to 2 mg per pound of body weight, repeated every 12 hours as
indicated.
(2) Indications for use. For control of bacterial diarrhea caused by
organisms susceptible to neomycin and to reduce smooth muscle
contractions.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[79 FR 28816, May 20, 2014]
Sec. 520.88 Amoxicillin oral dosage forms.
Sec. 520.88a Amoxicillin trihydrate film-coated tablets.
(a) Specifications. Each tablet contains amoxicillin trihydrate
equivalent to 50, 100, 150, 200, or 400 milligrams (mg) amoxicillin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. Administer orally 5 mg
per pound (/lb) of body weight, twice a day for 5 to 7 days.
(ii) Indications for use. Treatment of infections of the respiratory
tract (tonsillitis, tracheobronchitis), genitourinary tract (cystitis),
gastrointestinal tract (bacterial gastroenteritis), and soft tissues
(abscesses, lacerations, wounds), caused by susceptible strains of
Staphylococcus aureus, Streptococcus spp., Escherichia coli, Proteus
mirabilis, and bacterial dermatitis caused by S. aureus, Streptococcus
spp., and P. mirabilis.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(2) Cats--(i) Amount. Administer orally 5 to 10 mg/lb of body
weight, once daily for 5 to 7 days.
(ii) Indications for use. Treatment of infections caused by
susceptible organisms as follows: upper respiratory tract due to S.
aureus, Streptococcus spp., and E. coli; genitourinary tract (cystitis)
due to S. aureus, Streptococcus spp., E. coli, and P. mirabilis;
gastrointestinal tract due to E. coli; and skin and soft tissue
(abscesses, lacerations,
[[Page 124]]
and wounds) due to S. aureus, Streptococcus spp., E. coli, and
Pasteurella multocida.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
[57 FR 37319, Aug. 18, 1992, as amended at 60 FR 55658, Nov. 2, 1995; 79
FR 28816, May 20, 2014]
Sec. 520.88b Amoxicillin trihydrate for oral suspension.
(a) Specifications. When reconstituted, each milliliter contains
amoxicillin trihydrate equivalent to 50 milligrams (mg) amoxicillin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(1) Conditions of use--(i) Dogs--(A) Amount. Administer orally 5 mg
per pound (/lb) of body weight, twice a day for 5 to 7 days.
(B) Indications for use. Treatment of infections caused by
susceptible strains of organisms as follows: respiratory tract
(tonsillitis, tracheobronchitis) caused by Staphylococcus aureus,
Streptococcus spp., Escherichia coli, and Proteus mirabilis;
genitourinary tract (cystitis) caused by S. aureus, Streptococcus spp.,
E. coli, and P. mirabilis; gastrointestinal tract (bacterial
gastroenteritis) caused by S. aureus, Streptococcus spp., E. coli, and
P. mirabilis; bacterial dermatitis caused by S. aureus, Streptococcus
spp., and P. mirabilis; and soft tissues (abscesses, lacerations, and
wounds) caused by S. aureus, Streptococcus spp., E. coli, and P.
mirabilis.
(C) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
(ii) Cats--(A) Amount. Administer orally 5 to 10 mg/lb of body
weight, once daily for 5 to 7 days.
(B) Indications for use. Treatment of infections caused by
susceptible strains of organisms as follows: upper respiratory tract due
to Staphylococcus spp., Streptococcus spp., Hemophilus spp., E. coli,
Pasteurella spp., and P. mirabilis; genitourinary tract (cystitis) due
to S. aureus, Streptococcus spp., E. coli, P. mirabilis, and
Corynebacterium spp.; gastrointestinal tract due to E. coli, Proteus
spp., Staphylococcus spp., and Streptococcus spp.; skin and soft tissue
(abscesses, lacerations, and wounds) due to Staphylococcus spp.,
Streptococcus spp., E. coli, and Pasteurella multocida.
(C) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
(2) [Reserved]
(c) Sponsors. See Nos. 000856 and 051311 in Sec. 510.600(c) of this
chapter.
(1) Conditions of use. Dogs--(i) Amount. Administer orally 5 mg/lb
of body weight, twice a day for 5 to 7 days.
(ii) Indications for use. Treatment of bacterial dermatitis due to
S. aureus, Streptococcus spp., Staphylococcus spp., and E. coli, and
soft tissue infections (abscesses, wounds, lacerations) due to S.
aureus, Streptococcus spp., E. coli, P. mirabilis and Staphylococcus
spp.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(2) [Reserved]
[57 FR 37319, Aug. 18, 1992; 57 FR 42623, Sept. 15, 1992, as amended at
60 FR 55658, Nov. 2, 1995; 62 FR 13302, Mar. 20, 1997; 67 FR 67521, Nov.
6, 2002; 68 FR 54658, Sept. 18, 2003; 68 FR 55824, Sept. 29, 2003; 79 FR
28816, May 20, 2014]
Sec. 520.88c Amoxicillin trihydrate oral suspension.
(a) Specifications. Each 0.8-milliliter dose contains amoxicillin
trihydrate equivalent to 40 milligrams (mg) amoxicillin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.510 of this chapter.
(d) Conditions of use in swine--(1) Amount. Administer 40 mg orally
twice a day using a dosing pump. Treat animals for 48 hours after all
symptoms have subsided but not beyond 5 days.
(2) Indications for use. Treatment of baby pigs under 10 pounds for
porcine colibacillosis caused by Escherichia coli susceptible to
amoxicillin.
(3) Limitations. Do not slaughter during treatment or for 15 days
after latest treatment. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
[57 FR 37319, Aug. 18, 1992, as amended at 60 FR 55658, Nov. 2, 1995; 79
FR 28817, May 20, 2014]
[[Page 125]]
Sec. 520.88d Amoxicillin trihydrate soluble powder.
(a) Specifications. Each gram of powder contains amoxicillin
trihydrate equivalent to 115.4 milligrams (mg) amoxicillin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.38 of this chapter.
(d) Conditions of use in preruminating calves including veal
calves--(1) Amount. Administer 400 mg per 100 pounds of body weight
twice daily by drench or in milk. Treatment should be continued for 48
hours after all symptoms have subsided but not to exceed 5 days.
(2) Indications for use. Treatment of bacterial enteritis when due
to susceptible Escherichia coli in preruminating calves including veal
calves.
(3) Limitations. Do not slaughter animals during treatment or for 20
days after the latest treatment. Federal law restricts this drug to use
by or on the order of a licensed veterinarian
[57 FR 37319, Aug. 18, 1992; 57 FR 42623, Sept. 15, 1992; 58 FR 18304,
Apr. 8, 1993, as amended at 60 FR 55658, Nov. 2, 1995; 62 FR 5525, Feb.
6, 1997; 79 FR 28817, May 20, 2014]
Sec. 520.88e Amoxicillin trihydrate boluses.
(a) Specifications. Each bolus contains amoxicillin trihydrate
equivalent to 400 milligrams (mg) amoxicillin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.38 of this chapter.
(d) Conditions of use in cattle--(1) Amount. Administer 400 mg per
100 pounds of body weight twice daily. Treatment should be continued for
48 hours after all symptoms have subsided but not to exceed 5 days.
(2) Indications for use. Treatment of bacterial enteritis when due
to susceptible Escherichia coli in preruminating calves including veal
calves.
(3) Limitations. Do not slaughter animals during treatment or for 20
days after the latest treatment. Federal law restricts this drug to use
by or on the order of a licensed veterinarian.
[57 FR 37320, Aug. 18, 1992, as amended at 60 FR 55659, Nov. 2, 1995; 62
FR 5526, Feb. 6, 1997; 79 FR 28817, May 20, 2014]
Sec. 520.88f Amoxicillin trihydrate tablets.
(a) Specifications. Each tablet contains amoxicillin trihydrate
equivalent to 50, 100, 200, or 400 milligrams (mg) amoxicillin.
(b) Sponsors. See Nos. 051311 and 054771 in Sec. 510.600(c) of this
chapter.
(c) Conditions of use in dogs--(1) Amount. Administer 5 mg per pound
of body weight twice daily for 5 to 7 days or 48 hours after all
symptoms have subsided.
(2) Indications for use. For treatment of bacterial dermatitis due
to Staphylococcus aureus, Streptococcus spp., Staphylococcus spp., and
Escherichia coli; and soft tissue infections (abscesses, wounds,
lacerations) due to S. aureus, Streptococcus spp., E. coli, Proteus
mirabilis, and Staphylococcus spp.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[79 FR 28817, May 20, 2014]
Sec. 520.88g Amoxicillin trihydrate and clavulanate potassium
film-coated tablets.
(a) Specifications. Each tablet contains amoxicillin trihydrate and
clavulanate potassium, equivalent to either 50 milligrams of amoxicillin
and 12.5 milligrams clavulanic acid, or 100 milligrams of amoxicillin
and 25 milligrams clavulanic acid, or 200 milligrams amoxicillin and 50
milligrams clavulanic acid or 300 milligrams amoxicillin and 75
milligrams clavulanic acid.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. 6.25 milligrams
(equivalent to 5 milligrams amoxicillin and 1.25 milligrams clavulanic
acid) per pound of body weight twice daily for 5 to 7 days or for 48
hours after all signs have subsided. Deep pyoderma may require treatment
for 21 days; do not treat for more than 30 days.
(ii) Indications for use. Treatment of skin and soft tissue
infections such as wounds, abscesses, cellulitis, superficial/juvenile
and deep pyoderma due to susceptible strains of beta-lactamase
(penicillinase) Staphylococcus aureus, nonbeta-lactamase S.
[[Page 126]]
aureus, Staphylococcus spp., Streptococcus spp., and Escherichia coli.
Treatment of periodontal infections due to susceptible strains of
aerobic and anaerobic bacteria.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(2) Cats--(i) Amount. 62.5 milligrams (1 milliliter) (50 milligrams
amoxicillin and 12.5 milligrams clavulanic acid) twice daily for 5 to 7
days or for 48 hours after all signs have subsided. Urinary tract
infections may require treatment for 10 to 14 days or longer. The
maximum duration of treatment should not exceed 30 days.
(ii) Indications for use. Treatment of skin and soft tissue
infections, such as wounds, abscesses and cellulitis/dermatitis due to
susceptible strains of beta-lactamase (penicillinase) producing S.
aureus, nonbeta-lactamase producing S. aureus, Staphylococcus spp.,
Streptococcus spp., E. coli, and Pasteurella spp. Also, treatment of
urinary tract infections (cystitis) due to susceptible strains of E.
coli.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
[57 FR 37320, Aug. 18, 1992, as amended at 60 FR 55659, Nov. 2, 1995; 63
FR 13121, Mar. 18, 1998; 79 FR 28817, May 20, 2014]
Sec. 520.88h Amoxicillin trihydrate and clavulanate potassium for oral
suspension.
(a) Specifications. When reconstituted, each milliliter contains
amoxicillin trihydrate equivalent to 50 milligrams of amoxicillin with
clavulanate potassium equivalent to 12.5 milligrams of clavulanic acid.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. 6.25 milligrams
(equivalent to 5 milligrams amoxicillin and 1.25 milligrams clavulanic
acid) per pound of body weight twice daily for 5 to 7 days or for 48
hours after all signs have subsided. Deep pyoderma may require treatment
for 21 days; do not treat for more than 30 days.
(ii) Indications for use. Treatment of skin and soft tissue
infections such as wounds, abscesses, cellulitis, superficial/juvenile
and deep pyoderma due to susceptible strains of beta-lactamase
(penicillinase) producing Staphylococcus aureus, nonbeta-lactamase
Staphylococcus aureus, Staphylococcus spp., Streptococcus spp., and
Escherichia coli. Treatment of periodontal infections due to susceptible
strains of aerobic and anaerobic bacteria.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(2) Cats--(i) Amount. 62.5 milligrams (1 milliliter) (50 milligrams
amoxicillin and 12.5 milligrams clavulanic acid) twice daily. Administer
48 hours after all signs have subsided. Maximum duration of treatment
should not exceed 30 days.
(ii) Indications for use. Treatment of feline skin and soft tissue
infections, such as wounds, abscesses and cellulitis/dermatitis due to
susceptible strains of beta-lactamase (penicillinase) producing S.
aureus, nonbeta-lactamase S. aureus, Staphylococcus spp., Streptococcus
spp., E. coli, Pasteurella multocida, and Pasteurella spp.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
[57 FR 37320, Aug. 18, 1992, as amended at 60 FR 55659, Nov. 2, 1995; 63
FR 13121, Mar. 18, 1998; 79 FR 28817, May 20, 2014]
Sec. 520.90 Ampicillin oral dosage forms.
Sec. 520.90a [Reserved]
Sec. 520.90b Ampicillin tablets.
(a) Specifications. Each tablet contains ampicillin trihydrate
equivalent to 50 or 100 milligrams of ampicillin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs--(1) Amount. 5 milligrams per pound of
body weight, at 8-hour intervals, 1 to 2 hours prior to feeding, to be
continued 36 to 48 hours after all symptoms have subsided. If no
improvement is seen within 5 days, stop treatment, reevaluate diagnosis,
and change therapy.
(2) Indications for use. Oral treatment of infections caused by
susceptible organisms as follows: Upper respiratory infections,
tonsillitis, and bronchitis due to Streptococcus spp., Staphylococcus
[[Page 127]]
spp., Escherichia coli, Proteus mirabilis, and Pasteurella spp., urinary
tract infections (cystitis) due to Streptococcus spp., Staphylococcus
spp., E., coli, P. mirabilis, and Enterococcus spp.; gastrointestinal
infections due to Staphylococcus spp., Streptococcus spp., Enterococcus
spp., and E. coli. ; infections associated with abscesses, lacerations,
and wounds caused by Staphylococcus spp., and Streptococcus spp.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[57 FR 37321, Aug. 18, 1992, as amended at 60 FR 55659, Nov. 2, 1995; 79
FR 28818, May 20, 2014]
Sec. 520.90c Ampicillin capsules.
(a) Specifications. Each capsule contains ampicillin trihydrate
equivalent to 125, 250, or 500 milligrams of ampicillin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. 5 to 10 milligrams per
pound of body weight two or three times daily. In severe or acute
conditions, 10 milligrams per pound of body weight, three times daily.
Administer 1 to 2 hours prior to feeding.
(ii) Indications for use. Treatment against strains of gram-negative
and gram-positive organisms sensitive to ampicillin and associated with
respiratory tract infections (tracheobronchitis and tonsillitis);
urinary tract infections (cystitis); bacterial gastroenteritis;
generalized infections (septicemia) associated with abscesses,
lacerations, and wounds; and bacterial dermatitis.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(2) Cats--(i) Amount. 10 to 30 milligrams per pound of body weight
or three times daily. Administer 1 to 2 hours prior to feeding.
(ii) Indications for use. Treatment against strains of gram-negative
and gram-positive organisms sensitive to ampicillin and associated with
respiratory tract infections (bacterial pneumonia); urinary tract
infections (cystitis); and generalized infections (septicemia)
associated with abscesses, lacerations, and wounds.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
[57 FR 37321, Aug. 18, 1992, as amended at 58 FR 61016, Nov. 19, 1993;
79 FR 28818, May 20, 2014]
Sec. 520.90d Ampicillin for oral suspension.
(a) Specifications. When reconstituted as directed, each milliliter
contains ampicillin trihydrate equivalent to 25 milligrams of
ampicillin.
(b) Sponsor. See No. 055529 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. Administer to 10
milligrams per pound of body weight orally, 2 or 3 times daily, 1 to 2
hours prior to feeding. In severe or acute conditions, 10 milligrams per
pound of body weight 3 times daily. Duration of treatment is usually 3
to 5 days. Continue treatment 48 hours after the animal's temperature
has returned to normal and all other signs of infection have subsided.
(ii) Indications for use. Treatment of respiratory tract infections
(tracheobronchitis and tonsillitis) due to Escherichia coli, Pseudomonas
spp., Proteus spp., Staphylococcus spp., and Streptococcus spp., urinary
tract infections (cystitis) due to E. coli, Staphylococcus spp.,
Streptococcus spp., and Proteus spp.; bacterial gastroenteritis due to
E. coli; generalized infections (septicemia) associated with abscesses,
lacerations, and wounds, due to Staphylococcus spp. and Streptococcus
spp.; bacterial dermatitis due to Staphylococcus spp., Streptococcus
spp., Proteus spp., and Pseudomonas spp.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(2) Cats--(i) Amount. Administer 10 to 30 milligrams per pound of
body weight orally, 2 or 3 times daily, 1 to 2 hours prior to feeding.
Duration of treatment is usually 3 to 5 days. Continue treatment 48
hours after the animal's temperature has returned to normal and all
other signs of infection have subsided.
(ii) Indications for use. Treatment of respiratory tract infections
(bacterial pneumonia) due to Staphylococcus spp., Streptococcus spp., E.
coli, and Proteus spp.; urinary tract infections (cystitis)
[[Page 128]]
due to E. coli, Staphylococcus spp., Streptococcus spp., Proteus spp.,
and Corynebacterium spp.; generalized infections (septicemia) associated
with abscesses, lacerations, and wounds, due to Staphylococcus spp.,
Streptococcus spp., Bacillus spp., and Pasteurella spp.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
[57 FR 37321, Aug. 18, 1992, as amended at 58 FR 61016, Nov. 19, 1993;
79 FR 28818, May 20, 2014]
Sec. 520.90e Ampicillin for soluble powder.
(a) Specifications. Each gram contains ampicillin trihydrate
equivalent to 88.2 milligrams of ampicillin.
(b) Sponsor. See No. 055529 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.40 of this chapter.
(d) Conditions of use. Swine(1) Amount. 5 milligrams of ampicillin
per pound of body weight twice daily, orally by gavage or in drinking
water for up to 5 days.
(2) Indications for use. Oral treatment of porcine colibacillosis
(Escherichia coli) and salmonellosis (Salmonella spp.) infections in
swine up to 75 pounds of body weight, and bacterial pneumonia caused by
Pasteurella multocida, Staphylococcus spp., Streptococcus spp., and
Salmonella spp.
(3) Limitations. Treated swine must not be slaughtered for food
during treatment and for 24 hours following the last treatment. Federal
law restricts this drug to use by or on the order of a licensed
veterinarian.
[57 FR 37322, Aug. 18, 1992, as amended at 58 FR 61016, Nov. 19, 1993;
79 FR 28818, May 20, 2014]
Sec. 520.90f Ampicillin boluses.
(a) Specifications. Each bolus contains ampicillin trihydrate
equivalent to 400 milligrams of ampicillin.
(b) Sponsors. See sponsor numbers in Sec. 510.600(c) of this
chapter as follows:
(1) No. 055529 for use as in paragraph (d)(1) of this section;
(2) No. 054771 for use as in paragraph (d)(2) of this section.
(c) Related tolerances. See Sec. 556.40 of this chapter.
(d) Conditions of use. Nonruminating calves--(1) Amount. 5
milligrams per pound of body weight twice daily for up to 5 days.
(i) Indications for use. Oral treatment of colibacillosis caused by
Escherichia coli, bacterial enteritis caused by Salmonella spp., and
bacterial pneumonia caused by Pasteurella spp.
(ii) Limitations. Treated calves must not be slaughtered for food
during treatment and for 15 days after the last treatment. Federal law
restricts this drug to use by or on the order of a licensed
veterinarian.
(2) Amount. 5 milligrams per pound of body weight twice daily not to
exceed 4 days.
(i) Indications for use. Oral treatment of bacterial enteritis
(colibacillosis) caused by E. coli.
(ii) Limitations. Treated calves must not be slaughtered for food
during treatment and for 7 days after the last treatment. Federal law
restricts this drug to use by or on the order of a licensed
veterinarian.
[57 FR 37322, Aug. 18, 1992, as amended at 58 FR 61016, Nov. 19, 1993;
60 FR 55659, Nov. 2, 1995; 79 FR 28818, May 20, 2014]
Sec. 520.100 Amprolium.
(a) Specifications. (1) Each milliliter of solution contains 96
milligrams (mg) amprolium (9.6 percent solution).
(2) Each gram of powder contains 200 mg amprolium (20 percent).
(3) Each ounce (28.4 grams) of crumbles contains 355 mg amprolium
(1.25 percent).
(b) Sponsors. See sponsors in 510.600(c) of this chapter.
(1) No. 016592 for use of products described in paragraph (a) of
this section as in paragraph (d) of this section.
(2) No. 066104 for use of product described in paragraph (a)(1) of
this section as in paragraph (d) of this section.
(3) No. 000859 for use of product described in paragraph (a)(1) of
this section as in paragraph (d) of this section.
(4) No. 061623 for use of products described in paragraphs (a)(1)
and (a)(2) of this section as in paragraph (d) of this section.
(c) Related tolerances. See Sec. 556.50 of this chapter.
[[Page 129]]
(d) Conditions of use--(1) Growing chickens, turkeys, and laying
hens. It is used in drinking water as follows:
(i) Amount. Administer at the 0.012 percent level in drinking water
as soon as coccidiosis is diagnosed and continue for 3 to 5 days (in
severe outbreaks, give amprolium at the 0.024 percent level); continue
with 0.006 percent amprolium-medicated water for an additional 1 to 2
weeks.
(ii)Indications for use. For the treatment of coccidiosis.
(iii) Limitations. Use as the sole source of amprolium.
(2) Calves. Administer crumbles top-dressed on or thoroughly mixed
in the daily feed ration; administer concentrate solution or soluble
powder as a drench or in drinking water as follows:
(i) Indications for use and amounts--(A) As an aid in the prevention
of coccidiosis caused by Eimeria bovis and E. zurnii, administer 5 mg
per kilogram (mg/kg) body weight for 21 days during periods of exposure
or when experience indicates that coccidiosis is likely to be a hazard.
(B) As an aid in the treatment of coccidiosis caused by E. bovis and
E. zurnii, administer 10 mg/kg body weight for 5 days.
(ii) Limitations. Withdraw 24 hours before slaughter. A withdrawal
period has not been established for this product in preruminating
calves. Do not use in calves to be processed for veal. Use as the sole
source of amprolium.
[71 FR 56346, Sept. 27, 2006, as amended at 72 FR 60551, Oct. 25, 2007;
73 FR 45611, Aug. 6, 2008; 73 FR 70276, Nov. 20, 2008; 74 FR 10484, Mar.
11, 2009; 76 FR 38554, July 1, 2011; 76 FR 40808, July 12, 2011; 78 FR
23, Jan. 2, 2013; 78 FR 17596, Mar. 22, 2013; 78 FR 57058, Sept. 17,
2013]
Sec. 520.110 Apramycin sulfate soluble powder.
(a) Specifications. A water soluble powder used to make a medicated
drinking water containing apramycin sulfate equivalent to 0.375 gram of
apramycin activity per gallon of drinking water.
(b) Sponsor. See No. 000986 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.52 of this chapter.
(d) Conditions of use in swine--(1) Amount. Administer in drinking
water at the rate of 12.5 milligrams of apramycin per kilogram (5.7
milligrams per pound) of body weight per day for 7 days.
(2) Indications for use. For the control of porcine colibacillosis
(weanling pig scours) caused by strains of Escherichia coli sensitive to
apramycin.
(3) Limitations. Prepare fresh medicated water daily. Do not
slaughter treated swine for 28 days following treatment.
[47 FR 15771, Apr. 13, 1982, as amended at 49 FR 19642, May 9, 1984; 53
FR 37753, Sept. 28, 1988; 79 FR 28818, May 20, 2014]
Sec. 520.154 Bacitracin oral dosage forms.
Sec. 520.154a Bacitracin methylene disalicylate.
(a) Specifications. Each pound of soluble powder contains the
equivalent of 50 grams of bacitracin activity for use as in paragraph
(d)(1) or (d)(2) of this section, or the equivalent of 200 grams of
bacitracin activity for use as in paragraph (d) of this section.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.70 of this chapter.
(d) Conditions of use--(1) Growing turkeys--(i) Amount. 400
milligrams (mg) per gallon (gal) in drinking water.
(ii) Indications for use. Aid in the control of transmissible
enteritis complicated by organisms susceptible to bacitracin methylene
disalicylate.
(iii) Limitations. Prepare a fresh solution daily.
(2) Broiler and replacement chickens--(i) Amount. 100 mg per gal in
drinking water.
(A) Indications for use. Aid in the prevention of necrotic enteritis
caused by Clostridium perfringens susceptible to bacitracin methylene
disalicylate.
(B) Limitations. Prepare a fresh solution daily.
(ii) Amount. 200 to 400 mg per gal in drinking water. Administer
continuously 5 to 7 days or as long as clinical signs persist, then
reduce to prevention levels (100 mg/gal).
(A) Indications for use. Treatment of necrotic enteritis caused by
C.
[[Page 130]]
perfringens susceptible to bacitracin methylene disalicylate.
(B) Limitations. Prepare a fresh solution daily.
(3) Swine--(i) Amount. 1 gram per gallon in drinking water.
(ii) Indications for use. Treatment of swine dysentery associated
with Treponema hyodysenteriae. Administer continuously for 7 days or
until signs of dysentery disappear.
(iii) Limitations. Prepare a fresh solution daily. Treatment not to
exceed 14 days. If symptoms persist after 4 to 5 days consult a
veterinarian. Not to be given to swine that weigh more than 250 pounds.
(4) Growing quail--(i) Amount. 400 mg per gal in drinking water.
(ii) Indications for use. For prevention of ulcerative enteritis due
to Clostridium colinum susceptible to bacitracin methylene disalicylate.
(iii) Limitations. Prepare fresh solution daily. Use as sole source
of drinking water.
[57 FR 37322, Aug. 18, 1992; 57 FR 42623, Sept. 15, 1992, as amended at
63 FR 38474, July 17, 1998; 64 FR 13068, Mar. 17, 1999; 76 FR 53050,
Aug. 25, 2011; 79 FR 28818, May 20, 2014]
Sec. 520.154b Bacitracin methylene disalicylate and streptomycin
sulfate powder.
(a) Specifications. Each gram of powder contains 200 units
bacitracin methylene disalicylate and streptomycin sulfate equivalent to
20 milligrams of streptomycin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs(1) Amount. Administer 1 level
teaspoonful per 10 pounds of body weight three times daily, mixed in a
small quantity of liquid or feed.
(2) Indications for use. For the treatment of bacterial enteritis
caused by pathogens susceptible to bacitracin and streptomycin such as
Escherichia coli, Proteus spp., Staphylococcus spp., and Streptococcus
spp., and for the symptomatic treatment of associated diarrhea.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[71 FR 17702, Apr. 7, 2006, as amended at 79 FR 28818, May 20, 2014]
Sec. 520.154c Bacitracin zinc soluble powder.
(a) Specifications. Each pound contains the equivalent of not less
than 5 grams of bacitracin.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.70 of this chapter.
(d) Conditions of use--(1) Broiler chickens--(i) Amount. 100
milligrams per gallon in drinking water.
(A) Indications for use. Prevention of necrotic enteritis caused by
Clostridium perfringens susceptible to bacitracin zinc.
(B) Limitations. Prepare a fresh solution daily.
(ii) Amount. 200 to 400 milligrams per gallon in drinking water.
(A) Indications for use. Control of necrotic enteritis caused by
Clostridium perfringens susceptible to bacitracin zinc.
(B) Limitations. Prepare a fresh solution daily.
(2) Growing quail--(i) Amount. 500 milligrams per gallon in drinking
water for 5 days followed by 165 milligrams per gallon in drinking water
for 10 days.
(ii) Indications for use. Control of ulcerative enteritis caused by
Clostridium spp. susceptible to bacitracin zinc.
(iii) Limitations. Prepare a fresh solution daily.
[57 FR 37322, Aug. 18, 1992, as amended at 67 FR 78355, Dec. 24, 2002;
79 FR 28818, May 20, 2014]
Sec. 520.222 Bunamidine hydrochloride.
(a) Chemical name. N,N-Dibutyl-4-(hexyloxy)-1-naphthamidine
hydrochloride.
(b) Specifications. The drug is an oral tablet containing 100, 200,
or 400 milligrams of bunamidine hydrochloride.
(c) Sponsor. See No. 000061 in Sec. 510.600(c) of this chapter.
(d) Conditions of use. (1) The drug is intended for oral
administration to dogs for the treatment of the tapeworms Dipylidium
caninum, Taenia pisiformis, and Echinococcus granulosus, and to cats for
the treatment of the tapeworms Dipylidium caninum and Taenia
taeniaeformis.
(2) It is administered to cats and dogs at the rate of 25 to 50
milligrams per
[[Page 131]]
kilogram of body weight. The drug should be given on an empty stomach
and food should not be given for 3 hours following treatment.
(3) Tablets should not be crushed, mixed with food, or dissolved in
liquid. Repeat treatments should not be given within 14 days. The drug
should not be given to male dogs within 28 days prior to their use for
breeding. Do not administer to dogs or cats having known heart
conditions.
(4) For use only by or on the order of a licensed veterinarian.
[40 FR 13838, Mar. 27, 1975, as amended at 42 FR 13018, Mar. 8, 1977; 46
FR 48642, Oct. 2, 1981; 61 FR 8873, Mar. 6, 1996; 62 FR 61624, Nov. 19,
1997]
Sec. 520.246 Butorphanol tablets.
(a) Specifications. Each tablet contains butorphanol tartrate
equivalent to 1, 5, or 10 milligrams (mg) butorphanol base.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs--(1) Amount. Administer 0.25 mg
butorphanol base per pound of body weight. Repeat at intervals of 6 to
12 hours as required. Treatment should not normally be required for
longer than 7 days.
(2) Indications for use. For the relief of chronic nonproductive
cough associated with tracheobronchitis, tracheitis, tonsillitis,
laryngitis, and pharyngitis associated with inflammatory conditions of
the upper respiratory tract.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[79 FR 28818, May 20, 2014]
Sec. 520.260 n-Butyl chloride.
(a)(1) Specifications. n-Butyl chloride capsules, veterinary contain
272 milligrams or 816 milligrams of n-butyl chloride in each capsule.
(2) Sponsor. See No. 021091 in Sec. 510.600(c) of this chapter.
(3) Conditions of use. (i) It is used for the removal of ascarids
(Toxocara canis and Toxascaris leonina) and hookworms (Ancylostoma
caninum, Ancylostoma braziliense, and Uncinaria stenocephala) from dogs
and of the ascarid (Toxocara cati) and hookworm (Ancylostoma tubaeforme)
from cats.
(ii)(a) Animals should not be fed for 18 to 24 hours before being
given the drug. Puppies and kittens should be wormed at 6 weeks of age.
However, if heavily infested, they may be wormed at 4 or 5 weeks of age.
Administration of the drug should be followed in \1/2\ to 1 hour with a
teaspoonful to a tablespoonful of milk of magnesia or 1 or 2 milk of
magnesia tablets. Normal rations may be resumed 4 to 8 hours after
treatment. Puppies and kittens should be given a repeat treatment in a
week or 10 days. After that they should be treated every 2 months (or as
symptoms reappear) until a year old. When the puppy or kitten is a year
old, one treatment every 3 to 6 months is sufficient.
(b) For dogs or cats that have been wormed regularly, treatment
every 3 to 6 months will be sufficient. If a dog or cat has not been
wormed previously and has the symptoms of large roundworms a dose should
be given and repeated in 10 days. Removal of hookworms may require 3 or
4 doses at 10-day intervals.
(c) Puppies, dogs, cats, or kittens weighing 1 to 3 pounds should be
given 2 capsules per dose which contain 272 milligrams of n-butyl
chloride each. Such animals weighing 4 to 5 pounds should be given 3
such capsules. Animals weighing 6 to 7 pounds should be given 4 such
capsules and animals weighing 8 to 9 pounds should be given 5 such
capsules. Animals weighing 10 to 20 pounds should be given 3 capsules
which contain 816 milligrams of n-butyl chloride each, animals weighing
20 to 40 pounds should be given 4 such capsules and animals weighing
over 40 pounds should be given 5 such capsules with the maximum dosage
being 5 capsules, each of which contains 816 milligrams of n-butyl
chloride.
(iii) A veterinarian should be consulted before using in severely
debilitated dogs or cats and also prior to repeated use in cases which
present signs of persistent parasitism.
(b)(1) Specifications. n-Butyl chloride capsules contain 221, 442,
884, or 1,768 milligrams or 4.42 grams of n-butyl chloride in each
capsule.
(2) Sponsors. See No. 023851 in Sec. 510.600(c) of this chapter for
221, 442,
[[Page 132]]
884, or 1,768 milligram or 4.42 gram capsules; No. 038782 for 884 or
1,768 milligram or 4.42 gram capsules; and No. 054771 for 221 milligram
capsules.
(3) Conditions of use. (i) It is used for the removal of ascarids
(Toxocara canis and Toxascaris leonina) and hookworms (Ancylostoma
caninum, Ancylostoma braziliense, and Uncinaria stenocephala) from dogs.
(ii)(a) Dogs should not be fed for 18 to 24 hours before being given
the drug. Administration of the drug should be followed in \1/2\ to 1
hour with a mild cathartic. Normal feeding may be resumed 4 to 8 hours
after treatment. Animals subject to reinfection may be retreated in 2
weeks.
(b) The drug is administered orally to dogs. Capsules containing 221
milligrams of n-butyl chloride are administered to dogs weighing under 5
pounds at a dosage level of 1 capsule per 1\1/4\ pound of body weight.
Capsules containing 442 milligrams of n-butyl chloride are administered
to dogs weighing under 5 pounds at a dosage level of 1 capsule per 2\1/
2\ pounds body weight. Capsules containing 884 milligrams of n-butyl
chloride are administered to dogs as follows: Weighing under 5 pounds, 1
capsule; weighing 5 to 10 pounds, 2 capsules; weighing 10 to 20 pounds,
3 capsules; weighing 20 to 40 pounds, 4 capsules; over 40 pounds, 5
capsules. Capsules containing 1,768 milligrams of n-butyl chloride are
administered at a dosage level of 1 capsule per dog weighing 5 to 10
pounds. Capsules containing 4.42 grams of n-butyl chloride are
administered at a dosage level of 1 capsule per dog weighing 40 pounds
or over.
(iii) A veterinarian should be consulted before using in severely
debilitated dogs.
[40 FR 13838, Mar. 27, 1975, as amended at 40 FR 39858, Aug. 29, 1975;
44 FR 10059, Feb. 16, 1979; 54 FR 38515, Sept. 19, 1989; 55 FR 24556,
June 18, 1990; 64 FR 15684, Apr. 1, 1999; 70 FR 50182, Aug. 26, 2005; 78
FR 14669, Mar. 7, 2013; 79 FR 28818, May 20, 2014]
Editorial Note: At 78 FR 14669, Mar. 7, 2013, Sec. 520.260 was
amended by adding paragraphs (b)(1) through (3); however, the amendment
could not be incorporated because (b)(1) through (3) already existed.
Sec. 520.300 Cambendazole oral dosage forms.
Sec. 520.300a Cambendazole suspension.
(a) Specifications. Each fluid ounce contains 0.9 gram of
cambendazole.
(b) Sponsor. No. 050604 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in horses--(1) Amount. Administer by stomach
tube or as a drench at a dose of 0.9 gram of cambendazole per 100 pounds
of body weight (20 milligrams per kilogram).
(2) Indications for use. For the control of large strongyles
(Strongylus vulgaris, S. edentatus, S. equinus); small strongyles
(Trichonema, Poteriostomum, Cylicobrachytus, Craterostomum,
Oesophagodontus); roundworms (Parascaris); pinworms (Oxyuris); and
threadworms (Strongyloides).
(3) Limitations. Do not use in horses intended for human
consumption. Federal law restricts this drug to use by or on the order
of a licensed veterinarian.
[40 FR 13838, Mar. 27, 1975. Redesignated at 41 FR 1276, Jan. 7, 1976,
and amended at 42 FR 3838, Jan. 21, 1977; 62 FR 63270, Nov. 28, 1997; 79
FR 28818, May 20, 2014]
Sec. 520.300b Cambendazole pellets.
(a) Specifications. The drug is in feed pellets containing 5.3
percent cambendazole.
(b) Sponsor. No. 050604 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in horses--(1) Amount. Administer 20
milligrams cambendazole per kilogram body weight (6 ounces per 1,000
pounds) by mixing with normal grain ration given at one feeding. Doses
for individual horses should be mixed and fed separately to assure that
each horse will consume the correct amount. For animals maintained on
premises where reinfection is likely to occur, re-treatments may be
necessary. For most effective results, re-treat in 6 to 8 weeks.
(2) Indications for use. For the control of large strongyles
(Strongylus vulgaris, S. edentatus, S. equinus); small strongyles
(Trichonema, Poteriostomum, Cylicobrachytus, Craterostomum,
Oesophagodontus); roundworms (Parascaris); pinworms (Oxyuris); and
threadworms (Strongyloides).
(3) Limitations. Do not administer to pregnant mares during first 3
months
[[Page 133]]
of pregnancy. Do not use in horses intended for human consumption.
Consult your veterinarian for assistance in the diagnosis, treatment,
and control of parasitism.
[41 FR 1276, Jan. 7, 1976, as amended at 42 FR 3838, Jan. 21, 1977; 62
FR 63270, Nov. 28, 1997; 79 FR 28818, May 20, 2014]
Sec. 520.300c Cambendazole paste.
(a) Specifications. The drug is a paste containing 45 percent
cambendazole.
(b) Sponsor. No. 050604 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in horses--(1) Amount. Administer 20
milligrams cambendazole per kilogram body weight (5 grams per 550 pounds
(250 kilograms)) by depositing the paste on the back of the tongue using
a dosing gun. For animals maintained on premises where reinfection is
likely to occur, re-treatments may be necessary. For most effective
results, re-treat in 6 to 8 weeks.
(2) Indications for use. For the control of large strongyles
(Strongylus vulgaris, S. edentatus, S. equinus); small strongyles
(Trichonema, Poteriostomum, Cylicobrachytus, Craterostomum,
Oesophagodontus); roundworms (Parascaris); pinworms (Oxyuris); and
threadworms (Strongyloides).
(3) Limitations. Do not administer to pregnant mares during first 3
months of pregnancy. Do not use in horses intended for human
consumption. Consult your veterinarian for assistance in the diagnosis,
treatment, and control of parasitism.
[41 FR 1276, Jan. 7, 1976, as amended at 42 FR 3838, Jan. 21, 1977; 62
FR 63270, Nov. 28, 1997; 79 FR 28819, May 20, 2014]
Sec. 520.301 Caramiphen ethanedisulfonate and ammonium chloride tablets.
(a) Specifications. Each tablet contains 10 milligrams of 5st
caramiphen ethanedisulfonate and 80 milligrams of ammonium chloride.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs--(1) Amount. One tablet per 15 to 30
pounds of body weight every 4 to 6 hours.
(2) Indications for use. For relief of cough.
[43 FR 55385, Nov. 28, 1978, as amended at 79 FR 28819, May 20, 2014.
Redesignated at 80 FR 13229, Mar. 13, 2015]
Sec. 520.302 Carnidazole tablets.
(a) Specifications. Each tablet contains 10 milligrams of
carnidazole.
(b) Sponsor. See 053923 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Amount. Adult pigeons: 1 tablet (10
milligrams); newly weaned pigeons: \1/2\ tablet (5 milligrams).
(2) Indications for use. For treating trichomoniasis (canker) in
ornamental and homing pigeons.
(3) Limitations. Not for use in pigeons intended for human food.
Consult your veterinarian for assistance in the diagnosis, treatment,
and control of parasitism or when severely ill birds do not respond to
treatment.
[54 FR 32336, Aug. 7, 1989. Redesignated at 80 FR 13229, Mar. 13, 2015]
Sec. 520.304 Carprofen.
(a) Specifications. (1) Each caplet contains 25, 75, or 100
milligrams (mg) carprofen.
(2) Each chewable tablet contains 25, 75, or 100 mg carprofen.
(b) Sponsors. See sponsors in Sec. 510.600(c) of this chapter for
uses as in paragraph (d) of this section.
(1) No. 054771 for use of products described in paragraph (a) of
this section as in paragraph (d) of this section.
(2) Nos. 000115, 000859, 055529, and 062250 for use of product
described in paragraph (a)(1) as in paragraph (d) of this section.
(3) No. 026637 for use of product described in paragraph (a)(2) of
this section as in paragraph (d) of this section.
(c) [Reserved]
(d) Conditions of use in dogs--(1) Amount. 2 mg per pound (/lb) of
body weight once daily or 1 mg/lb twice daily. For the control of
postoperative pain, administer approximately 2 hours before the
procedure.
(2) Indications for use. For the relief of pain and inflammation
associated with osteoarthritis and for the control of postoperative pain
associated with soft tissue and orthopedic surgeries.
[[Page 134]]
(3) Limitations. Federal Law restricts this drug to use by or on the
order of a licensed veterinarian.
[61 FR 66581, Dec. 18, 1996, as amended at 64 FR 32181, June 16, 1999;
66 FR 63165, Dec. 5, 2001; 67 FR 6866, Feb. 14, 2002; 67 FR 65038, Oct.
23, 2002; 67 FR 65697, Oct. 28, 2002; 70 FR 30626, May 27, 2005; 71 FR
51995, Sept. 1, 2006; 72 FR 68478, Dec. 5, 2007; 74 FR 21768, May 11,
2009; 78 FR 52853, Aug. 27, 2013; 78 FR 66264, Nov. 5, 2013; 79 FR
28819, May 20, 2014. Redesignated and amended at 80 FR 13229, Mar. 13,
2015]
Sec. 520.314 Cefadroxil.
(a) Specifications.(1) Each tablet contains 50, 100, or 200
milligrams (mg) or 1 gram of cefadroxil.
(2) Each milliliter of suspension constituted from powder contains
50 mg of cefadroxil.
(b) Sponsor. See No. 000010 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs and cats--(1) Amount--(i) Dogs.
Administer 10 mg per pound (/lb) body weight twice daily orally.
(ii) Cats. Administer 10 mg/lb body weight once daily orally.
(2) Indications for use--(i) Dogs. For the treatment of skin and
soft tissue infections including cellulitis, pyoderma, dermatitis, wound
infections, and abscesses due to susceptible strains of Staphylococcus
aureus. For the treatment of genitourinary tract infections (cystitis)
due to susceptible strains of Escherichia coli, Proteus mirabilis, and
S. aureus.
(ii) Cats. For the treatment of skin and soft tissue infections
including abscesses, wound infections, cellulitis, and dermatitis caused
by susceptible strains of Pasteurella multocida, S. aureus,
Staphylococcus epidermidis, and Streptococcus spp.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[75 FR 10165, Mar. 5, 2010]
Sec. 520.370 Cefpodoxime tablets.
(a) Specifications. (1) Each tablet contains cefpodoxime proxetil
equivalent to 100 or 200 milligrams (mg) cefpodoxime.
(2) Each chewable tablet contains cefpodoxime proxetil equivalent to
100 or 200 mg cefpodoxime.
(b) Sponsors. See sponsors in Sec. 510.600(c) of this chapter for
uses as follows:
(1) No. 026637 for use of product in paragraph (a)(1) of this
section as in paragraph (c) of this section.
(2) No. 054771 for use of products in paragraph (a) of this section
as in paragraph (c) of this section.
(c) Conditions of use in dogs--(1) Amount. 5 to 10 mg per kilogram
(2.3 to 4.5 mg per pound) body weight daily for 5 to 7 days, or for 2 to
3 days beyond the cessation of clinical signs, up to a maximum of 28
days.
(2) Indications for use. For the treatment of skin infections
(wounds and abscesses) caused by susceptible strains of Staphylococcus
pseudintermedius, S. aureus, Streptococcus canis (group G, -hemolytic),
Escherichia coli, Pasteurella multocida, and Proteus mirabilis.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[69 FR 52815, Aug. 30, 2004, as amended at 78 FR 5714, Jan. 28, 2013; 79
FR 28819, May 20, 2014; 80 FR 13229, Mar. 13, 2015]
Sec. 520.376 Cephalexin.
(a) Specifications. Each chewable tablet contains 75, 150, 300, or
600 milligrams (mg) cephalexin.
(b) Sponsor. See No. 051311 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. Administer 22 mg per
kilogram of body weight twice daily for 28 days.
(ii) Indications for use. For the treatment of secondary superficial
bacterial pyoderma in dogs caused by susceptible strains of
Staphylococcus pseudintermedius.
(iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(2) [Reserved]
[77 FR 47512, Aug. 9, 2012]
Sec. 520.390 Chloramphenicol oral dosage forms.
Sec. 520.390a Chloramphenicol tablets.
(a) Specifications. Each tablet contains 50, 100, 250, or 500
milligrams (mg); 1 or 2.5 grams (g) of chloramphenicol.
[[Page 135]]
(b) Sponsors. See Sec. 510.600(c) of this chapter:
(1) For use as in paragraphs (c)(1), (c)(2)(i), and (c)(3) of this
section:
(i) No. 054628 for 100-, 250-, and 500-mg; and 1- and 2.5-g tablets;
(ii) No. 054771 for 100-, 250-, and 500-mg tablets;
(2) For use as in paragraphs (c)(1), (c)(2)(ii), and (c)(3) of this
section:
(i) No. 061623 for 50-, 100-, 250-, and 500-mg; and 1-g tablets;
(ii) [Reserved]
(c) Conditions of use in dogs--(1) Amount. Administer 25 mg per
pound of body weight by mouth every 6 hours.
(2) Indications for use--(i) For the treatment of bacterial
pulmonary infections, bacterial infections of the urinary tract,
bacterial enteritis, and bacterial infections associated with canine
distemper caused by susceptible organisms.
(ii) For the treatment of bacterial gastroenteritis associated with
bacterial diarrhea, bacterial pulmonary infections, and bacterial
infections of the urinary tract caused by susceptible organisms.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian. Federal law prohibits the extralabel
use of this drug in food-producing animals.
[77 FR 4896, Feb. 1, 2012, as amended at 78 FR 21059, Apr. 9, 2013; 79
FR 28819, May 20, 2014]
Sec. 520.390b Chloramphenicol capsules.
(a) Specifications. Each capsule contains 50, 100, 250, or 500
milligrams (mg) chloramphenicol.
(b) Sponsors. See Nos. 050057 and 054771 in Sec. 510.600(c) of this
chapter for use as in paragraph (d) of this section.
(c) Special considerations. Federal law prohibits the extralabel use
of this product in food-producing animals.
(d) Conditions of use in dogs--(1) Amount. 25 mg per pound of body
weight every 6 hours.
(2) Indications for use. For treatment of bacterial pulmonary
infections, bacterial infections of the urinary tract, bacterial
enteritis, and bacterial infections associated with canine distemper
caused by susceptible organisms.
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[70 FR 75398, Dec. 20, 2005, as amended at 73 FR 18442, Apr. 4, 2008; 75
FR 55676, Sept. 14, 2010; 79 FR 28819, May 20, 2014]
Sec. 520.390c Chloramphenicol palmitate oral suspension.
(a) Specifications. Each milliliter contains chloramphenicol
palmitate equivalent to 30 milligrams of chloramphenicol.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. Dogs(1) Amount. 25 milligrams per pound of
body weight every 6 hours. If no response is obtained in 3 to 5 days,
discontinue use and reevaluate diagnosis.
(2) Indications for use. Treatment of bacterial pulmonary
infections, infections of the urinary tract, enteritis, and infections
associated with canine distemper that are caused by organisms
susceptible to chloramphenicol.
(3) Limitations. Not for use in animals that are raised for food
production. Must not be used in meat-, egg-, or milk-producing animals.
The length of time that residues persist in milk or tissues has not been
determined. Federal law restricts this drug to use by or on the order of
a licensed veterinarian.
[57 FR 37323, Aug. 18, 1992; 57 FR 42623, Sept. 15, 1992, as amended at
79 FR 28819, May 20, 2014]
Sec. 520.420 Chlorothiazide tablets and boluses.
(a)(1) Specifications. Each tablet contains 0.25 gram of
chlorothiazide.
(2) Sponsor. See No. 050604 in Sec. 510.600(c) of this chapter.
(3) Conditions of use--(i) Amount. Usual dosage is 5 to 10
milligrams per pound of body weight two or three times daily.
(ii) Indications for use. For use in dogs for treatment of
congestive heart failure and renal edema.
(iii) Limitations. (a) Dosage must be adjusted to meet the changing
needs of the individual animal. In mild and responsive cases, it is
suggested that a dose of 5 milligrams per pound of body weight be
administered two or three times daily. In moderately edematous and
moderately responsive animals, a
[[Page 136]]
dose of 7.5 to 10 milligrams per pound of body weight may be
administered three times daily. Severe conditions may require higher
doses. Certain animals may respond adequately to intermittent therapy;
in these cases, the drug may be administered either every other day or
for 3 to 5 days each week.
(b) Animals should be regularly and carefully observed for early
signs of fluid and electrolyte imbalance. Take appropriate
countermeasures if this should occur. In some dogs, hypochloremic
alkalosis may occur (that is, excretion of chloride in relation to
sodium is excessive; the plasma bicarbonate level increases and
alkalosis results). Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
(b)(1) Specifications. Each bolus contains 2 grams of
chlorothiazide.
(2) Sponsor. See No. 000006 in Sec. 510.600(c) of this chapter.
(3) Conditions of use--(i) Amount. 2 grams once or twice daily for 3
or 4 days.
(ii) Indications for use. For use in cattle as an aid in reduction
of postparturient udder edema.
(iii) Limitations. Animals should be regularly and carefully
observed for early signs of fluid and electrolyte imbalance. Take
appropriate countermeasures if this should occur. Milk taken from dairy
animals during treatment and for 72 hours (six milkings) after latest
treatment must not be used for food. Federal law restricts this drug to
use by or on the order of a licensed veterinarian.
[43 FR 39085, Sept. 1, 1978, as amended at 62 FR 63270, Nov. 28, 1997;
79 FR 28819, May 20, 2014]
Sec. 520.434 Chlorphenesin carbamate tablets.
(a) Specifications. Each tablet contains 400 milligrams of
chlorphenesin carbamate.
(b) Sponsor. See No. 054771 in Sec. 510.600(c) of this chapter.
(c) Conditions of use in dogs--(1) Amount. 50 milligrams per pound
of body weight on first day; 25 milligrams per pound of body weight each
following day. Divide total daily dose into 2 or 3 equal doses--
administer at 12- or 8-hour intervals.
(2) Indications for use. For use as an adjunct to therapy of acute
inflammatory and traumatic conditions of skeletal muscles. The drug
provides relief of the signs of discomfort associated with myositis,
muscle sprains, traumatic injuries, stifle injuries--especially when
administered before or after surgery--and invertebral disc syndrome (can
be used concurrently with adrenal corticosteroids).
(3) Limitations. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[44 FR 16009, Mar. 16, 1979, as amended at 79 FR 28819, May 20, 2014]
Sec. 520.441 Chlortetracycline powder.
(a) Specifications. Chlortetracycline powder contains not less than
15 milligrams per gram chlortetracycline hydrochloride, or
chlortetracycline bisulfate equivalent to 25.6, 64 or 102.4 grams per
pound (56.4, 141 or 225.6 milligrams per gram) chlortetracycline
hydrochloride.
(b) Sponsors. See sponsors in Sec. 510.600(c) of this chapter for
use as in paragraph (d) of this section.
(1) No. 069254 for use as in paragraph (d) of this section.
(2) Nos. 000010 and 054771 for use as in paragraph (d) of this
section.
(3) No. 054628 for use as in paragraphs (d)(4)(i)(A), (d)(4)(i)(B),
and (d)(4)(ii) through (d)(4)(iv) of this section. (d)(4)(ii) through
(iv) of this section.
(4) Nos. 012286 and 076475 for use as in paragraphs (d)(4)(i)(A),
(d)(4)(i)(B), (d)(4)(ii), and (d)(4)(iii) of this section.
(c) Related tolerances. See Sec. 556.150 of this chapter.
(d) Conditions of use. (1) Use as chlortetracycline hydrochloride in
drinking water as follows:
(i) Swine--(A) Amount. Ten milligrams per pound of body weight daily
in divided doses.
(1) Indications for use. Control and treatment of bacterial
enteritis (scours) caused by Escherichia coli and bacterial pneumonia
associated with Pasteurella spp., Actinobacillus pleuropneumoniae
(Hemophilus spp.), and Klebsiella spp.
(2) Limitations. Prepare a fresh solution twice daily; as sole
source of chlortetracycline; administer for not more than 5 days.
[[Page 137]]
(B) [Reserved]
(ii) [Reserved]
(2) Use as chlortetracycline hydrochloride in a drench or drinking
water as follows:
(i) Calves--(A) Amount. Ten milligrams per pound of body weight
daily in divided doses.
(1) Control and treatment of bacterial enteritis (scours) caused by
E. coli and bacterial pneumonia (shipping fever) associated with
Pasteurella spp., A. pleuropneumoniae (Hemophilus spp.), and Klebsiella
spp.
(2) Limitations. Prepare fresh solution daily; as sole source of
chlortetracycline; administer for not more than 5 days; do not slaughter
animals for food within 24 hours of treatment; do not administer this
product with milk or milk replacers; administer 1 hour before or 2 hours
after feeding milk or milk replacers; a withdrawal period has not been
established in preruminating calves; do not use in calves to be
processed for veal.
(B) [Reserved]
(ii) [Reserved]
(3) [Reserved]
(4) The following uses of chlortetracycline hydrochloride or
chlortetracycline bisulfate in drinking water or drench were reviewed by
the National Academy of Sciences/National Research Council (NAS/NRC) and
found effective:
(i) Chickens--(A) Amount. 200 to 400 milligrams per gallon.
(1) Indications for use. Control of infectious synovitis caused by
Mycoplasma synoviae.
(2) Limitations. Prepare fresh solution daily; as sole source of
chlortetracycline; do not use for more than 14 days; do not slaughter
animals for food within 24 hours of treatment; do not use in laying
chickens.
(B) Amount. 400 to 800 milligrams per gallon.
(1) Indications for use. Control of chronic respiratory disease and
air-sac infections caused by M. gallisepticum and E. coli.
(2) Limitations. Prepare fresh solution daily; as sole source of
chlortetracycline; do not use for more than 14 days; do not slaughter
animals for food within 24 hours of treatment; do not use in laying
chickens.
(C) Amount. One thousand milligrams per gallon.
(1) Indications for use. Control of mortality due to fowl cholera
caused by Pasteurella multocida susceptible to chlortetracycline.
$(2) Limitations. See paragraph (d)(4)(i)(A)(2) of this section.
(ii) Growing turkeys--(A) Amount. 400 milligrams per gallon.
(1) Indications for use. Control of infectious synovitis caused by
M. synoviae.
(2) Limitations. Prepare fresh solution daily; as sole source of
chlortetracycline; do not use for more than 14 days; do not slaughter
animals for food within 24 hours of treatment.
(B) Amount. 25 milligrams per pound of body weight daily.
(1) Indications for use. Control of complicating bacterial organisms
associated with bluecomb (transmissible enteritis, coronaviral
enteritis).
(2) Limitations. Prepare fresh solution daily; as sole source of
chlortetracycline; do not use for more than 14 days; do not slaughter
animals for food within 24 hours of treatment.
(iii) Swine--(A) Amount. 10 milligrams per pound body weight daily
in divided doses.
(B) Indications for use. Control and treatment of bacterial
enteritis (scours) caused by E. coli and Salmonella spp. and bacterial
pneumonia associated with Pasteurella spp., Actinobacillus
pleuropneumoniae (Hemophilus spp.), and Klebsiella spp.
(C) Limitations. Prepare fresh solution daily; as sole source of
chlortetracycline; do not use for more than 5 days. For Nos. 000010 and
021930, do not slaughter animals for food within 5 days of treatment.
For No. 000010, do not slaughter animals for food within 24 hours of
treatment.
(iv) Calves, beef cattle, and nonlactating dairy cattle--(A) Amount.
10 milligrams per pound daily in divided doses.
(B) Indications for use. Control and treatment of bacterial
enteritis (scours) caused by E. coli and Salmonella spp. and bacterial
pneumonia (shipping fever complex) associated with Pasteurella spp., A.
pleuropneumoniae (Hemophilus spp.), and Klebsiella spp.
[[Page 138]]
(C) Limitations. Prepare fresh solution daily; use as a drench; as
sole source of chlortetracycline; do not use for more than 5 days; do
not slaughter animals for food within 24 hours of treatment; do not use
in lactating cattle; do not administer this product with milk or milk
replacers; administer 1 hour before or 2 hours after feeding milk or
milk replacers; a withdrawal period has not been established in
preruminating calves; do not use in calves to be processed for veal.
(5) Use in a drench or drinking water as follows:
(i) Chickens--(A) Amount. 200 to 400 mg/gal, for 7 to 14 days.
(1) Indications for use. Control of infectious synovitis caused by
M. synoviae susceptible to chlortetracycline.
(2) Limitations. Prepare fresh solution daily; use as the sole
source of chlortetracycline; do not use for more than 14 consecutive
days; do not use in laying chickens; do not administer to chickens
within 24 hours of slaughter.
(B) Amount. 400 to 800 mg/gal, for 7 to 14 days.
(1) Indications for use. Control of chronic respiratory disease
(CRD) and air-sac infections caused by M. gallisepticum and E. coli
susceptible to chlortetracycline.
(2) Limitations. As in paragraph (d)(5)(i)(A)(2) of this section.
(C) Amount. One thousand mg/gal, for 7 to 14 days.
(1) Indications for use. Control of mortality due to fowl cholera
caused by Pasteurella multocida susceptible to chlortetracycline.
(2) Limitations. As in paragraph (d)(5)(i)(A)(2) of this section.
(ii) Growing Turkeys--(A) Amount. 400 mg/gal, for 7 to 14 days.
(1) Indications for use. Control of infectious synovitis caused by
Mycoplasma synoviae susceptible to chlortetracycline.
(2) Limitations. Prepare fresh solution daily; use as the sole
source of chlortetracycline; do not use for more than 14 consecutive
days; do not administer to growing turkeys within 24 hours of slaughter.
(B) Amount. 25 mg/lb body weight daily, for 7 to 14 days.
(1) Indications for use. Control of complicating bacterial organisms
associated with bluecomb (transmissible enteritis, coronaviral
enteritis) susceptible to chlortetracycline.
(2) Limitations. As in paragraph (d)(5)(ii)(A)(2) of this section.
(iii) Swine--(A) Amount. 10 mg/lb body weight daily, for 3 to 5
days.
(B) Indications for use. Control and treatment of bacterial
enteritis (scours) caused by E. coli and Salmonella spp., and bacterial
pneumonia associated with Pasteurella spp., A. pleuropneumoniae, and
Klebsiella spp. susceptible to chlortetracycline.
(C) Limitations. Prepare fresh solution daily; use as the sole
source of chlortetracycline; do not use for more than 5 days; do not
administer to swine within 24 hours of slaughter.
(iv) Calves, beef cattle, and nonlactating dairy cattle--(A) Amount.
10 mg/lb body weight daily in divided doses, for 3 to 5 days.
(B) Indications for use. Control and treatment of bacterial
enteritis (scours) caused by Escherichia coli and Salmonella spp., and
bacterial pneumonia associated with Pasteurella spp., Histophilus spp.,
and Klebsiella spp. susceptible to chlortetracycline.
(C) Limitations. Prepare fresh solution daily; use as a drench; use
as the sole source of chlortetracycline; do not use for more than 5
days; do not administer to cattle within 24 hours of slaughter; do not
use in lactating dairy cattle; do not administer this product with milk
or milk replacers; administer 1 hour before or 2 hours after feeding
milk or milk replacers; a withdrawal period has not been established in
preruminating calves; do not use in calves to be processed for veal.
[57 FR 37324, Aug. 18, 1992]
Editorial Note: For Federal Register citations affecting Sec.
520.441, see the List of CFR Sections Affected, which appears in the
Finding Aids section of the printed volume and at www.fdsys.gov.
Sec. 520.443 Chlortetracycline tablets and boluses.
(a) Specifications. Each tablet/bolus contains 25, 250, or 500
milligrams (mg) chlortetracycline hydrochloride.
(b) Sponsor. See No. 054628 in Sec. 510.600(c) of this chapter.
[[Page 139]]
(c) Related tolerances. See Sec. 556.150 of this chapter.
(d) Conditions of use in calves--(1) Amount. One 250 milligram bolus
per 50 pounds of body weight twice a day for 3 to 5 days.
(i) Indications for use. Treatment of bacterial enteritis (scours)
caused by Escherichia coli and bacterial pneumonia associated with
Pasteurella spp., Klesbsiella spp., and Hemophilus spp.
(ii) Limitations. Administer bolus directly by mouth or crush and
dissolve in milk or water for drenching or bucket feeding; if no
improvement is noted after 3 days of treatment, consult a veterinarian;
do not use for more than 5 days; do not administer within 24 hours of
slaughter.
(2) Amount. One 25 milligram tablet for each 5 pounds of body weight
every 12 hours daily for 3 to 5 days.
(i) Indications for use. Control and treatment of bacterial
enteritis (scours) caused by E. coli and Salmonella spp. and bacterial
pneumonia associated with Pasteurella spp., Hemophilus spp., and
Klebsiella spp., susceptible to chlortetracycline.
(ii) Limitations. Administer tablet directly by mouth or crush and
dissolve in water for drenching; if no improvement is noted after 3 days
of treatment, consult a veterinarian; do not use for more than 5 days;
when feeding milk or milk replacer, administration 1 hour before or 2
hours after feeding; do not administer within 24 hours of slaughter.
(3) Amount. One 500 milligram bolus per 100 pounds of body weight
twice a day for 3 to 5 days.
(i) Indications for use. Treatment of bacterial enteritis (scours)
caused by E. coli and Salmonella spp., and bacterial pneumonia
associated with Pasteurella spp., Hemophilus spp., and Klebsiella spp.,
susceptible to chlortetracycline.
(ii) Limitations. Administer directly by mouth or crush and dissolve
in water for drenching; if no improvement is noted after 3 days of
treatment, consult a veterinarian; do not use for more than 5 days; do
not administer within 24 hours of slaughter.
[57 FR 37325, Aug. 18, 1992, as amended at 67 FR 78355, Dec. 24, 2002.
Redesignated and amended at 76 FR 49649, Aug. 11, 2011; 78 FR 21059,
Apr. 9, 2013]
Sec. 520.445 Chlortetracycline and sulfamethazine powder.
(a) Specifications. Each pound of soluble powder contains
chlortetracycline bisulfate equivalent to 102.4 grams (g) of
chlortetracycline hydrochloride and sulfamethazine bisulfate equivalent
to 102.4 g of sulfamethazine.
(b) Sponsor. See No. 000010 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. Sec. 556.150 and 556.670 of this
chapter.
(d) Conditions of use in swine. Administer in drinking water as
follows:
(1) Amount. 250 milligrams (mg) of chlortetracycline and 250 mg of
sulfamethazine per gallon.
(2) Indications for use. For the prevention and treatment of
bacterial enteritis; as an aid in the reduction of the incidence of
cervical abscesses; and as an aid in the maintenance of weight gains in
the presence of bacterial enteritis and atrophic rhinitis.
(3) Limitations. Use as the sole source of chlortetracycline and
sulfonamide. Not to be used for more than 28 consecutive days. Withdraw
15 days before slaughter.
[76 FR 49649, Aug. 11, 2011]