[Title 21 CFR E]
[Code of Federal Regulations (annual edition) - April 1, 1996 Edition]
[Title 21 - FOOD AND DRUGS]
[Chapter I - FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES--(Continued)]
[Subchapter E - ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS]
[From the U.S. Government Publishing Office]
21
FOOD AND DRUGS
6
1996-04-01
1996-04-01
false
ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS
E
SUBCHAPTER E
FOOD AND DRUGS
FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES--(Continued)
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.
500.25 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.
500.35 Animal feeds contaminated with Salmonella microorganisms.
500.45 Use of polychlorinated biphenyls (PCB's) in the production,
handling, and storage of animal feed.
500.46 Hexachlorophene in animal drugs.
500.49 Chlorofluorocarbon propellants.
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 Operational definition of ``no residue''.
500.86 Marker residue and target tissue.
500.88 Regulatory method.
500.90 Waiver of requirements.
500.92 Implementation.
Authority: Secs. 201, 301, 402, 403, 409, 501, 502, 503, 512, 701 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342, 343,
348, 351, 352, 353, 360b, 371).
Source: 40 FR 13802, Mar. 27, 1975, unless otherwise noted.
Subpart A--[Reserved]
Subpart B--Specific Administrative Rulings and Decisions
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.
(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
(d) and (e) of this chapter. For animal feeds bearing or containing
anthelmintic drugs covered by approved applications, the labeling
revisions required for compliance with this section may be placed into
effect without the submission of supplemental applications as provided
for in Sec. 514.9 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.
[[Page 6]]
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 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 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]
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 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
[[Page 7]]
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. 500.35 Animal feeds contaminated with Salmonella microorganisms.
(a) Investigations by the Food and Drug Administration, the Centers
for Disease Control of the U.S. Public Health Service, the Animal Health
Division of the Agricultural Research Service, U.S. Department of
Agriculture, and by various State public health agencies have revealed
that processed fish meal, poultry meal, meat meal, tankage, and other
animal byproducts intended for use in animal feed may be contaminated
with Salmonella bacteria, an organism pathogenic to man and animals.
Contamination of these products may occur through inadequate heat
treatment of the product during its processing or through
recontamination of the heat-treated product during a time of improper
storage or handling subsequent to processing.
(b) Articles used in food for animals are included within the
definition of food in section 201(f) of the Federal Food, Drug, and
Cosmetic Act. Further, Salmonella contamination of such animal feeds
having the potentiality for producing infection and disease in animals
must be regarded as an adulterant within the meaning of section 402(a)
of the act. Therefore, the Food and Drug Administration will regard as
adulterated within the meaning of section 402(a) of the act shipments of
the following when intended for animal feed and encountered in
interstate commerce and found upon examination to be contaminated with
Salmonella microorganisms: Bone meal, blood meal, crab meal, feather
meal, fish meal, fish solubles, meat scraps, poultry meat meal, tankage,
or other similar animal byproducts, or blended mixtures of these.
[40 FR 13802, Mar. 27, 1975, as amended at 54 FR 18279, Apr. 28, 1989]
[[Page 8]]
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 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
[[Page 9]]
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.
(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. 500.49 Chlorofluorocarbon propellants.
The use of chlorofluorocarbons as propellants in self-pressurized
containers is prohibited from use in all animal drugs, animal food, and
related products as provided by Sec. 2.125 of this chapter.
[43 FR 11317, Mar. 17, 1978]
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
[[Page 10]]
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
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 therefor on a proposal to
omit such information from the dispensing package.
[[Page 11]]
(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 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
[[Page 12]]
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
under Sec. 5.10 of this chapter) that no residue of that compound will
be found in the food produced from those animals under conditions of use
reasonably certain to be followed in practice. This subpart provides an
operational definition of no residue and identifies the steps a sponsor
of a compound shall follow to secure the approval of the compound. FDA
guidelines contain the procedures and protocols FDA recommends for the
implementation of this subpart. These guidelines are available from the
Dockets Management Branch (HFA-305), Food and Drug Administration, rm.
1-23, 12420 Parklawn Dr., Rockville, MD 20857. Requests for these
guidelines should be identified with Docket No. 83D-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 oral, chronic,
dose-response studies and 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]
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.
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
permitted concentration.
Preslaughter withdrawal period or milk discard time means the time
after cessation of administration of the sponsored compound for the
residue of carcinogenic concern in the edible product to deplete to the
concentration that will satisfy the operational definition of no
residue.
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 in
the last tissue to deplete to its permitted concentration.
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 permitted concentration of residue of carcinogenic
concern for a specific edible tissue.
[[Page 13]]
So means the concentration of the 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. For the purpose of this
subpart, FDA will also assume that this So will correspond to the
concentration of residue of carcinogenic concern in the total human diet
that represents no significant increase in the risk of cancer to people.
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.
Sec. 500.84 Operational definition of ``no residue''.
(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 analyze the data from the bioassays using a
statistical extrapolation procedure.
(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.
(2) FDA will consider that ``no residue'' of the compound remains in
the edible tissue when conditions of use of the sponsored compound,
including any required preslaughter withdrawal period or milk discard
time, ensure that the concentration of the residue of carcinogenic
concern in the total diet of people will not exceed 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 of carcinogenic concern that is permitted in a
specific edible product.
Sec. 500.86 Marker residue and target tissue.
(a) For each edible tissue, the sponsor shall measure the depletion
of the residue of carcinogenic concern until its concentration is at or
below Sm.
(b) In one or more edible tissues, the sponsor shall also measure
the depletion of one or more potential marker residues until the
concentration of the residue of carcinogenic concern is at or below
Sm.
(c) From these data, FDA will select a target tissue and a marker
residue and designate the concentration of marker residue (Rm) that
the regulatory method must be capable of measuring in the target tissue.
FDA will select Rm such that the absence of the marker residue in
the target tissue above Rm can be taken as confirmation that the
residue of carcinogenic concern does not exceed Sm in each of the
edible tissues and, therefore, that the residue of carcinogenic concern
in the diet of people does not exceed So.
(d) When a compound is to be used in milk- or egg-producing animals,
milk or eggs must be the target tissue in addition to the tissue
selected to monitor for residues in the edible carcass.
(Approved by the Office of Management and Budget under control number
0910-0228)
Sec. 500.88 Regulatory method.
(a) The sponsor shall submit for evaluation and validation a
regulatory method developed to monitor compliance with FDA's operational
definition of no residue.
[[Page 14]]
(b) The regulatory method must reliably measure and confirm the
identity of the marker residue in the target tissue at concentrations
equal to and above Rm.
(c) FDA will publish in the Federal Register the complete regulatory
method for measuring the marker residue in the target tissue in
accordance with the provisions of sections 409(c)(3)(A), 512(d)(1)(H)
and (i), and 721(b)(5)(B) of the act.
(Approved by the Office of Management and Budget under control number
0910-0228)
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, Secs. 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, Secs. 500.82 through
500.90 apply.
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: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act (15
U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342, 343, 348,
371).
Source: 41 FR 38619, Sept. 10, 1976, unless otherwise noted.
[[Page 15]]
Subpart A--General Provisions
Sec. 501.1 Principal display panel of package form animal food.
The term principal display panel as it applies to food in package
form and as used in this part, means the part of a label that is most
likely to be displayed, presented, shown, or examined under customary
conditions of display for retail sale. The principal display panel shall
be large enough to accommodate all the mandatory label information
required to be placed thereon by this part with clarity and
conspicuousness and without obscuring design, vignettes, or crowding.
Where packages bear alternate principal display panels, information
required to be placed on the principal display panel shall be duplicated
on each principal display panel. For the purpose of obtaining uniform
type size in declaring the quantity of contents for all packages of
substantially the same size, the term area of the principal display
panel means the area of the side or surface that bears the principal
display panel, which area shall be:
(a) In the case of a rectangular package where one entire side
properly can be considered to be the principal display panel side, the
product of the height times the width of that side;
(b) In the case of a cylindrical or nearly cylindrical container, 40
percent of the product of the height of the container times the
circumference;
(c) In the case of any otherwise shaped container, 40 percent of the
total surface of the container: Provided, however, That where such
container presents an obvious principal display panel such as the top of
a triangular or circular package, the area shall consist of the entire
top surface. In determining the area of the principal display panel,
exclude tops, bottoms, flanges at tops and bottoms of cans, and
shoulders and necks of bottles or jars. In the case of cylindrical or
nearly cylindrical containers, information required by this part to
appear on the principal display panel shall appear within that 40
percent of the circumference which is most likely to be displayed,
presented, shown, or examined under customary conditions of display for
retail sale.
Sec. 501.2 Information panel of package for animal food.
(a) The term information panel as it applies to packaged food means
that part of the label immediately contiguous and to the right of the
principal display panel as observed by an individual facing the
principal display panel with the following exceptions:
(1) If the part of the label immediately contiguous and to the right
of the principal display panel is too small to accommodate the necessary
information or is otherwise unusable label space, e.g., folded flaps or
can ends, the panel immediately contiguous and to the right of this part
of the label may be used.
(2) If the package has one or more alternate principal display
panels, the information panel is immediately contiguous and to the right
of any principal display panel.
(3) If the top of the container is the principal display panel and
the package has no alternate principal display panel, the information
panel is any panel adjacent to the principal display panel.
(b) All information required to appear on the label of any package
of food pursuant to Secs. 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 Secs. 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.
[[Page 16]]
(iii) The label information includes a full list of ingredients in
accordance with regulations in this part.
(iv) The information required by paragraph (b) of this section
appears on the principal display panel or information panel label in
accordance with the provisions of this paragraph (c) except that the
type size is not less than \3/64\ inch in height.
(2) Packaged foods are exempt from the type size requirements of
this paragraph: Provided, That:
(i) The package is designed such that it has a single obvious
principal display panel as this term is defined in Sec. 501.1 and has no
other available surface area for an information panel or alternate
principal display panel.
(ii) The area of surface available for labeling on the principal
display panel of the package as this term is defined in Sec. 501.1 is
less than 12 square inches and bears all labeling appearing on the
package.
(iii) The label information includes a full list of ingredients in
accordance with regulations in this part.
(iv) The information required by paragraph (b) of this section
appears on the single, obvious principal display panel in accordance
with the provisions of this paragraph (c) except that the type size is
not less than \1/32\ inch in height.
(3) Packaged foods are exempt from the type size requirements of
this paragraph: Provided, That:
(i) The package is designed such that it has a total surface area
available to bear labeling of less than 12 square inches.
(ii) The label information includes a full list of ingredients in
accordance with regulations in this part.
(iii) The information required by paragraph (b) of this section
appears on the principal display panel or information panel label in
accordance with the provisions of this paragraph (c) except that the
type size is not less than \1/32\ inch in height.
(d) All information required to appear on the principal display
panel or on the information panel pursuant to this section shall appear
on the same panel unless there is insufficient space. In determining the
sufficiency of the available space, any vignettes, design, and other
nonmandatory label information shall not be considered. If there is
insufficient space for all of this information to appear on a single
panel, it may be divided between these two panels except that the
information required pursuant to any given section or part shall all
appear on the same panel. A food whose label is required to bear the
ingredient statement on the principal display panel may bear all other
information specified in paragraph (b) of this section on the
information panel.
(e) All information appearing on the information panel pursuant to
this section shall appear in one place without other intervening
material.
(f) If the label of any package of food is too small to accommodate
all of the information required by Secs. 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
[[Page 17]]
the statement of identity and shall be declared in letters of a type
size bearing a reasonable relation to the size of the letters forming
the other components of the statement of identity; except that if the
optional form is visible through the container or is depicted by an
appropriate vignette, the particular form need not be included in the
statement. This specification does not affect the required declarations
of identity under definitions and standards for foods promulgated
pursuant to section 401 of the act.
(d) This statement of identity shall be presented in bold type on
the principal display panel, shall be in a size reasonably related to
the most prominent printed matter on such panel, and shall be in lines
generally parallel to the base on which the package rests as it is
designed to be displayed.
(e) Under the provisions of section 403(c) of the Federal Food,
Drug, and Cosmetic Act, a food shall be deemed to be misbranded if it is
an imitation of another food unless its label bears, in type of uniform
size and prominence, the word imitation and, immediately thereafter, the
name of the food imitated.
(1) A food shall be deemed to be an imitation and thus subject to
the requirements of section 403(c) of the act if it is a substitute for
and resembles another food but is nutritionally inferior to that food.
(2) A food that is a substitute for and resembles another food shall
not be deemed to be an imitation provided it meets each of the following
requirements:
(i) It is not nutritionally inferior to the food for which it
substitutes and which it resembles.
(ii) Its label bears a common or usual name that complies with the
provisions of Sec. 502.5 of this chapter and that is not false or
misleading, or in the absence of an existing common or usual name, an
appropriately descriptive term that is not false or misleading. The
label may, in addition, bear a fanciful name which is not false or
misleading.
(3) A food for which a common or usual name is established by
regulation (e.g., in a standard of identity pursuant to section 401 of
the act, in a common or usual name regulation and may, in addition, bear
a fanciful name which is not false or misleading, and established
pursuant to part 502 of this chapter), and which complies with all of
the applicable requirements of such regulation(s), shall not be deemed
to be an imitation.
(4) Nutritional inferiority includes:
(i) Any reduction in the content of an essential nutrient that is
present in a measurable amount.
(ii) If the Commissioner concludes that a food is a substitute for
and resembles another food but is inferior to the food imitated for
reasons other than those set forth in this paragraph, he may propose
appropriate revisions to this regulation or he may propose a separate
regulation governing the particular food.
(f) A label may be required to bear the percentage(s) of a
characterizing ingredient(s) or information concerning the presence or
absence of an ingredient(s) or the need to add an ingredient(s) as part
of the common or usual name of the food pursuant to part 502 of this
chapter.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 14091, Mar. 15, 1977;
54 FR 18279, Apr. 28, 1989]
Sec. 501.4 Animal food; designation of ingredients.
(a) Ingredients required to be declared on the label of a food,
including foods that comply with standards of identity that require
labeling in compliance with this part 501, except those exempted by
Sec. 501.100, shall be listed by common or usual name in descending
order of predominance by weight on either the principal display panel or
the information panel in accordance with the provisions of Sec. 501.2.
(b) The name of an ingredient shall be a specific name and not a
collective (generic) name, except that:
(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
[[Page 18]]
Agriculture, or conforms to a definition and standard of identity
established pursuant to section 401 of the Federal Food, Drug, and
Cosmetic Act, shall be designated in the statement of ingredients on the
label of such food by either of the following alternatives:
(i) By declaring the established common or usual name of the
ingredient followed by a parenthetical listing of all ingredients
contained therein in descending order of predominance except that, if
the ingredient is a food subject to a definition and standard of
identity established in this subchapter E, only the ingredients required
to be declared by the definition and standard of identity need be
listed; or
(ii) By incorporating into the statement of ingredients in
descending order of predominance in the finished food, the common or
usual name of every component of the ingredient without listing the
ingredient itself.
(3) Skim milk, concentrated skim milk, reconstituted skim milk, and
nonfat dry milk may be declared as skim milk or nonfat milk.
(4) Milk, concentrated milk, reconstituted milk, and dry whole milk
may be declared as milk.
(5) Bacterial cultures may be declared by the word cultured followed
by the name of the substrate, e.g., made from cultured skim milk or
cultured buttermilk.
(6) Sweetcream buttermilk, concentrated sweetcream buttermilk,
reconstituted sweetcream buttermilk, and dried sweetcream buttermilk may
be declared as buttermilk.
(7) Whey, concentrated whey, reconstituted whey, and dried whey may
be declared as whey.
(8) Cream, reconstituted cream, dried cream, and plastic cream
(sometimes known as concentrated milkfat) may be declared as cream.
(9) Butteroil and anhydrous butterfat may be declared as butterfat.
(10) Dried whole eggs, frozen whole eggs, and liquid whole eggs may
be declared as eggs.
(11) Dried egg whites, frozen egg whites, and liquid egg whites may
be declared as egg whites.
(12) Dried egg yolks, frozen egg yolks, and liquid egg yolks may be
declared as egg yolks.
(13) A livestock or poultry feed may be declared by a collective
name listed in Sec. 501.110 if it is an animal feed within the meaning
of section 201(w) of the act and meets the requirements for the use of a
collective name as prescribed in Sec. 501.110 for certain feed
ingredients.
(14) [Reserved]
(15) When all the ingredients of a wheat flour are declared in an
ingredient statement, the principal ingredient of the flour shall be
declared by the name(s) specified in Secs. 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
[[Page 19]]
satisfied, in the case of a corporation, only by the actual corporate
name, which may be preceded or followed by the name of the particular
division of the corporation. In the case of an individual, partnership,
or association, the name under which the business is conducted shall be
used.
(c) Where the food is not manufactured by the person whose name
appears on the label, the name shall be qualified by a phrase that
reveals the connection such person has with such food; such as
``Manufactured for ------------,'' ``Distributed by ------------,'' or
any other wording that expresses the facts.
(d) The statement of the place of business shall include the street
address, city, state, and ZIP Code; however, the street address may be
omitted if it is shown in a current city directory or telephone
directory. The requirement for inclusion of the ZIP Code shall apply
only to consumer commodity labels developed or revised after the
effective date of this section. In the case of nonconsumer packages, the
ZIP Code shall appear either on the label or the labeling (including
invoice).
(e) If a person manufactures, packs, or distributes a food at a
place other than his principal place of business, the label may state
the principal place of business in lieu of the actual place where such
food was manufactured or packed or is to be distributed, unless such
statement would be misleading.
Sec. 501.8 Labeling of animal food with number of servings.
(a) The label of any package of a food which bears a representation
as to the number of servings contained in such package shall bear in
immediate conjunction with such statement, and in the same size type as
is used for such statement, a statement of the net quantity (in terms of
weight, measure, or numerical count) of each such serving; however, such
statement may be expressed in terms that differ from the terms used in
the required statement of net quantity of contents (for example,
cupfuls, tablespoonfuls, etc.) when such differing term is common to
cookery and describes a constant quantity. Such statement may not be
misleading in any particular. A statement of the number of units in a
package is not in itself a statement of the number of servings.
(b) If there exists a voluntary product standard promulgated
pursuant to the procedures found in 15 CFR part 10 by the Department of
Commerce, quantitatively defining the meaning of the term serving with
respect to a particular food, then any label representation as to the
number of servings in such packaged food shall correspond with such
quantitative definition. (Copies of published standards are available
upon request from the National Bureau of Standards, Department of
Commerce, Washington, DC 20234.)
Sec. 501.15 Animal food; prominence of required statements.
(a) A word, statement, or other information required by or under
authority of the act to appear on the label may lack that prominence and
conspicuousness required by section 403(f) of the act by reason (among
other reasons) of:
(1) The failure of such word, statement, or information to appear on
the part or panel of the label which is presented or displayed under
customary conditions of purchase;
(2) The failure of such word, statement, or information to appear on
two or more parts or panels of the label, each of which has sufficient
space therefor, and each of which is so designed as to render it likely
to be, 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
[[Page 20]]
other word, statement, or information, or to any design or device; or
(6) Smallness or style of type in which such word, statement, or
information appears, insufficient background contrast, obscuring designs
or vignettes, or crowding with other written, printed, or graphic
matter.
(b) No exemption depending on insufficiency of label space, as
prescribed in regulations promulgated under section 403(e) or (i) of the
act, shall apply if such insufficiency is caused by:
(1) The use of label space for any word, statement, design, or
device which is not required by or under authority of the act to appear
on the label;
(2) The use of label space to give greater conspicuousness to any
word, statement, or other information that is required by section 403(f)
of the act; or
(3) The use of label space for any representation in a foreign
language.
(c)(1) All words, statements, and other information required by or
under authority of the act to appear on the label or labeling shall
appear thereon in the English language: Provided, however, That in the
case of articles distributed solely in the Commonwealth of Puerto Rico
or in a territory where the predominant language is one other than
English, the predominant language may be substituted for English.
(2) If the label contains any representation in a foreign language,
all words, statements, and other information required by or under
authority of the act to appear on the label shall appear thereon in the
foreign language.
(3) If any article of labeling (other than a label) contains any
representation in a foreign language, all words, statements, and other
information required by or under authority of the act to appear on the
label or labeling shall appear on such article of labeling.
Sec. 501.17 Animal food labeling warning statements.
(a) Self-pressurized containers. (1) The label of a food packaged in
a self-pressurized container and intended to be expelled from the
package under pressure shall bear the following warning:
Warning--Avoid spraying in eyes. Contents under pressure. Do not
puncture or incinerate. Do not store at temperature above 120 deg. F.
Keep out of reach of children.
(2) In the case of products intended for use by children, the phrase
``except under adult supervision'' may be added at the end of the last
sentence in the warning required by paragraph (a)(1) of this section.
(3) In the case of products packaged in glass containers, the word
``break'' may be substituted for the word ``puncture'' in the warning
required by paragraph (a)(1) of this section.
(4) The words ``Avoid spraying in eyes'' may be deleted from the
warning required by paragraph (a)(1) of this section in the case of a
product not expelled as a spray.
(b) Self-pressurized containers with halocarbon or hydrocarbon
propellants. (1) In addition to the warning required by paragraph (a) of
this section, the label of a food packaged in a self-pressurized
container in which the propellant consists in whole or in part of a
halocarbon or a hydrocarbon shall bear the following warning:
Warning--Use only as directed. Intentional misuse by deliberately
concentrating and inhaling the contents can be harmful or fatal.
(2) The warning required by paragraph (b)(1) of this section is not
required for the following products:
(i) Products expelled in the form of a foam or cream, which contain
less than 10 percent propellant in the container.
(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) Self-pressurized containers with a chlorofluorocarbon
propellant. (1) In addition to the warning required by paragraphs (a)
and (b) of this section, the label on each package of a food in a self-
pressurized container in which the propellant consists in whole or in
part of a fully halogenated chlorofluoroalkane (chlorofluorocarbon)
shall bear the following warning:
Warning--Contains a chlorofluorocarbon that may harm the
[[Page 21]]
public health and environment by reducing the ozone in the upper
atmosphere.
(2) The warning required by paragraph (c)(1) of this section shall
appear on an appropriate panel with such prominence and conspicuousness
as to render it likely to be read and understood by ordinary individuals
under normal conditions of purchase. The warning may appear on a firmly
affixed tag, tape, card, or sticker or similar overlabeling attached to
the package. The warning shall comply in all other respects with
Sec. 501.2, e.g., type-size requirements.
(3) The warning required by paragraph (c)(1) of this section is
applicable only to self-pressurized containers that use a
chlorofluorocarbon in whole or in part as a propellant to expel from the
container liquid or solid material different from the propellant.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 22033, Apr. 29, 1977]
Sec. 501.18 Misbranding of animal food.
(a) Among representations in the labeling of a food which render
such food misbranded is a false or misleading representation with
respect to another food or a drug, device, or cosmetic.
(b) The labeling of a food which contains two or more ingredients
may be misleading by reason (among other reasons) of the designation of
such food in such labeling by a name which includes or suggests the name
of one or more but not all such ingredients, even though the names of
all such ingredients are stated elsewhere in the labeling.
(c) Among representations in the labeling of a food which render
such food misbranded is any representation that expresses or implies a
geographical origin of the food or any ingredient of the food except
when such representation is either:
(1) A truthful representation of geographical origin.
(2) A trademark or trade name provided that as applied to the
article in question its use is not deceptively misdescriptive. A
trademark or trade name comprised in whole or in part of geographical
words shall not be considered deceptively misdescriptive if it:
(i) Has been so long and exclusively used by a manufacturer or
distributor that it is generally understood by the consumer to mean the
product of a particular manufacturer or distributor; or
(ii) Is so arbitrary or fanciful that it is not generally understood
by the consumer to suggest geographic origin.
(3) A part of the name required by applicable Federal law or
regulation.
(4) A name whose market significance is generally understood by the
consumer to connote a particular class, kind, type, or style of food
rather than to indicate geographical origin.
Subpart B--Specific Animal Food Labeling Requirements
Sec. 501.22 Animal foods; labeling of spices, flavorings, colorings, and chemical preservatives.
(a)(1) The term artificial flavor or artificial flavoring means any
substance, the function of which is to impart flavor, which is not
derived from a spice, fruit or fruit juice, vegetable or vegetable
juice, edible yeast, herb, bark, bud, root, leaf or similar plant
material, meat, fish, poultry, eggs, dairy products, or fermentation
products thereof. Artificial flavor includes the substances listed in
Secs. 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.
[[Page 22]]
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.
(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.
[[Page 23]]
(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 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
[[Page 24]]
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:
(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
[[Page 25]]
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.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 14091, Mar. 15, 1977;
42 FR 15675, Mar. 22, 1977]
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
[[Page 26]]
levels and do not have any technical or functional effect in that food.
(iii) Substances migrating to food from equipment or packaging or
otherwise affecting food that are not food additives as defined in
section 201(s) of the act; or if they are food additives as so defined,
they are used in conformity with regulations established pursuant to
section 409 of the act.
(b) A food repackaged in a retail establishment is exempt from the
following provisions of the act if the conditions specified are met.
(1) Section 403(e)(1) of the act (requiring a statement on the label
of the name and place of business of the manufacturer, packer, or
distributor).
(2) Section 403(g)(2) of the act (requiring the label of a food
which purports to be or is represented as one for which a definition and
standard of identity has been prescribed to bear the name of the food
specified in the definition and standard and, insofar as may be required
by the regulation establishing the standard the common names of the
optional ingredients present in the food), if the food is displayed to
the purchaser with its interstate labeling clearly in view, or with a
counter card, sign, or other appropriate device bearing prominently and
conspicuously the information required by these provisions.
(3) Section 403(i)(1) of the act (requiring the label to bear the
common or usual name of the food), if the food is displayed to the
purchaser with its interstate labeling clearly in view, or with a
counter card, sign, or other appropriate device bearing prominently and
conspicuously the common or usual name of the food, or if the common or
usual name of the food is clearly revealed by its appearance.
(c) [Reserved]
(d) Except as provided by paragraphs (e) and (f) of this section, a
shipment or other delivery of a food which is, in accordance with the
practice of the trade, to be processed, labeled, or repacked in
substantial quantity at an establishment other than that where
originally processed or packed, shall be exempt, during the time of
introduction into and movement in interstate commerce and the time of
holding in such establishment, from compliance with the labeling
requirements of section 403 (c), (e), (g), (h), (i), (j) and (k) of the
act if:
(1) The person who introduced such shipment or delivery into
interstate commerce is the operator of the establishment where such food
is to be processed, labeled, or repacked; or
(2) In case such person is not such operator, such shipment or
delivery is made to such establishment under a written agreement, signed
by and containing the post office addresses of such person and such
operator, and containing such specifications for the processing,
labeling, or repacking, as the case may be, of such food in such
establishment as will ensure, if such specifications are followed, that
such food will not be adulterated or misbranded within the meaning of
the act upon completion of such processing, labeling, or repacking. Such
person and such operator shall each keep a copy of such agreement until
2 years after the final shipment or delivery of such food from such
establishment, and shall 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
[[Page 27]]
shipment, delivery, or part is adulterated or misbranded within the
meaning of the act when so removed; or
(ii) Upon refusal by the operator of the establishment where such
food is to be processed, labeled, or repacked, to make available for
inspection a copy of the agreement as required by such paragraph.
(f) [Reserved]
(g) The label declaration of a harmless marker used to identify a
particular manufacturer's product may result in unfair competition
through revealing a trade secret. Exemption from the label declaration
of such a marker is granted, therefore, provided that the following
conditions are met:
(1) The person desiring to use the marker without label declaration
of its presence has submitted to the Commissioner of Food and Drugs full
information concerning the proposed usage and the reasons why he
believes label declaration of the marker should be subject to this
exemption; and
(2) The person requesting the exemption has received from the
Commissioner of Food and Drugs a finding that the marker is harmless and
that the exemption has been granted.
Sec. 501.103 Petitions requesting exemptions from or special requirements for label declaration of ingredients.
The Commissioner of Food and Drugs, either on his own initiative or
on behalf of any interested person who has submitted a petition pursuant
to part 10 of this chapter may issue a proposal to amend Sec. 501.4 to
specify the manner in which an ingredient(s) shall be declared, i.e., by
specific or class name, or Sec. 501.100 to exempt an ingredient(s) from
the requirements for label declaration.
[41 FR 38619, Sept. 10, 1976, as amended at 42 FR 15675, Mar. 22, 1977]
Sec. 501.105 Declaration of net quantity of contents when exempt.
(a) The principal display panel of a food in package form shall bear
a declaration of the net quantity of contents. This shall be expressed
in the terms of weight, measure, numerical count, or a combination of
numerical count and weight or measure. The statement shall be in terms
of fluid measure if the food is liquid, or in terms of weight if the
food is solid, semisolid, or viscous, or a mixture of solid and liquid;
except that such statement may be in terms of dry measure if the food is
a fresh fruit, fresh vegetable, or other dry commodity that is
customarily sold by dry measure. If there is a firmly established
general consumer usage and trade custom of declaring the contents of a
liquid by weight, or a solid, semisolid, or viscous product by fluid
measure, it may be used. Whenever the Commissioner determines that an
existing practice of declaring net quantity of contents by weight,
measure, numerical count, or a combination in the case of a specific
packaged food does not facilitate value comparisons by consumers and
offers opportunity for consumer confusion, he will by regulation
designate the appropriate term or terms to be used for such commodity.
(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
[[Page 28]]
consumer usage and trade custom of employing different common fractions
in the net quantity declaration of a particular commodity, they may be
employed. A common fraction shall be reduced to its lowest terms; a
decimal fraction shall not be carried out to more than two places. A
statement that includes small fractions of an ounce shall be deemed to
permit smaller variations than one which does not include such
fractions.
(e) The declaration shall be located on the principal display panel
of the label, and with respect to packages bearing alternate principal
panels it shall be duplicated on each principal display panel.
(f) The declaration shall appear as a distinct item on the principal
display panel, shall be separated (by at least a space equal to the
height of the lettering used in the declaration) from other printed
label information appearing above or below the declaration and (by at
least a space equal to twice the width of the letter ``N'' of the style
of type used in the quantity of contents statement) from other printed
label information appearing to the left or right of the declaration. It
shall not include any term qualifying a unit of weight, measure, or
count (such as jumbo quart and full gallon) that tends to exaggerate the
amount of the food in the container. It shall be placed on the principal
display panel within the bottom 30 percent of the area of the label
panel in lines generally parallel to the base on which the package rests
as it is designed to be displayed: Provided, That on packages having a
principal display panel of 5 square inches or less, the requirement for
placement within the bottom 30 percent of the area of the label panel
shall not apply when the declaration of net quantity of contents meets
the other requirements of this part.
(g) The declaration shall accurately reveal the quantity of food in
the package exclusive of wrappers and other material packed therewith;
provided that in the case of foods packed in containers designed to
deliver the food under pressure, the declaration shall state the net
quantity of the contents that will be expelled when the instructions for
use as shown on the container are followed. The propellant is included
in the net quantity declaration.
(h) The declaration shall appear in conspicuous and easily legible
boldface print or type in distinct contrast (by typography, layout,
color, embossing, or molding) to other matter on the package; except
that a declaration of net quantity blown, embossed, or molded on a glass
or plastic surface is permissible when all label information is so
formed on the surface. Requirements of conspicuousness and legibility
shall include the specifications that:
(1) The ratio of height to width (of the letter) shall not exceed a
differential of 3 units to 1 unit (no more than 3 times as high as it is
wide).
(2) Letter heights pertain to upper case or capital letters. When
upper and lower case or all lower case letters are used, it is the lower
case letter ``o'' or its equivalent that shall meet the minimum
standards.
(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
[[Page 29]]
(4) of this section shall be increased by \1/16\ of an inch.
(j) On packages containing less than 4 pounds or 1 gallon and
labeled in terms of weight or fluid measure:
(1) The declaration shall be expressed both in ounces, with
identification by weight or by liquid measure and, if applicable (1
pound or 1 pint or more) followed in parentheses by a declaration in
pounds for weight units, with any remainder in terms of ounces or common
or decimal fractions of the pound (see examples set forth in paragraphs
(m) (1) and (2) of this section), or in the case of liquid measure, in
the largest whole units (quarts, quarts and pints, or pints, as
appropriate) with any remainder in terms of fluid ounces or common or
decimal fractions of the pint or quart (see examples in paragraphs (m)
(3) and (4) of this section).
(2) If the net quantity of contents declaration appears on a random
package, that is a package which is one of a lot, shipment, or delivery
of packages of the same consumer commodity with varying weights and with
no fixed weight pattern, it may, when the net weight exceeds 1 pound, be
expressed in terms of pounds and decimal fractions of the pound carried
out to not more than two decimal places. When the net weight does not
exceed 1 pound, the declaration on the random package may be in decimal
fractions of the pound in lieu of ounces (see example in paragraph
(m)(5) of this section).
(3) The declaration may appear in more than one line. The term net
weight shall be used when stating the net quantity of contents in terms
of weight. Use of the terms net or net contents in terms of fluid
measure or numerical count is optional. It is sufficient to distinguish
avoirdupois ounce from fluid ounce through association of terms; for
example, Net wt. 6 oz. or 6 oz. net wt. and 6 fl. oz. or net contents 6
fl. oz.
(k) On packages containing 4 pounds or 1 gallon or more and labeled
in terms of weight or fluid measure, the declaration shall be expressed
in pounds for weight units with any remainder in terms of ounces or
common or decimal fraction of the pound, or in the case of fluid
measure, it shall be expressed in the largest whole unit (gallons
followed by common or decimal fraction of a gallon or by the next
smaller whole unit or units (quarts, or quarts and pints)) with any
remainder in terms of fluid ounces or common or decimal fractions of the
pint or quart (see paragraph (m)(6) of this section).
(l) [Reserved]
(m) Examples: (1) A declaration of 1\1/2\ pounds weight shall be
expressed as Net Wt. 24 oz. (1 lb. 8 oz.), Net Wt. 24 oz. (1\1/2\ lb.),
or Net Wt. 24 oz. (1.5 lb.).
(2) A declaration of \3/4\ pound avoirdupois weight shall be
expressed as Net Wt. 12 oz.
(3) A declaration of 1 quart liquid measure shall be expressed as
Net 32 fl. oz. (1 qt.).
(4) A declaration of 1\3/4\ quarts liquid measure shall be expressed
as Net contents 56 fluid ounces (1 quart 1\1/2\ pints) or as Net 56
fluid oz. (1 qt. 1 pt. 8 oz.), but not in terms of quart and ounce such
as Net 56 fluid oz. (1 quart 24 ounces).
(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. pint pt.
ounce oz. quart qt.
pound lb. fluid fl.
gallon gal.
(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
[[Page 30]]
supplemental net quantity statements and may be located on the principal
display panel.
(p) A separate statement of the net quantity of contents in terms of
the metric system is not regarded as a supplemental statement and an
accurate statement of the net quantity of contents in terms of the
metric system of weight or measure may also appear on the principal
display panel or on other panels.
(q) The declaration of net quantity of contents shall express an
accurate statement of the quantity of contents of the package.
Reasonable variations caused by loss or gain of moisture during the
course of good distribution practice or by unavoidable deviations in
good manufacturing practice will be recognized. Variations from stated
quantity of contents shall not be unreasonably large.
(r) [Reserved]
(s) On a multiunit retail package, a statement of the quantity of
contents shall appear on the outside of the package and shall include
the number of individual units, the quantity of each individual unit,
and, in parentheses, the total quantity of contents of the multiunit
package in terms of avoirdupois or fluid ounces, except that such
declaration of total quantity need not be followed by an additional
parenthetical declaration in terms of the largest whole units and
subdivisions thereof, as required by paragraph (j)(1) of this section. A
multiunit retail package may thus be properly labeled: 6-16 oz.
bottles--(96 fl. oz.) or 3-16 oz. cans--(net wt. 48 oz). For the
purposes of this section, multiunit retail package means a package
containing two or more individually packaged units of the identical
commodity and in the same quantity, intended to be sold as part of the
multiunit retail package but capable of being individually sold in full
compliance with all requirements of the regulations in this part. Open
multiunit retail packages that do not obscure the number of units nor
prevent examination of the labeling on each of the individual units are
not subject to this paragraph if the labeling of each individual unit
complies with the requirements of paragraphs (f) and (i) of this
section.
(t) Where the declaration of net quantity of contents is in terms of
net weight and/or drained weight or volume and does not accurately
reflect the actual quantity of the contents or the product falls below
the applicable standard of fill of container because of equipment
malfunction or otherwise unintentional product variation, and the label
conforms in all other respects to the requirements of this chapter
(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
[[Page 31]]
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 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: Secs. 201, 403, 701 of the Federal Food, Drug, and
Cosmetic Act (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
[[Page 32]]
the food has a material bearing on price or consumer acceptance or when
the labeling or the appearance of the food may otherwise create an
erroneous impression that such ingredient(s) or component(s) is present
in an amount greater than is actually the case. The following
requirements shall apply unless modified by a specific regulation in
this part.
(1) The percentage of a characterizing ingredient or component shall
be declared on the basis of its quantity in the finished product (i.e.,
weight/weight in the case of solids, or volume/volume in the case of
liquids).
(2) The percentage of a characterizing ingredient or component shall
be declared by the words ``containing (or contains) ---- percent (or %)
----'' or ``---- percent (or %) ----'' with the first blank filled in
with the percentage expressed as a whole number not greater than the
actual percentage of the ingredient or component named and the second
blank filled in with the common or usual name of the ingredient or
component. The word ``containing'' (or ``contains''), when used, shall
appear on a line immediately below the part of the common or usual name
of the food required by paragraph (a) of this section. For each
characterizing ingredient or component, the words ``---- percent (or %)
----''shall appear following or directly below the word ``containing''
(or ``contains''), or directly below the part of the common or usual
name of the food required by paragraph (a) of this section when the word
``containing'' (or ``contains'') is not used, in easily legible boldface
print or type in distinct contrast to other printed or graphic matter,
and in a height not less than the larger of the following alternatives:
(i) Not less than one-sixteenth inch in height on packages having a
principal display panel with an area of 5 square inches or less and not
less than one-eighth inch in height if the area of the principal display
panel is greater than 5 square inches; or
(ii) Not less than one-half the height of the largest type appearing
in the part of the common or usual name of the food required by
paragraph (a) of this section.
(c) The common or usual name of a food shall include a statement of
the presence or absence of any characterizing ingredient(s) or
component(s) and/or the need for the user to add any characterizing
ingredient(s) or component(s) when the presence or absence of such
ingredient(s) or component(s) in the food has a material bearing on
price or consumer acceptance or when the labeling or the appearance of
the food may otherwise create an erroneous impression that such
ingredient(s) or component(s) is present when it is not, and consumers
may otherwise be misled about the presence or absence of the
ingredient(s) or component(s) in the food. The following requirements
shall apply unless modified by a specific regulation in this part.
(1) The presence or absence of a characterizing ingredient or
component shall be declared by the words ``containing (or contains) ----
------'' or ``containing (or contains) no ----------'' 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
[[Page 33]]
on behalf of any interested person who has submitted a petition, may
publish a proposal to issue, amend, or revoke, under this part, a
regulation prescribing a common or usual name for a food, pursuant to
part 10 of this chapter.
(b) If the principal display panel of a food for which a common or
usual name regulation is established is too small to accommodate all
mandatory requirements, the Commissioner may establish by regulation an
acceptable alternative, e.g., a smaller type size. A petition requesting
such a regulation, which would amend the applicable regulation, shall be
submitted pursuant to part 10 of this chapter.
[42 FR 4716, Jan. 25, 1977; 42 FR 10980, Feb. 25, 1977. Redesignated at
42 FR 14091, Mar. 15, 1977, and amended at 42 FR 15675, Mar. 22, 1977;
42 FR 24254, May 13, 1977]
PART 505--INTERPRETIVE STATEMENTS RE: WARNINGS ON ANIMAL DRUGS FOR OVER-THE-COUNTER SALE--Table of Contents
Subpart A--Definitions and Interpretations
Sec.
505.3 Warnings on animal drugs intended for administration to diseased
animals.
Subpart B--[Reserved]
Subpart C--Voluntary Warning and Caution Statements
505.20 Recommended animal drug warning and caution statements.
Authority: Secs. 201, 501, 502, 503, 512, 701 of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 360b, 371).
Source: 40 FR 13805, Mar. 27, 1975, unless otherwise noted.
Subpart A--Definitions and Interpretations
Sec. 505.3 Warnings on animal drugs intended for administration to diseased animals.
None of the warning or caution statements recommended for use in the
labeling of drugs intended for administration to diseased animals shall
be construed to suggest or imply that any product of a diseased animal
is suitable for food use. (See section 402(a)(5) of the act.)
Subpart B--[Reserved]
Subpart C--Voluntary Warning and Caution Statements
Sec. 505.20 Recommended animal drug warning and caution statements.
ACETYLAMINONITROTHIAZOLE FOR POULTRY.
Warning--Discontinue use at least 1 week before slaughtering birds
for food to eliminate the drug from the food.
AMINONITROTHIAZOLE (2-AMINO-5-NITROTHIAZOLE) FOR POULTRY.
Warning--Discontinue use at least 1 week before slaughtering birds
for food to eliminate the drug from the food.
ANESTHETICS FOR EXTERNAL USE (LOCAL ANESTHETICS).
Caution--Not for prolonged use. If the condition for which this
preparation is used persists or if a rash or irritation develops,
discontinue use and consult veterinarian.
ANTHELMINTICS.
Caution--Consult veterinarian before using in severely debilitated
animals.
ANTHELMINTICS: PHENOTHIAZINE.
Warning--Do not treat lactating dairy animals.
Caution--Consult veterinarian before using in severely debilitated
animals. Individual animals are occasionally sensitive to phenothiazine.
ANTIHISTAMINICS FOR EXTERNAL USE.
Caution--If the condition for which this preparation is used
persists or if a rash or irritation develops, discontinue use and
consult veterinarian.
ANTISEPTICS FOR EXTERNAL USE.
Caution--In case of deep or puncture wounds or serious burns consult
veterinarian. If redness, irritation, or swelling persists or increases,
discontinue use and consult veterinarian.
CARBOLIC ACID (PHENOL) PREPARATIONS (MORE THAN 0.5 PERCENT) FOR EXTERNAL
USE.
Caution--Use only as directed. Avoid contact with the eyes and
mucous membranes. Do not apply to large areas of broken skin. Do not use
on cats.
[[Page 34]]
CORTISONE, HYDROCORTISONE, PREDNISOLONE AND PREDNISONE PREPARATIONS FOR
EXTERNAL USE.
Caution--Do not use where infection (pus) is present, since the drug
may allow infection to spread. If redness, irritation, or swelling
persists or increases, discontinue use and consult veterinarian.
COUNTERIRRITANTS AND RUBEFACIENTS.
Caution--Do not apply to irritated skin or if excessive irritation
develops. Avoid getting into eyes or on mucous membranes.
CREOSOTE, CRESOLS, GUAIACOL, AND SIMILAR SUBSTANCES IN PREPARATIONS FOR
EXTERNAL USE.
Caution--Use only as directed. Avoid contact with the eyes and
mucous membranes. Do not apply to large areas of broken skin. Not
recommended for use on cats.
DIARRHEA PREPARATIONS.
Caution--If symptoms persist after using this preparation for 2 or 3
days, consult veterinarian.
DISPENSERS PRESSURIZED BY GASEOUS PROPELLANT FOR DRUGS FOR EXTERNAL USE.
Caution--Keep away from eyes or other mucous membranes. Avoid
inhaling.
This warning is not necessary for preparations especially designed
for use on mucous membranes.
Warning--Contents under pressure. Do not puncture. Do not use or
store near heat or open flame. Exposure to temperatures above 130 deg.
Farenheit may cause bursting. Never throw container into fire or
incinerator.
DRESSINGS, PROTECTIVE SPRAY-ON TYPE.
Caution--In case of deep or puncture wounds or serious burns or if
redness, irritation, or swelling persists or increases, consult
veterinarian.
Keep away form eyes or other mucous membranes. Avoid inhaling.
See also Dispensers Pressurized by Gaseous Propellant * * * for
additional warnings to be included for products under pressure.
ESTROGEN PELLETS IN CATTLE AND SHEEP.
Warning--Implant pellets in ---------- (name of the anatomical area)
only. Any other location may result in violation of Federal law. Do not
attempt salvage of implanted site for human or animal food.
NICARBAZIN FOR POULTRY.
Warning--Do not feed to laying hens in production. Discontinue use
at least 4 days before slaughtering birds for food to eliminate the drug
from the food.
OPHTHALMIC PREPARATIONS.
Caution--If condition persists or increases discontinue use and
consult veterinarian. Keep container tightly closed.
Solutions should also include the following statement: ``Do not
touch applicator tip to any surface, since this may contaminate
solution.''
SALMONELLOSIS TREATMENTS FOR POULTRY.
Important--Poultry that have survived salmonella outbreaks should
not be kept for laying-house replacements or breeders, unless tests show
that they are not carriers.
SULFONAMIDE PREPARATIONS (SYSTEMIC).
Caution--If symptoms persist after using this preparation for 2 or 3
days, consult veterinarian.
SULFONAMIDES FOR EXTERNAL USE.
Caution--If redness, irritation, or swelling persists or increases,
discontinue use and consult veterinarian.
If the preparation has not been sterilized, the following statement
should also be used.
Caution--This preparation has not been sterilized. Do not use in
body cavities or deep wounds.
[40 FR 13805, Mar. 27, 1975, as amended at 47 FR 51563, Nov. 14, 1982]
[[Page 35]]
PART 507--THERMALLY PROCESSED LOW-ACID FOODS PACKAGED IN HERMETICALLY SEALED CONTAINERS--Table of Contents
Subpart A--General Provisions
Sec.
507.3 Definitions.
507.5 Current good manufacturing practice.
507.10 Personnel.
Subpart B--[Reserved]
Subpart C--Equipment
507.40 Equipment and procedures.
Subpart D--Control of Components, Food Product Containers, Closures, and
In-Process Materials
507.60 Containers.
Subpart E--Production and Process Controls
507.81 Product preparation.
507.83 Establishing scheduled processes.
507.87 Operations in the thermal processing room.
507.89 Deviations in processing, venting, or control of critical
factors.
Subpart F--Records and Reports
507.100 Processing and production records.
Authority: Secs. 402, 701, 704 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 342, 371, 374); sec. 361 of the Public Health
Service Act (42 U.S.C. 264).
Source: 44 FR 48598, Aug. 17, 1979, unlesss otherwise noted.
Subpart A--General Provisions
Sec. 507.3 Definitions.
For the purposes of this part, the following definitions apply:
(a) Aseptic processing and packaging means the filling of a
commercially sterilized cooled product into presterilized containers,
followed by aseptic hermetical sealing, with a presterilized closure, in
an atmosphere free of microorganisms.
(b) Bleeders mean openings used to remove air that enters with steam
from retorts and steam chambers and to promote circulation of steam in
such retorts and steam chambers. Bleeders may serve as a means of
removing condensate.
(c) Come-up-time means the time which elapses between the
introduction of steam into the closed retort and the time when the
retort reaches the required processing temperature.
(d) Commercial processor includes any person engaged in commercial,
custom, or institutional (church, school, penal, or other organization)
processing of food, including pet food. Persons engaged in the
production of foods that are to be used in market or consumer tests are
also included.
(e) Commercial sterility. (1) ``Commercial sterility'' of thermally
processed food means the condition achieved--
(i) By the application of heat which renders the food free of--
(a) Microorganisms capable of reproducing in the food under normal
nonrefrigerated conditions of storage and distribution; and
(b) Viable microorganisms (including spores) of public health
significance; or
(ii) By the control of water activity and the application of heat,
which renders the food free of microorganisms capable of reproducing in
the food under normal nonrefrigerated conditions of storage and
distribution.
(2) ``Commercial sterility'' of equipment and containers used for
aseptic processing and packaging of food means the condition achieved by
application of heat, chemical sterilant(s), or other appropriate
treatment that renders the equipment and containers free of viable
microorganisms having public health significance, as well as
microorganisms of nonhealth significance, capable of reproducing in the
food under normal nonrefrigerated conditions of storage and
distribution.
(f) Critical factor means any property, characteristic, condition,
aspect, or other parameter, variation of which may affect the scheduled
process and the attainment of commercial sterility.
(g) Flame sterilizer means an apparatus in which hermetically sealed
containers are agitated at atmospheric pressure, by either continuous,
discontinuous, or reciprocating movement, with impinging gas flames to
achieve sterilization temperatures. A
[[Page 36]]
holding period in a heated section may follow the initial heating
period.
(h) Headspace, gross is the vertical distance between the level of
the product (generally the liquid surface) in an upright rigid container
and the top edge of the container (the top of the double seam of a can
or the top edge of a glass jar).
(i) Headspace, net of a container is the vertical distance between
the level of the product (generally the liquid surface) in the upright
rigid container and the inside surface of the lid.
(j) Hermetically sealed container means a container that is designed
and intended to be secure against the entry of microorganisms and
thereby to maintain the commercial sterility of its contents after
processing.
(k) Incubation means the holding of a sample(s) at a specified
temperature for a specified period of time for the purpose of permitting
or stimulating the growth of microorganisms.
(l) Initial temperature means the average temperature of the
contents of the coldest container to be processed at the time the
thermal processing cycle begins, as determined after thorough stirring
or shaking of the filled and sealed container.
(m) Lot means that amount of a product produced during a period of
time indicated by a specific code.
(n) Low-acid foods means any foods, other than alcoholic beverages,
with a finished equilibrium pH greater than 4.6 and a water activity
(aw) greater than 0.85. Tomatoes and tomato products having a
finished equilibrium pH less than 4.7 are not classed as low-acid foods.
(o) Minimum thermal process means the application of heat to food,
either before or after sealing in a hermetically sealed container, for a
period of time and at a temperature scientifically determined to be
adequate to ensure destruction of microorganisms of public health
significance.
(p) Operating process means the process selected by the processor
that equals or exceeds the minimum requirements set forth in the
scheduled process.
(q) Retort means any closed vessel or other equipment used for the
thermal processing of foods.
(r) Scheduled process means the process selected by the processor as
adequate under the conditions of manufacture for a given product to
achieve commercial sterility. This process may be in excess of that
necessary to ensure destruction of microorganisms of public health
significance, and shall be at least equivalent to the process
established by a competent processing authority to achieve commercial
sterility.
(s) Shall is used to state mandatory requirements.
(t) Should is used to state recommended or advisory procedures or to
identify recommended equipment.
(u) Vacuum-packed products means those products that are sealed in a
container under the vacuum specified in the scheduled process, the
maintenance of which vacuum is critical to the adequacy of the scheduled
process.
(v) Vents means openings through the retort shell, controlled by
gate, plug cock, or other adequate valves used for the elimination of
air during the venting period.
(w) Water activity (aw) is a measure of the free moisture in a
product and is the quotient of the water vapor pressure of the substance
divided by the vapor pressure of pure water at the same temperature.
Sec. 507.5 Current good manufacturing practice.
The criteria in Secs. 507.10, 507.40, 507.60, 507.81, 507.83,
507.87, 507.89, and 507.100 shall apply in determining whether the
facilities, methods, practices, and controls used by the commercial
processor in the manufacture, processing, or packing of low-acid foods
in hermetically sealed containers are operated or administered in a
manner adequate to protect the public health.
Sec. 507.10 Personnel.
The operators of processing systems, retorts, aseptic processing and
packaging systems and product formulating systems (including systems
wherein water activity is used in conjunction with thermal processing)
and container closure inspectors shall be under the operating
supervision of a person who has attended a school approved by the
Commissioner for giving instruction
[[Page 37]]
appropriate to the preservation technology involved and who has been
identified by that school as having satisfactorily completed the
prescribed course of instruction. This person shall supervise only in
those areas for which a school approved by the Commissioner identifies
the person as having satisfactorily completed training.
Subpart B--[Reserved]
Subpart C--Equipment
Sec. 507.40 Equipment and procedures.
(a) Equipment and procedures for pressure processing in steam in
still retorts--(1) Indicating mercury-in-glass thermometer. Each retort
shall be equipped with at least one mercury-in-glass thermometer whose
divisions are easily readable to 1 deg. F and whose temperature range
does not exceed 17 deg. F per inch of graduated scale. Thermometers
shall be tested for accuracy against a known accurate standard
thermometer upon installation and at least once a year thereafter, or
more frequently if necessary, to ensure their accuracy. Records of
thermometer accuracy checks that specify date, standard used, method
used, and person performing the test should be maintained. Each
thermometer should have a tag, seal, or other means of identity that
includes the date on which it was last tested for accuracy. A
thermometer that has a divided mercury column or that cannot be adjusted
to the standard shall be repaired or replaced before further use of the
retort. Thermometers shall be installed where they can be accurately and
easily read. Bulbs of indicating thermometers shall be installed either
within the retort shell or in external wells attached to the retort.
External wells or pipes shall be connected to the retort through at
least a \3/4\-inch diameter opening and equipped with a \1/16\-inch or
larger bleeder opening so located as to provide a full flow of steam
past the length of the thermometer bulb. The bleeders for external wells
shall emit steam continuously during the entire processing period. The
mercury thermometer--not the recorder chart--shall be the reference
instrument for indicating the processing temperature.
(2) Temperature-recording device. Each still retort shall have an
accurate temperature-recording device. Graduations on the temperature-
recording devices shall not exceed 2 deg. F within a range of 10 deg. F
of the processing temperature. Each chart shall have a working scale of
not more than 55 deg. F per inch within a range of 20 deg. F of the
processing temperature. The temperature chart shall be adjusted to agree
as nearly as possible with, but to be in no event higher than, the known
accurate mercury-in-glass thermometer during the process time. A means
of preventing unauthorized changes in adjustment shall be provided. A
lock, or a notice from management posted at or near the recording device
which provides a warning that only authorized persons are permitted to
make adjustments, is a satisfactory means for preventing unauthorized
changes. The recorder may be combined with the steam controller and may
be a recording-controlling instrument. The temperature-recorder bulb
shall be installed either within the retort shell or in a well attached
to the shell. Each temperature-recorder bulb well shall have a \1/16\-
inch or larger bleeder which emits steam continuously during the
processing period. Air-operated temperature controllers should have
adequate filter systems to ensure a supply of clean, dry air.
(3) Pressure gages. Each retort should be equipped with a pressure
gage that should be graduated in divisions of 2 pounds or less.
(4) Steam controller. Each retort shall be equipped with an
automatic steam controller to maintain the retort temperature. This may
be a recording-controlling instrument when combined with a recording
thermometer. The steam controller may be air-operated and actuated by a
temperature sensor positioned near the mercury-in-glass thermometer in
the retort; a steam controller activated by the steam pressure of the
retort is acceptable if it is carefully maintained mechanically so that
it operates satisfactorily.
(5) Steam inlet. The steam inlet to each still retort shall be large
enough to provide sufficient steam for proper operation of the retort.
Steam may enter either the top portion or the bottom portion of the
retort but, in any
[[Page 38]]
case, shall enter the portion of the retort opposite the vent; for
example, steam inlet in bottom portion and vent in top portion.
(6) Crate supports. A bottom crate support shall be used in vertical
still retorts. Baffle plates shall not be used in the bottom of still
retorts.
(7) Steam spreaders. Steam spreaders are continuations of the steam
inlet line inside the retort. Horizontal still retorts shall be equipped
with steam spreaders that extend the length of the retort. For steam
spreaders along the bottom of the retort, the perforations should be
along the top 90 deg. of this pipe, that is, within 45 deg. on either
side of the top center. Horizontal still retorts over 30 feet long
should have two steam inlets connected to the spreader. In vertical
still retorts, the steam spreaders, if used, should be perforated along
the center line of the pipe facing the interior of the retort or along
the sides of the pipe. The number of perforations should be such that
the total cross-sectional area of the perforations is equal to 1\1/2\ to
2 times the cross-sectional area of the smaller restriction in the steam
inlet line.
(8) Bleeders. Bleeders, except those for thermometer wells, shall be
one-eighth inch or larger and shall be wide open during the entire
process, including the come-up-time. For horizontal still retorts,
bleeders shall be located within approximately 1 foot of the outermost
locations of containers at each end along the top of the retort;
additional bleeders shall be located not more than 8 feet apart along
the top. Bleeders may be installed at positions other than those
specified above, as long as there is evidence in the form of heat
distribution data that they accomplish adequate removal of air and
circulation of steam within the retort. Vertical retorts shall have at
least one bleeder opening located in that portion of the retort opposite
the steam inlet. In retorts having top steam inlet and bottom venting, a
bleeder shall be installed in the bottom of the retort to remove
condensate. All bleeders shall be arranged so that the operator can
observe that they are functioning properly.
(9) Stacking equipment and position of containers. Crates, trays,
gondolas, etc., for holding containers shall be made of strap iron,
adequately perforated sheet metal, or other suitable material. When
perforated sheet metal is used for the bottoms, the perforations should
be approximately the equivalent of 1-inch holes on 2-inch centers. If
dividers are used between the layers of containers, they should be
perforated as above. The positioning of containers in the retort, when
specified in the scheduled process, shall be in accordance with that
process.
(10) Air valves. Retorts using air for pressure cooling shall be
equipped with a suitable valve to prevent air leakage into the retort
during processing.
(11) Water valves. Retorts using water for cooling shall be equipped
with a suitable valve to prevent leakage of water into the retort during
processing.
(12) Vents. Vents shall be installed in such a way that air is
removed from the retort before timing of the process is started. Vents
shall be controlled by gate, plug cock, or other adequate type valves
which shall be fully open to permit rapid discharge of air from the
retort during the venting period. Vents shall not be connected directly
to a closed drain system. If the overflow is used as a vent, there shall
be an atmospheric break in the line before it connects to a closed
drain. The vent shall be located in that portion of the retort opposite
the steam inlet; for example, steam inlet in bottom portion and vent in
top portion. Where a retort manifold connects several vent pipes from a
single still retort, it shall be controlled by a gate, plug cock, or
other adequate type valve. The retort manifold shall be of a size that
the cross-sectional area of the pipe is larger than the total cross-
sectional area of all connecting vents. The discharge shall not be
directly connected to a closed drain without an atmospheric break in the
line. A manifold header connecting vents or manifolds from several still
retorts shall lead to the atmosphere. The manifold header shall not be
controlled by a valve and shall be of a size that the cross-sectional
area is at least equal to the total cross-sectional area of all
connecting retort manifold pipes from all retorts venting
simultaneously. Timing of the process shall
[[Page 39]]
not begin until the retort has been properly vented and the processing
temperature has been reached. Some typical installations and operating
procedures reflecting the requirements of this section for venting still
retorts are given in paragraphs (a)(12) (i)(a) through (d) and (ii)(a)
and (b) of this section.
(i) Venting horizontal retorts. (a) Venting through multiple 1-inch
vents discharging directly to atmosphere.
[GRAPHIC] [TIFF OMITTED] TR01FE93.002
Specifications. One 1-inch vent for every 5 feet of retort length,
equipped with a gate or plug cock valve and discharging to atmosphere;
end vents not more than 2\1/2\ feet from ends of retort.
Venting method. Vent valves should be wide open for at least 5
minutes and to at least 225 deg. F, or at least 7 minutes and to at
least 220 deg. F.
(b) Venting through multiple 1-inch vents discharging through a
manifold to atmosphere.
[GRAPHIC] [TIFF OMITTED] TR01FE93.003
Specifications. One 1-inch vent for every 5 feet of retort length;
and vents not over 2\1/2\ feet from ends of retort: Size of manifold--
for retorts less than 15 feet in length, 2\1/2\ inches; for retorts 15
feet and over in length, 3 inches.
Venting method. Manifold vent gate or plug cock valve should be wide
open for at least 6 minutes and to at least 225 deg. F, or for at least
8 minutes and to at least 220 deg. F.
(c) Venting through water spreaders.
[GRAPHIC] [TIFF OMITTED] TR01FE93.004
Size of vent and vent valve. For retorts less than 15 feet in
length, 2 inches; for retorts 15 feet and over in length, 2\1/2\ inches.
Size of water spreader. For retorts less than 15 feet in length,
1\1/2\ inches; for retorts 15 feet and over in length, 2 inches. The
number of holes should be such that their total cross-sectional area is
approximately equal to the cross-sectional area of the vent pipe inlet.
Venting method. Water spreader vent gate or plug cock valve should
be wide open for at least 5 minutes and to at least 225 deg. F, or for
at least 7 minutes and to at least 220 deg. F.
(d) Venting through a single 2\1/2\-inch top vent (for retorts not
exceeding 15 feet in length).
[GRAPHIC] [TIFF OMITTED] TR01FE93.005
Specifications: A 2\1/2\-inch vent equipped with a 2\1/2\-inch gate
or plug cock valve and located within 2 feet of the center of the
retort.
Venting method: Vent gate or plug cock valve should be wide open for
at least 4 minutes and to at least 220 deg. F.
(ii) Venting vertical retorts. (a) Venting through a 1\1/2\-inch
overflow.
[[Page 40]]
[GRAPHIC] [TIFF OMITTED] TR01FE93.006
Specifications. A 1\1/2\-inch overflow pipe equipped with a 1\1/2\-
inch gate or plug cock valve and with not more than 6 feet of 1\1/2\-
inch pipe beyond the valve before break to the atmosphere or to a
manifold header.
Venting method. Vent gate or plug cock valve should be wide open for
at least 4 minutes and to at least 218 deg. F, or for at least 5 minutes
and to at least 215 deg. F.
(b) Venting through a single 1-inch side or top vent.
[GRAPHIC] [TIFF OMITTED] TR01FE93.007
Specifications. A 1-inch vent in lid or top side, equipped with a 1-
inch gate or plug cock valve and discharging directly into the
atmosphere or to a manifold header.
Venting method. Vent gate or plug cock valve should be wide open for
at least 5 minutes and to at least 230 deg. F, or for at least 7 minutes
and to at least 220 deg. F.
(iii) Other installations and operating procedures that deviate from
the above specifications may be used if there is evidence in the form of
heat distribution data, which shall be kept on file, that they
accomplish adequate venting of air.
(13) Critical factors. Critical factors specified in the scheduled
process shall be measured and recorded on the processing record at
intervals of sufficient frequency to ensure that the factors are within
the limits specified in the scheduled process.
(i) When maximum fill-in or drained weight is specified in the
scheduled process, it shall be measured and recorded at intervals of
sufficient frequency to ensure that the weight of the product does not
exceed the maximum for the given container size specified in the
scheduled process.
(ii) Closing machine vacuum in vacuum-packed products shall be
observed and recorded at intervals of sufficient frequency to ensure
that the vacuum is as specified in the scheduled process.
(iii) Such measurements and recordings should be made at intervals
not to exceed 15 minutes.
(iv) When the product style results in stratification or layering of
the primary product in the containers, the positioning of containers in
the retort shall be according to the scheduled process.
(b) Equipment and procedures for pressure processing in water in
still retorts--(1) Indicating mercury-in-glass thermometer. Each retort
shall be equipped with at least one mercury-in-glass thermometer whose
divisions are easily readable to 1 deg. F and whose temperature range
does not exceed 17 deg. F per inch of graduated scale. Thermometers
shall be tested for accuracy against a known accurate standard
thermometer upon installation and at least once a year thereafter, or
more frequently if necessary, to ensure their accuracy. Records of
thermometer accuracy checks which specify date, standard used, method
used, and person performing the test should be maintained. Each
thermometer should have a tag, seal, or other means of identity that
includes the date when it was last tested for accuracy. A thermometer
that has a divided mercury column or that cannot be adjusted to the
standard shall be repaired or replaced before further use of the retort.
Thermometers shall be installed where they can be accurately and easily
read. Bulbs of indicating thermometers shall be located in such a
position that they are beneath the surface of the water throughout the
process. On horizontal retorts, this entry should be made in the side at
the center, and the thermometer bulbs shall be inserted directly into
the retort shell. In both vertical and horizontal retorts, the
thermometer bulbs shall extend directly into the water a minimum of at
least 2 inches without a
[[Page 41]]
separable well or sleeve. The mercury thermometer--not the recorder
chart--shall be the reference instrument for indicating the processing
temperature.
(2) Temperature-recording device. Each still retort shall have an
accurate temperature-recording device. Graduations on the temperature-
recording devices shall not exceed 2 deg. F within a range of 10 deg. F
of the processing temperature. Each chart shall have a working scale of
not more than 55 deg. F per inch within a range of 20 deg. F of the
processing temperature. The temperature chart shall be adjusted to agree
as nearly as possible with, but to be in no event higher than, the known
accurate mercury-in-glass thermometer during the process time. A means
of preventing unauthorized changes in adjustment shall be provided. A
lock, or a notice from management posted at or near the recording device
which provides a warning that only authorized persons are permitted to
make adjustments, is a satisfactory means for preventing unauthorized
changes. The recorder may be combined with the steam controller and may
be a recording-controlling instrument. The recording-thermometer bulb
should be located adjacent to the bulb of the mercury-in-glass
thermometer, except in the case of a vertical retort equipped with a
combination recorder-controller. In such vertical retorts, the
temperature recorder-control bulb shall be located at the bottom of the
retort below the lowest crate rest in such a position that the steam
does not strike it directly. In horizontal retorts, the temperature
recorder-control bulb shall be located between the water surface and the
horizontal plane passing through the center of the retort so that there
is no opportunity for direct steam impingement on the control bulb. Air-
operated temperature controllers should have adequate filter systems to
ensure a supply of clean, dry air.
(3) Pressure gages. (i) Each retort should be equipped with a
pressure gage, which should be graduated in divisions of 2 pounds or
less.
(ii) Each retort should have an adjustable pressure relief or
control valve of a capacity sufficient to prevent an undesired increase
in retort pressure when the water valve is wide open and should be
installed in the overflow line.
(4) Steam controller. Each retort shall be equipped with an
automatic steam controller to maintain the retort temperature. This may
be a recording-controlling instrument when combined with a recording
thermometer.
(5) Steam introduction. Steam shall be distributed in the bottom of
the retort in a manner adequate to provide uniform heart distribution
throughout the retort. In vertical retorts, uniform steam distribution
can be achieved by any of several methods. In horizontal retorts, the
steam distributor shall run the length of the bottom of the retort with
perforations distributed uniformly along the upper part of the pipe.
(6) Crate supports. A bottom crate support shall be used in vertical
still retorts. Baffle plates shall not be used in the bottom of the
retort. Centering guides should be installed so as to ensure that there
is about a 1\1/2\-inch clearance between the side wall of the crate and
the retort wall.
(7) Stacking equipment and position of containers. Crates, trays,
gondolas, etc., for holding containers shall be made of strap iron,
adequately perforated sheet metal, or other suitable material. When
perforated sheet metal is used for the bottoms, the perforations should
be approximately the equivalent of 1-inch holes on 2-inch centers. If
divider plates are used between the layers of containers, they should be
perforated as above. The positioning of containers in the retort, when
specified in the scheduled process, shall be in accordance with that
process. Divider racks, trays, or other means of positioning of flexible
containers shall be designed and employed to ensure even circulation of
heating medium around all containers in the retort.
(8) Drain valve. A nonclogging, water-tight valve shall be used.
Screens should be installed over all drain openings.
(9) Water level indicator. There shall be a means of determining the
water level in the retort during operation, e.g., by using a gage, water
glass, or petcock(s). Water shall cover the top layer of containers
during the entire come-up-time and processing periods
[[Page 42]]
and should cover the top layer of containers during the cooling periods.
The operator shall check and record the water level at intervals
sufficient to ensure its adequacy.
(10)(i) Air supply and controls. In both horizontal and vertical
still retorts for pressure processing in water, a means shall be
provided for introducing compressed air at the proper pressure and rate.
The proper pressure shall be controlled by an automatic pressure control
unit. A check valve shall be provided in the air supply line to prevent
water from entering the system. Air or water circulation shall be
maintained continuously during the come-up-time and during processing
and cooling periods; the adequacy of the air or water circulation for
uniform heat distribution within the retort shall be established in
accordance with procedures recognized by a competent processing
authority and records shall be kept on file; if air is used to promote
circulation, it shall be introduced into the steam line at a point
between the retort and the steam control valve at the bottom of the
retort.
(ii) Water circulation. When a water circulating system is used for
heat distribution, it shall be installed in such a manner that water
will be drawn from the bottom of the retort through a suction manifold
and discharged through a spreader which extends the length of the top of
the retort. The holes in the water spreader shall be uniformly
distributed and should have an aggregate area not greater than the
cross-section area of the outlet line from the pump. The suction outlets
should be protected with nonclogging screens to keep debris from
entering the circulating system. The pump shall be equipped with a pilot
light or other signaling device to warn the operator when it is not
running, and with a bleeder to remove air when starting operations.
Alternative methods for circulation of water in the retort may be used
when established by a competent authority as adequate for even heat
distribution.
(11) Cooling water supply. In vertical retorts the cooling water
should be introduced at the top of the retort between the water and
container levels; in horizontal retorts the cooling water should be
introduced into the suction side of the pump. A check valve should be
included in the cooling water line.
(12) Retort headspace. The headspace necessary to control the air
pressure should be maintained between the water level and the top of the
retort shell.
(13) Vertical and horizontal still retorts. Vertical and horizontal
still retorts should follow the arrangements in the diagrams below in
this paragraph. Other installation and operating procedures that deviate
from these arrangements may be used, as long as there is evidence in the
form of heat distribution data or other suitable information, which
shall be kept on file, that demonstrates that the heat distribution is
adequate.
[[Page 43]]
[GRAPHIC] [TIFF OMITTED] TR01FE93.008
[[Page 44]]
Legend For Vertical and Horizontal Still Retorts
A--Water line.
B--Steam line.
C--Temperature control.
D--Overflow line.
E1--Drain line.
E2--Screens.
F--Check valves.
G--Line from hot water storage.
H--Suction line and manifold.
I--Circulating pump.
J--Petcocks.
K--Recirculating line.
L--Steam distributor.
M--Temperature-controller bulb.
N--Thermometer.
O--Water spreader.
P--Safety valve.
Q--Vent valve for steam processing.
R--Pressure gage.
S--Inlet air control.
T--Pressure control.
U--Air line.
V--To pressure control instrument.
W--To temperature control instrument.
X--Wing nuts.
Y1--Crate support.
Y2--Crate guides.
Z--Constant flow orifice valve.
Z1--Constant flow orifice valve used during come-up.
Z2--Constant flow orifice valve used during cook.
(14) Critical factors. Critical factors specified in the scheduled
process shall be measured and recorded on the processing record at
intervals of sufficient frequency to ensure that the factors are within
the limits specified in the scheduled process.
(i) When maximum fill-in or drained weight is specified in the
scheduled process, it shall be measured and recorded at intervals of
sufficient frequency to ensure that the weight of the product does not
exceed the maximum for the given container size specified in the
scheduled process.
(ii) Closing machine vacuum in vacuum-packed products shall be
observed and recorded at intervals of sufficient frequency to ensure
that the vacuum is as specified in the scheduled process.
(iii) Such measurements and recordings should be made at intervals
not to exceed 15 minutes.
(iv) When the product style results in stratification or layering of
the primary product in the containers, the positioning of containers in
the retort shall be according to the scheduled process.
(c) Equipment and procedures for pressure processing in steam in
continuous agitating retorts--(1) Indicating mercury-in-glass
thermometer. Each retort shall be equipped with at least one mercury-in-
glass thermometer whose divisions are easily readable to 1 deg. F and
whose temperature range does not exceed 17 deg. F per inch of graduated
scale. Thermometers shall be tested for accuracy against a known
accurate standard thermometer upon installation and at least once a year
thereafter, or more frequently if necessary, to ensure their accuracy.
Records of thermometer accuracy checks which specify date, standard
used, method used, and person performing the test should be maintained.
Each thermometer should have a tag, seal, or other means of identity
that includes the date on which it was last tested for accuracy. A
thermometer that has a divided mercury column or that cannot be adjusted
to the standard shall be repaired or replaced before further use of the
retort. Thermometers shall be installed where they can be accurately and
easily read. Bulbs in indicating thermometers shall be installed either
within the retort shell or in external wells attached to the retort.
External wells or pipes shall be connected to the retort through at
least a \3/4\-inch diameter opening, and equipped with a \1/16\-inch or
larger bleeder opening so located as to provide a full flow of steam
past the length of the thermometer bulb. The bleeders for external wells
shall emit steam continuously during the entire processing period. The
mercury thermometer--not the recorder chart--shall be the reference
instrument for indicating the processing temperature.
(2) Temperature-recording device. Each retort shall have an accurate
temperature-recording device. Graduations on the temperature-recording
devices shall not exceed 2 deg. F within a range of 10 deg. F of the
processing temperature. Each chart shall have a working scale of not
more than 55 deg. F per inch within a range of 20 deg. F of the
processing temperature. The temperature chart shall be adjusted to agree
as nearly as possible with, but to be in no event higher than, the known
accurate mercury-in-
[[Page 45]]
glass thermometer during the process time. A means of preventing
unauthorized changes in adjustment shall be provided. A lock, or a
notice from management posted at or near the recording device that
provides a warning that only authorized persons are permitted to make
adjustments, is a satisfactory means of preventing unauthorized changes.
The recorder may be combined with the steam controller and may be a
recording-controlling instrument. The temperature-recorder bulb shall be
installed either within the retort shell or in a well attached to the
shell. Each temperature-recorder bulb well shall have a \1/16\-inch or
larger bleeder opening emitting steam continuously during the processing
period. Air-operated temperature controllers should have adequate filter
systems to ensure a supply of clean, dry air.
(3) Pressure gages. Each retort should be equipped with a pressure
gage that should be graduated in divisions of 2 pounds or less.
(4) Steam controller. Each retort shall be equipped with an
automatic steam controller to maintain the retort temperature. This may
be a recording-controlling instrument when combined with a recording
thermometer. A steam controller activated by the steam pressure of the
retort is acceptable if it is carefully maintained mechanically so that
it operates satisfactorily.
(5) Bleeders. Bleeders, except those for thermometer wells, shall be
one-eighth inch or larger and shall be wide open during the entire
process, including the come-up-time. Bleeders shall be located within
approximately 1 foot of the outermost location of containers at each end
along the top of the retort; additional bleeders shall be located not
more than 8 feet apart along the top of the retort. All bleeders shall
be arranged so that the operator can observe that they are functioning
properly. The condensate bleeder shall be checked with sufficient
frequency to ensure adequate removal of condensate or shall be equipped
with an automatic alarm system(s) that would serve as a continuous
monitor of condensate-bleeder functioning. Visual checks should be done
at intervals of not more than 15 minutes. A record of such checks should
be kept to show that the bleeder is functioning properly.
(6) Venting and condensate removal. Vents shall be located in that
portion of the retort opposite the steam inlet. Air shall be removed
before processing is started. Heat distribution data or documentary
proof from the manufacturer or from a competent processing authority,
demonstrating that adequate venting is achieved, shall be kept on file.
At the time steam is turned on, the drain should be opened for a time
sufficient to remove steam condensate from the retort, and provision
shall be made for continuing drainage of condensate during the retort
operation. The condensate bleeder in the bottom of the shell serves as
an indicator of continuous condensate removal.
(7) Retort speed timing. The rotational speed of the retort shall be
specified in the scheduled process. The speed shall be adjusted and
recorded when the retort is started, at any time a speed change is made,
and at intervals of sufficient frequency to ensure that the retort speed
is maintained as specified in the scheduled process. These adjustments
and recordings should be made every 4 hours or less. Alternatively, a
recording tachometer may be used to provide a continuous record of the
speed. A means of preventing unauthorized speed changes on retorts shall
be provided. A lock, or a notice from management posted at or near the
speed adjustment device that provides a warning that only authorized
persons are permitted to make adjustments, is a satisfactory means of
preventing unauthorized changes.
(8) Emergency stops. If a retort jams or breaks down during
processing operations, necessitating cooling the retort for repairs, the
retort shall be operated in such a way that ensures that the product is
commercially sterile, or the retort is to be cooled promptly and all
containers either reprocessed, repacked and reprocessed, or discarded.
When operated as a still retort, all containers shall be given a full
still retort process before the retort is cooled. If, in such an
emergency, a scheduled still process or another process established to
ensure commercial sterility is to be used, it shall be made readily
available to the retort operator.
[[Page 46]]
(i) Any containers in the retort intake valve or in transfer valves
between cooker shells of a continuous retort at the time of breakdown
shall either be reprocessed, repacked and reprocessed, or discarded.
(ii) Both the time at which the reel stopped and the time the retort
was used for a still retort process, if so used, shall be marked on the
recording chart and entered on the other production records required in
this chapter. If the alternative procedure of prompt cooling is
followed, the subsequent handling methods used for the containers in the
retort at the time of stopping and cooling shall be entered on the
production records.
(9) Temperature drop. If the temperature of the continuous retort
drops below the temperature specified in the scheduled process while
containers are in the retort, the retort reel shall be stopped promptly.
An automatic device should be used to stop the reel when the temperature
drops below the specified process temperature. Before the reel is
restarted, all containers in the retort shall be given a complete
scheduled still retort process if the temperature drop was 10 deg. F or
more below the specified temperature, or alternatively, container entry
to the retort shall be stopped and the reel restarted to empty the
retort. The discharged containers shall be either reprocessed, repacked
and reprocessed, or discarded. Both the time at which the reel stopped
and the time the retort was used for a still retort process, if so used,
shall be marked on the recording chart and entered on the other
production records required in this chapter. If the alternative
procedure of emptying the retort is followed, the subsequent handling
methods used for the containers in the retort at the time of the
temperature drop shall be entered on the production records. If the
temperature drop was less than 10 deg. F, a scheduled authorized
emergency still process approved by a qualified person(s) having expert
knowledge of thermal processing requirements may be used before
restarting the retort reel. Alternatively, container entry to the retort
shall be stopped and an authorized emergency agitating process may be
used before container entry to the retort is restarted. When emergency
procedures are used, no containers may enter the retort and the process
and procedures used shall be noted on the production records.
(10) Critical factors. Critical factors specified in the scheduled
process shall be measured and recorded on the processing record at
intervals of sufficient frequency to ensure that the factors are within
the limits specified in the scheduled process. The minimum headspace of
containers, if specified in the scheduled process, shall be measured and
recorded at intervals of sufficient frequency to ensure that the
headspace is as specified in the scheduled process. The headspace of
solder-tipped, lap seam (vent hole) cans may be measured by net weight
determinations. The headspace of double seamed cans may also be measured
by net weight determinations for homogeneous liquids, taking into
account the specific can end profile and other factors which affect the
headspace, if proof of the accuracy of such measurements is maintained
and the procedure and resultant headspace is in accordance with the
scheduled process. When the product consistency is specified in the
scheduled process, the consistency of the product shall be determined by
objective measurements on the product taken from the filler before
processing and recorded at intervals of sufficent frequency to ensure
that the consistency is as specified in the scheduled process. Minimum
closing machine vacuum in vacuum-packed products, maximum fill-in or
drained weight, minimum net weight, and percent solids shall be as
specified in the scheduled process for all products when deviations from
such specifications may affect the scheduled process. All measurements
and recordings of critical factors should be made at intervals not to
exceed 15 minutes.
(d) Equipment and procedures for pressure processing in steam in
discontinuous agitating retorts--(1) Indicating mercury-in-glass
thermometer. Each retort shall be equipped with at least one mercury-in-
glass thermometer whose divisions are easily readable to 1 deg. F and
whose temperature range does not exceed 17 deg. F per inch of graduated
scale. Thermometers shall be tested for accuracy
[[Page 47]]
against a known accurate standard thermometer upon installation and at
least once a year thereafter, or more frequently if necessary, to ensure
their accuracy. Records of thermometer accuracy checks which specify
date, standard used, method used, and person performing the test should
be maintained. Each thermometer should have a tag, seal, or other means
of identity that includes the date on which it was last tested for
accuracy. A thermometer that has a divided mercury column or that cannot
be adjusted to the standard shall be repaired or replaced before further
use of the retort. Thermometers shall be installed where they can be
accurately and easily read. Bulbs of indicating thermometers shall be
installed either within the retort shell or in external wells attached
to the retort. External wells or pipes shall be connected to the retort
through at least a \3/4\-inch-diameter opening, and equipped with a \1/
16\-inch or larger bleeder opening so located as to provide a full flow
of steam past the length of the thermometer bulb. The bleeder for
external wells shall emit steam continuously during the entire
processing period. The mercury thermometer--not the recorder chart--
shall be the reference instrument for indicating the processing
temperature.
(2) Temperature-recording device. Each retort shall have an accurate
temperature-recording device. Graduations on the temperature-recording
devices shall not exceed 2 deg. F within a range of 10 deg. F of the
processing temperature. Each chart shall have a working scale of not
more than 55 deg. F per inch within a range of 20 deg. F of the
processing temperature. The temperature chart shall be adjusted to agree
as nearly as possible with, but to be in no event higher than, the known
accurate mercury-in-glass thermometer during the process time. A means
of preventing unauthorized changes in adjustment shall be provided. A
lock, or a notice from management posted at or near the recording device
that provides a warning that only authorized persons are permitted to
make adjustments, is a satisfactory means for preventing unauthorized
changes. The recorder may be combined with the steam controller and may
be a recording-controlling instrument. The temperature-recorder bulb
shall be installed either within the retort shell or in a well attached
to the shell. Each temperature-recorder bulb well shall have a \1/16\-
inch or larger bleeder opening emitting steam continuously during the
processing period. Air-operated temperature controllers should have
adequate filter systems to ensure a supply of clean, dry air.
(3) Pressure gages. Each retort should be equipped with a pressure
gage, which should be graduated in divisions of 2 pounds or less.
(4) Steam controller. Each retort shall be equipped with an
automatic steam controller to maintain the retort temperature. This may
be a recording-controlling instrument when combined with a recording
thermometer. A steam controller activated by the steam pressure of the
retort is acceptable if it is mechanically maintained so that it
operates satisfactorily.
(5) Bleeders. Bleeders, except those for thermometer wells, shall be
one-eighth inch or larger and shall be wide open during the entire
process, including the come-up-time. Bleeders shall be located within
approximately 1 foot of the outermost location of containers at each end
along the top of the retort; additional bleeders shall be located not
more than 8 feet apart along the top. Bleeders may be installed at
positions other than those specified above, as long as there is evidence
in the form of heat distribution data that they accomplish adequate
removal of air and circulation of heat within the retort. In retorts
having top steam inlet and bottom venting, a bleeder shall be installed
in the bottom of the retort to remove condensate. All bleeders shall be
arranged in a way that enables the operator to observe that they are
functioning properly.
(6) Venting and condensate removal. The air in each retort shall be
removed before processing is started. Heat distribution data or
documentary proof from the manufacturer or from a competent processing
authority, demonstrating that adequate venting is achieved, shall be
kept on file. At the time steam is turned on, the drain should be opened
for a time sufficient to remove steam condensate from the retort and
provision should be made for
[[Page 48]]
continuing drainage of condensate during the retort operation.
(7) Retort speed timing. The rotational speed of the retort shall be
specified in the scheduled process. The speed shall be adjusted, as
necessary, to ensure that the speed is as specified in the scheduled
process. The rotational speed as well as the process time shall be
recorded for each retort load processed. Alternatively, a recording
tachometer may be used to provide a continuous record of the speed. A
means of preventing unauthorized speed changes on retorts shall be
provided. A lock, or a notice from management posted at or near the
speed-adjustment device that provides a warning that only authorized
persons are permitted to make adjustments, is a satisfactory means of
preventing unauthorized changes.
(8) Critical factors. Critical factors specified in the scheduled
process shall be measured and recorded on the processing record at
intervals of sufficient frequency to ensure that the factors are within
the limits specified in the scheduled process. The minimum headspace of
containers in each retort load to be processed, if specified in the
scheduled process, shall be measured and recorded at intervals of
sufficient frequency to ensure that the headspace is as specified in the
scheduled process. The headspace of solder-tipped, lap seam (vent hole)
cans may be measured by net weight determinations. When the product
consistency is specified in the scheduled process, the consistency of
the product shall be determined by objective measurements on the product
taken from the filler before processing and recorded at intervals of
sufficient frequency to ensure that the consistency is as specified in
the scheduled process. Minimum closing machine vacuum in vacuum-packed
products, maximum fill-in or drained weight, minimum net weight, and
percent solids shall be as specified in the scheduled process for all
products for which deviations from such specifications may affect the
scheduled process. All measurements and recordings of critical factors
should be made at intervals not to exceed 15 minutes.
(e) Equipment and procedures for pressure processing in water in
discontinuous agitating retorts--(1) Indicating mercury-in-glass
thermometer. Each retort shall be equipped with at least one mercury-in-
glass thermometer whose divisions are easily readable to 1 deg. F and
whose temperature range does not exceed 17 deg. F per inch of graduated
scale. Thermometers shall be tested for accuracy against a known
accurate standard thermometer upon installation and at least once a year
thereafter, or more frequently if necessary, to ensure their accuracy.
Records of thermometer accuracy checks which specify date, standard use,
method used, and person performing the test should be maintained. Each
thermometer should have a tag, seal, or other means of identity that
includes the date on which it was last tested for accuracy. A
thermometer that has a divided mercury column or that cannot be adjusted
to the standard shall be repaired or replaced before further use of the
retort. Thermometers shall be installed where they can be accurately and
easily read. Bulbs of indicating thermometers shall be installed either
within the retort shell or in external wells attached to the retort. The
mercury thermometer--not the recorder chart--shall be the reference
instrument for indicating the processing temperature.
(2) Temperature-recording device. Each retort shall have an accurate
temperature-recording device. Graduations on the temperature-recording
devices shall not exceed 2 deg. F within a range of 10 deg. F of the
processing temperature. Each chart shall have a working scale of not
more than 55 deg. F per inch within a range of 20 deg. F of the
processing temperature. The temperature chart shall be adjusted to agree
as nearly as possible with, but to be in no event higher than, the known
accurate mercury-in-glass thermometer during the process time. A means
of preventing unauthorized changes in adjustment shall be provided. A
lock, or a notice from management posted at or near the recording device
that provides a warning that only authorized persons are permitted to
make adjustment, is a satisfactory means for preventing unauthorized
changes. This recorder may be combined with the steam controller and may
be a recording-controlling instrument. The temperature-recorder bulb
shall be installed either within the
[[Page 49]]
retort shell or in a well attached to the shell. Air-operated
temperature controllers should have adequate filter systems to ensure a
supply of clean dry air.
(3) Pressure gages. Each retort should be equipped with a pressure
gage which should be graduated in divisions of 2 pounds of less.
(4) Steam controller. Each retort shall be equipped with an
automatic steam controller to maintain the retort temperature. This may
be a recording-controlling instrument when combined with a recording
thermometer.
(5) Retort speed timing. The rotational speed of the retort shall be
specified in the scheduled process. The speed shall be adjusted, as
necessary, to ensure that the speed is as specified in the scheduled
process. The rotational speed as well as the process time shall be
recorded for each retort load processed. Alternatively, a recording
tachometer may be used to provide a continuous record of the speed. A
means of preventing unauthorized speed changes shall be provided. A
lock, or a notice from management posted at or near the speed adjustment
device that provides a warning that only authorized persons are
permitted to make adjustment, is a satisfactory means of preventing
unauthorized changes.
(6) Air supply and controls. Means shall be provided for introducing
compressed air at the proper pressure and rate, which shall be
controlled by an automatic pressure control unit. A check value shall be
provided in the air supply line to prevent water from entering the
system.
(7) Critical factors. Critical factors specified in the scheduled
process shall be measured and recorded on the processing record at
intervals of sufficient frequency to ensure that the factors are within
the limits specified in the scheduled process. The minimum headspace of
containers, if specified in the scheduled process, shall be measured and
recorded at intervals of sufficient frequency to ensure that the
headspace is as specified in the scheduled process. The headspace of
solder-tipped, lap seam (vent hole) cans may be measured by net weight
determinations. When the product consistency is specified in the
scheduled process, the consistency of the product shall be determined by
objective measurements on the product taken from the filler before
processing and recorded at intervals of sufficient frequency to ensure
that the consistency is as specified in the scheduled process. Minimum
closing machine vaccum in vacuum-packed products, maximum fill-in or
drained weight, minimum net weight, and percent solids shall be as
specified in the scheduled process for all products when deviations from
such specifications may affect the scheduled process. All measurements
and recordings of critical factors should be made at intervals not to
exceed 15 minutes.
(f) Equipment and procedures for pressure processing in steam in
hydrostatic retorts--(1) Indicating mercury-in-glass thermometer. Each
retort shall be equipped with at least one mercury-in-glass thermometer
whose divisions are easily readable to 1 deg. F and whose temperature
range does not exceed 17 deg. F per inch of graduated scale.
Thermometers shall be tested for accuracy against a known accurate
standard thermometer upon installation and at least once a year
thereafter, or more frequently if necessary, to ensure their accurancy.
Records of thermometer accuracy checks which specify date, standard
used, method used, and person performing the test should be maintained.
Each thermometer should have a tag, seal, or other means of identity
that includes the date on which it was last tested for accuracy. A
thermometer that has a divided mercury column or that cannot be adjusted
to the standard shall be repaired or replaced before further use of the
retort. Thermometers shall be installed where they can be accurately and
easily read. The thermometer shall be located in the steam dome near the
steam-water interface. When the scheduled process specifies maintenance
of particular temperatures in the hydrostatic water legs, a mercury-in-
glass thermometer shall be located in each hydrostatic water leg in a
position near the bottom automatic recorder. The mercury thermometer--
not the recorder chart--shall be the reference instrument for indicating
the processing temperature.
(2) Temperature-recording device. Each retort shall have an accurate
[[Page 50]]
temperature-recording device. Graduations on the temperature-recording
devices shall not exceed 2 deg. F within a range of 10 deg. F of the
processing temperature. Each chart shall have a working scale of not
more than 55 deg. F per inch within a range of 20 deg. F of the
processing temperature. The temperature chart shall be adjusted to agree
as nearly as possible with, but to be in no event higher than, the known
accurate mercury-in-glass thermometer during the process time. A means
of preventing unauthorized changes in adjustment shall be provided. A
lock, or a notice from management posted at or near the recording device
that provides a warning that only authorized persons are permitted to
make adjustments, is a satisfactory means for preventing unauthorized
changes. The recorder may be combined with the steam controller and may
be a recording-controlling instrument. The temperature-recorder bulb
shall be installed either within the steam dome or in a well attached to
the dome. Each temperature-recorder bulb well shall have a \1/16\-inch
or larger bleeder opening which emits steam continuously during the
processing period. Additional temperature-recorder bulbs shall be
installed in the hydrostatic water legs if the scheduled process
specifies maintenance of particular temperatures in the hydrostatic
water legs. Air-operated temperature controllers should have adequate
filter systems to ensure a supply of clean dry air.
(3) Pressure gages. Each retort should be equipped with a pressure
gage which should be graduated in divisions of 2 pounds or less.
(4) Recording of temperatures. Temperatures indicated by the
mercury-in-glass thermometer or thermometers shall be entered on a
suitable form during processing operations. Temperatures shall be
recorded by an accurate automatic recorder or recorders at the following
points:
(i) In the steam chamber between the steam-water interface and the
lowest container position.
(ii) Near the top and the bottom of each hydrostatic water leg if
the scheduled process specifies maintenance of particular temperatures
in the legs.
(5) Steam controller. Each retort shall be equipped with an
automatic steam controller to maintain the retort temperature. This may
be a recording-controlling instrument when combined with a recording
thermometer. A steam controller activated by the steam pressure of the
retort is acceptable if it is carefully mechanically maintained so that
it operates satisfactorily.
(6) Venting. Before the start of processing operations, the retort
steam chamber or chambers shall be vented to ensure removal of air.
(7) Bleeders. Bleeder openings \1/4\-inch or larger shall be located
at the top of the steam chamber or chambers opposite the point of steam
entry. Bleeders shall be wide open and shall emit steam continuously
during the entire process, including the come-up-time. All bleeders
shall be arranged in such a way that the operator can observe that they
are functioning properly.
(8) Retort speed. The speed of the container-conveyor chain shall be
specified in the scheduled process and shall be determined and recorded
at the start of processing and at intervals of sufficient frequency to
ensure that the retort speed is maintained as specified. The speed
should be determined and recorded every 4 hours. An automatic device
should be used to stop the chain when the temperature drops below that
specified in the scheduled process. A means of preventing unauthorized
speed changes shall be provided. A lock, or a notice from management
posted at or near the speed-adjusting device that provides a warning
that only authorized persons are permitted to make adjustments, is a
satisfactory means of preventing unauthorized changes.
(9) Critical factors. Critical factors specified in the scheduled
process shall be measured and recorded on the processing record at
intervals of sufficient frequency to ensure that the factors are within
the limits specified in the scheduled process.
(i) When maximum fill-in or drained weight is specified in the
scheduled process, it shall be measured and recorded at intervals of
sufficient frequency to ensure that the weight of the product does not
exceed the maximum
[[Page 51]]
for the given container size specified in the scheduled process.
(ii) Closing machine vacuum in vacuum-packed products shall be
observed and recorded at intervals of sufficient frequency to ensure
that the vacuum is as specified in the scheduled process.
(iii) Such measurements and recordings should be made at intervals
not to exceed 15 minutes.
(g) Aseptic processing and packaging systems--(1) Product
sterilizer--(i) Equipment--(a) Temperature-indicating device. Each
product sterilizer shall be equipped with at least one mercury-in-glass
thermometer or an equivalent temperature-indicating device, such as a
thermocouple-recorder. Mercury-in-glass thermometers shall have
divisions that are easily readable to 1 deg. F and whose temperature
range does not exceed 17 deg. F per inch of graduated scale.
Thermometers and temperature-indicating devices shall be tested for
accuracy against a known accurate standard thermometer upon installation
and at least once a year thereafter, or more frequently if necessary, to
ensure their accuracy. Records of accuracy checks which specify date,
standard used, method used, and person performing the test should be
maintained. Each thermometer and temperature-indicating device should
have a tag, seal, or other means of identity that includes the date on
which it was last tested for accuracy. A thermometer that has a divided
mercury column or that cannot be adjusted to essential agreement with
the standard shall be repaired or replaced. Thermometers and
temperature-indicating devices shall be installed where they can be
accurately and easily read. The temperature-indicating device shall be
the reference instrument for indicating the processing temperature.
(b) Temperature-recording device. There shall be an accurate
temperature recording device on each product sterilizer. The device
shall be installed in the product at the holding-tube outlet between the
holding tube and the inlet to the cooler. Temperature-recording devices
shall have graduations that do not exceed 2 deg. F within a range of
10 deg. F of the processing temperature. Each chart shall have a working
scale of not more than 55 deg. F per inch within a range of 20 deg. F of
the desired product-sterilization temperature. The temperature chart
shall be adjusted to agree as nearly as possible with, but to be in no
event higher than, a known accurate mercury-in-glass thermometer. A
means of preventing unauthorized changes in adjustment shall be
provided. A lock, or a notice from management posted at or near the
recording device that provides a warning that only authorized persons
are permitted to make adjustments, is a satisfactory means for
preventing unauthorized changes.
(c) Temperature recorder-controller. An accurate temperature
recorder-controller shall be located in the product sterilizer at the
final heater outlet. It shall be capable of ensuring that the desired
product sterilization temperature is maintained. The chart graduations
shall not exceed 2 deg. F within a range of 10 deg. F of the desired
product sterilization temperature. Air-operated temperature controllers
should have adequate filter systems to ensure a supply of clean, dry
air.
(d) Product-to-product regenerators. When a product-to-product
regenerator is used to heat the cold unsterilized product entering the
sterilizer by means of a heat exchange system, it shall be designed,
operated, and controlled so that the pressure of the sterilized product
in the regenerator is greater than the pressure of any unsterilized
product in the regenerator to ensure that any leakage in the regenerator
is from the sterilized product into the unsterilized product.
(e) Differential pressure recorder-controller. When a product-to-
product regenerator is used, there shall be an accurate differential
pressure recorder-controller installed on the regenerator. The scale
divisions shall not exceed 2 pounds per square inch on the working scale
of not more than 20 pounds per square inch per inch. The controller
shall be tested for accuracy against a known accurate standard pressure
indicator upon installation and at least once every 3 months of
operation thereafter, or more frequently if necessary, to ensure its
accuracy. One pressure sensor shall be installed at the sterilized
product regenerator outlet and the other pressure sensor shall be
[[Page 52]]
installed at the unsterilized product regenerator inlet.
(f) Metering pump. A metering pump shall be located upstream from
the holding tube and shall be operated to maintain the required rate of
product flow. A means of preventing unauthorized speed changes shall be
provided. A lock, or a notice from management posted at or near the
speed-adjusting device that provides a warning that only authorized
persons are permitted to make adjustments, is a satisfactory means of
preventing unauthorized changes.
(g) Product holding tube. The product-sterilizing holding tube shall
be designed to give continuous holding of every particle of food for at
least the minimum holding time specified in the scheduled process. The
holding tube shall be designed so that no portion of the tube between
the product inlet and the product outlet can be heated, and it must be
sloped upward at least 0.25 inch per foot.
(h) Flow-diversion systems. If a processor elects to install a flow-
diversion system, it should be installed in the product piping located
between the product cooler and the product filler or aseptic surge tank
and should be designed to divert flow away from the filler or aseptic
surge tank automatically. Controls and/or warning systems should be
designed and installed with necessary sensors and actuators to operate
whenever the sterilizing temperature in the holding tube or pressure
differential in the product regenerator drops below specified limits.
Flow-diversion systems should be designed and operated in accordance
with recommendations of an aseptic processing and packaging authority.
(i) Equipment downstream from the holding tube. Product coolers,
aseptic surge tanks, or any other equipment downstream from the holding
tube, with rotating or reciprocating shafts, valve stems, instrument
connections, or other such points, are subject to potential entry of
microorganisms into the product. Such locations in the system should be
equipped with steam seals or other effective barriers at the potential
access points. Appropriate means should be provided to permit the
operator to monitor the performance of the seals or barriers during
operation.
(ii) Operation--(a) Startup. Before the start of aseptic processing
operations the product sterilizer and all product-contact surfaces
downstream shall be brought to a condition of commercial sterility.
(b) Temperature drop in product-sterilizing holding tube. When
product temperature in the holding tube drops below the temperature
specified in the scheduled process, product flow should be diverted away
from the filler or aseptic surge tank by means of a flow-diversion
system. If for any reason product subjected to a temperature drop below
the scheduled process is filled into containers, the product shall be
segregated from product that received the scheduled process. The
processing deviation shall be handled in accordance with Sec. 507.89.
The product holding tube and any further system portions affected shall
be returned to a condition of commercial sterility before product flow
is resumed to the filler or to the aseptic surge tank.
(c) Loss of proper pressures in the regenerator. When a regenerator
is used, the product may lose sterility whenever the pressure of
sterilized product in the regenerator is less than 1 pound per square
inch greater than the pressure of unsterilized product in the
regenerator. In this case, product flow should be diverted away from the
filler or aseptic surge tank by means of the flow-diversion system. If
for any reason the product is filled into containers, the product shall
be segregated from product that received the scheduled process and shall
be reprocessed or destroyed. Product flow to the filler or to the
aseptic surge tank shall not be resumed until the cause of the improper
pressure relationships in the regenerator has been corrected and the
affected system(s) has been returned to a condition of commercial
sterility.
(d) Loss of sterile air pressure or other protection level in the
aseptic surge tank. When an aseptic surge tank is used, conditions of
commercial sterility may be lost when the sterile air overpressure or
other means of protection drops below the scheduled process value.
Product flow to and/or from the aseptic surge tank shall not be
[[Page 53]]
resumed until the potentially contaminated product in the tank is
removed, and the aseptic surge tank has been returned to a condition of
commercial sterility.
(e) Records. Readings at the following points shall be observed and
recorded at the start of aseptic packaging operations and at intervals
of sufficient frequency to ensure that these values are as specified in
the scheduled process: Temperature-indicating device in holding tube
outlet; temperature recorder in holding tube outlet; temperature
recorder-controller at final heater outlet; differential pressure
recorder-controller, if a product-to-product regenerator is used;
product flow rate as established by the metering pump or as determined
by filling and closing rates and, if an aseptic surge tank is used,
sterile air pressure or other protection means; and proper performance
of seam seals or other similar devices. The measurements and recordings
should be made at intervals not to exceed 1 hour.
(2) Container sterilizing, filling, and closing operation--(i)
Equipment--(a) Recording device. The container and closure sterilization
system and product filling and closing system shall be instrumented to
demonstrate that the required sterilization is being accomplished
continuously. Automatic recording devices shall be used to record, when
applicable, the sterilization media flow rates, temperature,
concentration, or other factors. When a batch system is used for
container sterilization, the sterilization conditions shall be recorded.
(b) Timing method(s). A method(s) shall be used either to give the
retention time of containers, and closures if applicable, in the
sterilizing environment specified in the scheduled process, or to
control the sterilization cycle at the rate specified in the scheduled
process. A means of preventing unauthorized speed changes must be
provided. A lock, or a notice from management posted at or near the
speed adjusting device that provides a warning that only authorized
persons are permitted to make adjustments, is a satisfactory means of
preventing unauthorized changes.
(ii) Operation--(a) Startup. Before the start of packaging
operations, both the container and closure sterilizing system and the
product filling and closing system shall be brought to a condition of
commercial sterility.
(b) Loss of sterility. A system shall be provided to stop packaging
operations, or alternatively to ensure segregation of any product
packaged when the packaging conditions fall below scheduled processes.
Compliance with this requirement may be accomplished by diverting
product away from the filler, by preventing containers from entering the
filler, or by other suitable means. In the event product is packaged
under conditions below those specified in the scheduled process, all
such product shall be segregated and handled in accordance with
Sec. 507.89. In the event of loss of sterility, the system(s) shall be
returned to a condition of commercial sterility before resuming
packaging operations.
(c) Records. Observations and measurements of operating conditions
shall be made and recorded at intervals of sufficient frequency to
ensure that commercial sterility of the food product is being achieved;
such measurements shall include the sterilization media flow rates,
temperatures, the container and closure rates (if applicable) through
the sterilizing system, and the sterilization conditions if a batch
system is used for container sterilization. The measurements and
recordings should be made at intervals not to exceed 1 hour.
(3) Incubation. Incubation tests should be conducted on a
representative sample of containers of product from each code; records
of the test results should be maintained.
(4) Critical factors. Critical factors specified in the scheduled
process shall be measured and recorded on the processing record at
intervals of sufficient frequency to ensure that the factors are within
the limits specified in the scheduled process. Such measurements and
recordings should be done at intervals not to exceed 15 minutes.
(h) Equipment and procedures for flame sterilizers. The container
conveyor speed shall be specified in the scheduled process. The
container conveyor speed shall be measured and recorded
[[Page 54]]
at the start of operations and at intervals of sufficient frequency to
ensure that the conveyor speed is as specified in the scheduled process.
Such measurements and recordings should be done at 1-hour intervals.
Alternatively, a recording tachometer may be used to provide a
continuous record of the speed. A means of preventing changes in flame
intensity and unauthorized speed changes on the conveyor shall be
provided. A lock, or a notice from management posted at or near the
speed adjusting device that provides a warning that only authorized
persons are permitted to make adjustments, is a satisfactory means of
preventing unauthorized changes. The surface temperature of at least one
container from each conveyor channel shall be measured and recorded at
the entry and at the end of the holding period at intervals of
sufficient frequency to ensure that the temperatures specified in the
scheduled process are maintained. Such measurements and recordings
should be done at intervals not to exceed 15 minutes.
(1) Process interruption. In the event of process interruption
wherein the temperature of the product may have dropped, an authorized,
scheduled emergency plan approved by a qualified person having expert
knowledge of the process requirements may be used.
(2) Critical factors. Critical factors specified in the scheduled
process shall be measured and recorded on the processing record at
intervals of sufficient frequency to ensure that the factors are within
the limits specified in the scheduled process.
(i) Equipment and procedures for thermal processing of foods wherein
critical factors such as water activity are used in conjunction with
thermal processing. The methods and controls used for the manufacture,
processing, and packing of such foods shall be as established in the
scheduled process and shall be operated or administered in a manner
adequate to ensure that the product is safe. The time and temperature of
processing and other critical factors specified in the scheduled process
shall be measured with instruments having the accuracy and dependability
adequate to ensure that the requirements of the scheduled process are
met. All measurements shall be made and recorded at intervals of
sufficient frequency to ensure that the critical factors are within the
limits specified in the scheduled process.
(j) Other systems. All systems, whether or not specifically
mentioned in this part, for the thermal processing of low-acid foods in
hermetically sealed containers shall conform to the applicable
requirements of this part and the methods and controls used for the
manufacture, processing, and packing of these foods shall be as
established in the scheduled process. These systems shall be operated or
administered in a manner adequate to ensure that commercial sterility is
achieved. Critical factors specified in the scheduled process shall be
measured and recorded at intervals of sufficient frequency to ensure
that the critical factors are within the limits specified in the
scheduled process.
Subpart D--Control of Components, Food Product Containers, Closures, and
In-Process Materials
Sec. 507.60 Containers.
(a) Closures. Regular observations shall be maintained during
production runs for gross closure defects. Any such defects shall be
recorded and corrective action taken and recorded. At intervals of
sufficient frequency to ensure proper closure, the operator, closure
supervisor, or other qualified container closure inspection person shall
visually examine either the top seam of a can randomly selected from
each seaming head or the closure of any other type of container being
used and shall record the observations made. For double-seam cans, each
can should be examined for cutover or sharpness, skidding or
deadheading, false seam, droop at the crossover or lap, and condition of
inside of countersink wall for evidence of broken chuck. Such
measurements and recordings should be made at intervals not to exceed 30
minutes. Additional visual closure inspections shall be made immediately
following a jam in a closing machine, after closing machine adjustment,
or after startup of a machine following a prolonged shutdown. All
pertinent observations
[[Page 55]]
shall be recorded. When irregularities are found, the corrective action
shall be recorded.
(1) Teardown examinations for double-seam cans shall be performed by
a qualified individual and the results therefrom shall be recorded at
intervals of sufficient frequency on enough containers from each seaming
station to ensure maintenance of seam integrity. Such examinations and
recordings should be made at intervals not to exceed 4 hours. The
results of the teardown examinations shall be recorded and the
corrective action taken, if any, shall be noted.
(i) Required and optional can seam measurements:
(a) Micrometer measurement system:
Required Optional
Cover hook Overlap (by calculation).
Body hook Countersink.
Width (length, height)
Tightness (observation for wrinkle)
Thickness
(b) Seam scope or projector:
Required Optional
Body hook Width (length, height).
Overlap Cover hook.
Tightness (observation for wrinkle)
Countersink
Thickness by micrometer
[[Page 56]]
[GRAPHIC] [TIFF OMITTED] TR01FE93.009
(c) Can double seam terminology:
(1) Crossover: The portion of a double seam at the lap.
(2) Cutover: A fracture, sharp bend, or break in the metal at the
top of the inside portion of the double seam.
[[Page 57]]
(3) Deadhead: A seam which is incomplete due to chuck spinning in
the countersink.
(4) Droop: Smooth projection of double seam below bottom of normal
seam.
(5) False seam: A small seam breakdown where the cover hook and the
body hook are not overlapped.
(6) Lap: Two thicknesses of material bonded together.
(ii) Two measurements at different locations, excluding the side
seam, shall be made for each double seam characteristic if a seam scope
or seam projector is used. When a micrometer is used, three measurements
shall be made at points approximately 120 deg. apart, excluding the side
seam.
(iii) Overlap length can be calculated by the following formula:
The theoretical overlap length = CH + BH + T - W,
where
CH = cover hook
BH = body hook
T = cover thickness, and
W = seam width (height, length)
(2) For glass containers with vacuum closures, capper efficiency
must be checked by a measurement of the cold water vacuum. This shall be
done before actual filling operations, and the results shall be
recorded.
(3) For closures other than double seams and glass containers,
appropriate detailed inspections and tests shall be conducted by
qualified personnel at intervals of sufficient frequency to ensure
proper closing machine performance and consistently reliable hermetic
seal production. Records of such tests shall be maintained.
(b) Cooling water. Container cooling water shall be chlorinated or
otherwise sanitized as necessary for cooling canals and for recirculated
water supplies. There should be a measurable residual of the sanitizer
employed at the water discharge point of the container cooler.
(c) Coding. Each hermetically sealed container of low-acid processed
food shall be marked with an identifying code that shall be permanently
visible to the naked eye. When the container does not permit the code to
be embossed or inked, the label may be legibly perforated or otherwise
marked, if the label is securely affixed to the product container. The
required identification shall identify in code the establishment where
packed, the product contained therein, the year packed, the day packed,
and the period during which packed. The packing period code shall be
changed with sufficient frequency to enable ready identification of lots
during their sale and distribution. Codes may be changed on the basis of
one of the following: intervals of 4 to 5 hours; personnel shift
changes; or batches, as long as the containers that constitute the batch
do not extend over a period of more than one personnel shift.
(d) Postprocess handling. When cans are handled on belt conveyors,
the conveyors should be so constructed as to minimize contact by the
belt with the double seam, i.e., cans should not be rolled on the double
seam. All worn and frayed belting, can retarders, cushions, etc. should
be replaced with new nonporous material. All tracks and belts that come
into contact with the can seams should be thoroughly scrubbed and
sanitized at intervals of sufficient frequency to avoid product
contamination. Automatic equipment used in handling filled containers
should be so designed and operated as to preserve the can seam or other
container closure integrity.
Subpart E--Production and Process Controls
Sec. 507.81 Product preparation.
(a) Before using raw materials and ingredients susceptible to
microbiological contamination, the processor shall ensure that those
materials and ingredients are suitable for use in processing low-acid
food. Compliance with this requirement may be accomplished by receiving
the raw materials and ingredients under a supplier's guarantee that they
are suitable for use, by examining them for their microbiological
condition, or by other acceptable means.
(b) Blanching by heat, when required in the preparation of food for
canning, should be effected by heating the food to the required
temperature, holding it at this temperature for the required time, and
then either rapidly cooling the food or passing it to subsequent
[[Page 58]]
processing without delay. Thermophilic growth and contamination in
blanchers should be minimized by the use of adequate operating
temperatures and by cleaning. If the blanched food product is washed
before filling, potable water should be used.
(c) The filling of containers, either mechanically or by hand, shall
be controlled so as to ensure that the filling requirements specified in
the scheduled process are met.
(d) The exhausting of containers for the removal of air shall be
controlled so as to meet the conditions for which the process was
designed. Compliance with the requirement may be accomplished by heat
exhausting, mechanical exhausting, hot brining, or steam injection.
(e) When the maintenance of pH (above 4.6) of a normally low-acid
food is a basis for a scheduled process, there shall be careful
supervision to ensure that the equilibrium pH of the finished product
meets that of the scheduled process. The methodology described in
Sec. 114.90 of this chapter should be used.
(f) When the scheduled process sets forth critical factors to
prevent the growth of microorganisms not destroyed by the thermal
process, the factors shall be carefully controlled to ensure that the
limits established in the scheduled process are not exceeded. When
normally low-acid foods require sufficient solute to permit safe
processing at low temperatures, such as in boiling water, there shall be
careful supervision to ensure that the equilibrium water activity
(aw) of the finished product meets that of the scheduled process.
The scheduled thermal processes for foods having an aw greater than
0.85 and less than the aw that would allow the growth of spores of
microorganisms of public health significance shall be sufficient to
render the food free of microorganisms capable of reproducing in the
food under normal nonrefrigerated conditions of storage and
distribution.
Sec. 507.83 Establishing scheduled processes.
Scheduled processes for low-acid foods shall be established by
qualified persons having expert knowledge of thermal processing
requirements for low-acid foods in hermetically sealed containers and
having adequate facilities for making such determinations. The type,
range, and combination of variations encounted in commercial production
shall be adequately provided for in establishing the scheduled process.
Critical factors, e.g., minimum headspace, consistency, maximun fill-in
or drained weight, aw, etc., that may affect the scheduled process,
shall be specified in the scheduled process. Acceptable scientific
methods of establishing heat sterilization processes shall include, when
necessary, but shall not be limited to, microbial thermal death time
data, process calculations based on product heat penetration data, and
inoculated packs. Calculation shall be performed according to procedures
recognized by competent processing authorities. If incubation tests are
necessary for process confirmation, they shall include containers from
test trials and from actual commercial production runs during the period
of instituting the process. The incubation tests for confirmation of the
scheduled processes should include the containers from the test trials
and a number of containers from each of four or more actual commercial
production runs. The number of containers from actual commercial
production runs should be determined on the basis of recognized
scientific methods to be of a size sufficient to ensure the adequacy of
the process. Complete records covering all aspects of the establishment
of the process and associated incubation tests shall be prepared and
shall be permanently retained by the person or organization making the
determination.
Sec. 507.87 Operations in the thermal processing room.
(a) Operating processes and retort venting procedures to be used for
each product and container size being packed shall either be posted in a
conspicuous place near the processing equipment or be made readily
available to the retort or processing system operator and any duly
authorized employee of the Food and Drug Administration. Scheduled
processes must be
[[Page 59]]
made readily available to the supervisor and any duly authorized
employee of the Food and Drug Administration.
(b) A system for product traffic control in the retort room shall be
established to prevent unretorted product from bypassing the retort
process. Each retort basket, truck, car, or crate used to hold
containers in a retort, or one or more containers therein, shall, if it
contains any retorted food product, be plainly and conspicuously marked
with a heat-sensitive indicator, or by other effective means that will
indicate visually, to thermal processing personnel, those units that
have been retorted. A visual check shall be performed to determine
whether or not the appropriate change has occurred in the heat-sensitive
indicator as a result of retorting for all retort baskets, trucks, cars,
or crates, to ensure that each unit of product has been retorted. A
written record of these checks should be made.
(c) The initial temperature of the contents of the containers to be
processed shall be determined and recorded with sufficient frequency to
ensure that the temperature of the product is no lower than the minimum
initial temperature specified in the scheduled process. For those
operations that use water during the filling of the retort or during
processing, provision shall be made to ensure that the water will not,
before the start of each thermal process, lower the initial temperature
of the product below that specified in the scheduled process.
(d) Timing devices used in recording thermal process time
information shall be accurate to the extent needed to ensure that the
processing time and venting time specified in the scheduled process are
achieved. Pocket or wrist watches are not considered satisfactory for
timing purposes. Digital clocks may be used if the operating process and
the venting schedule have a 1-minute or greater safety factor over the
scheduled process.
(e) Clock times on recording-temperature charts should reasonably
correspond to the time of day on the written processing records to
provide correlation of these records.
(f) The steam supply to the thermal processing system shall be
adequate to the extent needed to ensure that sufficient steam pressure
is maintained during thermal processing, regardless of other demands of
steam by the plant.
(g) If mufflers are used on bleeders or vent systems, evidence that
the bleeders or vents are operated in a manner that does not
significantly impede the removal of air shall be kept on file. This
evidence may be in the form of heat distribution data or other
satisfactory evidence such as a letter from the manufacturer, the
designer, or a competent processing authority.
Sec. 507.89 Deviations in processing, venting, or control of critical factors.
Whenever any process is less than the scheduled process or when
critical factors are out of control for any low-acid food or container
system as disclosed from records by processor check or otherwise, the
commercial processor of that low-acid food shall either fully reprocess
that portion of the production involved, keeping full records of the
reprocessing conditions or, alternatively, shall set aside that portion
of the product involved for further evaluation as to any potential
public health significance. Such evaluation shall be made by a competent
processing authority and shall be in accordance with procedures
recognized by competent processing authorities as being adequate to
detect any potential hazard to public health. Unless this evaluation
demonstrates that the product had been given a thermal process that
rendered it free of microorganisms of potential public health
significance, the product set aside shall be either fully reprocessed to
render it commercially sterile or destroyed. A record shall be made of
the evaluation procedures used and the results. Either upon completion
of full reprocessing and the attainment of commercial sterility or after
the determination that no significant potential for public health hazard
exists, that portion of the product involved may be shipped in normal
distribution. Otherwise, the portion of the product involved shall be
destroyed. All process deviations involving a failure to satisfy the
minimum requirements of the
[[Page 60]]
scheduled process, including emergencies arising from a jam or breakdown
of a continuous agitating retort necessitating cooling the retort for
repairs, shall be recorded and made the subject of a separate file (or a
log identifying the appropriate data) detailing those deviations and the
actions taken.
Subpart F--Records and Reports
Sec. 507.100 Processing and production records.
(a) Processing and production information shall be entered at the
time it is observed by the retort or processing system operator, or
other designated person, on forms that include the product, the code
number, the date, the retort or processing system number, the size of
container, the approximate number of containers per coding interval, the
initial temperature, the actual processing time, the mercury-in-glass
and recording thermometer readings, and other appropriate processing
data. Closing machine vacuum in vacuum-packed products, maximum fill-in
or drained weight, or other critical factors specified in the scheduled
process shall also be recorded. In addition, the following records shall
be maintained:
(1) Still retorts. Time steam on; time temperature up to processing
temperature; time steam off; venting time and temperature to which
vented.
(2) Agitating retorts. Functioning of condensate bleeder; retort
speed; and, when specified in the scheduled process, headspace,
consistency, maximum drained weight, minimum net weight, and percent
solids.
(3) Hydrostatic retorts. The temperature in the steam chamber
between the steam-water interface and the lowest container position;
speed of the container conveyor chain; and, when the scheduled process
specifies maintenance of particular temperatures in the hydrostatic
water legs, the temperatures near the top and the bottom of each
hydrostatic water leg.
(4) Aseptic processing and packaging systems. Product temperature in
the holding tube outlet as indicated by the temperature-indicating
device and the temperature recorder; product temperature in the final
heater outlet as indicated by the temperature recorder-controller;
differential pressure as indicated by the differential pressure
recorder-controller, if a product-to-product regenerator is used;
product flow rate, as determined by the metering pump or by filling and
closing rates; sterilization media flow rate or temperature or both;
retention time of containers, and closures when applicable, in the
sterilizing environment; and, when a batch system is used for container
and/or closure sterilization, sterilization cycle times and
temperatures.
(5) Flame sterilizers. Container conveyor speed; surface temperature
at the beginning and at the end of the holding period; nature of
container.
(6) Food preservation methods wherein critical factors such as water
activity are used in conjunction with thermal processing. Product
formulation and scheduled processes used, including the thermal process,
its associated critical factors, as well as other critical factors, and
results of aw!determinations.
(7) Other systems. Critical factors specified in the formulation of
the product or in the scheduled process.
(b) Recording thermometer charts shall be identified by date, retort
number, and other data as necessary, so they can be correlated with the
written record of lots processed. Each entry on the processing and
production records shall be made by the retort or processing system
operator, or other designated person, at the time the specific retort or
processing system condition or operation occurs, and this retort or
processing system operator or other designated person shall sign or
initial each record form. Not later than 1 working day after the actual
process, and before shipment or release for distribution, a
representative of plant management who is qualified by suitable training
or experience shall review all processing and production records for
completeness and to ensure that the product received the scheduled
process. The records, including the recording thermometer chart(s),
shall be signed or initialed and dated by the reviewer.
(c) Written records of all container closure examinations shall
specify the
[[Page 61]]
product code, the date and time of container closure inspections, the
measurements obtained, and all corrective actions taken. Records shall
be signed or initialed by the container closure inspector and reviewed
by management with sufficient frequency to ensure that the containers
are hermetically sealed.
(d) Records shall be maintained to identify the initial distribution
of the finished product to facilitate, when necessary, the segregation
of specific food lots that may have become contaminated or otherwise
rendered unfit for their intended use.
(e) Copies of all records provided for in this part, except those
required under Sec. 507.83 establishing scheduled processes, shall be
retained at the processing plant for a period of not less than 1 year
from the date of manufacture, and at the processing plant or other
reasonably accessible location for an additional 2 years. If, during the
first year of the 3-year record-retention period, the processing plant
is closed for a prolonged period between seasonal packs, the records may
be transferred to some other reasonably accessible location at the end
of the seasonal pack.
PART 508--EMERGENCY PERMIT CONTROL--Table of Contents
Subpart A--General Provisions
Sec.
508.3 Definitions.
508.5 Determination of the need for a permit.
508.6 Revocation of determination of need for permit.
508.7 Issuance or denial of permit.
508.10 Suspension and reinstatement of permit.
508.12 Manufacturing, processing, or packing without a permit or in
violation of a permit.
508.19 Establishment of requirements for exemption from section 404 of
the act.
Subpart B--Requirements and Conditions for Exemption From or Compliance
With an Emergency Permit
508.35 Thermal processing of low-acid animal foods packaged in
hermetically sealed containers.
Authority: Secs. 402, 404, 701 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 342, 344, 371).
Source: 41 FR 38637, Sept. 10, 1976, unless otherwise noted.
Subpart A--General Provisions
Sec. 508.3 Definitions.
(a) The definitions contained in section 201 of the Federal Food,
Drug, and Cosmetic Act are applicable to such terms when used in this
part.
(b) Commissioner means the Commissioner of Food and Drugs.
(c) Act means the Federal Food, Drug, and Cosmetic Act, as amended.
(d) Permit means an emergency permit issued by the Commissioner
pursuant to section 404 of the act for such temporary period of time as
may be necessary to protect the public health.
(e) Manufacture, processing, or packing of food in any locality
means activities conducted in a single plant or establishment, a series
of plants under a single management, or all plants in an industry or
region, by a manufacturer, processor, or packer.
Sec. 508.5 Determination of the need for a permit.
(a) Whenever the Commissioner determines after investigation that a
manufacturer, processor, or packer of a food for which a regulation has
been promulgated in subpart B of this part does not meet the mandatory
conditions and requirements established in such regulation, he shall
issue to such manufacturer, processor, or packer an order determining
that a permit shall be required before the food may be introduced or
delivered for introduction into interstate commerce by that person. The
order shall specify the mandatory conditions and requirements with which
there is a lack of compliance.
(1) The manufacturer, processor, or packer shall have 3 working days
after receipt of such order within which to file objections. Such
objections may be filed by telegram, telex, or any other mode of written
communication addressed to the Food and Drug Administration, Center for
Food Safety and Applied Nutrition, 200 C St. SW., Washington, DC 20204.
If such objections are filed, the determination is stayed
[[Page 62]]
pending a hearing to be held within 5 working days after the filing of
objections on the issues involved unless the Commissioner determines
that the objections raise no genuine and substantial issue of fact to
justify a hearing.
(2) If the Commissioner finds that there is an imminent hazard to
health, the order shall contain this finding and the reasons therefor,
and shall state that the determination of the need for a permit is
effective immediately pending an expedited hearing.
(b) A hearing under this section shall be conducted by the
Commissioner or his designee at a location agreed upon by the objector
and the Commissioner or, if such agreement cannot be reached, at a
location designated by the Commissioner. The manufacturer, processor, or
packer shall have the right to cross-examine the Food and Drug
Administration's witnesses and to present witnesses on his own behalf.
(c) Within 5 working days after the hearing, and based on the
evidence presented at the hearing, the Commissioner shall determine
whether a permit is required and shall so inform the manufacturer,
processor, or packer in writing, with the reasons for his decision.
(d) The Commissioner's determination of the need for a permit
constitutes final agency action from which appeal lies to the courts.
The Commissioner will not stay a determination of the need for a permit
pending court appeal except in unusual circumstances, but will
participate in expediting any such appeal.
[41 FR 38637, Sept. 10, 1976, as amended at 54 FR 18279, Apr. 28, 1989]
Sec. 508.6 Revocation of determination of need for permit.
(a) A permit shall be required only during such temporary period as
is necessary to protect the public health.
(b) Whenever the Commissioner has reason to believe that a permit
holder is in compliance with the mandatory requirements and conditions
established in subpart B of this part and is likely to remain in
compliance, he shall, on his own initiative or on the application of the
permit holder, revoke both the determination of need for a permit and
the permit that had been issued. If denied, the applicant shall, upon
request, be afforded a hearing conducted in accordance with Sec. 508.5
(b) and (c) as soon as practicable. Such revocation is without prejudice
to the initiation of further permit proceedings with respect to the same
manufacturer, processor, or packer should later information again show
the need for a permit.
Sec. 508.7 Issuance or denial of permit.
(a) After a determination and notification by the Commissioner in
accordance with the provisions of Sec. 508.5 that a manufacturer,
processor, or packer requires a permit, such manufacturer, processor, or
packer may not thereafter introduce or deliver for introduction into
interstate commerce any such food manufactured, processed, or packed by
him unless he holds a permit issued by the Commissioner or obtains
advance written approval of the Food and Drug Administration pursuant to
Sec. 508.12(a).
(b) Any manufacturer, processor, or packer for whom the Commissioner
has made a determination that a permit is necessary may apply to the
Commissioner for the issuance of such a permit. The application shall
contain such data and information as is necessary to show that all
mandatory requirements and conditions for the manufacture, processing,
or packing of a food for which regulations are established in subpart B
of this part are met and, in particular, shall show that the deviations
specified in the Commissioner's determination of the need for a permit
have been corrected or suitable interim measures established. Within 10
working days after receipt of such application, (except that the
Commissioner may extend such time an additional 10 working days where
necessary), the Commissioner shall issue a permit, deny the permit, or
offer the applicant a hearing conducted in accordance with Sec. 508.5
(b) and (c) as to whether the permit should be issued. The Commissioner
shall issue such a permit to which shall be attached, in addition to the
mandatory requirements and conditions of subpart B of this part, any
additional requirements or conditions which may be necessary to protect
the public health if he finds that all
[[Page 63]]
mandatory requirements and conditions of subpart B of this part are met
or suitable interim measures are established.
(c) Denial of a permit constitutes final agency action from which
appeal lies to the courts. The Commissioner will not stay such denial
pending court appeal except in unusual circumstances, but will
participate in expediting any such appeal.
Sec. 508.10 Suspension and reinstatement of permit.
(a) Whenever the Commissioner finds that a permit holder is not in
compliance with the mandatory requirements and conditions established by
the permit, he shall immediately suspend the permit and so inform the
permit holder, with the reasons for the suspension.
(b) Upon application for reinstatement of a permit, the Commissioner
shall, within 10 working days, reinstate the permit if he finds that the
person is in compliance with the mandatory requirements and conditions
established by the permit or deny the application.
(c) Any person whose permit has been suspended or whose application
for reinstatement has been denied may request a hearing. The hearing
shall be conducted by the Commissioner or his designee within 5 working
days of receipt of the request at a location agreed upon by the objector
and the Commissioner or, if an agreement cannot be reached, at a
location designated by the Commissioner. The permit holder shall have
the right to present witnesses on his own behalf and to cross-examine
the Food and Drug Administration's witnesses.
(d) Within 5 working days after the hearing, and based on the
evidence presented at the hearing, the Commissioner shall determine
whether the permit shall be reinstated and shall so inform the permit
holder, with the reasons for his decision.
(e) Denial of an application for reinstatement of a permit
constitutes final agency action from which appeal lies to the courts.
The Commissioner will not stay such denial pending court appeal except
in unusual circumstances, but will participate in expediting any such
appeal.
Sec. 508.12 Manufacturing, processing, or packing without a permit or in violation of a permit.
(a) A manufacturer, processor, or packer may continue at his own
risk to manufacture, process, or pack without a permit a food for which
the Commissioner has determined that a permit is required. All food so
manufactured, processed, or packed during such period without a permit
shall be retained by the manufacturer, processor, or packer and may not
be introduced or delivered for introduction into interstate commerce
without the advance written approval of the Food and Drug
Administration. Such approval may be granted only upon an adequate
showing that such food is free from microorganisms of public health
significance. The manufacturer, processor, or packer may provide to the
Commissioner, for his consideration in making any such determination, an
evaluation of the potential public health significance of such food by a
competent authority in accordance with procedures recognized as being
adequate to detect any potential hazard to public health. Within 20
working days after receipt of a written request for such written
approval the Food and Drug Administration shall either issue such
written approval or deny the request. If the request is denied, the
applicant shall, upon request, be afforded a prompt hearing conducted in
accordance with Sec. 508.5 (b) and (c).
(b) Except as provided in paragraph (a) of this section, no
manufacturer, processor, or packer may introduce or deliver for
introduction into interstate commerce without a permit or in violation
of a permit a food for which the Commissioner has determined that a
permit is required. Where a manufacturer, processor, or packer utilizes
a consolidation warehouse or other storage facility under his control,
interstate shipment of any such food from the point of production to
that warehouse or storage facility shall not violate this paragraph,
provided that no further introduction or delivery for introduction into
interstate commerce is made from that consolidated warehouse or storage
facility except as provided in paragraph (a) of this section.
[[Page 64]]
Sec. 508.19 Establishment of requirements for exemption from section 404 of the act.
(a) Whenever the Commissioner finds after investigation that the
distribution in interstate commerce of any class of food may, by reason
of contamination with microorganisms during the manufacture, processing,
or packing thereof in any locality, be injurious to health, and that
such injurious nature cannot be adequately determined after such
articles have entered interstate commerce, he shall promulgate
regulations in subpart B of this part establishing requirements and
conditions governing the manufacture, processing, or packing of the food
necessary to protect the public health. Such regulations may be proposed
by the Commissioner on his own initiative or in response to a petition
from any interested person pursuant to part 10 of this chapter.
(b) A manufacturer, processor, or packer of a food for which a
regulation has been promulgated in subpart B of this part shall be
exempt from the requirement for a permit only if he meets all of the
mandatory requirements and conditions established in that regulation.
[41 FR 38637, Sept. 10, 1976, as amended at 42 FR 4717, Jan. 25, 1977;
42 FR 15675, Mar. 22, 1977]
Subpart B--Requirements and Conditions for Exemption From or Compliance
With an Emergency Permit
Sec. 508.35 Thermal processing of low-acid animal foods packaged in hermetically sealed containers.
(a) Inadequate or improper manufacture, processing, or packing of
thermally processed low-acid foods in hermetically sealed containers may
result in the distribution in interstate commerce of processed foods
that may be injurious to health. The harmful nature of such foods cannot
be adequately determined after these foods have entered into interstate
commerce. The Commissioner of Food and Drugs therefore finds that, in
order to protect the public health, it may be necessary to require any
commercial processor, in any establishment engaged in the manufacture,
processing, or packing of thermally processed low-acid foods in
hermetically sealed containers, to obtain and hold a temporary emergency
permit provided for under section 404 of the Federal Food, Drug, and
Cosmetic Act. Such a permit may be required whenever the Commissioner
finds, after investigation, that the commercial processor has failed to
fulfill all the requirements of this section, including registration and
the filing of process information, and the mandatory portions of part
507 of this chapter. These requirements are intended to ensure safe
manufacture, processing, and packing procedures and to permit the Food
and Drug Administration to verify that these procedures are being
followed. Such failure shall constitute a prima facie basis for the
immediate application of the emergency permit control provisions of
section 404 of the act to that establishment, pursuant to the procedures
established in subpart A of this part.
(b) The definitions in Sec. 507.3 of this chapter are applicable
when such terms are used in this section.
(c) Registration and process filing--(1) Registration. A commercial
processor when first engaging in the manufacture, processing, or packing
of thermally processed low-acid foods in hermetically sealed containers
in any state, as defined in section 201(a)(1) of the act, shall, not
later than 10 days after first so engaging, register with the Food and
Drug Administration on Form FD-2541 (food canning establishment
registration) information including (but not limited to) his name,
principal place of business, the location of each establishment in which
such processing is carried on, the processing method in terms of the
type of processing equipment employed, and a list of the low-acid foods
so processed in each such establishment. These forms are available from
the Center for Food Safety and Applied Nutrition, (HFS-565), Food and
Drug Administration, 200 C St. SW., Washington, DC 20204, or at any Food
and Drug Administration district office. The completed form shall be
submitted to the Center for Food Safety and Applied Nutrition, (HFS-
617), Food and Drug
[[Page 65]]
Administration, 200 C St. SW., Washington, DC 20204. Commercial
processors presently so engaged shall register not later than July 13,
1973. Commercial processors duly registered in accordance with this
section shall notify the Food and Drug Administration not later than 90
days after such commercial processor ceases or discontinues the
manufacture, processing, or packing of thermally processed foods in any
establishment: Provided, That such notification shall not be required as
to the temporary cessation necessitated by the seasonal character of the
particular establishment's production or caused by temporary conditions
including but not limited to strikes, lockouts, fire, or acts of God.
(2) Process filing. A commercial processor engaged in the thermal
processing of low-acid foods packaged in hermetically sealed containers
shall, not later than 60 days after registration and prior to the
packing of a new product, provide the Food and Drug Administration
information as to the scheduled processes including but not limited to
the processing method, type of retort or other thermal processing
equipment employed, minimum initial temperatures, times and temperatures
of processing, sterilizing value (F0), or other equivalent
scientific evidence of process adequacy, critical control factors
affecting heat penetration, and source and date of the establishment of
the process, for each such low-acid food in each container size:
Provided, That the filing of such information does not constitute
approval of the information by the Food and Drug Administration, and
that information concerning processes and other data so filed shall be
regarded as trade secrets within the meaning of 21 U.S.C. 331(j) and 18
U.S.C. 1905. This information shall be submitted on the following forms
as appropriate: Form FD-2541a (food canning establishment and process
filing for still retort processes), form FD-2541b (food canning
establishment and process filing for agitating processes), or form FD-
2541c (food canning establishment and process filing for other than
still retort and agitating processes). These forms are available from
the Center for Food Safety and Applied Nutrition, (HFS-565), Food and
Drug Administration, 200 C St. SW., Washington, DC 20204, or at any Food
and Drug Administration district office. The completed form(s) shall be
submitted to the Food and Drug Administration, Center for Food Safety
and Applied Nutrition, (HFS-617), Food and Drug Administration, 200 C
St. SW., Washington, DC 20204.
(i) If all the necessary information is not available for existing
products, the processor shall, at the time the existing information is
provided to the Food and Drug Administration request in writing an
extension of time for submission of such information, specifying what
additional information is to be supplied and the date by which it is to
be submitted. Within 30 working days after receipt of such request the
Food and Drug Administration shall either grant or deny such request in
writing.
(ii) If a packer intentionally makes a change in a previously filed
scheduled process by reducing the initial temperature or retort
temperature, reducing the time of processing, or changing the product
formulation, the container, or any other condition basic to the adequacy
of scheduled process, he shall prior to using such changed process
obtain substantiation by qualified scientific authority as to its
adequacy. Such substantiation may be obtained by telephone, telegram, or
other media, but must be promptly recorded, verified in writing by the
authority, and contained in the packer's files for review by the Food
and Drug Administration. Within 30 days after first use, the packer
shall submit to the Center for Food Safety and Applied Nutrition, (HFS-
617), 200 C St. SW., Washington, DC 20204 a complete description of the
modifications made and utilized, together with a copy of his file record
showing prior substantiation by a qualified scientific authority as to
the safety of the changed process. Any intentional change of a
previously filed scheduled process or modification thereof in which the
change consists solely of a higher initial temperature, a higher retort
temperature, or a longer processing time, shall not be considered a
change subject to this paragraph, but if thereafter that modification is
to be regularly scheduled, the modified process shall be promptly
[[Page 66]]
filed as a scheduled process, accompanied by full information on the
specified forms as provided in this paragraph.
(iii) Many packers employ an ``operating'' process in which retort
operators are instructed to use retort temperatures and/or processing
times slightly in excess of those specified in the scheduled process as
a safety factor to compensate for minor fluctuations in temperature or
time to assure that the minimum times and temperatures in the scheduled
process are always met. This would not constitute a modification of the
scheduled process.
(3) Process adherence and information. (i) A commercial processor
engaged in the thermal processing of low-acid foods packaged in
hermetically sealed containers in any registered establishment shall
process each low-acid food in each container size in conformity with at
least the scheduled processes and modifications filed pursuant to
paragraph (c)(2) of this section.
(ii) Process information availability: When requested by the Food
and Drug Administration in writing, a commercial processor engaged in
thermal processing of low-acid foods packaged in hermetically sealed
containers shall provide the Food and Drug Administration with any
information concerning processes and procedures which is deemed
necessary by the Food and Drug Administration to determine the adequacy
of the process: Provided, That the furnishing of such information does
not constitute approval of the information by the Food and Drug
Administration, and that the information concerning processes and other
data so furnished shall be regarded as trade secrets within the meaning
of 21 U.S.C. 331(j) and 18 U.S.C. 1905.
(d) A commercial processor engaged in the thermal processing of low-
acid foods packaged in hermetically sealed containers shall promptly
report to the Food and Drug Administration any instance of spoilage or
process deviation the nature of which indicates potential health
significance where any lot of such food has in whole or in part entered
distribution.
(e) A commercial processor engaged in thermal processing of low-acid
foods packaged in hermetically sealed containers shall promptly report
to the Food and Drug Administration any instance wherein any lot of such
food, which may be injurious to health by reason of contamination with
microorganisms, has in whole or in part entered distribution.
(f) A commercial processor engaged in the thermal processing of low-
acid foods packaged in hermetically sealed containers shall have
prepared and in his files a current procedure which he will use for
products under his control and which he will ask his distributor to
follow, including plans for effecting recalls of any product that may be
injurious to health; for identifying, collecting, warehousing, and
controlling the product; for determining the effectiveness of such
recall; for notifying the Food and Drug Administration of any such
recall; and for implementing such recall program.
(g) All operators of retorts, thermal processing systems, aseptic
processing and packaging systems, or other thermal processing systems,
and container closure inspectors shall be under the operating
supervision of a person who has attended a school approved by the
Commissioner for giving instruction in retort operations, aseptic
processing and packaging systems operations or other thermal processing
systems operations, and container closure inspections, and has
satisfactorily completed the prescribed course of instruction: Provided,
That this requirement shall not apply in the State of California as
listed in paragraph (j) of this section and shall not apply until March
25, 1975 in any other State. The Commissioner will not withhold approval
of any school qualified to give such instruction.
(h) A commercial processor engaged in the thermal processing of low-
acid foods packaged in hermetically sealed containers shall prepare,
review, and retain at the processing plant for a period of not less than
1 year, and at the processing plant or other reasonably accessible
location for an additional 2 years, all records of processing,
deviations in processing, container closure inspections, and other
records specified in part 507 of this chapter. If during the first year
of the 3-year record retention period the processing plant is closed for
[[Page 67]]
a prolonged period between seasonal packs, the records may be
transferred to some other reasonably accessible location at the end of
the seasonal pack. Upon written demand during the course of a factory
inspection pursuant to section 704 of the act by a duly authorized
employee of the Food and Drug Administration, a commercial processor
shall permit the inspection and copying by such employee of these
records to verify the adequacy of processing, the integrity of container
closures, and the coding of the products.
(i) This section shall not apply to the commercial processing of any
food processed under the continuous inspection of the meat and poultry
inspection program of the Animal and Plant Health Inspection Service of
the Department of Agriculture under the Federal Meat Inspection Act (34
Stat. 1256, as amended by 81 Stat. 584 (21 U.S.C. 601 et seq.)) and the
Poultry Products Inspection Act (71 Stat. 441, as amended by 82 Stat.
791; 21 U.S.C. 451 et seq.).
(j) Compliance with State regulations: (1) Wherever the Commissioner
finds that any State regulates the commercial thermal processing of low-
acid foods in accordance with effective regulations specifying at least
the requirements of part 507 of this chapter, he shall issue a notice
stating that compliance with such State regulations shall constitute
compliance with part 507 of this chapter. However, the provisions of
this section shall remain applicable to the commercial processing of
low-acid foods in any such State, except that, either the State through
its regulatory agency or each processor of low-acid foods in such State
shall file with the Center for Food Safety and Applied Nutrition, the
registration information and the processing information prescribed in
paragraph (c) of this section.
(2) The Commissioner finds that the regulations adopted by the State
of California under the laws relating to cannery inspections governing
thermal processing of low-acid foods packaged in hermetically sealed
containers satisfy the requirements of part 507 of this chapter.
Accordingly, processors, who under the laws relating to cannery
inspections are licensed by the State of California and who comply with
such state regulations, shall be deemed to comply with the requirements
of part 507 of this chapter.
(k) Imports: (1) This section shall apply to any foreign commercial
processor engaged in the thermal processing of low-acid foods packaged
in hermetically sealed containers and offering such foods for import
into the United States except that, in lieu of providing for the
issuance of an emergency permit under paragraph (a) of this section, the
Commissioner will request the Secretary of the Treasury to refuse
admission into the United States, pursuant to section 801 of the act, of
any such low-acid foods which the Commissioner determines, after
investigation, may result in the distribution in interstate commerce of
processed foods that may be injurious to health as set forth in
paragraph (a) of this section.
(2) Any such food refused admission shall not be admitted until such
time as the Commissioner may determine that the commercial processor
offering the food for import is in compliance with the requirements and
conditions of this section and that such food is not injurious to
health. For the purpose of making such determination, the Commissioner
reserves the right for a duly authorized employee of the Food and Drug
Administration to inspect the commercial processor's manufacturing,
processing, and packing facilities.
(l) The following data and information submitted to the Food and
Drug Administration pursuant to this section 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
information.
(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
[[Page 68]]
provision is available for public disclosure.
(3) Quantitative or semiquantitative formulas.
[41 FR 38637, Sept. 10, 1976, as amended at 42 FR 15675, Mar. 22, 1977;
54 FR 18280, Apr. 28, 1989; 61 FR 14481, Apr. 2, 1996]
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: Secs. 306, 402, 406, 408, 409, 701 of the Federal Food,
Drug, and Cosmetic Act (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 Dockets Management
Branch before the notice is published. The notice shall invite public
comment on the action level.
[[Page 69]]
(d) A regulation may be established in subpart D of this part to
identify a food containing a naturally occurring poisonous or
deleterious substance which will be deemed to be adulterated under
section 402(a)(1) of the act. These regulations do not constitute a
complete list of such foods.
[42 FR 52821, Sept. 30, 1977, as amended at 55 FR 20786, May 21, 1990]
Sec. 509.5 Petitions.
The Commissioner of Food and Drugs, either on his own initiative or
on behalf of any interested person who has submitted a petition, may
issue a proposal to establish, revoke, or amend a regulation under this
part. Any such petition shall include an adequate factual basis to
support the petition, shall be in the form set forth in Sec. 10.30 of
this chapter, and will be published in the Federal Register for comment
if it contains reasonable grounds for the proposed regulation.
[42 FR 52821, Sept. 30, 1977, as amended at 54 FR 18280, Apr. 28, 1989]
Sec. 509.6 Added poisonous or deleterious substances.
(a) Use of an added poisonous or deleterious substance, other than a
pesticide chemical, that is also a food additive will be controlled by a
regulation issued under section 409 of the act when possible. When such
a use cannot be approved under the criteria of section 409 of the act,
or when the added poisonous or deleterious substance is not a food
additive, a tolerance, regulatory limit, or action level may be
established pursuant to the criteria in paragraphs (b), (c), or (d) of
this section. Residues resulting from the use of an added poisonous or
deleterious substance that is also a pesticide chemical will ordinarily
be controlled by a tolerance established in a regulation issued under
sections 406, 408, or 409 of the act by the U.S. Environmental
Protection Agency (EPA). When such a regulation has not been issued, an
action level for an added poisonous or deleterious substance that is
also a pesticide chemical may be established by the Food and Drug
Administration. The Food and Drug Administration will request EPA to
recommend such an action level pursuant to the criteria established in
paragraph (d) of this section.
(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
[[Page 70]]
and Drug Administration may regard the food as adulterated within the
meaning of section 402(a)(1) of the act, without regard to the criteria
in paragraph (b) of this section or in section 406 of the act. An action
level will be withdrawn when a tolerance or regulatory limit for the
same substance and use has been established.
(e) Tolerances will be established under authority appropriate for
action levels (sections 306, 402(a), and 701(a) of the act, together
with section 408 or 409 of the act, if appropriate) as well as under
authority appropriate for tolerances (sections 406 and 701 of the act).
In the event the effectiveness of a tolerance is stayed pursuant to
section 701(e)(2) of the act by the filing of an objection, the order
establishing the tolerance shall be deemed to be an order establishing
an action level until final action is taken upon such objection.
[42 FR 52821, Sept. 30, 1977, as amended at 55 FR 20786, May 21, 1990]
Sec. 509.7 Unavoidability.
(a) Tolerances and action levels in this part are established at
levels based on the unavoidability of the poisonous or deleterious
substance concerned and do not establish a permissible level of
contamination where it is avoidable.
(b) Compliance with tolerances, regulatory limits, and action levels
does not excuse failure to observe either the requirement in section
402(a)(4) of the act that food may not be prepared, packed, or held
under insanitary conditions or the other requirements in this chapter
that food manufacturers must observe current good manufacturing
practices. Evidence obtained through factory inspection or otherwise
indicating such a violation renders the food unlawful, even though the
amounts of poisonous or deleterious substances are lower than the
currently established tolerances, regulatory limits, or action
levels.The manufacturer of food must at all times utilize quality
control procedures which will reduce contamination to the lowest level
currently feasible.
[42 FR 52821, Sept. 30, 1977, as amended at 55 FR 20786, May 21, 1990]
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
[[Page 71]]
PCB's in establishments manufacturing food-packaging materials.
(b) The following special provisions are necessary to preclude the
accidental PCB contamination of food-packaging materials:
(1) New equipment or machinery for manufacturing food-packaging
materials shall not contain or use PCB's.
(2) On or before September 4, 1973, the management of establishments
manufacturing food-packaging materials shall:
(i) Have the heat exchange fluid used in existing equipment for
manufacturing food-packaging materials sampled and tested to determine
whether it contains PCB's or verify the absence of PCB's in such
formulations by other appropriate means. On or before Sept. 4, 1973, any
such fluid formulated with PCB's must to the fullest extent possible
commensurate with current good manufacturing practices be replaced with
a heat exchange fluid that does not contain PCB's.
(ii) Eliminate to the fullest extent possible commensurate with
current good manufacturing practices from the establishment any other
PCB-containing equipment, machinery and materials wherever there is a
reasonable expectation that such articles could cause food-packaging
materials to become contaminated with PCB's either as a result of normal
use or as a result of accident, breakage, or other mishap.
(iii) The toxicity and other characteristics of fluids selected as
PCB replacements must be adequately determined so that the least
potentially hazardous replacement is used. In making this determination
with respect to a given fluid, consideration should be given to (a) its
toxicity; (b) the maximum quantity that could be spilled onto a given
quantity of food before it would be noticed, taking into account its
color and odor; (c) possible signaling devices in the equipment to
indicate a loss of fluid, etc.; and (d) its environmental stability and
tendency to survive and be concentrated through the food chain. The
judgment as to whether a replacement fluid is sufficiently non-hazardous
is to be made on an individual installation and operation basis.
(c) The provisions of this section do not apply to electrical
transformers 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.
[[Page 72]]
(3) 10 parts per million in paper food-packaging material intended
for or used with finished animal feed and any components intended for
animal feeds. The tolerance shall not apply to paper food-packaging
material separated from the food therein by a functional barrier which
is impermeable to migration of PCB's.
(b) A compilation entitled ``Analytical Methodology for
Polychlorinated Biphenyls, February 1973'' for determining compliance
with the tolerances established in this section is available from the
Dockets Management Branch, Food and Drug Administration, rm. 1-23, 12420
Parklawn Dr., Rockville, MD 20857.
Note: At 38 FR 22794, Aug. 24, 1973, the following appeared
concerning Sec. 509.30(a)(9) (formerly Sec. 122.10(a)(9)):
* * * Sec. 509.30(a)(9) is hereby stayed pending full review of the
objections and requests for hearing.* * *
In the interim, as stated in the final order (38 FR 18098) the Food
and Drug Administration will enforce the temporary tolerance level
established by Sec. 509.30(a)(9) by seizing any paper food-packaging
material shipped in interstate commerce after September 4, 1973
containing higher than the specified level of PCB's as adulterated in
violation of sec. 402 of the act.
[42 FR 52821, Sept. 30, 1977, as amended at 46 FR 8460, Jan. 27, 1981;
59 FR 14365, Mar. 28, 1994]
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.
510.45 Packaging requirements for drugs for animal use.
510.95 Designated journals.
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.
510.120 Suspension of approval of new-drug applications for certain
diethylstilbestrol and diethylstilbestrol-containing drugs.
Subpart C--Exportation of New Animal Drugs
510.200 Export of new animal drug.
Subpart D--Records and Reports
510.300 Records and reports concerning experience with new animal drugs
for which an approved application is in effect.
510.301 Records and reports concerning experience with animal feeds
bearing or containing new animal drugs for which an approved
application is in effect.
510.302 Reporting forms.
510.305 Maintenance of copies of approved applications for animal feed
bearing or containing new animal drugs.
510.310 Records and reports for new animal drugs approved before June
20, 1963.
Subpart E--Requirements for Specific New Animal Drugs
510.410 Corticosteroids for oral, injectable, and ophthalmic use in
animals; warnings and labeling requirements.
510.413 Chloroform used as an ingredient (active or inactive) in animal
drug products.
510.440 Injectable iron preparations.
510.455 New animal drug requirements regarding free-choice
administration in feeds.
Subpart F--Animal Use Exemptions from Certification and Labeling
Requirements
510.515 Animal feeds bearing or containing new animal drugs subject to
the provisions of section 512(n) of the act.
Subpart G--Sponsors of Approved Applications
510.600 Names, addresses, and drug labeler codes of sponsors of
approved applications.
[[Page 73]]
Authority: Secs. 201, 301, 501, 502, 503, 512, 701, 721 of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353,
360b, 371, 379e).
Source: 40 FR 13807, Mar. 27, 1975, unless otherwise noted.
Subpart A--General Provisions
Sec. 510.3 Definitions and interpretations.
As used in this part:
(a) The term act means the Federal Food, Drug, and Cosmetic Act, as
amended (secs. 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C.
321-392).
(b) Department means the Department of Health and Human Services.
(c) Secretary means the Secretary of Health and Human Services.
(d) Commissioner means the Commissioner of Food and Drugs.
(e) Person means individuals, partnerships, corporations, and
associations.
(f) The definitions and interpretations of terms contained in
section 201 of the act shall be applicable to such terms when used in
the regulations in this part.
(g) The term new animal drug means any drug intended for use for
animals other than man, including any drug intended for use in animal
feed but not including such animal feed:
(1) The composition of which is such that such drug is not generally
recognized, among experts qualified by scientific training and
experience to evaluate the safety and effectiveness of animal drugs, as
safe and effective for use under the conditions prescribed, recommended,
or suggested in the labeling thereof; except that such a drug not so
recognized shall not be deemed to be a new animal drug if at any time
prior to June 25, 1938, it was subject to the Food and Drug Act of June
30, 1906, as amended, and if at such time its labeling contained the
same representations concerning the conditions of its use; or
(2) The composition of which is such that such drug, as a result of
investigations to determine its safety and effectiveness for use under
such conditions, has become so recognized but which has not, otherwise
than in such investigations, been used to a material extent or for a
material time under such conditions.
(h) The term animal feed means an article which is intended for use
for food for animals other than man and which is intended for use as a
substantial source of nutrients in the diet of the animal, and is not
limited to a mixture intended to be the sole ration of the animal.
(i) The newness of an animal drug, including a new animal drug
intended for use in or on animal feed, may arise by reason of: (1) The
newness for its intended drug use of any substance of which the drug is
comprised, in whole or in part, whether it be an active substance or a
menstruum, excipient, carrier, coating, or other component; (2) the
newness for its intended drug use of 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) The term sponsor means the person responsible for an
investigation of a new animal drug, including responsibility for
compliance with applicable
[[Page 74]]
provisions of the act and regulations. 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.
(l) Designated journal(s) means journals listed in Sec. 510.95.
[40 FR 13807, Mar. 27, 1975, as amended at 50 FR 7517, Feb. 22, 1985; 54
FR 22741, May 26, 1989]
Sec. 510.4 Biologics; products subject to license control.
An animal drug produced and distributed in full conformance with the
animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21
U.S.C. 151 et seq.) and any regulations issued thereunder shall not be
deemed to be subject to section 512 of the Federal Food, Drug, and
Cosmetic Act.
Sec. 510.7 Consignees of new animal drugs for use in the manufacture of animal feed.
(a) A new animal drug intended for use in the manufacture of animal
feed shall be deemed to be unsafe unless at the time of its removal from
the establishment of a manufacturer, packer, or distributor of such
drug, such manufacturer, packer, or distributor has an unrevoked written
statement from the consignee of such drug, or a notice from the
Secretary, to the effect that with respect to the use of such drug in
animal feed the consignee:
(1) Is the holder of an approved application under Sec. 514.2 of
this chapter; or
(2) Will, if the consignee is not a user of the drug, ship such drug
only to a holder of an approved application under Sec. 514.2 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.
Sec. 510.45 Packaging requirements for drugs for animal use.
The packaging requirements for antibiotic drugs for veterinary use
are described under Sec. 432.1 of this chapter, except that antibiotic
drugs for veterinary use need not be packaged for dispensing in
containers of colorless, transparent glass.
Sec. 510.95 Designated journals.
The following journals are available to the Food and Drug
Administration and thus permit waiving of the submission of reprints and
summaries covering reports contained in these journals to the extent
that such requirements are waived in the regulations in this part:
All Pet's Magazine (Jersey City).
American Journal of Veterinary Research (Chicago).
Animal Health (Journal of the Animal Health Trust) (London).
Animal Nutrition & Health (Sausalito, CA).
Animal Production (Edinburgh).
Avian Diseases (Amherst).
British Poultry Science (Edinburgh).
Canadian Journal of Comparative Medicine and Veterinary Science
(Gardenvale, Quebec).
Canadian Veterinary Journal (Guelph, Ontario).
Cornell Veterinarian (Ithaca).
Experimental Parasitology (New York).
The Feed Bag (Milwaukee).
Feedstuffs (Minneapolis).
Hoard's Dairyman (Fort Atkinson).
Journal of the American Veterinary Medical Association (Chicago).
Journal of Animal Science (Albany).
Journal of Dairy Science (Champaign).
Journal of Economic Entomology (Baltimore).
Journal of Small Animal Practice (London).
Modern Veterinary Practice (formerly North American Veterinarian)
(Wheaton, IL).
National Hog Farmer (Grundy Center, IA).
New Zealand Veterinary Journal (Wellington).
Poultry Science (Guelph, Ontario).
Praktische Tierarzt (Postfach, Germany).
Research in Veterinary Science (Chicago).
Small Animal Clinician (Kansas City, MO).
Veterinaermedizin (Konstanz, Germany).
Veterinarian (London).
Veterinarian (International) (New York).
The Veterinary Bulletin (Farnham Royal, England).
Veterinary Medicine (Kansas City, MO).
Veterinary Record (Croydon, England).
[[Page 75]]
Zentralblatt Fuer Veterinaermedizin Zentr. Veterinaermed (Berlin).
[40 FR 13807, Mar. 27, 1975, as amended at 50 FR 7517, Feb. 22, 1985]
Subpart B--Specific Administrative Rulings and Decisions
Sec. 510.105 Labeling of drugs for use in milk-producing animals.
(a) Part 540 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)(D) 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 warning, ``Milk that has been taken
from animals during treatment and within ------ hours (------ milkings)
after the latest treatment must not be used for food,'' the blanks to be
filled in with the number of hours (not to exceed 96) and milkings that
the manufacturer has determined by appropriate investigation is needed
to insure that the milk will not carry 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.
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 (---- milkings) after the latest treatment must not be used
for food'', the first blank being filled in with the figure, which shall
not be greater than 96, that the Commissioner has authorized the
manufacturer of the drug to use, and the second figure shall be the
first number divided by 12. 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 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, he
may exempt the drug from bearing either of the above warning statements.
Sec. 510.110 Antibiotics used in food-producing animals.
(a) The Food and Drug Administration in the interest of fulfilling
its responsibilities with regard to protection of the public health has
requested an evaluation of the public health aspects of the use of
antibiotics in veterinary medical and nonmedical uses. There is
particular concern with regard to the potential hazards associated with
the extensive use of antibiotics administered to food-producing animals.
Accordingly, an ad hoc committee on the Veterinary Medical and
Nonmedical Uses of Antibiotics was established by the Food and Drug
Administration to study and advise the Commissioner of Food and Drugs on
the uses of antibiotics in veterinary medicine and for various
nonmedical purposes as such uses may affect the enforcement of the
Federal Food, Drug, and Cosmetic Act with respect to their safety and
effectiveness.
(b) Based upon an evaluation of the conclusions of said Committee
and other relevant material, Sec. 510.112 was published in the Federal
Register of August 23, 1966 (31 FR 11141), asking
[[Page 76]]
sponsors of drugs containing any antibiotic intended for use in food-
producing animals to submit data to establish whether such antibiotic
and its metabolites are present as residues in edible tissues, milk, and
eggs from treated animals. The data on the residues of antibiotics in
milk from intramammary infusion preparations were requested within 60
days and the data on all other products were requested within 180 days
following the date of publication of Sec. 510.112 in the Federal
Register.
(c) An evaluation of the data now available shows that use of many
antibiotic preparations cause residues in edible products of treated
animals for varying and, in some cases, for long periods of time
following the last administration. Because of the accumulation of new
information with regard to the development of resistance of bacteria to
antibiotics, the ability of bacteria to transfer this resistance, and
the development of sensitivity to antibiotics in humans, unauthorized
and unsafe residues of antibiotics cannot be permitted in food obtained
from treated animals.
(d) Based on evaluation of information available, including the
conclusions of the aforementioned ad hoc Committee, the Commissioner
concludes that antibiotic preparations intended for use in food-
producing animals, other than topical and ophthalmic preparations, are
not generally recognized among qualified experts as having been shown to
be safe for their intended use(s) within the meaning of section 201(s)
of the Federal Food, Drug, and Cosmetic Act.
(e) Therefore, all exemptions from the provisions of section 409 of
the act for use of antibiotics in food-producing animals based on
sanctions or approvals granted prior to enactment of the Food Additives
Amendment of 1958 (Pub. L. 85-929; 72 Stat. 1784) will be revoked and
the uses which are concluded to be safe will be covered by food additive
regulations. On those products for which there are inadequate residue
data, actions will be initiated to amend or revoke antibiotic
regulations under the provisions of section 507 of the act, or 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
(except certifiable antibiotics), including medicated premixes intended
for use in food-producing animals, are deemed to be new drugs as well as
food additives. An antibiotic application (see Sec. 431.50 of this
chapter) will be required for all medicated premixes containing
certifiable antibiotics.
[40 FR 13807, Mar. 27, 1975, as amended at 54 FR 18280, Apr. 28, 1989]
Sec. 510.112 Antibiotics used in veterinary medicine and for nonmedical purposes; required data.
(a) An ad hoc committee, Committee on the Veterinary Medical and
Nonmedical Uses of Antibiotics, was formed by the Food and Drug
Administration to study, and advise the Commissioner on, the use of
antibiotics in veterinary medicine and for various nonmedical purposes
as such uses may affect the enforcement of the Federal Food, Drug, and
Cosmetic Act with respect to the safety and effectiveness of such
substances. A copy of the report may be obtained from the Food and Drug
Administration, Office of Public Affairs, Room 15-05, Parklawn Building,
5600 Fishers Lane, Rockville, MD 20857.
(b) On the basis of the report of the Committee and other
information, sponsors of drugs containing any antibiotic intended for
use in food-producing animals shall submit data for determining whether
or not such antibiotics and their metabolites are present as residues in
edible tissues, milk, and eggs from treated animals; however, in the
case of a drug for which such data have already been submitted and for
which a regulation has been promulgated under section 409 of the act,
only such data as has been
[[Page 77]]
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]
Sec. 510.120 Suspension of approval of new-drug applications for certain diethylstilbestrol and diethylstilbestrol-containing drugs.
In the matter of suspension of approval of New-Drug Application Nos.
7175, 7310, 8254, 9105, 9506, 9532, 11121: [Mattox and Moore, Inc.,
Indianapolis, IN; Vineland Poultry Laboratories, Vineland, NJ; George N.
Bell Co., Indianapolis, IN, respondents (FDC-D-49, 50, and 55)].
Following the public hearing held in the above-identified matter,
beginning on April 25, 1960, and finally terminating on June 17, 1960,
and issuance of tentative findings of fact, conclusions of law and
facts, and tentative order, the Commissioner of Food and Drugs on
December 15, 1961, issued final findings of fact, conclusions of law and
facts and a final order. This final order concluded that all the
products involved were unsafe within the meaning of section 505(e) of
the Federal Food, Drug, and Cosmetic Act, in that the drug
diethylstilbestrol is capable of producing and has produced cancer in
animals and that this drug may be expected to produce, excite or
stimulate the growth of certain cancers in human beings.
This final order was appealed to the U.S. District Court for the
District of New Jersey, pursuant to the then effective provisions of
section 505(h) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
355(h)). On August 20, 1964, this Court set aside this final order and
remanded the case to the Food and Drug Administration with directions to
reconsider the case in conformity with the opinion of the Court.
(Goldhaft et al. t/a Vineland Poultry Laboratories v. George P. Larrick,
et al.; Civil Action No. 122-62.)
Pursuant to the above-described opinion and order of the Court this
case has been reconsidered.
Based on the substantial evidence of record, and pursuant to section
505(e) of the act (21 U.S.C. 355(e)) and part 310 of title 21 of the
Code of Federal Regulations.
It is ordered, That:
1. New-Drug Application 7175, covering the drug ``Tend-A-Wate,''
filed by Mattox & Moore, Inc., be, and is hereby suspended.
2. New-Drug Application 9532, covering the drugs ``Tend-A-Wate
537,'' ``Tend-A-Wate 539,'' and ``Tend-A-Wate 545,'' filed by Mattox &
Moore, Inc., be, and is hereby suspended.
3. New-Drug Application 7310, covering the drug ``Tenderettes,''
filed by Vineland Poultry Laboratories, be, and is hereby suspended.
4. New-Drug Application 9105, covering the drug ``Caponade,'' filed
by Vineland Poultry Laboratories, be, and is hereby suspended.
5. New-Drug Application 11121, covering the drug ``Stilboserts,''
filed by George N. Bell, Manufacturing Chemists, be, and is hereby
suspended.
6. New-Drug Application 8254, covering the drug ``No-Brood,'' filed
by
[[Page 78]]
Mattox and Moore, Inc., be, and is hereby suspended.
7. New-Drug Application 9506, covering the drug ``Anti-Brood,''
filed by Vineland Poultry Laboratories, be, and is hereby suspended.
Subpart C--Exportation of New Animal Drugs
Sec. 510.200 Export of new animal drug.
Before a new animal drug or an animal feed bearing or containing a
new animal drug may be exported, it must comply with the regulations
promulgated under section 512 of the act.
Subpart D--Records and Reports
Sec. 510.300 Records and reports concerning experience with new animal drugs for which an approved application is in effect.
(a) On receiving notification that an application submitted pursuant
to Sec. 514.1 of this chapter for a new animal drug is approved, the
applicant shall establish and maintain such records and make such
reports as are specified in this section to facilitate a determination
as to whether there may be grounds for suspending or withdrawing
approval of the application or whether any applicable regulation should
be amended or repealed. The applicant shall maintain adequately
organized and indexed files containing full reports of information
pertinent to the safety or effectiveness of the new animal drug that
have not previously been submitted as part of his application for the
drug and which are received or otherwise obtained by him from any
source, as follows:
(1) Unpublished reports of clinical or other animal experience,
studies, investigations, and tests conducted by the applicant or
reported to him by any person involving the new animal drug that is the
subject of the application or any related drugs. An adequate summary and
bibliography of reports in the scientific literature would ordinarily
suffice. (The application must identify at the time of each report
submission, each drug he considers related to the subject drug.)
(2) Experience, investigations, studies, or tests involving the
chemical or physical properties or any other properties of the new
animal drug, such as its behavior or properties in relation to
microorganisms, including both the effects of the drug on microorganisms
and the effect of microorganisms on the drug.
(3) For information required by this section, adequate
identification of its source, when known, including the name and post
office address of the person who furnishes such information.
(4) Copies of all mailing pieces and other labeling, and, if it is a
prescription new animal drug, all advertising other than that contained
in the application used in promoting the drug, and copies of the
currently used package labeling that gives full information for use of
the drug whether or not such labeling is contained in the application.
(5) Information concerning the quantity of the new animal drug
distributed in a manner and form that facilitates estimates of the
incidence of any adverse effects reported to be associated with the use
of the drug. This does not require disclosure of financial, pricing, or
sales data.
(6) Information concerning any previously unreported changes from
the conditions described in an application conforming to the conditions
of Sec. 514.8(a)(5) of this chapter.
(b) The applicant shall submit to the Food and Drug Administration
copies of the records and reports described in paragraph (a) of this
section, except routine assay and control records, appropriately
identified with the new animal drug application(s) to which they relate,
as follows:
(1) Immediately upon receipt by the applicant, complete records or
reports covering information of the following kinds:
(i) Information concerning a mixup in the new animal drug or its
labeling with another article.
(ii) Information concerning any bacteriological or significant
physical or other change or deterioration in the new animal 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.
(2) As soon as possible, and in any event within 15 working days of
its
[[Page 79]]
receipt by the applicant, complete records of reports concerning any
information of the following kinds:
(i) Information concerning any unexpected side effects, injury,
toxicity, or sensitivity reaction or any unexpected incidence or
severity thereof associated with clinical use, studies, investigations,
or tests, whether or not determined to be attributable to the new animal
drug, except that this requirement shall not apply to the submission of
information described in a written communication to the applicant from
the Food and Drug Administration as types of information that may be
submitted at other designated intervals. Unexpected as used in this
subdivision refers to conditions or developments not previously
submitted as part of the new animal drug application, or conditions and
developments occurring at a rate higher than that shown by information
previously submitted as part of the application.
(ii) Information concerning any unusual failure of the new animal
drug to exhibit its expected pharmacological activities.
(3) When mailing pieces, any other labeling, and advertising are
devised for promotion of the new animal drug, specimens shall be
submitted at the time of initial dissemination of such labeling and at
the time of initial publication of any advertisement for a prescription
drug. Mailing pieces and labeling designed to contain samples of a drug
shall be complete except for the omission of the drug.
(4) All the kinds of information described in paragraph (a) of this
section, other than that submitted under the provisions of paragraphs
(b) (1), (2), and (3) of this section, shall be submitted as follows
unless otherwise ordered in a written communication from the
Commissioner:
(i) At intervals within 6 months beginning with the date of approval
of the new animal drug application during the first year following such
date, and at yearly intervals thereafter.
(ii) Whenever an applicant is required to submit reports under the
provisions of paragraph (b)(4)(i) of this section with respect to more
than one approved application for preparations containing the same new
animal drug so that the same item(s) of information is (are) required to
be reported for more than one application, he may elect to submit as a
part of the report for one such application all the information common
to such applications in lieu of reporting separately and repetitively on
each. The applicant shall state when this is done and identify all the
new animal drug applications for which the reports are submitted.
(iii) The submitted copies of records and reports shall include all
the required information that was received or otherwise obtained by the
applicant during the designated intervals.
(5) On written order of the Commissioner, within the time stated in
such order or agreed to by the applicant and the Commissioner, any
designated records or reports containing the kinds of information
described in this section shall be submitted.
(c) The applicant shall, upon request of any properly authorized
officer or employee of the Department at reasonable times, permit such
officers to have access to and copy and verify any records and reports
established and maintained under the provisions of this section.
(d) If the Food and Drug Administration finds 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 the provisions of this section, or
that the applicant has refused to permit access to or copying of, or
verification of such records or reports, the Commissioner shall give the
applicant notice and opportunity for a hearing on the question of
whether to withdraw the approval of the application, as provided in
Sec. 514.200 of this chapter.
(e) Upon written request of the applicant stating reasonable grounds
therefor, the Commissioner will make available any information in
possession of the Food and Drug Administration of the kinds the
applicant is required to maintain under the provisions of this section,
except information readily available to the applicant from other sources
or information which the Commissioner concludes is confidential.
[[Page 80]]
(f) The applicant required to establish and maintain records and
make reports required by this section includes any person whose name
appears on the labeling of the drug as its manufacturer, packer, or
distributor under an approval or who is engaged in the manufacturing,
processing, packing, or labeling of the drug under an approval of the
new animal drug application or any supplement to it; however, to avoid
unnecessary duplication in the submission of reports, any such
applicant's obligation to submit a report may be met by its submission
on his behalf, designated as such, by another person responsible for
reporting.
Sec. 510.301 Records and reports concerning experience with animal feeds bearing or containing new animal drugs for which an approved 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) 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.
(b) As soon as possible, and in any event within 15 working days of
its receipt by the applicant, complete records or reports concerning any
information of the following kinds:
(1) Information concerning any unexpected side effect, injury,
toxicity, or sensitivity reaction or any unexpected incidence or
severity thereof associated with clinical uses, studies, investigations,
or tests, whether or not determined to be attributable to the new animal
drug, except that this requirement shall not apply to the submission of
information described in a written communication to the applicant from
the Food and Drug Administration as types of information that may be
submitted at other designated intervals. Unexpected as used in this
paragraph refers to conditions or developments not previously submitted
as part of the new animal drug application or 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 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]
Sec. 510.302 Reporting forms.
(a) The information described in Sec. 510.300, except that described
in paragraphs (b) (1) and (2) of that section, shall be submitted
appropriately identified with the new animal drug application(s) to
which they relate in duplicate on Form FD-2301 ``Transmittal of Periodic
Reports and Promotional Material for New Animal Drugs.''
(b) All adverse experiences with new animal drugs as described in
Sec. 510.300(b)(2) or Sec. 510.301(b) whether or not related to a
required periodic report submitted on a Form FD-2301, shall be reported
on Form FD-1932 ``Adverse Drug Reaction'' (except as provided in
paragraph (c) of this section). Reports of adverse drug experiences may
be submitted initially in the form of a written communication, but any
such communication shall be followed promptly (but not necessarily
within the prescribed 15 working days) by a completed Form FD-1932. A
separate ``Adverse Drug Reaction'' form should be submitted for each
patient where feasible.
(c) In lieu of Form FD-1932 the holder of an approved new animal
drug application may submit:
(1) A computerized report if the information contained therein and
the sequence in which it is presented are equivalent to that required by
Form
[[Page 81]]
FD-1932 and the report is submitted in duplicate. Such reports will
require initial approval by the Food and Drug Administration prior to
use; and
(2) Copies of reports of reactions appearing in the published
scientific literature may be submitted.
(d) Forms FD-1932 and FD-2301, with instructions for their use, may
be obtained from the Food and Drug Administration, Department of Health
and Human Services, Center for Veterinary Medicine, 7500 Standish Pl.,
Rockville, MD 20855.
[40 FR 13807, Mar. 27, 1975, as amended at 41 FR 35844, Aug. 25, 1976;
54 FR 18280, Apr. 28, 1989; 57 FR 6475, Feb. 25, 1992]
Sec. 510.305 Maintenance of copies of approved applications for animal feed bearing or containing new animal drugs.
Each applicant shall maintain in a single accessible location on the
premises of each establishment to which an approved medicated feed
application (Form FDA 1900) or supplemental application applies either:
(a) A copy of the approved medicated feed application (Form FDA
1900) and a sample of the approved labeling; or
(b) Identification of the approved medicated feed application in a
single file or in a single readable document that includes:
(1) The application number and date of its approval;
(2) The name(s) of the premix(es) and the concentration of the
drug(s) contained in the premix(es);
(3) The name(s) of the approved manufacturer(s) of the premix(es);
(4) The concentration of the drug(s) in the finished medicated feed;
and
(5) A sample of the approved labeling.
[41 FR 36203, Aug. 27, 1976, as amended at 51 FR 7391, Mar. 3, 1986]
Sec. 510.310 Records and reports for new animal drugs approved before June 20, 1963.
(a) This section applies to new animal drugs, including antibiotics
and medicated feed premixes bearing or containing new animal drugs,
approved before June 20, 1963, on the basis of a new drug application,
master file, antibiotic regulation, or food additive regulation.
(b) Sponsors of new animal drugs identified in paragraph (a) of this
section shall submit the following information, in duplicate, for each
dosage form of each such drug by November 21, 1980:
(1) If the new animal drug is currently marketed: (i) A copy of the
label on the package of the drug and of the package insert or brochure
bearing directions or information for use of the product.
(ii) If the label, brochure, or package insert is not identical in
content to the one for the new animal drug as originally approved, the
sponsor shall also report what changes have been made (other than minor
changes in arrangement or printing or changes of an editorial nature)
and explain why they were made, and shall submit data supporting such
changes if the data have not previously been submitted.
(iii) If clinical experience reported to or otherwise received by
the sponsor indicates the need for change in claims for effectiveness or
in side effects, warnings, or contraindications in the labeling or
advertising currently in use, the sponsor shall submit a supplemental
application proposing such changes in the labeling and a showing that
any advertising will be appropriately revised.
(iv) If the clinical or other experience reported to or otherwise
obtained by the sponsor has revealed any information concerning any side
effect, injury, toxicity, or sensitivity reaction, or any unexpected
incidence or severity thereof, which by kind, or incidence or severity
is not fully disclosed in the labeling, whether or not determined to be
attributable to the drug, this information shall be submitted. Such
information shall include full reports of all available information with
respect to any deaths apparently related to a drug administration
whether or not determined to be attributable to the drug. Any such
information previously submitted need not be resubmitted.
(v) If the clinical or other experience reported to or otherwise
obtained by the sponsor within the past 2 years has revealed any
information with respect to a distributed batch concerning any mixup in
the drug or its labeling with another article; any bacteriological or
[[Page 82]]
any significant chemical, physical, or other change or deterioration of
the drug; or any failure of one or more distributed batches to meet
specifications established in the new animal drug application or in the
antibiotic regulations, this information shall be submitted. Any
unresolved experience of the kinds listed in this paragraph shall be
reported even though it occurred before the 2-year period.
(2) If the new animal drug is no longer marketed, but it is the
subject of an approval that is still in effect:
(i) Identification of the dosage form of the new animal drug or
medicated feed premix by its established and proprietary names, if any;
(ii) The formula showing quantitatively each ingredient of the drug
to the extent disclosed on the label (a copy of the label will
ordinarily fulfill this requirement);
(iii) The route of administration;
(iv) The new animal drug or other identification or application
number;
(v) The date and reason for discontinuing its marketing.
(c) Approval of applications covering products which are no longer
marketed may be withdrawn under Sec. 514.115 of this chapter on the
basis of a request for its withdrawal submitted in writing by a person
holding an approved application. Such withdrawal of approval will be
made on the ground that the drug subject to such application is no
longer being marketed, provided information is furnished in support of
this finding and provided certain other conditions exist as specified in
that section. A written request for such withdrawal will be construed as
a waiver of an opportunity for a hearing.
(d) Sponsors of new animal drugs identified in paragraph (a) of this
section are exempt from the reporting requirements of this section if:
(1) Their product is no longer marketed, and information has
previously been submitted to the Food and Drug Administration regarding
discontinuation of marketing including the date and reason for such
action, and any existing approval for the product has been withdrawn; or
(2) As a result of a supplemental approval granted beginning June
20, 1963, the sponsor is presently reporting under the requirements of
Sec. 510.300.
(e) After the submission of the initial reports required by
paragraph (b) of this section, each sponsor shall maintain records and
submit yearly reports of the kinds required by Sec. 510.300.
(f) All reports required by this section shall be addressed to the
Division of Surveillance (HFV-210), Center for Veterinary Medicine, Food
and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, and
shall be distinctly marked ``New Animal Drug (or Antibiotic) Report''
together with the applicable new animal drug application number,
antibiotic account number, or other identification on the envelope.
[45 FR 42261, June 24, 1980, as amended at 54 FR 18280, Apr. 28, 1989;
57 FR 6475, Feb. 25, 1992]
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:
[[Page 83]]
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. 510.413 Chloroform used as an ingredient (active or inactive) in animal drug products.
(a) Chloroform has been used as an ingredient in animal drug
products such as cough preparations, linaments, and some pastes.
Although considered safe for many years, recent information has become
available associating chloroform with carcinogenic effects in animals.
Studies conducted by the National Cancer Institute have demonstrated
that the oral administration of chloroform to mice and rats induced
hepatocellular carcinomas (liver cancer) in mice and renal tumors in
male rats.
(b) Any drug product intended for use in or on animals and
containing chloroform as an ingredient is deemed to be either (1) a new
animal drug within the meaning of section 201(v) of the act, and unsafe
within the meaning of section 512 of the act and adulterated under
section 501 of the act and subject to regulatory action under sections
301, 501, and 512 of the act; or (2) misbranded under section 502 of the
act, and therefore subject to regulatory action under sections 301 and
502 of the act. Any animal drug product containing chloroform in
residual amounts from its use as a processing solvent during manufacture
of the drug product, or from the synthesis of a drug ingredient, is not,
for the purpose of this regulation, considered to contain chloroform as
an ingredient.
(c) Any holder of an approved new animal drug application for a drug
product containing chloroform as an ingredient shall submit to the Food
and Drug Administration on or before October 3, 1977, a supplemental
application providing for a revised formulation removing chloroform as
an ingredient.
(1) The supplemental application shall contain:
(i) A full list of articles used as components and a full statement
of the composition of the drug product.
(ii) The date that the composition of the drug product will be
changed.
(iii) Data showing that the change in composition does not interfere
with any assay or other control procedures used in manufacturing the
drug product, or that the assay and other control procedures are revised
to make them adequate.
(iv) Data available to establish the stability of the revised
formulation and, if the data are too limited to support a conclusion
that the drug will retain its declared potency for a reasonable
marketing period, a commitment from the applicant:
(a) To test the stability of marketed batches at reasonable
intervals;
(b) To submit the data as they become available; and
(c) To recall from the market any batch found to fall outside the
approved specifications for the drug.
(v) Copies of the label and all other labeling to be used for the
drug product--a total of nine copies if in final printed form, three
copies if in draft form.
(2) If such drug product contains more than 1 percent chloroform,
the revised formulation containing no chloroform shall not be marketed
before the receipt of written notice of approval of the supplemental
application by the Food and Drug Administration.
(3) If such drug product now contains 1 percent or less chloroform,
the revised formulation containing no chloroform may be marketed after
submission of the supplemental application but prior to the receipt of
written notice of its approval by the Food and Drug Administration.
(d) Any sponsor of a ``Notice of Claimed Investigational Exemption
for a New Animal Drug'' (INAD notice) for an animal drug product
containing chloroform as an ingredient shall amend the INAD notice on or
before October 3, 1977, to revise the
[[Page 84]]
formulation removing chloroform as an ingredient.
(e) The Commissioner will initiate action to withdraw approval of a
new animal drug application or terminate an INAD notice in accordance
with the applicable provisions of section 512 of the act and parts 511
and 514 of this chapter upon failure of a holder of an approved new
animal drug application or sponsor of an INAD notice to comply with the
provisions of paragraph (c) or (d) of this section.
(f) Any drug product intended for animal use containing chloroform
as an ingredient that is introduced or delivered for introduction into
interstate commerce following the effective date of this regulation will
be subject to regulatory action under sections 301, 501, 502, and 512 of
the act.
[42 FR 44226, Sept. 2, 1977, as amended at 60 FR 38480, July 27, 1995]
Sec. 510.440 Injectable iron preparations.
There has been an increasing interest in the use of injectable iron
compounds for the prevention or treatment of iron-deficiency anemia in
animals. Although some such preparations have been shown to be safe,
such articles are regarded as new animal drugs within the meaning of the
Federal Food, Drug, and Cosmetic Act. Accordingly, an approved new
animal drug application is required prior to the marketing of such
preparations within the jurisdiction of the act. In addition to the need
for demonstrating the safety of such articles, the labeling of such
preparations should not only recommend appropriate dosages of iron but
also declare the amount (in milligrams) of available iron (Fe) per
milliliter of the subject product.
Sec. 510.455 New animal drug requirements regarding free-choice administration in feeds.
(a) For the purpose of this section, free-choice administration of
animal drugs in feeds involves feeds that are placed in feeding or
grazing areas and are not intended to be consumed fully at a single
feeding or to constitute the entire diet of the animal. Such methods of
administering drugs 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 animal
drugs. The manufacture of medicated free-choice feeds is subject to the
current good manufacturing practice regulations for medicated feeds.
(b) The Food and Drug Administration has concluded that there are
questions about the safety and effectiveness of drugs when administered
in free-choice feeds. Therefore, such methods of administration cause
the drugs so administered to be new animal drugs, for which approved new
animal drug applications (NADA's) are required. (See Sec. 510.3(i)). In
addition, the exemption from the requirement of an approved medicated
feed application provided in Sec. 558.4 of this chapter does not apply
to any free-choice medicated feed.
(c) An NADA or supplemental NADA for products for free-choice
feeding submitted for approval under section 512(b) of the act shall
provide for:
(1) The manufacture of a finished product for the free-choice
administration of a new animal drug. Such an approval will not provide a
basis upon which an application can be approved under section 512(m) of
the act; or
(2) The manufacture of a Type A medicated article for use in the
subsequent manufacture of a free-choice medicated feed. The approved
NADA will provide a basis upon which an application can be approved
under section 512(m) of the act. Data for a specific free-choice product
may, if desired, be generated and submitted to the Food and Drug
Administration by the manufacturer of the free-choice feed in the form
of a master file which can be referenced in the NADA or supplemental
NADA submitted by the new animal drug sponsor.
(d) Approval of the NADA or supplemental NADA submitted under
paragraph (c) of this section will be reflected in a regulation in part
558 of this chapter published under section 512(i) of the act. The
regulation will either state the formulation of the approved free-choice
product or specify the specific free-choice administration products in
which the drug is approved
[[Page 85]]
for use. If the approval is for a Type A medicated article, the
regulation in part 558 of this chapter will indicate that each use of
the Type A medicated article in a free-choice product must be the
subject of an approved supplemental NADA.
(e) An application submitted under section 512(m) of the act to
provide for manufacture of a specific free-choice feed from an approved
Type A medicated article will be approved if, in addition to the
information required by the medicated feed application, it includes a
reference to the exact formula of the product to be manufactured as
follows:
(1) The formula is the same as the one published in the new animal
drug regulations; or
(2) The data in a master file have been referenced in an NADA or
supplemental NADA; and
(3) Use of the Type A medicated article in the specific formulation
has been approved on the basis that:
(i) The formula is the same as the one for which acceptable data
have been submitted in a master file by the medicated feed applicant; or
(ii) The medicated feed applicant has written authority to reference
a master file that has acceptable data for the formula in question.
(Approved by the Office of Management and Budget under control number
0910-0205)
[51 FR 19827, June 3, 1986]
Subpart F--Animal Use Exemptions From Certification and Labeling
Requirements
Sec. 510.515 Animal feeds bearing or containing new animal drugs subject to the provisions of section 512(n) of the act.
Animal feeds that bear or contain penicillin, chlortetracycline,
feed grade zinc bacitracin, and bacitracin methylene disalicylate, with
or without added suitable nutritive ingredients are exempt from the
certification requirements of section 512 of the act provided they are
the subject of and in compliance with regulations for their use in this
subchapter E, part 558 of this chapter, or any one of the paragraphs of
this section:
(a) Where indicated in paragraph (b) of this section it is
manufactured with or without one, but only one, of the following
ingredients in a quantity, by weight of feed, as hereinafter indicated:
(1) Arsanilic acid: Not less than 0.005 percent and not more than
0.01 percent.
(2) Sodium arsanilate: Not less than 0.005 percent and not more than
0.01 percent.
(3) 3-Nitro-4-hydroxyphenylarsonic acid: Not less than 0.0025
percent and not more than 0.0075 percent except in chicken or turkey
feed which shall contain not less than 0.0025 percent and not more than
0.005 percent.
(b) It is intended for use in any one of the following conditions
set forth in this paragraph:
(1)--(6) [Reserved]
(7)(i) It is intended for use solely as a treatment for complicated,
chronic respiratory disease (air-sac infection), infectious sinusitis,
blue comb (nonspecific infectious enteritis, mud fever), and
hexamitiasis in poultry, and/or bacterial swine enteritis; its labeling
contains adequate directions and warnings for such use; and it contains,
per ton of feed, not less than 100 grams of chlortetracycline, or
oxytetracycline, or a combination of such drugs.
(a) When intended for the uses specified in this paragraph
(b)(7)(i), it may also contain, in the amount specified, one, but only
one, of the ingredients prescribed by paragraph (a) of this section. If
it is intended for use solely in poultry, it may contain 0.1 percent of
para-aminobenzoic acid or the sodium or potassium salt of para-
aminobenzoic acid.
(b) If it is intended for use solely in the treatment of the
diseases of chickens described in this paragraph (b)(7)(i), it contains,
per ton of feed, not less than 100 grams and not more than 200 grams of
chlortetracycline and it contains not less than 0.4 percent and not more
than 0.8 percent of dietary calcium, then representations may be made in
its labeling to the effect that the reduced amount of calcium aids in
increasing the concentrations of the antibiotic in the blood of treated
birds; the labeling of such medicated feed
[[Page 86]]
shall include that required by Sec. 558.128 of this chapter.
(ii) [Reserved]
(iii) It is also intended for use in the treatment of coccidiosis in
chickens caused by E. tenella and E. necatrix; its labeling bears
adequate directions and warnings for such use (including the directions
and warnings required by paragraph (b)(7)(i) of this section); and it
contains, per ton of feed, 200 grams of chlortetracycline and 0.4
percent to 0.55 percent of dietary calcium.
(8)--(9) [Reserved]
(10) It is intended for use solely in the treatment of chronic
respiratory disease (air-sac infection), infectious sinusitis, and blue
comb (nonspecific infectious enteritis) in poultry and/or bacterial
swine enteritis; its labeling bears adequate directions and warnings for
such use; and it contains, per ton of feed, the equivalent of 100 grams
of penicillin. When intended for uses specified in this paragraph, it
may also contain, in the amount specified, one, but only one, of the
ingredients prescribed by paragraph (a) of this section.
(11)--(12) [Reserved]
(13) It is intended for use solely in the treatment of chronic
respiratory disease (air-sac infection) and infectious sinusitis in
poultry; its labeling bears adequate directions and warnings for such
use; and it contains not less than 0.1 percent para-aminobenzoic acid or
the sodium or potassium salt or para-aminobenzoic acid.
(14)--(16) [Reserved]
(17)(i) It is intended for use solely as an aid in the treatment of
chronic respiratory disease (air-sac infection), infectious sinusitis,
blue comb (nonspecific infectious enteritis, mud fever) in poultry; its
labeling bears adequate directions and warnings for such use; and it
contains not less than 100 grams of chlortetracycline or oxytetracycline
or a combination of these two drugs per ton of food.
(ii) [Reserved]
(18)--(24) [Reserved]
(25) It is a medicated cattle feed containing chlortetracycline in
the amounts and for the purposes indicated in Sec. 558.128 of this
chapter, and its labeling bears adequate directions and warnings for
such use.
(26)--(28) [Reserved]
(29) It is intended for use solely as an aid in reducing the
incidence of bacterial diarrhea in laboratory mice; its labeling bears
adequate directions and warnings for such use; and it contains not less
than 100 grams of chlortetracycline per ton of feed.
(c) It is intended for use as follows:
----------------------------------------------------------------------------------------------------------------
Product Species Use levels Indications for use
----------------------------------------------------------------------------------------------------------------
1. Nicarbazin................. Chickens................ 0.01 to 0.02 percent..... For use in the prevention
Procaine penicillin......... ......do................ 2.4 to 50 g/ton.......... of outbreaks of
coccidiosis in poultry
flocks; growth promotion
and feed efficiency.
2. Nicarbazin................. ......do................ 0.01 to 0.02 percent..... Do.
Bacitracin methylene ......do................ 4 to 50 g/ton............
disalicylate.
3. Nicarbazin................. ......do................ 0.01 to 0.02 percent..... For use as an aid in the
prevention of coccidiosis
in poultry flocks; growth
promotion and feed
efficiency; improving
pigmentation.
Bacitracin methylene ......do................ 4 to 50 g/ton............
disalicylate.
3-Nitro-4- ......do................ 0.0025 to 0.005 percent..
hydroxyphenylarsonic acid.
4. Nicarbazin................. ......do................ 0.01 to 0.02 percent..... Do.
Procaine penicillin......... ......do................ 2.4 to 50 g/ton..........
3-Nitro-4- ......do................ 0.0025 to 0.005 percent..
hydroxyphenylarsonic acid.
5. Chlortetracycline.......... Swine................... 10 to 50 g/ton........... Enhancement of growth and
Arsanilic acid.............. ......do................ 0.005 to 0.01 percent.... feed efficiency.
6. Chlortetracycline.......... Sheep................... 20 g/ton................. As an aid in the reduction
of losses due to
enterotoxemia.
7. Chlortetracycline.......... ......do................ 80 mg per head per day... It is intended for use as
an aid in reducing the
incidence of vibrionic
abortion in breeding
sheep; it is to be
administered continuously
during pregnancy.
[[Page 87]]
8. Chlortetracycline.......... Cattle.................. Feed contains the As an aid in the reduction
following quantities of of bacterial diarrhea in
chlortetracycline, by dairy cattle or as an aid
weight, for the in reduction of losses due
conditions indicated: to respiratory infection
(1) For the prevention (infectious
of foot rot and as an rhinotracheitis--shipping
aid in the reduction of fever complex) or as an
bacterial diarrhea in aid in the prevention of
dairy cattle; 0.1 mg/lb foot rot in cattle.
of body weight per day;
and (2) as an aid in the
reduction of losses due
to respiratory infection
(infectious
rhinotracheitis--shippin
g fever complex) in
dairy cattle: 0.1 mg/lb
of body weight per day,
except that if it is
intended for use for
more than 30 days it may
contain
chlortetracycline, in a
quantity by weight of
feed to provide 70 mg
per head per day.
----------------------------------------------------------------------------------------------------------------
[41 FR 8299, Feb. 25, 1976, as amended at 41 FR 11011, Mar. 15, 1976; 42
FR 18614, Apr. 8, 1977; 47 FR 42102, Sept. 24, 1982; 47 FR 51563, Nov.
16, 1982; 56 FR 41912, Aug. 23, 1991; 58 FR 30119, May 26, 1993]
Subpart G--Sponsors of Approved Applications
Sec. 510.600 Names, addresses, and drug labeler codes of sponsors of approved applications.
(a) Section 512(i) of the act requires publication of names and
addresses of sponsors of approved applications for new animal drugs.
(b) In this section each name and address is identified by a
numerical drug labeler code. The labeler codes identify the sponsors of
the new animal drug applications associated with the regulations
published pursuant to section 512(i) of the act. The codes appear in the
appropriate regulations and serve as a reference to the names and
addresses listed in this section. The drug labeler code is established
pursuant to section 510 of the act.
(c) The names, addresses, and drug labeler codes of sponsors of
approved new animal drug applications are as follows:
(1) Alphabetical Listing of Sponsors
------------------------------------------------------------------------
Drug
Firm name and address labeler
code
------------------------------------------------------------------------
Abbott Laboratories, North Chicago, IL 60064................ 000074
ADM Animal Health & Nutrition Div., P.O. Box 2508, Fort
Wayne, IN 46801-2508....................................... 012286
Affiliated Laboratories Division, Whitmoyer Laboratories,
Inc., 19 North Railroad St., Myerstown, PA 17067........... 011825
Ag-Mark, Inc., P.O. Box 127, Teachey, NC 28464.............. 024174
Agri Laboratories, Ltd., P.O. Box 3103, St. Joseph, MO 64503 057561
Agribusiness Marketers, Inc., 2667 West Dual, Baton Rouge,
LA 70815................................................... 015563
Agri-Tech, Inc., 4722 Broadway, Kansas City, MO 64112....... 017762
Carl S. Akey, Inc., P.O. Box 607, Lewisburg, OH 45338....... 017790
A. L. Pharma, Inc., One Executive Drive, P.O. Box 1399, Fort
Lee, NJ 07024.............................................. 046573
Albers Milling Co., Carnation Bldg., 5045 Wilshire Blvd.,
Los Angeles, CA 90036...................................... 017826
Albion Laboratories, Inc., 101 North Main, Clearfield, UT
84015...................................................... 011485
Allied Pharmacal, Division of K.C. Pharmacal, Inc., 1234
Clay St., North Kansas City, MO 64116...................... 012983
Altana Inc., 60 Baylis Rd., Melville, NY 11747.............. 025463
American Cyanamid, Division of American Home Products, P.O.
Box 1339, Fort Dodge, IA 50501............................. 010042
American Scientific Laboratories, A Division of Schering
Corp., Bloomfield, NJ 07003................................ 000138
American Veterinary Products, Inc., 749 South Lemay, Suite
A3-231, Fort Collins, CO 80524............................. 045984
Anika Research, Inc., 160 New Boston St., Woburn, MA 01801.. 060865
Anthony Products Co., 5600 Peck Rd., Arcadia, CA 91006...... 000864
Argent Laboratories, 8702 152d Ave. NE., Redmond, WA 98052.. 051212
Arkansas Micro Specialties Inc., P.O. Box 308, Highway 71
North, Lowell, AR 72745.................................... 047863
Ausa International, Inc., Rt. 8, P.O. Box 324-12, Tyler, TX
75703...................................................... 059521
Ayerst Laboratories, Division of American Home Products
Corp., 685 Third Ave., New York, NY 10017.................. 000046
Babineaux's Veterinary Products, Inc., 6425 Airline Highway,
Metairie, LA 70003......................................... 021188
[[Page 88]]
Balfour Guthrie & Co., Ltd., 315 North H St., Fresno, CA
93701...................................................... 043728
Bayer Corp., Agriculture Division, Animal Health, P.O. Box
390, Shawnee, Mission, KS 66201............................ 000859
Biocraft Laboratories, Inc., 92 Route 46, Elmwood Park, NJ
07407...................................................... 000332
Bioproducts, Inc., 320 Springside Dr., Suite 300, Fairlawn,
OH 44333-2435.............................................. 051359
Boehringer Ingelheim Animal Health, Inc., 2621 North Belt
Highway, St. Joseph, MO 64502.............................. 000010
Bristol Laboratories, Division of Bristol-Myers Co., P.O.
Box 4755, Syracuse, NY 13221-4755.......................... 000015
Carnation Co., 5045 Wilshire Blvd., Los Angeles, CA 90036... 047019
Chanelle Pharmaceuticals Manufacturing Ltd., Loughrea,
County Galway, Ireland..................................... 061651
Chemdex, Inc., 12340 Santa Fe Dr., Lenexa, KS 66215......... 017287
Ciba-Geigy Animal Health, Ciba-Geigy Corp., P.O. Box 18300,
Greensboro, NC 27419-8300.................................. 058198
Combe, Inc., 1101 Westchester Ave., White Plains, NY 10604.. 011509
ConAgra Pet Products Co., 3902 Leavenworth St., Omaha, NE
68105...................................................... 021091
Cooper U.S.A., Inc., P.O. Box 12338, Research Triangle Park,
NC 27709................................................... 011492
Cooperative Research Farms, Box 69, Charlotteville, NY 12036 051267
Cross Vetpharm Group Ltd., Broomhill Rd., Tallaght, Dublin
24, Ireland................................................ 061623
Custom Feed Blenders Corp., 540 Hawkeye Ave., Fort Dodge, IA
50501...................................................... 046987
Custom Feed Services Corp., 2100 N. 13th St., Norfolk, NE
68701...................................................... 017473
Cutter Laboratories, Inc., Fourth and Parker St., Berkeley,
CA 94710................................................... 000161
Cyanamid Agricultural de Puerto Rico, Inc., P.O. Box 243,
Manati, PR 00701........................................... 043781
Danbury Pharmacal, Inc., 131 West St., Danbury, CT 06810.... 000591
Dawes Laboratories, Inc., 450 State St., Chicago Heights, IL
60411...................................................... 024264
Delmarva Laboratories, Inc., 2200 Wadebridge Rd., P.O. Box
525, Midlothian, VA 23113.................................. 059079
Diamond Shamrock Corp., Nutrition & Animal Health Div., 1100
Superior Ave., Cleveland, OH 44114......................... 025001
DuPont Merck Pharmaceutical Co., DuPont Merck Plaza, MR2117,
Wilmington, DE 19805....................................... 000056
Elanco Animal Health, A Division of Eli Lilly & Co., Lilly
Corporate Center, Indianapolis, IN 46285................... 000986
Eon Labs Manufacturing, Inc. 227-15 North Conduit Ave.,
Laurelton, NY 11413........................................ 000185
Evsco Pharmaceuticals, An Affiliate of IGI, Inc., Box 209,
Harding Hwy., Buena, NJ 08310.............................. 017030
Farmers Feed & Supply Co., Ninth St. at Northwestern Tracks,
Tipton, IA 52772........................................... 043744
Farmland Industries, Inc., Kansas City, MO 64116............ 021676
Farnam Companies, Inc., 301 West Osborn, Phoenix, AZ 85013-
3928....................................................... 017135
Feed Products, Inc., 1000 West 47th Ave., Denver, CO 80211.. 013959
Feed Service Co., Inc., 303 Lundin Blvd., P.O. Box 698,
Mankato, MN 56001.......................................... 030841
John J. Ferrante, 11 Fairway Lane, Trumbull, CT 06611....... 058034
Fermenta Animal Health Co., 10150 North Executive Hills
Blvd., Kansas City, MO 64153............................... 054273
Fisons plc, Pharmaceutical Division, 12 Derby Rd.,
Loughborough, Leicestershire, LE11 OBB, England............ 012525
Fleming Laboratories, Inc., P.O. Box 34384, Charlotte, NC
28234...................................................... 015565
Fort Dodge Laboratories, Division of American Home Products
Corp., 800 Fifth St. NW., Fort Dodge, IA 50501............. 000856
Franklin Laboratories, Inc., P.O. Box 717, Fort Dodge, IA
50501...................................................... 010290
Fujisawa USA, Inc., Deerfield, IL 60015-2548................ 000469
Furst-McNess Co., Freeport, IL 61032........................ 010439
Gland-O-Lac Co., 1818 Leavenworth St., Omaha, NE 68102...... 043735
Global Pharmaceutical Corp., Castor and Kensington Aves.,
Philadelphia, PA 19124..................................... 000115
H. Clay Glover Co., Inc., 1001 Franklin Ave., Garden City,
NY 11530................................................... 010471
Golden Sun Feeds, Inc., 111 South Fifth St., Estherville, IA
51334...................................................... 021780
Gooch Feed Mill Corp., 540 South St., Lincoln, NE 68501..... 021798
Michael Gordon, Inc., P.O. Box 8091, San Francisco, CA 94118 049047
Gossett Nutrition, Inc., 1676 Cascade Dr., Marion, OH 43302. 050972
Grain Processing Corp., Muscatine, IA 52761................. 022591
Growmark, Inc., 1701 Towanda Ave., Bloomington, IL 61701.... 020275
G. C. Hanford Manufacturing Co., P.O. Box 1017, Syracuse, NY
13201...................................................... 010515
Halocarbon Laboratories, Division of Halocarbon Products
Corp., 887 Kinderkamack Rd., P.O. Box 661, River Ridge, NJ
07661...................................................... 012164
Happy Jack, Inc., Snow Hill, NC 28580....................... 023851
Heinold Feeds, Inc., P.O. Box 377, Kouts, IN 46347.......... 043727
Henwood Feed Additives, Division of Feed Specialties Co.,
Inc., 211 Western Rd., Box 577, Lewisburg, OH 45338........ 026186
Hess & Clark, Inc., Seventh and Orange Sts., Ashland, OH
44805...................................................... 050749
Dow B. Hickam, Inc., Pharmaceuticals, P.O. Box 35413,
Houston, TX 77035.......................................... 000514
Hoechst-Roussel Agri-Vet Co., Route 202-206 North,
Somerville, NJ 08876....................................... 012799
Hoffmann-La Roche, Inc., Nutley, NJ 07110................... 000004
Hubbard Milling Co., 424 North Front St., Mankato, MN 56001. 012190
ICI Americas, Inc., Wilmington, DE 19897.................... 011511
I. D. Russell Co. Laboratories, 1301 Iowa Ave., Longmont, CO
80501...................................................... 017144
I.M.S. Inc., 13619 Industrial Rd., Omaha, NE 68137.......... 050639
Illini Feeds, Box T, Oneida, IL 61467....................... 037310
Indiana Farm Bureau Cooperative Association, Inc., 120 E.
Market St., Indianapolis, IN 46204......................... 021502
Inhalon Pharmaceuticals, Inc., P.O. Box 21170, Lehigh
Valley, PA 18002........................................... 060307
International Nutrition, Inc., 6664 ``L'' St., Omaha, NE
68117...................................................... 043733
Intervet, Inc., P.O. Box 318, 405 State St., Millsboro, DE
19966...................................................... 057926
Ivy Laboratories, Inc., 8857 Bond Street, Overland Park, KS
66214...................................................... 021641
J. C. Feed Mills, 1050 Sheffield, P.O. Box 224, Waterloo, IA
50704...................................................... 039741
[[Page 89]]
Jorgensen Laboratories, Inc., 1450 North Van Buren Ave.,
Loveland, CO 80538......................................... 045087
K. C. Pharmacal, Inc., 1310 Atlantic, P.O. Box 7496, North
Kansas City, MO 64116...................................... 038782
KASCO-EFCO Laboratories, Inc., P.O. Box 730, Hicksville, NY
11802...................................................... 010616
Kerber Milling Co., Box 152, 1817 E. Main St., Emmetsburg,
IA 50536................................................... 029341
Lambert-Kay, A Division of Carter-Wallace, Inc., P.O. Box
1001, Half Acre Rd., Cranbury, NJ 08512-0181............... 011615
Land O'Lakes, Inc., Agricultural Services, 2827 Eighth
Avenue South, Fort Dodge IA 50501.......................... 034500
Dr. LeGear, Inc., 4161 Beck Ave., St. Louis, MO 63116....... 011950
Lemmon Co., Sellersville, PA 18960.......................... 000693
Lloyd, Inc., 604 W. Thomas Ave., Shenandoah, IA 51601....... 061690
Luitpold Pharmaceuticals, Inc., Animal Health Division,
Shirley, NY 11967.......................................... 010797
M & M Livestock Products Co., Eagle Grove, IA 50533......... 026282
Macleod Pharmaceuticals, Inc., 2600 Canton Ct., Fort
Collins, CO 80525.......................................... 058711
Mallinckrodt Veterinary, Inc., Mundelein, IL 60060.......... 011716
Mattox & Moore, Inc., 1503 East Riverside Drive,
Indianapolis, IN 46207..................................... 027863
McClellan Laboratories, Inc., 19600 Sixth Ave., Lakeview, CA
92353...................................................... 043738
McNeil Laboratories, Inc., Camp Hill Rd., Fort Washington,
PA 19034................................................... 000045
Med-Pharmex, Inc., Biomed laboratories, 325 East Arrow Hwy.,
suite 502, San Dimas, CA 91773............................. 051259
Merck Research Laboratories, Division of Merck & Co., Inc.,
Rahway, NJ 07065........................................... 000006
Micro Chemical, Inc., Amarillo, TX 79105.................... 047126
Mid-Continent Agrimarketing, Inc., 8833 Quivira Rd.,
Overland Park, KS 66214.................................... 059620
Moorman Manufacturing Co., Quincy, IL 62301................. 021930
Mountaire Vitamins, Inc., 400 North Poplar St., P.O. Box
9210, North Little Rock, AR 72119.......................... 043734
Music City Supplement Co., 401 Cowan St., Nashville, TN
37202...................................................... 017519
Natchez Animal Supply Co., 201 John R. Junkin Dr., Natchez,
MS 39120................................................... 049968
Nixon and Co., Kiewitt Plaza, Omaha, NE 88501............... 043729
Norbrook Laboratories, Ltd., Station Works, Newry BT35 6JP,
Northern Ireland........................................... 055529
Norco Mills of Norfolk, Inc., P.O. Box 56, Norfolk, NE 68701 027190
Nutra-Blend Corp., P.O. Box 485, Neosho, MO 64850........... 050568
NutriBasics Co., North Highway 71, P.O. Box 1014, WIllmar,
MN 56201................................................... 053740
Nylos Trading Co., Inc., P.O. Box 2, Route 202, Pomona, NY
10970...................................................... 027454
Ohmeda Pharmaceutical Products Division Inc., Liberty
Corner, NJ 07938-0804...................................... 010019
Orion Corp. FARMOS, Research and Development,
Pharmaceuticals, P.O. Box 425, SF-20101 Turku, Finland..... 052483
Osborn Laboratories, Inc., 2d and Oak Sts., Le Sueur, MN
56058...................................................... 012487
OXIS International, Inc., 6040 N. Cutter Circle, Suite 317,
Portland, OR 97217-3935.................................... 024991
Peavey Co., 730 Second Ave. South, Minneapolis, MN 55402.... 028459
Pegasus Laboratories, Inc., 8809 Ely Rd., Pensacola, FL
32514...................................................... 055246
Pennfield Oil Co., 14040 Industrial Rd., Omaha, NE 68137.... 053389
Peter Hand Foundation, 2 East Madison St., Waukegan, IL
60085...................................................... 043737
Pfizer, Inc., 235 East 42d St., New York, NY 10017.......... 000069
Pharmacia, Inc., P.O. Box 16529, Columbus, OH 43216-6529.... 000016
Phoenix Pharmaceutical, Inc., 4621 Easton Rd., P.O. Box 6457
Farleigh Station, St. Joseph, MO 64506-0457................ 057319
Phoenix Scientific, Inc. 3915 South 48th St. Terrace, P.O.
Box 6457, St. Joseph, MO 64506-0457........................ 059130
Planalquimica Industrial Ltda., Rua das Magnolias nr. 2405,
Jardim das Bandeiras, CEP 13053-120, Campinas, Sao Paulo,
Brazil..................................................... 060728
PM Ag Products, Inc., 1055 West 175th St., Homewood, IL
60430...................................................... 036904
PM Resources, Inc., 13001 St. Charles Rock Rd., Bridgeton,
MO 63044................................................... 060594
Premier Malt Products, Inc., Milwaukee, WI 53201............ 032707
Protein Blenders, Inc., Box 631, Highway 218 South, Iowa
City, IA 52240............................................. 033999
Protiva, A Unit of Monsanto Co., 800 North Lindbergh Blvd.,
St. Louis, MO 63167........................................ 059945
Purina Mills, Inc., P.O. Box 66812, St. Louis, MO 63166-6812 017800
Quali-Tech Products, Inc., 318 Lake Hazeltine Drive, Chaska,
MN 55318................................................... 016968
The Rath Packing Co., P.O. Box 330, Waterloo, IA 50704...... 028260
Rhone Merieux Canada, Inc., 345 Boul. Labbe Blvd., North
Victoriaville, QC, G6P 1B1 Canada.......................... 047015
Rhone Merieux, Inc., 7101 College Blvd., Overland Park, KS
66210...................................................... 050604
Rhone-Poulenc, Inc., P.O. Box 125, Black Horse Lane,
Monmouth Junction, NJ 08852................................ 011526
A. H. Robins Co., P.O. Box 518, Fort Dodge, IA 50501-0518... 000031
Roussel-UCLAF, Division Agro-Veterinaire, 163 Avenue
Gambetta, 75020 Paris, France.............................. 012579
RSR Laboratories, Inc., 501 Fifth St., Bristol, TN 37620.... 058670
Sandoz Agro, Inc., 1300 East Touhy Ave., Des Plaines, IL
60018...................................................... 011536
R. P. Scherer North America, P.O. Box 5600, Clearwater, FL
33518...................................................... 011014
Schering-Plough Animal Health Corp., P.O. Box 529, Galloping
Hill Rd., Kenilworth, NJ 07033............................. 000061
G. D. Searle & Co., P.O. Box 5110, Chicago, IL 60680........ 000014
Seeco Inc., Box 1014, North Highway 71, Willmar, MN 56201... 011749
Shell Chemical Co., Division of Shell Oil Co., Animal
Health, One Shell Plaza, Houston, TX 77001................. 011461
Solvay Animal Health, Inc., 1201 Northland Dr., Mendota
Heights, MN 55120.......................................... 053501
South St. Paul Feeds, Inc., 500 Farwell Ave., South St.
Paul, MN 55075............................................. 001800
Southern Micro-Blenders, Inc., 3801 North Hawthorne St.,
Chattanooga, TN 37406...................................... 049685
Springfield Milling Corp., Vigorena Feeds, Springfield, MN
56087...................................................... 035955
Square Deal Fortification Co., Kouts, IN 46347.............. 036108
[[Page 90]]
Squire Laboratories, Inc., 100 Mill St., Revere, MA 02151... 017153
Steris Laboratories, Inc., 620 North 51st Ave., Phoenix, AZ
85043-4705................................................. 000402
Sterling Winthrop, Inc., 9 Great Valley Pkwy., Malvern, PA
19355...................................................... 000934
Summit Hill Laboratories, P.O. Box 535, Navesink, NJ 07752.. 037990
Syntex Animal Health, Division of Syntex Agribusiness, Inc.,
3401 Hillview Ave., Palo Alto, CA 94304.................... 000033
Tevcon Ind., Inc., 8904 J St., Omaha, NE 68127.............. 011757
Texas Vitamin Co., P.O. Box 18417, 10695 Aledo St., Dallas,
TX 57218................................................... 000842
TRINADA, Inc., One Executive Dr., P.O. Box 1399, Fort Lee,
NJ 07024................................................... 058690
Triple ``F,'' Inc., 10104 Douglas Ave., Des Moines, IA 50322 011490
Tutag Pharmaceuticals, Inc., 2599 W. Midway Blvd.,
Broomfield, CO 80020....................................... 000124
United Vaccines, A Harlan Sprague Dawley, Inc., Co., P.O.
Box 4220, Madison, WI 53711................................ 058639
The Upjohn Co., Kalamazoo, MI 49001......................... 000009
V.P.O., Inc., 4444 S. 76th St., Omaha, NE 68127............. 043743
Vet-A-Mix, Inc., P.O. Box A, Shenandoah, IA 51601........... 011789
Vetem, S.p.A., Viale E. Bezzi 24, 20146 Milano, Italy....... 055882
Veterinary Laboratories, Inc., 12340 Santa Fe Dr., Lenexa,
KS 66215................................................... 000857
Veterinary Service, Inc., 416 North Jefferson St., P.O. Box
2467, Modesto, CA 95354.................................... 033008
Wade Jones Co., Inc., 409 North Bloomington, Lowell, AR
72745...................................................... 047864
Walco International, Inc., 15 West Putnam, Porterville, CA
93257 049185
Waterloo Mills Co., 2050 Mitchell Ave., Waterloo, IA 50704.. 017139
Wayne Feed Division, Continental Grain Co., P.O. Box 459,
Libertyville, IL 60048..................................... 034936
Webel Feeds, Inc., R.R. 3, Pittsfield, IL 62363............. 035098
Wendt Laboratories , Inc., 100 Nancy Dr., Belle Plaine, MN
56011...................................................... 015579
West Agro, Inc., 11100 N. Congress Ave., Kansas City, MO
64153...................................................... 033392
Westchester Veterinary Products, Inc., 180 Mamaroneck Ave.,
White Plains, NY 10601..................................... 043732
Western Chemical, Inc., 1269 Lattimore Rd., Ferndale, WA
98248...................................................... 050378
Western Serum Co., P.O. Box 7025, Phoenix, AZ 85011......... 011398
Wildlife Laboratories, Inc., 1401 Duff Dr., Suite 600, Fort
Collins, CO 80524.......................................... 053923
Wyeth Laboratories, Division American Home Products Corp.,
P.O. Box 8299, Philadelphia, PA 19101...................... 000008
Yoder Feed, Division of Yoder, Inc., Kalona, IA 52247....... 035369
Young's Inc., Roaring Spring, PA 16673...................... 035393
Zema Corp., P.O. Box 12803, Research Triangle Park, Durham,
NC 27709................................................... 050906
Zenith Laboratories, Inc., 50 Williams Dr., Ramsey, NJ 07446 000172
------------------------------------------------------------------------
(2) Numerical Listing of Sponsors
------------------------------------------------------------------------
Drug labeler code Firm name and address
------------------------------------------------------------------------
000004............................. Hoffmann-La Roche, Inc., Nutley, NJ
07110.
000006............................. Merck Research Laboratories,
Division of Merck & Co., Inc.,
Rahway, NJ 07065.
000008............................. Wyeth Laboratories, Division
American Home Products Corp., P.O.
Box 8299, Philadelphia, PA 19101.
000009............................. The Upjohn Co., Kalamazoo, MI
49001.
000010............................. Boehringer Ingelheim Animal Health,
Inc., 2621 North Belt Highway, St.
Joseph, MO 64502.
000014............................. G. D. Searle & Co., P.O. Box 5110,
Chicago, IL 60680.
000015............................. Bristol Laboratories, Division of
Bristol-Myers Co., P.O. Box 4755,
Syracuse, NY 13221-4755.
000016............................. Pharmacia, Inc., P.O. Box 16529,
Columbus OH 43216-6529.
000031............................. A. H. Robins Co., P.O. Box 518,
Fort Dodge, IA 50501-0518.
000033............................. Syntex Animal Health Division of
Syntex Agribusiness, Inc., 3401
Hillview Ave., Palo Alto, CA
94304.
000045............................. McNeil Laboratories, Inc., Camp
Hill Rd., Fort Washington, PA
19034.
000046............................. Ayerst Laboratories, Division of
American Home Products Corp., 685
Third Ave., New York, NY 10017.
000056............................. DuPont Merck Pharmaceutical Co.,
DuPont Merck Plaza, MR2117,
Wilmington, DE 19805.
000061............................. Schering-Plough Animal Health
Corp., P.O. Box 529, Galloping
Hill Rd., Kenilworth, NJ 07033.
000069............................. Pfizer, Inc., 235 East 42d St., New
York, NY 10017.
000074............................. Abbott Laboratories, North Chicago,
IL 60064.
000115............................. Global Pharmaceutical Corp., Castor
and Kensington Aves.,
Philadelphia, PA 19124.
000124............................. Tutag Pharmaceuticals, Inc., 2599
W. Midway Blvd., Broomfield, CO
80020.
000138............................. American Scientific Laboratories, A
Division of Schering Corp.,
Bloomfield, NJ 07003.
000161............................. Cutter Laboratories, Inc., Fourth
and Parker St., Berkeley, CA
94710.
000172............................. Zenith Laboratories, Inc., 50
Williams Dr., Ramsey, NJ 07446.
000185............................. Eon Labs Manufacturing, Inc., 227-
15 North Conduit Ave., Laurelton,
NY 11413.
000332............................. Biocraft Laboratories, Inc., 92
Route 46, Elmwood Park, NJ 07407.
000402............................. Steris Laboratories, Inc., 620
North 51st Ave., Phoenix, AZ 85043-
4705.
000469............................. Fujisawa USA, Inc., Deerfield, IL
60015-2548.
000514............................. Dow B. Hickam, Inc.,
Pharmaceuticals, P.O. Box 35413,
Houston, TX 77035.
000591............................. Danbury Pharmacal, Inc., 131 West
St., Danbury, CT 06810.
000693............................. Lemmon Co., Sellersville, PA 18960.
000794............................. S. B. Penick & Co., 1050 Wall St.
West, Lyndhurst, NJ 07071.
000842............................. Texas Vitamin Co., P.O. Box 18417,
10695 Aledo St., Dallas, TX 57218.
000856............................. Fort Dodge Laboratories, Division
of American Home Products, 800
Fifth St. NW., Fort Dodge, IA
50501.
000857............................. Veterinary Laboratories, Inc.,
12340 Santa Fe Dr., Lenexa, KS
66215.
[[Page 91]]
000859............................. Bayer Corp., Agriculture Division,
Animal Health, P.O. Box 390,
Shawnee Mission, KS 66201.
000864............................. Anthony Products Co., 5600 Peck
Rd., Arcadia, CA 91006.
000934............................. Sterling Winthrop, Inc., 9 Great
Valley Pkwy., Malvern, PA 19335.
000986............................. Elanco Animal Health, A Division of
Eli Lilly & Co., Lilly Corporate
Center, Indianapolis, IN 46285.
001800............................. South St. Paul Feeds, Inc., 500
Farwell Ave., South St. Paul, MN
55075.
010019............................. Ohmeda Pharmaceutical Products
Division, Inc., Liberty Corner, NJ
07938-0804.
010042............................. American Cyanamid, Division of
American Home Products, P.O. Box
1339, Fort Dodge, IA 50501
010290............................. Franklin Laboratories, Inc., P.O.
Box 717, Fort Dodge, IA 50501.
010290............................. Franklin Laboratories, P.O. Box
669, Amarillo, TX 79105.
010439............................. Furst-McNess Co., Freeport, IL
61032.
010471............................. H. Clay Glover Co., Inc., 1001
Franklin Ave., Garden City, NY
11530.
010515............................. G. C. Hanford Manufacturing Co.,
P.O. Box 1017, Syracuse, NY 13201.
010616............................. KASCO-EFCO Laboratories, Inc., P.O.
Box 730, Hicksville, NY 11802.
010797............................. Luitpold Pharmaceuticals, Inc.,
Animal Health Division, Shirley,
NY 11967.
011014............................. R. P. Scherer North America, P.O.
Box 5600, Clearwater, FL 33518.
011398............................. Western Serum Co., P.O. Box 7025,
Phoenix, AZ 85011.
011461............................. Shell Chemical Co., Division of
Shell Oil Co., Animal Health, One
Shell Plaza, Houston, TX 77001.
011485............................. Albion Laboratories, Inc., 101
North Main, Clearfield, UT 84015.
011490............................. Triple ``F,'' Inc., 10104 Douglas
Ave., Des Moines, IA 50322.
011492............................. Cooper U.S.A., Inc., P.O. Box
12338, Research Triangle Park, NC
27709.
011509............................. Combe, Inc., 1101 Westchester Ave.,
White Plains, NY 10604.
011511............................. ICI Americas, Inc., Wilmington, DE
19897.
011526............................. Rhone-Poulenc, Inc., P.O. Box 125,
Black Horse Lane, Monmouth
Junction, NJ 08852.
011536............................. Sandoz Agro, Inc., 1300 East Touhy
Ave., Des Plaines, IL 60018
011615............................. Lambert-Kay, A Division of Carter-
Wallace, Inc., P.O. Box 1001, Half
Acre Rd., Cranbury, NJ 08512-0181.
011716............................. Mallinckrodt Veterinary, Inc.,
Mundelein, IL 60060.
011749............................. Seeco Inc., Box 1014, North Highway
71, Willmar, MN 56201.
011789............................. Vet-A-Mix, Inc., P.O. Box A,
Shenandoah, IA 51601.
011825............................. Affiliated Laboratories Division,
Whitmoyer Laboratories, Inc., 19
North Railroad St., Myerstown, PA
19067.
011950............................. Dr. LeGear, Inc., 4161 Beck Ave.,
St. Louis, MO 63116.
012164............................. Halocarbon Laboratories, Division
of Halocarbon Products Corp., 887
Kinderkamack Rd., P.O. Box 661,
River Ridge, NJ 07661.
012190............................. Hubbard Milling Co., 424 North
Front St., Mankato, MN 56001.
012286............................. ADM Animal Health & Nutrition Div.,
P.O. Box 2508, Fort Wayne, IN
46801-2508.
012487............................. Osborn Laboratories, Inc., 2d and
Oak Sts., Le Sueur, MN 56058.
012525............................. Fisons plc, Pharmaceutical
Division, 12 Derby Rd.,
Loughborough, Leicestershire, LE11
OBB, England.
012579............................. Roussel-UCLAF, Division Agro-
Veterinaire, 163 Avenue Gambetta,
75020 Paris, France.
012799............................. Hoechst-Roussel Agri-Vet Co., Route
202-206 North, Somerville, NJ
08876.
012983............................. Allied Pharmacal, Division of K. C.
Pharmacal, Inc., 1234 Clay St.,
North Kansas City, MO 64116.
013959............................. Feed Products, Inc., 1000 West 47th
Ave., Denver, CO 80211.
015563............................. Agribusiness Marketers, Inc., 2667
West Dual, Baton Rouge, LA 70815.
015565............................. Fleming Laboratories, Inc., P.O.
Box 34384, Charlotte, NC 28234.
015579............................. Wendt Laboratories, Inc., 100 Nancy
Dr., Belle Plaine, MN 56011.
016968............................. Quali-Tech Products, Inc., 318 Lake
Hazeltine Dr., Chaska, MN 55318.
017030............................. Evsco Pharmaceuticals, An Affiliate
of IGI, Inc., Box 209, Harding
Hwy., Buena, NJ 08310.
017135............................. Farnam Companies, Inc., 301 West
Osborn, Phoenix, AZ 85013-3928.
017139............................. Waterloo Mills Co., 2050 Mitchell
Ave., Waterloo, IA 50704.
017144............................. I. D. Russell Co. Laboratories,
1301 Iowa Ave., Longmont, CO
80501.
017153............................. Squire Laboratories, Inc., 100 Mill
St., Revere, MA 02151.
017287............................. Chemdex, Inc., 12340 Santa Fe Dr.,
Lenexa, KS 66215.
017473............................. Custom Feed Services Corp., 2100 N.
13th St., Norfolk, NE 68701.
017519............................. Music City Supplement Co., 401
Cowan St., Nashville, TN 37202.
017762............................. Agri-Tech, Inc., 4722 Broadway,
Kansas City, MO 64112.
017790............................. Carl S. Akey, Inc., P.O. Box 607,
Lewisburg, OH 45338.
017800............................. Purina Mills, Inc., P.O. Box 66812,
St. Louis, MO 63166-6812.
017826............................. Albers Milling Co., Carnation
Bldg., 5045 Wilshire Blvd., Los
Angeles, CA 90036.
020275............................. Growmark, Inc., 1701 Towanda Ave.,
Bloomington, IL 61701.
021091............................. ConAgra Pet Products Co., 3902
Leavenworth St., Omaha, NE 68105.
021188............................. Babineaux's Veterinary Products,
Inc., 6425 Airline Highway,
Metairie, LA 70003.
021502............................. Indiana Farm Bureau Cooperative
Association, Inc., 120 E. Market
St., Indianapolis, IN 46204.
021641............................. Ivy Laboratories, Inc., 8857 Bond
Street, Overland Park, KS 66214.
021676............................. Farmland Industries, Inc., Kansas
City, MO 64116.
021780............................. Golden Sun Feeds, Inc., 111 South
Fifth St., Estherville, IA 51334.
021798............................. Gooch Feed Mill Corp., 540 South
St., Lincoln, NE 68501.
[[Page 92]]
021930............................. Moorman Manufacturing Co., Quincy,
IL 62301.
022591............................. Grain Processing Corp., Muscatine,
IA 52761.
023851............................. Happy Jack, Inc., Snow Hill, NC
28580.
024174............................. Ag-Mark, Inc., P.O. Box 127,
Teachey, NC 28464.
024264............................. Dawes Laboratories, Inc., 450 State
St., Chicago Heights, IL 60411.
024991............................. OXIS International, Inc., 6040 N.
Cutter Circle, Suite 317 Portland,
OR 97217-3935.
025001............................. Diamond Shamrock Corp., Nutrition &
Animal Health Div., 1100 Superior
Ave., Cleveland, OH 44114.
025463............................. Altana Inc., 60 Baylis Rd.,
Melville, NY 11747.
026186............................. Henwood Feed Additives, Division of
Feed Specialties Co., Inc., 211
Western Rd., Box 577, Lewisburg,
OH 45338.
026282............................. M & M Livestock Products Co., Eagle
Grove, IA 50533.
027190............................. Norco Mills of Norfolk, Inc., P.O.
Box 56, Norfolk, NE 68701.
027454............................. Nylos Trading Co., Inc., P.O. Box
2, Route 202, Pomona, NY 10970.
027863............................. Mattox & Moore, Inc., 1503 East
Riverside Dr., Indianapolis, IN
46207.
028260............................. The Rath Packing Co., P.O. Box 330,
Waterloo, IA 50704.
028459............................. Peavey Co., 730 Second Ave. South,
Minneapolis, MN 55402.
029341............................. Kerber Milling Co., Box 152, 1817
E. Main St., Emmetsburg, IA 50536.
030841............................. Feed Service Co., Inc., 303 Lundin
Blvd., P.O. Box 698, Mankato, MN
56001.
032707............................. Premier Malt Products, Inc.,
Milwaukee, WI 53201.
033008............................. Veterinary Service, Inc., 416 North
Jefferson St., P.O. Box 2467,
Modesto, CA 95354.
033392............................. West Agro, Inc., 11100 N. Congress
Ave., Kansas City, MO 64153.
033999............................. Protein Blenders, Inc., Box 631,
Highway 218 South, Iowa City, IA
52240.
034500............................. Land O'Lakes, Inc., Agricultural
Services, 2827 Eighth Avenue
South, Fort Dodge, IA 50501.
034936............................. Wayne Feed Division, Continental
Grain Co., P.O. Box 459,
Libertyville, IL 60048.
035098............................. Webel Feeds, Inc., R.R. 3,
Pittsfield, IL 62363.
035369............................. Yoder Feed, Division of Yoder,
Inc., Kalona, IA 52247.
035393............................. Young's, Inc., Roaring Spring, PA
16673.
035955............................. Springfield Milling Corp., Vigorena
Feeds, Springfield, MN 56087.
036108............................. Square Deal Fortification Co.,
Kouts, IN 46347.
036904............................. PM Ag Products, Inc., 1055 West
175th St., Homewood, IL 60430.
037310............................. Illini Feeds, Box T, Oneida, IL
61467.
037990............................. Summit Hill Laboratories, P.O. Box
535, Navesink, NJ 07752.
038782............................. K. C. Pharmacal, Inc., 1310
Atlantic, P.O. Box 7496, North
Kansas City, MO 64116.
039741............................. J. C. Feed Mills, 1050 Sheffield,
P.O. Box 224, Waterloo, IA 50704.
043727............................. Heinold Feeds, Inc., P.O. Box 377,
Kouts, IN 46347.
043728............................. Balfour Guthrie & Co., Ltd., 315
North H St., Fresno, CA 93701.
043729............................. Nixon and Co., Kiewitt Plaza,
Omaha, NE 88501.
043732............................. Westchester Veterinary Products,
Inc., 180 Mamaroneck Ave., White
Plains, NY 10601.
043733............................. International Nutrition, Inc., 6664
L St., Omaha, NE 68117.
043734............................. Mountaire Vitamins, Inc., 400 North
Poplar St., P.O. Box 9210, North
Little Rock, AR 72119.
043735............................. Gland-O-Lac Co., 1818 Leavenworth
St., Omaha, NE 68102.
043737............................. Peter Hand Foundation, 2 East
Madison St., Waukegan, IL 60085.
043738............................. McClellan Laboratories, Inc., 19600
Sixth Ave., Lakeview, CA 92353.
043743............................. V.P.O., Inc., 4444 South 76th St.,
Omaha, NE 68127.
043744............................. Farmers Feed & Supply Co., Ninth
St. at Northwestern Tracks,
Tipton, IA 52772.
043781............................. Cyanamid Agricultural de Puerto
Rico, Inc., P.O. Box 243, Manati,
PR 00701.
045087............................. Jorgensen Laboratories, Inc., 1450
North Van Buren Ave., Loveland, CO
80538.
045984............................. American Veterinary Products, Inc.,
749 South Lemay, Suite A3-231,
Fort Collins, CO 80524.
046573............................. A. L. Pharma, Inc., One Executive
Drive, P.O. Box 1399, Fort Lee, NJ
07024.
046987............................. Custom Feed Blenders Corp., 540
Hawkeye Ave., Fort Dodge, IA
50501.
047015............................. Rhone Merieux Canada, Inc., 345
Boul. Labbe Blvd., North
Victoriaville, QC, G6P 1B1 Canada.
047019............................. Carnation Co., 5045 Wilshire Blvd.,
Los Angeles, CA 90036.
047126............................. Micro Chemical, Inc., Amarillo, TX
79105.
047863............................. Arkansas Micro Specialties Inc.,
P.O. Box 308, Highway 71 North,
Lowell, AR 72745.
047864............................. Wade Jones Co., Inc., 409 North
Bloomington, Lowell, AR 72745.
049047............................. Michael Gordon, Inc., P.O. Box
1091, San Francisco, CA 94118.
049185............................. Walco International, Inc., 15 West
Putnam, Porterville, CA 93257.
049685............................. Southern Micro-Blenders, Inc., 3801
North Hawthorne St., Chattanooga,
TN 37406.
049968............................. Natchez Animal Supply Co., 201 John
R. Junkin Dr., Natchez, MS 39120.
050378............................. Western Chemical, Inc., 1269
Lattimore Rd., Ferndale, WA 98248.
050568............................. Nutra-Blend Corp., P.O. Box 485,
Neosho, MO 64850.
050604............................. Rhone Merieux, Inc., 7101 College
Blvd., Overland Park, KS 66210.
050639............................. I.M.S. Inc., 13619 Industrial Rd.,
Omaha, NE 68137.
050749............................. Hess & Clark, Inc., Seventh and
Orange Sts., Ashland, OH 44805.
050906............................. Zema Corp., P.O. Box 12803,
Research Triangle Park, Durham, NC
27709.
050972............................. Gossett Nutrition, Inc., 1676
Cascade Dr., Marion, OH 43302.
051212............................. Argent Laboratories, 8702 152d Ave.
NE., Redmond, WA 98052.
[[Page 93]]
051259............................. Med-Pharmex, Inc., Biomed
Laboratories, 325 East Arrow Hwy.,
Suite 502, San Dimas, CA 91773.
051267............................. Cooperative Research Farms, Box 69,
Charlotteville, NY 12036.
051359............................. Bioproducts, Inc., 320 Springside
Dr., Suite 300, Fairlawn, OH
44141.
052483............................. Orion Corp. FARMOS, Research and
Development, Pharmaceuticals, P.O.
Box 425, SF-20101 Turku, Finland.
053389............................. Pennfield Oil Co., 14040 Industrial
Rd., Omaha, NE 68137.
053501............................. Solvay Animal Health, Inc., 1201
Northland Dr., Mendota Heights, MN
55120.
053740............................. NutriBasics Co., North Highway 71,
P.O. Box 1014, WIllmar, MN 56201.
053923............................. Wildlife Laboratories, Inc., 1401
Duff Dr., Suite 600, Fort Collins,
CO 80524.
054273............................. Fermenta Animal Health Co., 10150
North Executive Hills Blvd.,
Kansas City, MO 64153.
055246............................. Pegasus Laboratories, Inc., 8809
Ely Rd., Pensacola, FL 32514.
055529............................. Norbrook Laboratories, Ltd.,
Station Works, Newry BT35 6JP,
Northern Ireland.
055882............................. Vetem, S.p.A., Viale E. Bezzi 24,
20146 Milano, Italy.
057319............................. Phoenix Pharmaceutical, Inc., 4621
Easton Rd., P.O. Box 6457 Farleigh
Station, St. Joseph, MO 64506-
0457.
057561............................. Agri Laboratories, Ltd., P.O. Box
3103, St. Joseph, MO 64503.
057926............................. Intervet, Inc., P.O. Box 318, 405
State St., Millsboro, DE 19966.
058034............................. John J. Ferrante, 11 Fairway Lane,
Trumbull, CT 06611.
058198............................. Ciba-Geigy Animal Health, Ciba-
Geigy Corp., P.O. Box 18300,
Greensboro, NC 27419-8300.
058639............................. United Vaccines, A Harlan Sprague
Dawley, Inc., Co., P.O. Box 4220,
Madison, WI 53711.
058670............................. RSR Laboratories, Inc., 501 Fifth
St., Bristol, TN 37620.
058690............................. TRINADA, Inc., One Executive Dr.,
P.O. Box 1399, Fort Lee, NJ 07024
058711............................. Macleod Pharmaceuticals, Inc., 2600
Canton Ct., Fort Collins, CO
80525.
059079............................. Delmarva Laboratories, Inc., 2200
Wadebridge Rd., P.O. Box 525,
Midlothian, VA 23113.
059130............................. Phoenix Scientific, Inc. 3915 South
48th St. Terrace, P.O. Box 6457,
St. Joseph, MO 64506-0457
059945............................. Protiva, A Division of Monsanto
Co., 800 North Lindbergh Blvd.,
St. Louis, MO 63167.
059521............................. Ausa International, Inc., Rt. 8,
P.O. Box 324-12, Tyler, TX 75703.
059620............................. Mid-Continent Agrimarketing, Inc.,
8833 Quivira Rd., Overland Park,
KS 66214.Blvd., St. Louis, MO
63167.
060307............................. Inhalon Pharmaceuticals, Inc., P.O.
Box 21170, Lehigh Valley, PA
18002.
060594............................. PM Resources, Inc., 13001 St.
Charles Rock Rd., Bridgeton, MO
63044.
060728............................. Planalquimica Industrial Ltda., Rua
das Magnolias nr. Jardim das
Bandeiras, CEP 13053-120,
Campinas, Sao Alto, Brazil.
060865............................. Anika Research, Inc., 160 New
Boston St., 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.
------------------------------------------------------------------------
[40 FR 13807, Mar. 27, 1975]
Editorial Note: For Federal Register citations affecting
Sec. 510.600, see the List of CFR Sections Affected in the Finding Aids
section of this volume.
PART 511--NEW ANIMAL DRUGS FOR INVESTIGATIONAL USE--Table of Contents
Authority: Secs. 201, 501, 502, 503, 512, 701 of the Federal Food,
Drug, and Cosmetic Act (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
[[Page 94]]
post office address of the expert or expert organization to whom the new
animal drug is shipped and the date, quantity, and batch or code mark of
each shipment and delivery for a period of 2 years after such shipment
and delivery. Upon the request of a properly authorized employee of the
Department at reasonable times, he shall make such records available for
inspection and copying.
(4) The exemption allowed in this paragraph shall not apply to any
new animal drug intended for in vitro use in the regular course of
diagnosing or treating disease, including antibacterial sensitivity
discs impregnated with any new animal drug or drugs, which discs are
intended for use in determining susceptibility of microorganisms to the
new animal drug or drugs.
(b) New animal drugs for clinical investigation in animals. A
shipment or other delivery of a new animal drug or an animal feed
containing a new animal drug intended for clinical investigational use
in animals shall be exempt from section 512(a) and (m) of the act if all
the following conditions are met:
(1) The label shall bear the statements:
Caution. Contains a new animal drug for use only in investigational
animals in clinical trials. Not for use in humans. Edible products of
investigational animals are not to be used for food unless authorization
has been granted by the U.S. Food and Drug Administration or by the U.S.
Department of Agriculture.
In the case of containers too small or otherwise unable to
accommodate a label with sufficient space to bear the caution statements
required by paragraph (a) or (b) of this section, the statements may be
included on the carton label and other labeling on or within the package
from which the new animal drug is to be dispensed.
(2) The person or firm distributing or causing the distribution of
the new animal drug or animal feed containing a new animal drug shall
use due diligence to assure that the new animal drug or animal feed
containing a new animal drug will actually be used for tests in animals
and is not used in humans.
(3) The person who introduced such shipment or who delivered the new
animal drug or animal feed containing a new animal drug for introduction
into interstate commerce shall maintain adequate records showing the
name and post office address of the investigator to whom the new animal
drug or animal feed containing a new animal drug is shipped and the
date, quantity, and batch or code mark of each shipment and delivery for
a period of 2 years after such shipment and delivery. 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
the Food and Drug Administration 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.
[[Page 95]]
(c) The maximum daily dose(s) to be administered to a given species,
the size of animal, maximum duration of administration, method(s) of
administration, and proposed withdrawal time, if any.
(vi) If a sponsor has transferred any obligations for the conduct of
any clinical study to a contract research organization, a statement
containing the name and address of the contract research organization,
identification of the clinical study, and a listing of the obligations
transferred. If all obligations governing the conduct of the study have
been transferred, a general statement of this transfer--in lieu of a
listing of the specific obligations transferred--may be submitted.
(5) Authorization for use of edible products derived from a treated
food-producing animal may be granted under the provisions of this
section and when the following specified conditions are met, except that
in the case of an animal administered any unlicensed experimental
veterinary biological product regulated under the viruses, serums,
toxins statute (21 U.S.C., chapter V, sec. 151 et seq.) the product
shall be exempt from the requirements of this section when U.S.
Department of Agriculture approval has been obtained as provided in 9
CFR 103.2. Conditional authorization may be granted in advance of
identification of the name(s) and address(es) of the clinical
investigator(s) as required by paragraph (b)(4)(iii) of this section.
Information required for authorization shall include, in addition to all
other requirements of this section, the following:
(i) Data to show that consumption of food derived from animals
treated at the maximum levels with the minimum withdrawal periods, if
any, specified in accordance with paragraph (b)(4)(v)(c) of this
section, will not be inconsistent with the public health; or
(ii) Data to show that food derived from animals treated at the
maximum levels and with the minimum withdrawal periods, if any,
specified in accordance with paragraph (b)(4)(v)(c) of this section,
does not contain drug residues or metabolites.
(iii) The name and location of the packing plant where the animals
will be processed, except that this requirement may be waived, on
request, by the terms of the authorization.
Authorizations granted under this paragraph do not exempt
investigational animals and their products from compliance with other
applicable inspection requirements. Any person who contests a refusal to
grant such authorization shall have an opportunity for a regulatory
hearing before the Food and Drug Administration pursuant to part 16 of
this chapter.
(6) On written request of the Food and Drug Administration, 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 the Food and Drug Administration and to all
investigators any findings
[[Page 96]]
associated with use of the new animal drug that may suggest significant
hazards pertinent to the safety of the new animal drug.
(iii) Shall not unduly prolong distribution of the new animal drug
for investigational use.
(iv) Shall not, nor shall any person acting for or on behalf of the
sponsor, represent that the new animal drug is safe or effective for the
purposes for which it is under investigation. This requirement is not
intended to restrict the full exchange of scientific information.
(v) Shall not commercially distribute nor test-market the new animal
drug until a new animal drug application is approved pursuant to section
512(c) of the act.
(9) If the shipment or other delivery of the new animal drug is
imported or offered for importation into the United States for clinical
investigational use in animals, it shall also meet the following
conditions:
(i) The importer of all such shipments or deliveries is an agent of
the foreign exporter residing in the United States or the ultimate
consignee, which person has, prior to such shipments and deliveries,
informed the Food and Drug Administration 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. 25.24 of this chapter or an environmental
assessment under Sec. 25.31 of this chapter.
(c) Withdrawal of eligibility to receive investigational-use new
animal drugs. (1) Whenever the Food and Drug Administration has
information indicating that an investigator has repeatedly or
deliberately failed to comply with the conditions of these exempting
regulations or has submitted false information either to the sponsor of
the investigation or in any required report, the Center for Veterinary
Medicine will furnish the investigator written notice of the matter
complained of in general terms and offer him an opportunity to explain
the matter in an informal conference and/or in writing. If an
explanation is offered but not accepted by the Center for Veterinary
Medicine, the investigator shall have an opportunity for a regulatory
hearing before the Food and Drug Administration pursuant to part 16 of
this chapter on the question of whether the investigator is entitled to
receive investigational new animal drugs.
(2) If, after evaluating all available information, including any
explanation presented by the investigator, the Commissioner determines
that the investigator has repeatedly or deliberately failed to comply
with the conditions of the exempting regulations in this section or has
repeatedly or deliberately submitted false information to the sponsor of
an investigation, the Commissioner will notify the investigator and the
sponsor of any investigation in which he has been named as a participant
that the investigator is not entitled to receive investigational use new
animal drugs with a statement of the basis for such determination.
(3) Each ``Notice of Claimed Investigational Exemption for a New
Animal Drug'' and each approved new animal drug application containing
data reported by an investigator who has been determined to be
ineligible to receive investigational-use new animal drugs will be
examined to determine whether he has submitted unreliable data that are
essential to the continuation of the investigation or essential to the
approval of any new animal drug application.
(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, he shall first notify the
sponsor, who shall have an opportunity for a regulatory hearing before
the Food and Drug Administration pursuant to part 16 of this chapter on
[[Page 97]]
whether the exemption should be terminated. If a danger to the public
health exists, however, he shall terminate the exemption forthwith and
notify the sponsor of the termination. In such event the sponsor shall
have an opportunity for a regulatory hearing before the Food and Drug
Administration pursuant to part 16 (see 42 FR 15675, March 22, 1977) of
this chapter on the question of whether the exemption should be
reinstated.
(5) If the Commissioner determines, after the unreliable data
submitted by the investigator are eliminated from consideration, that
the data remaining are such that a new animal drug application would not
have been approved, he will proceed to withdraw approval of the
application in accordance with section 512(e) of the act.
(6) An investigator who has been determined to be ineligible may be
reinstated as eligible to receive investigational-use new animal drugs
when the Commissioner determines that he has presented adequate
assurance that he will employ such new animal drugs solely in compliance
with the exempting regulations in this section for investigational-use
new animal drugs.
(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 the Food and Drug
Administration 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 the Food and Drug Administration.
(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.
[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]
PART 514--NEW ANIMAL DRUG APPLICATIONS--Table of Contents
Subpart A--General Provisions
Sec.
514.1 Applications.
514.2 Applications for animal feeds bearing or containing new animal
drugs.
514.6 Amended applications.
[[Page 98]]
514.7 Withdrawal of applications without prejudice.
514.8 Supplemental new animal drug applications.
514.9 Supplemental applications for animal feeds bearing or containing
new animal drugs.
514.10 Confidentiality of data and information in an investigational
new animal drug notice and a new animal drug application file
for an antibiotic drug.
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
514.100 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.
514.112 Return of applications for animal feeds bearing or containing
new animal drugs.
514.115 Withdrawal of approval of applications.
514.116 Notice of withdrawal of approval of application.
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 Procedure for hearings.
Subparts D--E [Reserved]
Subpart F--Judicial Review
514.235 Judicial review.
Authority: Secs. 501, 502, 512, 701, 721, 801 of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 351, 352, 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 described in paragraph (b) of this section. If
any part of the application is in a foreign language, an accurate and
complete English translation shall be appended to such part.
Translations of literature printed in a foreign language shall be
accompanied by copies of the original publication. The application must
be signed by the applicant or by an authorized attorney, agent, or
official. If the applicant or such authorized representative does not
reside or have a place of business within the United States, the
application must also furnish the name and post office address of, and
must be countersigned by, an authorized attorney, agent, or official
residing or maintaining a place of business within the United States.
Pertinent information may be incorporated in, and will be considered as
part of, an application on the basis of specific reference to such
information, including information submitted under the provisions of
Sec. 511.1 of this chapter, in the files of the Food and Drug
Administration; however, the reference must be specific in identifying
the information. Any reference to information furnished by a person
other than the applicant may not be considered unless its use is
authorized in a written statement signed by the person who submitted it.
(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:
(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:
[[Page 99]]
(a) Chemical structural formula or description for any new animal
drug substance.
(b) Relationship to other chemically or pharmacologically related
drugs.
(c) Description of dosage form and quantitative composition.
(ii) Scientific rationale and purpose the new animal drug is to
serve:
(a) Clinical purpose.
(b) Highlights of laboratory studies: The reasons why certain types
of studies were done or omitted as related to the proposed conditions of
use and to information already known about this class of compounds.
Emphasize any unusual or particularly significant pharmacological
effects or toxicological findings.
(c) Highlights of clinical studies: The rationale of the clinical
study plan showing why types of studies were done, amended, or omitted
as related to laboratory studies and prior clinical experience.
(d) Conclusions: A short statement of conclusions combining the
major points of effectiveness and safety as they relate to the use of
the new animal drug.
(3) Labeling. Three copies of each piece of all labeling to be used
for the article (total of 9).
(i) All labeling should be identified to show its position on, or
the manner in which it is to accompany the market package.
(ii) Labeling for nonprescription new animal drugs should include
adequate directions for use by the layman under all conditions of use
for which the new animal drug is intended, recommended, or suggested in
any of the labeling or advertising sponsored by the applicant.
(iii) Labeling for prescription veterinary drugs should bear
adequate information for use under which veterinarians can use the new
animal drug safely and for the purposes for which it is intended,
including those purposes for which it is to be advertised or
represented, in accord with Sec. 201.105 of this chapter.
(iv) All labeling for prescription or nonprescription new animal
drugs shall be submitted with any necessary use restrictions prominently
and conspicuously displayed.
(v) Labeling for new animal drugs intended for use in the
manufacture of medicated feeds shall include:
(a) Specimens of labeling to be used for such new animal drug with
adequate directions for the manufacture and use of finished feeds for
all conditions for which the new animal drug is intended, recommended,
or suggested in any of the labeling, including advertising, sponsored by
the applicant. Ingredient labeling may utilize collective names as
provided in Sec. 501.110 of this chapter.
(b) Representative labeling proposed to be used for Type B and Type
C medicated feeds containing the new animal drug.
(vi) Draft labeling may be submitted for preliminary consideration
of an application. Final printed labeling will ordinarily be required
prior to approval of an application. Proposed advertising for veterinary
prescription drugs may be submitted for comment or approval.
(4) Components and composition. A complete list of all articles used
for production of the new animal drug including a full list of the
composition of each article:
(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
[[Page 100]]
manufacture of the finished dosage form. All components should be
included in the batch formula regardless of whether they appear in the
finished product. Any calculated excess of an ingredient over the label
declaration should be designated as such and percent excess shown.
Reasonable variation may be specified.
(iii) If it is a new animal drug produced by fermentation:
(a) Source and type of microorganism used to produce the new animal
drug.
(b) Composition of media used to produce the new animal drug.
(c) Type of precursor used, if any, to guide or enhance production
of the antibiotic during fermentation.
(d) Name and composition of preservative, if any, used in the broth.
(e) A complete description of the extraction and purification
processes including the names and compositions of the solvents,
precipitants, ion exchange resins, emulsifiers, and all other agents
used.
(f) If the new animal drug is produced by a catalytic hydrogenation
process (such as tetracycline from chlortetracycline), a complete
description of each chemical reaction with graphic formulas used to
produce the new animal drug, including the names of the catalyst used,
how it is removed, and how the new animal drug is extracted and
purified.
(5) Manufacturing methods, facilities, and controls. A full
description of the methods used in, and the facilities and controls used
for, the manufacture, processing, and packing of the new animal drug.
This description should include full information with respect to any new
animal drug in sufficient detail to permit evaluation of the adequacy of
the described methods of manufacture, processing, and packing, and the
described facilities and controls to determine and preserve the
identity, strength, quality, and purity of the new animal drug, and the
following:
(i) If the applicant does not himself perform all the manufacturing,
processing, packaging, labeling, and control operations for any new
animal drug, he shall: Identify each person who will perform any part of
such operations and designate the part; and provide a signed statement
from each such person fully describing, directly or by reference, the
methods, facilities, and controls he will use in his part of the
operation. The statement shall include a commitment that no changes will
be made without prior approval by the Food and Drug Administration,
unless permitted under Sec. 514.8.
(ii) A description of the qualifications, including educational
background and experience, of the technical and professional personnel
who are responsible for assuring that the new animal drug has the
identity, strength, quality, and purity it purports or is represented to
possess, and a statement of their responsibilities.
(iii) A description of the physical facilities including building
and equipment used in manufacturing, processing, packaging, labeling,
storage, and control operations.
(iv) The methods used in the synthesis, extraction, isolation, or
purification of any new animal drug. When the specifications and
controls applied to such new animal drugs are inadequate in themselves
to determine its identity, strength, quality, and purity, 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
[[Page 101]]
batch records and the manner in which these records are used.
(b) The number of individuals checking weight or volume of each
individual ingredient entering into each batch of the new animal drug.
(c) A statement as to whether or not the total weight or volume of
each batch is determined at any stage of the manufacturing process
subsequent to making up a batch according to the formula card and, if
so, at what stage and by whom it is done.
(d) The precautions used in checking the actual package yield
produced from a batch of the new animal drug with the theoretical yield.
This should include a description of the accounting for such items as
discards, breakage, etc., and the criteria used in accepting or
rejecting batches of drugs in the event of an unexplained discrepancy.
(e) The precautions used to assure that each lot of the new animal
drug is packaged with the proper label and labeling, including
provisions for labeling storage and inventory control.
(f) Any special precautions used in the operations.
(vii) The analytical controls used during the various stages of the
manufacturing, processing, packaging, and labeling of the new animal
drug, including a detailed description of the collection of samples and
the analytical procedures to which they are subjected. The analytical
procedures should be capable of determining the active components within
a reasonable degree of accuracy and of assuring the identity of such
components.
(a) A description of practicable methods of analysis of adequate
sensitivity to determine the amount of the new animal drug in the final
dosage form should be included. The dosage form may be a finished
pharmaceutical product, a Type A medicated article, a Type B or a Type C
medicated feed, or a product for use in animal drinking water. Where two
or more active ingredients are included, methods should be quantitative
and specific for each active ingredient.
(b) If the article is one that is represented to be sterile, the
same information with regard to the manufacturing, processing,
packaging, and the collection of samples of the drug should be given for
sterility controls. Include the standards used for acceptance of each
lot of the finished drug.
(viii) An explanation of the exact significance of any batch control
numbers used in the manufacturing, processing, packaging, and labeling
of the new animal drug, including such control numbers that may appear
on the label of the finished article. State whether these numbers enable
determination of the complete manufacturing history of the product.
Describe any methods used to permit determination of the distribution of
any batch if its recall is required.
(ix) Adequate information with respect to the characteristics of and
the test methods employed for the container, closure, or other component
parts of the drug package to assure their suitability for the intended
use.
(x) A complete description of, and data derived from, studies of the
stability of the new animal drug in the final dosage form, including
information showing the suitability of the analytical methods used. A
description of 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
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control of the product. An application may be refused unless it includes
adequate information showing that the methods used in, and the
facilities and controls used for, the manufacturing, processing, and
packaging of the new animal drug are adequate to preserve its identity,
strength, quality, and purity in conformity with good manufacturing
practice and identifies each establishment, showing the location of the
plant conducting these operations.
(6) Samples. Samples of the new animal drug and articles used as
components and information concerning them may be requested by the
Center for Veterinary Medicine as follows:
(i) Each sample shall consist of four identical, separately packaged
subdivisions, each containing at least three times the amount required
to perform the laboratory test procedures described in the application
to determine compliance with its control specifications for identity and
assays. Each of the samples submitted shall be appropriately packaged
and labeled to preserve its characteristics, to identify the material
and the quantity in each subdivision of the sample, and to identify each
subdivision with the name of the applicant and the new animal drug
application to which it relates. Included are:
(a) A sample or samples of any reference standard and blank used in
the procedures described in the application for assaying each new animal
drug and other assayed components of the finished new animal drug.
(b) A representative sample or samples of each strength of the
finished dosage form proposed in the application and employed in the
clinical investigations and a representative sample or samples of each
new animal drug from the batch(es) employed in the production of such
dosage form.
(c) A representative sample or samples of finished market packages
of each strength of the dosage form of the new animal drug prepared for
initial marketing and, if any such sample is not from a representative
commercial-scale production batch, such a sample from a representative
commercial-scale production batch, and a representative sample or
samples of each new animal drug from the batch(es) employed in the
production of such dosage form, provided that in the case of new animal
drugs marketed in large packages the sample should contain only three
times a sufficient quantity of the new animal drug to allow for
performing the control tests for drug identity and assays.
(ii) The following information shall be included for the samples
when requested:
(a) For each sample submitted, full information regarding its
identity and the origin of any new animal drug contained therein
(including a statement whether it was produced on a laboratory, pilot-
plant, or full-production scale) and detailed results of all laboratory
tests made to determine the identity, strength, quality, and purity of
the batch represented by the sample, including assays.
(b) For any reference standard submitted, a complete description of
its preparation and the results of all laboratory tests on it. If the
test methods used differed from those described in the application, full
details of the 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
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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, consisting of adequate and well-controlled investigations,
including field investigation, by experts qualified by scientific
training and experience to evaluate the effectiveness of the new animal
drug involved, on the basis of which it could fairly and reasonably be
concluded by such experts 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 proposed labeling.
(iii) An application may be refused unless it contains detailed
reports of the investigations, including studies made on laboratory
animals, in which the purpose, methods, and results obtained are clearly
set forth of acute, subacute, and chronic toxicity, and unless it
contains appropriate clinical laboratory results related to safety and
efficacy. Such information should include identification of the person
who conducted each investigation, a statement of where the
investigations were conducted, and where the raw data are available in
the application.
(iv) All information pertinent to an evaluation of the safety and
effectiveness of the new animal drug received or otherwise obtained by
the applicant from any source, including information derived from other
investigations or commercial marketing (for example, outside the United
States), or reports in the scientific literature, both favorable and
unfavorable, involving the new animal drug that is the subject of the
application and related new animal drugs shall be submitted. An adequate
summary may be acceptable in lieu of 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 previously
investigated or marketed new animal drugs, an adequate summary of
preexisting information from preclinical and clinical investigation and
experience with its components, including all reports received or
otherwise obtained by the applicant suggesting side effects,
contraindications, and ineffectiveness in use of such components, shall
be submitted. Such summary should include an adequate bibliography of
publications
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about the components and may incorporate by reference information
concerning such components previously submitted to the Food and Drug
Administration by the applicant; with written authorization, information
may also be incorporated from the material that another applicant has on
file with the Food and Drug Administration. Each ingredient designated
as active in any new animal drug combination must make a contribution to
the effect in the manner claimed or suggested in the labeling, and, if
in the absence of express labeling claims of advantages for the
combination such a product purports to be better than either component
alone, it must be established that the new animal drug has that
purported effectiveness.
(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) [Reserved]
(10) Supplemental applications. If it is a supplemental application,
full information shall be submitted on each proposed change concerning
any statement made in the approved application.
(11) Applicant's commitment. It is understood that the labeling and
advertising for the new animal drug will prescribe, recommend, or
suggest its use only under the conditions stated in the labeling which
is part of this application and if the article is a prescription new
animal drug, it is understood that any labeling which furnishes or
purports to furnish information for use or which prescribes, recommends,
or suggests a dosage for use of the new animal drug will also contain,
in the same language and emphasis, information for its use including
indications, effects, dosages, routes, methods, and frequency and
duration of administration, any relevant hazards, contraindications,
side effects, and precautions contained in the labeling which is part of
this application. It is understood that all representations in this
application apply to the drug produced until changes are made in
conformity with Sec. 514.8.
(12) Additional commitments. (i) New animal drugs as defined in
Sec. 510.3 of this chapter, intended for use in the manufacture of
animal feeds in any State will be shipped only to persons who may
receive such drugs in accordance with Sec. 510.7 of this chapter.
(ii) The methods, facilities, and controls described under item 5 of
this application conform to the current good manufacturing practice
regulations in subchapter C of this chapter.
(iii) With respect to each nonclinical laboratory study contained in
the application, either a statement that the study was conducted in
compliance with the good laboratory practice regulations set forth in
part 58 of this chapter, or, if the study was not conducted in
compliance with such regulations, a
[[Page 105]]
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. 25.24 of this
chapter or an environmental assessment under Sec. 25.31 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.
(d) Minor use applications. Applications for minor use new animal
drugs:
(1) Definitions. For the purpose of this section:
(i) Minor use means the use of: (a) New animal drugs in minor animal
species, or (b) new animal drugs in any animal species for the control
of a disease that (1) occurs infrequently or (2) occurs in limited
geographic areas.
(ii) Minor species means animals other than cattle, horses, swine,
chickens, turkeys, dogs, and cats. Sheep are a minor species with
respect to effectiveness and animal safety data collection requirements;
sheep are a major species with respect to human safety data collection
requirements arising from the possible presence of drug residues in
food.
(2) Animal safety, effectiveness, human food safety, and
environmental considerations. Guidelines for the preparation and
submission of data to satisfy the requirements of section 512 of the act
regarding animal safety, effectiveness, human food safety, and
environmental considerations for new animal drugs intended for a minor
use (as defined in paragraph (d)(1)(i) of this section) are available
from the Industry Information Staff (HFV-11), Center for Veterinary
Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville, MD
20855.
(i) Animal safety and effectiveness. Where the guidelines do not
specifically provide for a particular minor use, the Center for
Veterinary Medicine, upon request, will advise interested persons on the
effectiveness and animal safety data regarding the minor use that will
be needed to satisfy the requirements of section 512 of the act. Where
scientifically appropriate, the Center for Veterinary Medicine will
allow the use of animal models and the extrapolation of data from a
major species to a minor species to satisfy the requirements of the act.
(ii) Human food safety and environmental considerations. These
guidelines do not specifically provide for a particular minor use.
Therefore, the Center for Veterinary Medicine will, upon
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request, advise interested persons of the data that will be needed.
Where scientifically appropriate, the Center for Veterinary Medicine
will allow the extrapolation of data from a major species to a minor
species to satisfy the requirements of the act.
(Approved by the Office of Management and Budget under control number
0910-0032)
[40 FR 13825, Mar. 27, 1975]
Editorial Note: For Federal Register citations affecting Sec. 514.1,
see the List of CFR Sections Affected in the Finding Aids section of
this volume.
Sec. 514.2 Applications for animal feeds bearing or containing new animal drugs.
(a) Applications (Form FDA 1900) to be filed under section 512(m) of
the act shall be completed, signed, and submitted in triplicate in the
form described in paragraphs (b) and (c) of this section.
(b) Each application for a Type B or Type C medicated feed, as
defined in Sec. 558.3 of this chapter, shall include the following
information:
(1) The name and address of the applicant.
(2) The registration number assigned pursuant to section 510 of the
act and last date of registration of each mill.
(3) Whether the submission is an original or supplemental
application.
(4) Identification of the Type A medicated article, as defined in
Sec. 558.3 of this chapter, used by generic name, potency, and
manufacturer.
(5) The species of animal(s) for which the feed is intended.
(6) The form of feed to be produced, i.e., mash, meal crumbles,
pellets, liquid, or other specified form.
(7) Whether the feed is a Type B or Type C medicated feed.
(8) Whether the feed is for sale or for own use (not for sale).
(9) Level of the drug(s) in the finished feed, and the amount of
Type A medicated article per ton contained therein.
(10) Identification of the regulation(s) in subchapter E of this
chapter on which approval relies.
(11) Labeling representative of each intended use as stated in the
claim. Each generic label shall include the claim, drug level, mixing
directions, feeding directions, caution and/or warning statements, and
any other special directions required by the published regulation. This
shall consist of bag labels, invoice copy, bulk labels, and placards
when applicable.
(12) A commitment to establish and maintain a program of sampling
and analysis consisting of an assay of the first batch manufactured,
followed thereafter by two samples at periodic intervals during the
calendar year. If a medicated feed contains a combination of drugs, only
one of the drugs need be subject to analysis each time, provided the one
tested is different from the one(s) previously tested. Reports of assays
shall be kept on the premises for not less than 1 year after the date of
manufacture of the medicated feed.
(13) A statement of the minimum and maximum assay value permitted
from the labeled amount of the drug.
(14) Identification of the agent authorized to act on behalf of the
applicant.
(15) The applicant's name, responsible individual's title and
original signature, and date.
(c) Upon approval, one copy of the application will be signed by an
authorized employee of the Food and Drug Administration designated by
the Commissioner, and it will be returned to the applicant.
(d) Applications (Form FDA 1900) may be obtained from the Public
Health Service, Consolidated Forms and Publications Distribution Center,
Washington Commerce Center, 3222 Hubbard Rd., Landover, MD 20785.
(Approved by the Office of Management and Budget under control number
0910-0011)
[51 FR 7391, Mar. 3, 1986, as amended at 55 FR 14831, Apr. 19, 1990]
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
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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 Supplemental new animal drug applications.
(a)(1) After a new animal drug application is approved, a
supplemental new animal drug application may propose changes. A
supplemental application may omit statements made in the approved
application concerning which no change is proposed. Each supplemental
application shall include up-to-date reports of any of the kinds of
information required by Sec. 510.300(a) of this chapter that has not
previously been submitted. A supplemental application shall be
accompanied by either a claim for categorical exclusion under Sec. 25.24
of this chapter or an environmental assessment under Sec. 25.31 of this
chapter.
(2) A supplemental new animal drug application shall be submitted
for any change beyond the variations provided for in the application,
including changes in the scale of production such as from pilot-plant to
production batch, that may alter the conditions of use, the labeling,
safety, effectiveness, identity, strength, quality, or purity of the new
animal drug, or the adequacy of the manufacturing methods, facilities,
or controls to preserve them.
(3) If it is a prescription drug, any mailing or promotional piece
used after the drug is placed on the market is labeling requiring a
supplemental application, unless:
(i) 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
(ii) Any other parts of the labeling are consistent with and not
contrary to such approved or permitted labeling.
(4) The supplemental application shall be submitted as follows. A
communication proposing a change in a new animal drug application should
provide for any one of the following kinds of changes:
(i) Revision in labeling, such as updating information pertaining to
effects, dosages, and side effects and contraindications, which includes
information headed ``side effects,'' ``warnings,'' ``precautions,'' and
``contraindications.''
(ii) Addition of claim.
(iii) Revision in manufacturing or control procedures; for example,
changes in components, composition, method of manufacture, analytical
control procedures, package or tablet size, etc.
(iv) Change in manufacturing facilities.
(v) Provision for outside firm to participate in the preparation,
distribution, or packaging of a new animal drug (new distributor,
packer, supplier, manufacturer, etc.); one firm per submission.
Any number of changes may be submitted at any one time; but if they fall
into different categories as listed in paragraphs (a)(4) (i) through (v)
of this section, the proposed changes should be covered by separate
communications. Where, however, a change necessitates an overlap in
categories, it should be submitted in a single communication. For
example, a change in tablet potency would require other changes such as
in components, composition, and labeling and should be submitted in a
single communication.
(5) The following kinds of changes may be placed into effect without
the approval of a supplemental application, if such change is fully
described in the next periodic report required under Sec. 510.300(b)(4)
of this chapter or, when such a report is not required, in a written
communication to the Food and Drug Administration within 60 days of
[[Page 108]]
the effective date of the change (this does not apply to a change
proposed because of any mixup or any bacteriological or 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 its
specifications):
(i) A different container size for solid oral dosage forms where
container and closure are of the same materials as those provided for in
the approved application.
(ii) Change in personnel not involving new facilities.
(iii) Change in equipment that does not alter the method of
manufacture of a new animal drug.
(iv) Change from one commercial batch size to another without any
change in manufacturing procedure.
(v) Change to more stringent specification without altering the
method described in the approved application.
(vi) Inclusion of additional specifications and methods without
deletion of those described in the approved application.
(vii) Alteration of specifications or methods for inactive
ingredients to bring them into compliance with new or revised
specifications or methods in an official compendium.
(viii) Initiation of a product identification coding system.
(ix) Addition to labeling of a reasonable expiration date where none
was previously used, with related conditions of drug storage when
appropriate, except when evidence shows that a significant deterioration
of the drug under marketing conditions has occurred which necessitates
the immediate submission of a report under Sec. 510.300(b)(1) of this
chapter. The report or written communication describing such change in
labeling should include stability data justifying the expiration date
and recommended conditions of storage.
(x) Change from paper labels to direct printing on glass or other
kinds of immediate containers without a change in text.
(6) Approval of a supplemental new animal drug application will not
be required to provide for an additional distributor to distribute a
drug which is the subject of an approved new animal drug application if
the conditions described below are met prior to putting such a change
into effect. An order may issue refusing approval if any condition is
not met or if any of the reasons for refusing or withdrawing approval,
as stated in section 512(d) and (e) of the act or Sec. 514.110 applies.
For the purposes of maintaining records and making reports under the
requirements of Sec. 510.300 of this chapter, a distributor provided for
under this section shall be considered an applicant within the meaning
of Sec. 510.300(b) of this chapter. Said conditions are:
(i) A supplemental application is furnished to the Food and Drug
Administration to provide for a designated distributor.
(ii) There are no changes from the conditions of the approved
application except for a different and suitable proprietary name of the
new animal drug (if one is used) and the name and address of the
distributor as used on the label and labeling. The name of the
distributor shall be accompanied by an appropriate qualifying phrase
such as ``manufactured for'' or ``distributed by.''
(iii) A distributor's statement is furnished to the Food and Drug
Administration identifying the category of his operations (for example,
wholesaler, retailer) and stating: That he will distribute the new
animal drug only under the labeling provided for in the new animal drug
application; that any other labeling or advertising for the drug will
prescribe, recommend, or suggest its use only under the conditions
stated in the labeling provided for in the application; and, if the drug
is a prescription article, that he is regularly and lawfully engaged in
the distribution or dispensing of prescription drugs.
(iv) Nine copies of the printed labels and other labeling to be used
by the distributor are submitted, identified with the new animal drug
application number.
(b) When necessary for the safety or effectiveness of the drug, a
supplemental new animal drug application shall specify a period of time
within which the proposed change will be made.
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(c) If a material change is made in the components' composition,
manufacturing methods, facilities, or controls, or in the labeling or
advertising, from the representations in an approved application for a
new animal drug (except changes conforming to the conditions set forth
in paragraph (a)(5) and (6) and/or paragraphs (d), (e), (f), and (g) of
this section), and the drug is marketed before a supplement is approved
for such change, approval of the application may be suspended or
withdrawn as provided in section 512(e) of the act.
(d) Changes of the following kinds proposed in supplemental new
animal drug applications should be placed into effect at the earliest
possible time:
(1) The addition to package labeling, promotional labeling, and
prescription drug advertising of additional warning, contraindication,
side effect, and precaution information.
(2) The deletion from package labeling, promotional labeling, and
drug advertising of false, misleading, or unsupported indications for
use or claims for effectiveness.
(3) Changes in the methods, facilities, or controls used for the
manufacture, processing, packing, or holding of the new animal drug
(other than utilization of establishments 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.
(e) The Food and Drug Administration will take no action against a
new animal drug or applicant solely because changes of the kinds
described in paragraph (d) of this section are placed into effect by the
applicant prior to his receipt of a written notice of approval of the
supplemental new animal drug application if all the following conditions
are met:
(1) The supplemental new animal drug application providing a full
explanation of the basis for the changes has been submitted, plainly
marked on the mailing cover and on the supplement, ``Special new animal
drug application Supplement--changes being effected.''
(2) The applicant specifically informs the Food and Drug
Administration of the date on which such changes are being effected and
submits to the Administration nine printed copies of any revised
labeling to be placed in use, identified with the new animal drug
application number.
(3) All promotional labeling and all drug advertising are promptly
revised consistent with the changes made in the labeling on or within
the new animal drug package.
(f) When a supplemental new animal drug application proposes changes
only of the kinds described in paragraph (d) of this section, and the
applicant informs the Food and Drug Administration that the changes are
being put into effect, such notification will be regarded as an
agreement by the applicant to an extension of the time for formal action
on the application.
(g) In addition to changes as permitted by paragraphs (d) and (e) of
this section, an applicant may place into effect changes proposed in a
supplement to a new animal drug application that became effective prior
to October 10, 1962, upon written notification from the Food and Drug
Administration that such action is permitted, without approval of the
supplemental application, pending the completion of the review of the
effectiveness of such drug by the National Academy of Sciences-National
Research Council and a determination as to whether there are grounds for
refusing approval under section 512(d) of the act or for invoking
section 512(e) of the act. The Food and Drug Administration will take no
action against a new animal drug or an applicant solely because changes
that have been permitted in a written communication are placed into
effect by the applicant prior to his receipt of a written notice of
approval of the supplemental new animal drug application.
(h) Except as provided in paragraphs (e) and (g) of this section, no
provision of this section shall limit the authority of the Secretary or
of the Commissioner to suspend or withdraw approval of a new animal drug
application in accord with the provisions of section 512(e) of the act
or to initiate any other regulatory proceedings with respect to a drug
or applicant under provisions of the act.
[[Page 110]]
(i) Changes from the conditions of an approved new animal drug
application in accord with the provisions of paragraphs (d), (e), and
(g) of this section are permitted on the basis of a temporary deferral
of final action on the supplemental application under the provisions of
section 512 (c), (d), or (e) of the act.
(j) When an applicant receives written notification from the Food
and Drug Administration, under the provisions of paragraph (g) of this
section, that he may place into effect changes proposed in a
supplemental application without approval of the supplemental
application, he may within 30 days submit a written request that the
Food and Drug Administration process the supplemental application. In
such case, the change shall not be put into effect until approved.
Within 180 days of the receipt of such written request, the Food and
Drug Administration will approve the supplemental application or furnish
notice of an opportunity for a hearing under the provisions of section
512 (d) or (e), or both, of the act on a proposal to refuse approval of
the supplemental application or to withdraw approval of the application
and supplements thereto.
(k) A supplement to an application that became effective prior to
October 10, 1962, may include a written statement to the effect that a
temporary deferral of final action under the provisions of paragraph
(d), (e), or (g) of this section is unacceptable to the applicant and
that the applicant requests action as provided in section 512(c) of the
act. Final action on such supplemental applications will be expedited in
accord with applicable provisions of section 512 of the act and
regulations in this subchapter E. In such cases, if the applicant places
into effect any of the proposed changes prior to his receipt of a
written notice of approval of the supplemental new animal drug
application, such action may be regarded by the Food and Drug
Administration as a basis for invoking the provisions of section 512(e)
(1)(D) of the act; that is, the applicant may be furnished notice of an
opportunity for a hearing on a proposal to withdraw approval of the
application on the ground that the application contains an untrue
statement of a material fact related to the changes from the conditions
approved in the application.
(l) A supplemental application that contains nonclinical laboratory
studies 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.
[40 FR 13825, Mar. 27, 1975, as amended at 50 FR 7517, Feb. 22, 1985; 50
FR 16668, Apr. 26, 1985]
Sec. 514.9 Supplemental applications for animal feeds bearing or containing new animal drugs.
(a) After an application for an animal feed bearing or containing a
new animal drug has been approved, a supplemental application may
propose changes.
(b) A supplemental application shall be submitted for any change
which deviates from the conditions under which the application was
originally approved.
(c) Each supplemental application shall be accompanied by a fully
completed Form FDA 1900 in triplicate including an explanation of the
changes proposed.
[40 FR 13825, Nov. 27, 1975, as amended at 42 FR 15675, Mar. 22, 1977;
50 FR 16668, Apr. 26, 1985; 51 FR 7391, Mar. 3, 1986]
Sec. 514.10 Confidentiality of data and information in an investigational new animal drug notice and a new animal drug application file for an antibiotic
drug.
(a) The rules established in Secs. 514.11 and 514.12 of this chapter
with regard to the confidentiality of an investigational new animal drug
notice and a new animal drug application file shall apply to such
notices and files for antibiotic drugs for new animal drug use.
(b) All records showing the Food and Drug Administration's testing
of and action on a particular lot of a certifiable antibiotic drug for
veterinary use are immediately available for public disclosure.
[[Page 111]]
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
Secs. 510.300 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 an approval has been published in the
Federal Register, unless it has previously been publicly 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 an approval has been published in the Federal
Register, no data or information contained in the file is available for
public disclosure before such approval is published, 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, 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 an approval has been published in the Federal Register,
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 on or 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 approval is
published in the Federal Register.
(a) The Center for Veterinary Medicine may at an appropriate time
prior to approval of the NADA require the applicant to prepare a summary
of such data and information, which will be reviewed and, where
appropriate, revised by the Center.
(b) The Center for Veterinary Medicine may prepare its own summary
of such data and information.
(3) A protocol for a test or study, unless it is shown to fall
within the exemption established for trade secrets and confidential
commercial information in Sec. 20.61 of this chapter.
(4) Adverse reaction reports, product experience reports, consumer
complaints, and other similar data and information, after deletion of:
(i) Names and any information that would identify the person using
the product.
(ii) Names and any information that would identify any third party
involved with the report, such as a physician, hospital, or other
institution.
(5) A list of all active ingredients and any inactive ingredients
previously disclosed to the public as defined in Sec. 20.81 of this
chapter.
(6) An assay method or other analytical method, unless it serves no
regulatory or compliance purpose and is shown to fall within the
exemption established in Sec. 20.61 of this chapter.
[[Page 112]]
(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]
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. 510.300 or Sec. 510.301 of this chapter of any information obtained
from:
(1) Investigations as to the safety, effectiveness, identity,
strength, quality, or purity of the drug, made by the applicant on the
drug, or
(2) Investigations or experience with the product that is the
subject of the
[[Page 113]]
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]
Subpart B--Administrative Actions on Applications
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
[[Page 114]]
Administration an adequate opportunity to inspect the facilities,
controls, and records pertinent to the application.
(f) On the basis of preliminary consideration of an application or
supplemental application containing typewritten or other draft labeling
in lieu of final printed labeling, an applicant may be informed that
such application is approvable when satisfactory final printed labeling
identical in content to such draft copy is submitted.
(g) When an application has been found incomplete on the basis of a
need for the kind of information described in Sec. 514.6, such
application shall be considered withdrawn without prejudice to future
filing on the date of issuance of the letter citing the inadequacies
contained in the application, unless within 30 days the sponsor chooses
to avail himself of the opportunity for hearing as prescribed by
Sec. 514.111.
Sec. 514.105 Approval of applications.
(a) Within 180 days after an application has been filed pursuant to
Sec. 514.1, if the Commissioner determines that none of the grounds for
denying approval specified in section 512(d) of the act applies:
(1) He 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.
(2) He shall notify the applicant by sending him a copy of the
proposed publication as described in paragraph (a)(1) of this section.
(b) Within 90 days after an application filed pursuant to Sec. 514.2
if the Commissioner determines that none of the grounds for denying
approval specified in section 512(m)(3) of the act applies, he shall
notify the applicant that it is approvable by signing and mailing to the
sponsor the original copy of the Form FDA 1900.
[40 FR 13825, Mar. 27, 1975, as amended at 51 FR 7392, Mar. 3, 1986]
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 drug not
exempted by Sec. 514.8(a)(3)(i) and (a)(3)(ii).
(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.
[[Page 115]]
(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 listed in
Sec. 514.8(d).
(xiv) Changes not requiring prior approval which are listed under
Sec. 514.8(a)(5) when submitted as supplemental applications.
(2) Category II. Supplements that may require a reevaluation of
certain safety or effectiveness data in the parent application. Category
II supplements include the following:
(i) A change in the active ingredient concentration or composition
of the final product.
(ii) A change in quality, purity, strength, and identity
specifications of the active or inactive ingredients.
(iii) A change in dose (amount of drug administered per dose).
(iv) A change in the treatment regimen (schedule of dosing).
(v) Addition of a new therapeutic claim to the approved uses of the
product.
(vi) Addition of a new or revised animal production claim.
(vii) Addition of a new species.
(viii) A change in the prescription or over-the-counter status of a
drug product.
(ix) A change in statements regarding side effects, warnings,
precautions, and contraindications, except the addition of approved
statements to container, package, and promotional labeling, and
prescription drug advertising.
(x) A change in the drug withdrawal period prior to slaughter or in
the milk discard time.
(xi) A change in the tolerance for drug residues.
(xii) A change in analytical methods for drug residues.
(xiii) A revised method of synthesis or fermentation of the new drug
substance.
(xiv) Updating or changes in the manufacturing process of the new
drug substance and/or final dosage form (other than a change in
equipment that does not alter the method of manufacture of a new animal
drug, or a change from one commercial batch size to another without any
change in manufacturing procedure), or changes in the methods,
facilities, or controls used for the manufacture, processing, packaging,
or holding of the new animal drug (other than use of an establishment
not covered by the approval that is in effect) that give increased
assurance that the drug will have the characteristics of identity,
strength, quality, and purity which it purports or is represented to
possess.
[55 FR 46052, Nov. 1, 1990; 55 FR 49973, Dec. 3, 1990; 56 FR 12422, Mar.
25, 1991]
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
[[Page 116]]
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 which addresses each of the items specified in the applicable
format under Sec. 25.31 of this chapter or fails to provide sufficient
information to establish that the requested action is subject to
categorical exclusion under Sec. 25.24 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, l975, as amended at 50 FR 7517, Feb. 22, 1985; 50
FR 16668, Apr. 26, 1985]
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)(i) 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 consisting of adequate and well-controlled investigations,
including clinical (field) investigation, by experts qualified by
scientific training and experience to evaluate the effectiveness of the
drug involved, on the basis of which it could fairly and reasonably be
concluded by such experts that the 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.
[[Page 117]]
(ii) The following principles have been developed over a period of
years and are recognized by the scientific community as the essentials
of adequate and well-controlled clinical (field) investigations. They
provide the basis for the determination whether there is substantial
evidence to support the claims of effectiveness for new animal drugs.
(a) The plan or protocol for the study and the report of the results
of the effectiveness study must include the following:
(1) A clear statement of the objectives of the study.
(2) A method of selection of the subjects that--
(i) Provides adequate assurance that they are suitable for the
purposes of the study, diagnostic criteria of the condition to be
treated or diagnosed, confirmatory laboratory tests where appropriate,
and, in the case of prophylactic agents, evidence of susceptibility and
exposure to the condition against which prophylaxis is desired;
(ii) Assigns the subjects to test groups in such a way as to
minimize bias; and
(iii) Assures comparability in test and control groups of pertinent
variables, such as species, age, sex, duration and severity of disease,
management practices, and use of drugs other than those being studied.
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 (a)(5)(ii)(a)(4)(i), (ii), or (iii) of this
section.
(3) An explanation of the methods of observation and recording of
the animal response variable studied and the means of excluding bias or
minimizing bias in the observations.
(4) A comparison of the results of treatment or diagnosis with a
control in such a fashion as to permit quantitative evaluation. The
precise nature of the control must be stated and an explanation given of
the methods used to minimize bias on the part of the observers and the
analysts of the data. Level and methods of ``blinding,'' if used, are to
be documented. Generally, four types of comparisons are recognized:
(i) No treatment: Where objective measurements of effectiveness are
available and placebo effect is negligible, comparison of the objective
results in comparable groups of treated and untreated animals.
(ii) Placebo control: Comparison of the results of use of the new
animal drug entity with an inactive preparation designed to resemble the
test drug as far as possible.
(iii) Active treatment control: An effective regimen of therapy may
be used for comparison, e.g., where the condition treated is such that
no treatment or administration of a placebo would be contrary to the
well-being of the animals.
(iv) Historical control: In some circumstances involving diseases
with high and predictable mortality (leukemia or tetanus) or with signs
and symptoms of predictable duration or severity (some forms of
parasitism, bovine hypocalcemia, canine eclampsia) or in the case of
prophylaxis where morbidity is predictable, the results of use of a new
animal drug entity may be compared quantitatively with prior experience
historically derived from the adequately documented natural history of
the disease or condition in comparable animals with no treatments or
with a regimen (therapeutic, diagnostic, prophylactic) whose
effectiveness is established.
(5) A summary of the methods of analysis and an evaluation of data
derived from the study, including any appropriate statistical methods.
(6) Any of the criteria in this paragraph (a)(5)(ii) may be waived
in whole or in part, either before the investigation or in the
evaluation of a completed study, by the Director of the Center for
Veterinary Medicine with respect to a specific clinical (field)
investigation. A petition for such a waiver may be filed by any person
who would be adversely affected by application of the criteria to a
particular clinical investigation. The petition should show that some or
all of the criteria are not reasonably applicable to the investigation
and that alternative procedures can be or have been followed, the
[[Page 118]]
results of which will yield or have yielded data that can and should be
accepted as substantial evidence of the drug's effectiveness. A petition
for a waiver shall set forth clearly and concisely the specific
provision or provisions in the criteria from which waiver is sought, why
the criteria are not reasonably applicable to the particular clinical
(field) investigation, what alternative procedures, if any, are to be or
have been employed, what results have been obtained, and the basis on
which it can be or has been concluded that the clinical (field)
investigation will yield or has yielded substantial evidence of
effectiveness, notwithstanding nonconformance with the criteria for
which waiver is requested.
(b) Standardized test drug: For such an investigation to be
considered adequate for consideration for approval of a new animal drug,
the test drug must be standardized as to identity, strength, quality,
purity, and dosage form to give significance to the results of the
investigation.
(c) Uncontrolled studies or partially controlled studies are not
acceptable as the sole basis for the approval of claims of
effectiveness. Such studies, carefully conducted and documented, may
provide corroborative support of well-controlled studies regarding
efficacy and may yield valuable data regarding safety of the test drug.
Such studies will be considered on their merits in the light of the
principles listed here, with the exception of the requirement for the
comparison of the treated subjects with controls. Isolated case reports,
random experience, and reports lacking the details which permit
scientific evaluation will not be considered.
(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. 25.31 of this chapter or fails to provide
sufficient information to establish that the requested action is subject
to categorical exclusion under Sec. 25.24 of this chapter.
(10) The drug fails to satisfy the requirements of subpart E of part
500 of this chapter.
(11) Any nonclinical laboratory study that is described in the
application and that is essential to show that the drug is safe for use
under the conditions prescribed, recommended, or suggested in its
proposed labeling, was not conducted in compliance with the good
laboratory practice regulations as set forth in part 58 of this chapter
and no reason for the noncompliance is provided or, if it is, the
differences between the practices used in conducting the study and the
good laboratory practice regulations do not support the validity of the
study.
(b) The Commissioner shall within 90 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 an animal feed bearing or containing a new animal drug that:
(1) There is not in effect a regulation established pursuant to
section 512(i) of the act (identified in such application)
[[Page 119]]
on the basis of which such application may be approved; or
(2) Such animal feed (including the proposed use of any new animal
drug therein or thereon) does not conform to an applicable regulation
published pursuant to section 512(i) of the act (identified in such
application), or that the purposes or conditions or indications of use
prescribed, recommended, or suggested in the labeling of such feed do
not conform to the applicable purposes and conditions or indications for
use (including warnings) published pursuant to section 512(i) of the act
or such labeling omits or fails to conform to other applicable
information published pursuant to such section; or
(3) 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
(4) Based on a fair evaluation of all the material facts, such
labeling is false or misleading in any particular.
(c) 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]
Sec. 514.112 Return of applications for animal feeds bearing or containing new animal drugs.
Applications submitted pursuant to Sec. 514.2 will be returned to
the applicant if such applications are incomplete or inaccurate or do
not contain an identification of the applicable regulation(s). These
regulations include those published pursuant to section 512(i) of the
act, and are found in part 558 of this chapter. In addition,
Sec. 510.515 of this chapter may also provide a basis on which approval
of the application relies, as required by Sec. 514.2(b)(10). All reasons
for the return of the application will be made known to the applicant.
[51 FR 7392, Mar. 3, 1986]
Sec. 514.115 Withdrawal of approval of applications.
(a) The Secretary may suspend approval of an application approved
pursuant to section 512(c) or (m)(2) 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) or (m)(2) 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,
[[Page 120]]
or tests by methods not deemed reasonably applicable when such
application was approved, evaluated together with the evidence available
to the Secretary when the application was approved, shows that such drug
is not shown to be safe for use under the conditions of use upon the
basis of which the application was approved or that section 512
(d)(1)(H) of the act applies to such drug; or
(iii) On the basis of new information before him with respect to
such drug, evaluated together with the evidence available to him when
the application was approved, there is a lack of substantial evidence
that such drug will have the effect it purports or is represented to
have under the conditions of use prescribed, recommended, or suggested
in the labeling thereof.
(4) That any nonclinical laboratory study that is described in the
application and that is essential to show that the drug is safe for use
under the conditions prescribed, recommended, or suggested in its
proposed labeling, was not conducted in compliance with the good
laboratory practice regulations as set forth in part 58 of this chapter
and no reason for the noncompliance is provided or, if it is, the
differences between the practices used in conducting the study and the
good laboratory practice regulations do not support the validity of the
study.
(c) The Commissioner may notify in writing the person holding an
application approved pursuant to section 512(c) or (m)(2) 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) or (m)(5)(A) 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) or
(m)(5)(B) 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 or animal feed, 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) or (m)(2)
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. An application providing for the manufacture of animal feeds
bearing or containing such drug and approved pursuant to section
512(m)(2) of the act shall be deemed as withdrawn upon publication in
the Federal Register of the order revoking the corresponding regulation.
[40 FR 13825, Mar. 27, 1975, as amended at 50 FR 7517, Feb. 22, 1985]
[[Page 121]]
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. 514.120 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 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
[[Page 122]]
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 Procedure for hearings.
Hearings relating to new animal drugs under section 512 (d), (e),
(m)(3), and (m)(4) of the act shall be governed by part 12 of this
chapter.
[42 FR 4717, Jan. 25, 1977, as amended at 42 FR 10980, Feb. 25, 1977; 42
FR 15675, Mar. 22, 1977]
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 520--ORAL DOSAGE FORM NEW ANIMAL DRUGS--Table of Contents
Sec.
520.23 Acepromazine maleate tablets.
520.44 Acetazolamide sodium soluble powder.
520.45 Albendazole oral dosage forms.
520.45a Albendazole suspension.
520.45b Albendazole paste.
520.48 Altrenogest solution.
520.62 Aminopentamide hydrogen sulphate tablets.
520.82 Aminopropazine fumarate oral dosage forms.
520.82a Aminopropazine fumarate tablets.
520.82b Aminopropazine fumarate, neomycin sulfate tablets.
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.
520.90a Ampicillin capsules.
520.90b Ampicillin trihydrate tablets.
520.90c Ampicillin trihydrate capsules.
520.90d Ampicillin trihydrate for oral suspension.
520.90e Ampicillin trihydrate soluble powder.
520.90f Ampicillin trihydrate boluses.
520.100 Amprolium oral dosage forms.
520.100a Amprolium drinking water.
520.100b Amprolium drench.
520.100c Amprolium crumbles.
520.110 Apramycin sulfate soluble powder.
520.154 Bacitracin oral dosage forms.
520.154a Soluble bacitracin methylene disalicylate.
520.154b Soluble bacitracin methylene disalicylate and streptomycin
sulfate oral powder.
520.154c Bacitracin zinc soluble powder.
520.182 Bicyclohexylammonium fumagillin.
520.222 Bunamidine hydrochloride.
520.246 Butorphanol tartrate tablets.
520.260 n-Butyl chloride capsules.
520.300 Cambendazole oral dosage forms.
520.300a Cambendazole suspension.
520.300b Cambendazole pellets.
520.300c Cambendazole paste.
520.310 Caramiphen ethanedisulfonate and ammonium chloride tablets.
520.312 Carnidazole tablets.
520.314 Cefadroxil tablets.
520.315 Cefadroxil powder for oral suspension.
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.
520.445 Chlortetracycline oral dosage forms.
520.445a Chlortetracycline bisulfate/sulfamethazine bisulfate soluble
powder.
520.445b Chlortetracycline powder (chlortetracycline hydrochloride or
chlortetracycline bisulfate).
[[Page 123]]
520.445c Chlortetracycline tablets and boluses.
520.446 Clindamycin hydrochloride capsules.
520.447 Clindamycin hydrochloride liquid.
520.462 Clorsulon drench.
520.500 Coumaphos crumbles.
520.530 Cythioate oral liquid.
520.531 Cythioate tablets.
520.540 Dexamethasone oral dosage forms.
520.540a Dexamethasone powder.
520.540b Dexamethasone tablets and boluses.
520.540c Dexamethasone chewable tablets.
520.550 Dextrose/glycine/electrolyte.
520.563 Diatrizoate meglumine and diatrizoate sodium oral solution.
520.580 Dichlorophene and toluene capsules.
520.600 Dichlorvos.
520.608 Dicloxacillin sodium monohydrate capsules.
520.620 Diethylcarbamazine oral dosage forms.
520.620a Diethylcarbamazine.
520.620b Diethylcarbamazine chewable tablets.
520.622 Diethylcarbamazine citrate oral dosage forms.
520.622a Diethylcarbamazine citrate tablets.
520.622b Diethylcarbamazine citrate syrup.
520.622c Diethylcarbamazine citrate chew- able tablets.
520.622d Diethylcarbamazine citrate capsules.
520.623 Diethylcarbamazine citrate, oxibendazole chewable tablets.
520.763 Dithiazanine iodide oral dosage forms.
520.763a Dithiazanine iodide tablets.
520.763b Dithiazanine iodide powder.
520.763c Dithiazanine iodide and piperazine citrate suspension.
520.784 Doxylamine succinate tablets.
520.804 Enalapril tablets.
520.812 Enrofloxacin tablets.
520.816 Epsiprantel tablets.
520.823 Erythromycin phosphate.
520.863 Ethylisobutrazine hydrochloride tablets.
520.903 Febantel oral dosage forms.
520.903a Febantel paste.
520.903b Febantel suspension.
520.903c [Reserved]
520.903d Febantel-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.
520.960 Flumethasone tablets.
520.970 Flunixin oral dosage forms.
520.970a Flunixin meglumine granules.
520.970b Flunixin meglumine paste.
520.1010 Furosemide oral dosage forms.
520.1010a Furosemide tablets or boluses.
520.1010b Furosemide powder.
520.1010c Furosemide syrup.
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 soluble powder.
520.1100 Griseofulvin.
520.1120 Haloxon oral dosage forms.
520.1120a Haloxon drench.
520.1120b Haloxon boluses.
520.1130 Hetacillin oral dosage forms.
520.1130a Hetacillin potassium capsules.
520.1130b Hetacillin potassium oral suspension.
520.1130c Hetacillin potassium tablets.
520.1157 Iodinated casein tablets.
520.1158 Iodochlorhydroxyquin boluses.
520.1182 Iron detran oral suspension.
520.1192 Ivermectin paste.
520.1193 Ivermectin tablets and chewable cubes.
520.1194 Ivermectin drench.
520.1195 Ivermectin liquid.
520.1196 Ivermectin and pyrantel (as pamoate salt) chewable tablet.
520.1204 Kanamycin sulfate, aminopentamide hydrogen sulfate, pectin,
bismuth subcarbonate, activated attapulgite suspension.
520.1205 Kanamycin sulfate, pectin, bismuth subcarbonate, activated
attapulgite tablets.
520.1242 Levamisole hydrochloride oral dosage forms.
520.1242a Levamisole hydrochloride drench and drinking water.
520.1242b Levamisole hydrochloride tablet or oblet (bolus).
520.1242c Levamisole hydrochloride and piperazine dihydrochloride.
520.1242d Levamisole resinate.
520.1242e Levamisole hydrochloride effervescent tablets.
520.1242f Levamisole hydrochloride gel.
520.1242g Levamisole resinate and famphur paste.
520.1263 Lincomycin hydrochloride monohydrate oral dosage forms.
520.1263a Lincomycin hydrochloride monohydrate tablets and sirup.
520.1263b Lincomycin hydrochloride monohydrate and spectinomycin
sulfate tetrahydrate soluble powder.
520.1263c Lincomycin hydrochloride soluble powder.
520.1284 Sodium liothyronine tablets.
520.1288 Lufenuron tablets.
520.1289 Lufenuron suspension.
520.1320 Mebendazole oral.
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.
[[Page 124]]
520.1331 Meclofenamic acid tablets.
520.1341 Megestrol acetate tablets.
520.1380 Methocarbamol tablets.
520.1408 Methylprednisolone tablets.
520.1409 Methylprednisolone, aspirin tablets.
520.1422 Metoserpate hydrochloride.
520.1430 Mibolerone.
520.1445 Milbemycin oxime tablets.
520.1448 Monensin oral dosage forms.
520.1448a Monensin blocks.
520.1448b Monensin-mineral granules.
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.
520.1468 Naproxen granules.
520.1484 Neomycin sulfate soluble powder.
520.1485 Neomycin sulfate oral solution.
520.1520 Niclosamide tablets.
520.1628 Oxfendazole powder and pellets.
520.1629 Oxfendazole paste.
520.1630 Oxfendazole suspension.
520.1631 Oxfendazole and trichlorfon paste.
520.1638 Oxibendazole paste.
520.1640 Oxibendazole suspension.
520.1660 Oxytetracycline.
520.1660a Oxytetracycline and carbomycin in combination.
520.1660b Oxytetracycline hydrochloride capsules.
520.1660c Oxytetracycline hydrochloride tablets.
520.1660d Oxytetracycline hydrochloride soluble powder.
520.1696 Penicillin oral dosage forms.
520.1696a Buffered penicillin powder, penicillin powder with buffered
aqueous diluent.
520.1696b Penicillin G potassium in drinking water.
520.1696c Penicillin V potassium for oral solution.
520.1696d Penicillin V potassium tablets.
520.1720 Phenylbutazone oral dosage forms.
520.1720a Phenylbutazone tablets and boluses.
520.1720b Phenylbutazone granules.
520.1720c Phenylbutazone paste.
520.1720d Phenylbutazone gel.
520.1802 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 monohydrochloride liquid.
520.1840 Poloxalene.
520.1846 Polyoxyethylene (23) lauryl ether blocks.
520.1870 Praziquantel tablets.
520.1871 Praziquantel/pyrantel pamoate tablets.
520.1872 Praziquantel, pyrantel pamoate, and febantel tablets.
520.1880 Prednisolone tablets.
520.1900 Primidone tablets.
520.1920 Prochlorperazine, isopropamide sustained release capsules.
520.1921 Prochlorperazine, isopropamide, with neomycin sustained-
release capsules.
520.1962 Promazine hydrochloride.
520.2002 Propiopromazine hydrochloride.
520.2022 Protokylol hydrochloride tablets.
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; pyrantel tartrate pellets.
520.2080 Ronnel oral dosage forms.
520.2087 Roxarsone soluble powder.
520.2088 Roxarsone tablets.
520.2089 Roxarsone liquid.
520.2095 Sarafloxacin soluble powder.
520.2100 Selenium, vitamin E capsules.
520.2122 Spectinomycin dihydrochloride oral solution.
520.2123 Spectinomycin dihydrochloride pentahydrate oral dosage forms.
520.2123a Spectinomycin dihydrochloride pentahydrate tablets.
520.2123b Spectinomycin dihydrochloride pentahydrate soluble powder.
520.2150 Stanozolol oral dosage forms.
520.2150a Stanozolol tablets.
520.2150b Stanozolol chewable tablets.
520.2158 Streptomycin/dihydrostreptomycin oral dosage forms.
520.2158a Streptomycin sulfate oral solution.
520.2158b Dihydrostreptomycin tablets.
520.2158c Dihydrostreptomycin oral suspension.
520.2160 Styrylpyridinium, diethylcarbamazine oral dosage forms.
520.2160a Styrylpyridinium, diethylcarbamazine tablets.
520.2160b Styrylpyridinium chloride, diethylcarbamazine (as base).
520.2160c Styrylpyridinium, diethylcarbamazine edible tablets.
520.2160d Styrylpyridinium, diethylcarbamazine film-coated tablets.
520.2170 Sulfabromomethazine sodium boluses.
520.2184 Sodium sulfachloropyrazine monohydrate.
520.2200 Sulfachlorpyridazine oral dosage forms.
520.2200a Sulfachlorpyridazine bolus.
520.2200b Sulfachlorpyridazine medicated milk and drinking water.
520.2200c Sulfachlorpyridazine tablets.
[[Page 125]]
520.2220 Sulfadimethoxine oral dosage forms.
520.2220a Sulfadimethoxine oral solution and soluble powder.
520.2220b Sulfadimethoxine tablets and boluses.
520.2220c Sulfadimethoxine oral suspension.
520.2220d Sulfadimethoxine-ormetoprim tablets.
520.2240 Sulfaethoxypyridazine.
520.2240a Sulfaethoxypyridazine drinking water.
520.2240b Sulfaethoxypyridazine tablets.
520.2260 Sulfamethazine oral dosage forms.
520.2260a Sulfamethazine oblets and boluses.
520.2260b Sulfamethazine sustained-release boluses.
520.2260c Sulfamethazine sustained-release tablets.
520.2261 Sulfamethazine sodium oral dosage forms.
520.2261a Sulfamethazine sodium drinking water solution.
520.2261b Sulfamethazine sodium soluble powder.
520.2280 Sulfamethizole and methenamine mandelate tablets.
520.2320 Sulfanitran and aklomide in combination.
520.2325 Sulfaquinoxaline oral dosage forms.
520.2325a Sulfaquinoxaline drinking water.
520.2325b Sulfaquinoxaline drench.
520.2330 Sulfisoxazole tablets.
520.2345 Tetracycline oral dosage forms.
520.2345a Tetracycline hydrochloride capsules.
520.2345b Tetracycline tablets.
520.2345c Tetracycline boluses.
520.2345d Tetracycline hydrochloride soluble powder.
520.2345e Tetracycline oral liquid.
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 tablets.
520.2380 Thiabendazole oral dosage forms.
520.2380a Thiabendazole top dressing and mineral protein feed block.
520.2380b Thiabendazole drench or oral paste.
520.2380c Thiabendazole bolus.
520.2380d Thiabendazole, piperazine citrate suspension.
520.2380e Thiabendazole with trichlorfon.
520.2380f Thiabendazole, piperazine phosphate powder.
520.2455 Tiamulin soluble powder.
520.2456 Tiamulin liquid concentrate.
520.2460 Ticarbodine oral dosage forms.
520.2460a Ticarbodine tablets.
520.2460b Ticarbodine capsules.
520.2473 Tioxidazole oral dosage forms.
520.2473a Tioxidazole granules.
520.2473b Tioxidazole paste.
520.2480 Triamcinolone tablets.
520.2481 Triamcinolone acetonide tablets.
520.2482 Triamcinolone acetonide oral powder.
520.2520 Trichlorfon oral dosage forms.
520.2520a Trichlorfon oral.
520.2520b Trichlorfon and atropine.
520.2520c Trichlorfon oral liquid.
520.2520d Trichlorfon paste.
520.2520e Trichlorofon boluses.
520.2520f Trichlorofon granules.
520.2520g Trichlorfon, phenothiazine, and piperazine dihydrochloride
powder.
520.2582 Triflupromazine hydrochloride tablets.
520.2604 Trimeprazine tartrate and prednisolone tablets.
520.2605 Trimeprazine tartrate and prednisolone capsules.
520.2610 Trimethoprim and sulfadiazine tablets.
520.2611 Trimethoprim and sulfadiazine oral paste.
520.2612 Trimethoprim and sulfadiazine oral suspension.
520.2613 Trimethoprim and sulfadiazine powder.
520.2640 Tylosin.
Authority: Sec. 512 of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 360b).
Source: 40 FR 13838, Mar. 27, 1975, unless otherwise noted.
Sec. 520.23 Acepromazine maleate tablets.
(a) Sponsors. See drug labeler codes in Sec. 510.600(c) of this
chapter for identification of sponsors as follows:
(1) For No. 000856, use of 5-, 10-, or 25-milligram tablets as in
paragraph (b) of this section.
(2) For No. 054273, use of 10- or 25-milligram tablets as in
paragraph (c) of this section.
(b) Conditions of use. It is used in dogs and cats as follows:
(1) Indications for use. It is used in dogs and cats as a
tranquilizer.
(2) Amount. Dogs: 0.25 to 1.0 milligram per pound of body weight;
Cats: 0.5 to 1.0 milligram per pound of body weight.
(3) Limitations. The drug is administered orally. Dosage may be
repeated as required. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
(c) Conditions of use. It is used in dogs as follows:
(1) Indications for use. It is used in dogs as an aid in
tranquilization and as a preanesthetic agent.
[[Page 126]]
(2) Amount. Dogs: 0.25 to 1.0 milligram per pound of body weight.
(3) Limitations. The drug is administered orally. Dosage may be
repeated as required. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
[46 FR 44443, Sept. 4, 1981, as amended at 49 FR 49091, Dec. 18, 1984;
52 FR 666, Jan. 8, 1987; 53 FR 40727, Oct. 18, 1988; 56 FR 37473, Aug.
7, 1991]
Sec. 520.44 Acetazolamide sodium soluble powder.
(a) Specifications. The drug is in a powder form containing
acetazolamide sodium, USP equivalent to 25 percent acetazolamide
activity.
(b) Sponsor. See No. 010042 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) It is used in dogs as an aid in the
treatment of mild congestive heart failure and for rapid reduction of
intraocular pressure.\1\
---------------------------------------------------------------------------
\1\ These conditions are NAS/NRC reviewed and deemed effective.
Applications for these uses need not include effectiveness data as
specified by Sec. 514.111 of this chapter, but may require
bioequivalency and safety information.
---------------------------------------------------------------------------
(2) It is administered orally at a dosage level of 5 to 15
milligrams per pound of body weight daily.\1\
(3) For use only by or on the order of a licensed veterinarian.\1\
Sec. 520.45 Albendazole oral dosage forms.
Sec. 520.45a Albendazole suspension.
(a)(1) Specifications. The product contains 11.36 percent
albendazole.
(2) Sponsor. See No. 000069 in Sec. 510.600 of this chapter.
(3) Related tolerances. See Sec. 556.34 of this chapter.
(4)(i) Conditions of use in cattle--(1) Amount. 4.54 milligrams per
pound of body weight (10 milligrams per kilogram).
(ii) 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 stage 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 phlebotomum), bankrupt worm
(Trichostrongylus colubriformis), nodular worm (Oesophagostomum
radiatum)); adult and 4th stage larvae of lungworms (Dictyocaulus
viviparus).
(iii) Limitations. Administer as a single oral dose using dosing gun
or dosing syringe. 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.
(2) [Reserved]
(b)(1) Specifications. The product contains 4.55 percent
albendazole.
(2) Sponsor. See No. 000069 in Sec. 510.600(c) of this chapter.
(3) Related tolerances. See Sec. 556.34 of this chapter.
(4) Conditions of use in sheep--(i) Amount. 7.5 milligrams per
kilogram of body weight (3.4 milligrams per pound).
(ii) Indications for use. For removal and control of the following
internal parasites of sheep: Adult liver flukes (Fasciola hepatica,
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. Administer as a single oral dose using dosing gun
or
[[Page 127]]
dosing syringe. 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. Consult your veterinarian for assistance in the
diagnosis, treatment, and control of parasitism.
[54 FR 25115, June 13, 1989, as amended at 56 FR 50653, Oct. 8, 1991; 59
FR 65711, Dec. 21, 1994; 60 FR 55658, Nov. 2, 1995; 61 FR 4875, Feb. 9,
1996]
Sec. 520.45b Albendazole paste.
(a) Specifications. The product contains 30 percent albendazole.
(b) Sponsor. See No. 000069 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]
Sec. 520.48 Altrenogest solution.
(a) Specifications. Each milliliter of altrenogest solution contains
2.2 milligrams of altrenogest.
(b) Sponsor. See No. 012579 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Amount. Administer orally at the rate of
1 milliliter per 110 pounds body weight (0.044 milligram per kilogram
body weight). Give one dose daily for 15 consecutive days.
(2) Indications for use. For suppression of estrus in mares.
(3) Limitations. For oral use in horses only; avoid contact with the
skin. Do not administer to horses intended for use as food. The drug is
contraindicated for use in mares having a previous or current history of
uterine inflammation (i.e., acute, subacute, or chronic endometritis).
Natural or synthetic gestagen therapy may exacerbate existing low-grade
or smoldering uterine inflammation into a fulminating uterine infection
in some instances. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[48 FR 40887, Sept. 12, 1983, as amended at 55 FR 26431, June 28, 1990]
Sec. 520.62 Aminopentamide hydrogen sulphate tablets.
(a) Chemical name. 4-(Dimethylamino)-2,2-diphenylvaleramide hydrogen
sulfate.
(b) Specifications. Each tablet contains 0.2 milligram of the drug.
(c) Sponsor. See No. 000856 in Sec. 510.600(c) of this chapter.
(d) Conditions of use. (1) It is intended for use in dogs and cats
only for the treatment of vomiting and/or diarrhea, nausea, acute
abdominal visceral spasm, pylorospasm, or hypertrophic gastritis.
Note: Not for use in animals with glaucoma because of the occurrence
of mydriasis.
(2) Dosage is administered by oral tablet every 8 to 12 hours, as
follows:
------------------------------------------------------------------------
Dosage in
Weight of animal in pounds milligrams
------------------------------------------------------------------------
Up to 10.................................................... 0.1
11 to 20.................................................... 0.2
21 to 50.................................................... 0.3
51 to 100................................................... 0.4
[[Page 128]]
Over 100.................................................... 0.5
------------------------------------------------------------------------
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.
(3) For use only by or on the order of a licensed veterinarian.
[40 FR 13838, Mar. 27, 1975, as amended at 53 FR 27851, July 25, 1988]
Sec. 520.82 Aminopropazine fumarate oral dosage forms.
Sec. 520.82a Aminopropazine fumarate tablets.
(a) Specifications. The drug is in tablet form. Each tablet contains
aminopropazine fumarate equivalent to 25 milligrams of aminopropazine
base.
(b) Sponsor. See No. 011716 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) The drug is used in dogs and cats for
reducing excessive smooth muscle contractions, such as occur in urethral
spasms associated with urolithiasis.\1\
(2) It is administered at a dosage level of 1 to 2 milligrams per
pound of body weight. The dosage can be repeated every 12 hours, as
indicated.\1\
(3) Not for use in animals intended for food purposes.
(4) For use only by or on the order of a licensed veterinarian.\1\
[40 FR 13838, Mar. 27, 1975, as amended at 46 FR 48642, Oct. 2, 1981; 61
FR 8873, Mar. 6, 1996]
Sec. 520.82b Aminopropazine fumarate, neomycin sulfate tablets.
(a) Specifications. The drug is in tablet form. Each tablet contains
both aminopropazine fumarate equivalent to 25 milligrams of
aminopropazine base and neomycin sulfate equivalent to 50 milligrams of
neomycin base.
(b) Sponsor. See No. 011716 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) The drug is used in dogs to control
bacterial diarrhea caused by organisms susceptible to neomycin and to
reduce smooth muscle contractions.\1\
---------------------------------------------------------------------------
\1\ These conditions are NAS/NRC reviewed and deemed effective.
Applications for these uses need not include effectiveness data as
specified by Sec. 514.111 of this chapter, but may require
bioequivalency and safety information.
---------------------------------------------------------------------------
(2) It is administered at a dosage level of one to two tablets per
10 pounds of body weight twice daily for 3 days.\1\
(3) Federal law restricts this drug to use by or on the order of a
licensed veterinarian.\1\
[40 FR 13838, Mar. 27, 1975, as amended at 46 FR 48642, Oct. 2, 1981; 61
FR 8873, Mar. 6, 1996]
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 of amoxicillin.
(b) Sponsor. See No. 000069 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. 5 milligrams per pound
of body weight, twice a day.
(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. Administer for 5 to 7 days or 48 hours after all
symptoms have subsided. If no improvement is seen in 5 days, review
diagnosis and change therapy. Federal law restricts this drug to use by
or on the order of a licensed veterinarian.
(2) Cats--(i) Amount. 50 milligrams (5 to 10 milligrams per pound of
body weight) once a day.
(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
[[Page 129]]
spp., E. coli, and P. mirabilis; gastrointestinal tract due to E. coli;
and skin and soft tissue (abscesses, lacerations, and wounds) due to S.
aureus, Streptococcus spp., E. coli, and Pasteurella multocida.
(iii) Limitations. Administer for 5 to 7 days or 48 hours after all
symptoms have subsided. If no improvement is seen in 5 days, review
diagnosis and change therapy. 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]
Sec. 520.88b Amoxicillin trihydrate for oral suspension.
(a) Specifications. When reconstituted, each milliliter contains
amoxicillin trihydrate equivalent to 50 milligrams of amoxicillin.
(b) Sponsor. See No. 000069 in Sec. 510.600(c) of this chapter.
(1) Conditions of use--(i) Dogs--(A) Amount. 5 milligrams per pound
of body weight twice daily.
(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. Use for 5 to 7 days or 48 hours after all symptoms
have subsided. Federal law restricts this drug to use by or on the order
of a licensed veterinarian.
(ii) Cats--(A) Amount. 50 milligrams (5 to 10 milligrams per pound)
once daily.
(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. Use for 5 to 7 days or 48 hours after all symptoms
have subsided. Federal law restricts this drug to use by or on the order
of a licensed veterinarian.
(2) [Reserved]
(c) Sponsor. See Nos. 000031 and 000332 in Sec. 510.600(c) of this
chapter.
(1) Conditions of use. Dogs--(i) Amount. 5 milligrams per pound of
body weight twice daily.
(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. Use for 5 to 7 days. Continue for 48 hours after
all symptoms have subsided. If no improvement is seen in 5 days, review
diagnosis and change therapy. 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]
Sec. 520.88c Amoxicillin trihydrate oral suspension.
(a) Specifications. Each 0.8-milliliter dose contains amoxicillin
trihydrate equivalent to 40 milligrams of amoxicillin.
(b) Sponsor. See No. 000069 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.510 of this chapter.
(d) Conditions of use. Swine--(1) Amount. 40 milligrams orally,
twice a day using a dosing pump.
(2) Indications for use. Treatment of baby pigs under 10 pounds for
porcine colibacillosis caused by Escherichia coli susceptible to
amoxicillin.
(3) Limitations. Treat animals for 48 hours after all symptoms have
subsided
[[Page 130]]
but not beyond 5 days. 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]
Sec. 520.88d Amoxicillin trihydrate soluble powder.
(a) Specifications. Each gram contains amoxicillin trihydrate
equivalent to 115.4 milligrams of amoxicillin.
(b) Sponsor. See No. 000069 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.38 of this chapter.
(d) Conditions of use. Nonruminating calves--(1) Amount. 400
milligrams per 100 pounds of body weight twice daily.
(2) Indications for use. Treatment of bacterial enteritis when due
to susceptible Escherichia coli in nonruminating calves.
(3) Limitations. Administer by drench or by mixing in milk.
Treatment should be continued for 48 hours after all symptoms have
subsided but not to exceed 5 days. For use in nonruminating calves only,
not for use in other animals which are raised for food production. 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]
Sec. 520.88e Amoxicillin trihydrate boluses.
(a) Specifications. Each bolus contains the equivalent of 400
milligrams of amoxicillin.
(b) Sponsor. See No. 000069 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.38 of this chapter.
(d) Conditions of use. Nonruminating calves--(1) Amount. 400
milligrams per 100 pounds of body weight twice daily.
(2) Indications for use. Treatment of bacterial enteritis when due
to susceptible Escherichia coli in nonruminating calves.
(3) Limitations. For oral use in nonruminating calves only, not for
use in other animals which are raised for food production. Treatment
should be continued for 48 hours after all symptoms have subsided but
not to exceed 5 days. 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]
Sec. 520.88f Amoxicillin trihydrate tablets.
(a) Specifications. Each tablet contains amoxicillin trihydrate
equivalent to 50, 100, 200, or 400 milligrams of amoxicillin.
(b) Sponsor. See Nos. 000031 or 000332 in Sec. 510.600(c) of this
chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. 5 milligrams per pound
of body weight twice a day.
(ii) Indications for use. 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.
(iii) Limitations. Use for 5 to 7 days or 48 hours after all
symptoms have subsided. If no improvement is seen in 5 days, review
diagnosis and change therapy. Federal law restricts this drug to use by
or on the order of a licensed veterinarian.
(2) [Reserved]
[57 FR 37320, Aug. 18, 1992]
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. 000069 in Sec. 510.600(c) of this chapter.
(c) Conditions of use--(1) Dogs--(i) Amount. 6.25 milligrams
(equivalent to
[[Page 131]]
5 milligrams amoxicillin and 1.25 milligrams clavulanic acid) per pound
of body weight twice daily.
(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. aureus,
Staphylococcus spp., Streptococcus spp., and Escherichia coli.
(iii) Limitations. Wounds, abscesses, cellulitis, and superficial/
juvenile pyoderma: Treat for 5 to 7 days or for 48 hours after all signs
have subsided. If no improvement is seen after 5 days of treatment,
discontinue therapy and reevaluate diagnosis. Deep pyoderma may require
treatment for 21 days; do not treat for more than 30 days. Not for use
in dogs maintained for breeding. 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.
(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. Skin and soft tissue infections: abscesses,
cellulitis/dermatitis should be treated for 5 to 7 days or for 48 hours
after all signs have subsided. If no response is seen after 3 days of
treatment, therapy should be discontinued and diagnosis reevaluated.
Urinary tract infections may require treatment for 10 to 14 days or
longer. The maximum duration of treatment should not exceed 30 days.
Safety of use in pregnant or breeding animals has not been established.
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]
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. 000069 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.
(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.
(iii) Limitations. Administer for 5 to 7 days or 48 hours after all
symptoms subsided. Deep pyoderma may require 21 days, not to exceed 30
days. If no improvement is seen in 5 days, discontinue therapy and
reevaluate the case. Not for use in dogs maintained for breeding.
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
of amoxicillin and 12.5 milligrams clavulanic acid) twice daily.
(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. Administer 48 hours after all symptoms have
subsided. If no improvement is seen after 3 days of treatment,
discontinue therapy and reevaluate diagnosis. Maximum duration of
treatment should not exceed 30 days. Not for use in cats maintained for
breeding. Federal law restricts this
[[Page 132]]
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]
Sec. 520.90 Ampicillin oral dosage forms.
Sec. 520.90a Ampicillin capsules.
(a) Specifications. Each capsule contains 125 milligrams or 250
milligrams of ampicillin.
(b) Sponsor. See No. 000008 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, e.g., one 125 mg capsule per 14 to 25 pounds,
given 2 to 4 times daily; for animals weighing 6 to 14 pounds, one
capsule twice daily.
(ii) Indications for use. Treatment of urinary tract infections
(cystitis) due to Proteus spp., hemolytic and nonhemolytic streptococci,
beta hemolytic streptococci, and Escherichia coli. In upper respiratory
tract infections tracheobronchitis (kennel cough), tonsillitis due to
alpha and beta hemolytic streptococci, hemolytic positive staphylococci,
E. coli, and Proteus spp. In infections associated with abscesses,
lacerations, and wounds due to Staphylococcus spp. and Streptococcus
spp.
(iii) Limitations. Bacteriologic studies to determine the causative
organisms and their susceptibility to ampicillin should be performed.
Use of the drug is contraindicated in animals with a history of an
allergic reaction to any of the penicillins. Ampicillin is
contraindicated in infections caused by penicillinase-producing
organisms. Not for use in animals which are raised for food production.
Federal law restricts this drug to use by or on the order of a licensed
veterinarian.
(2) Cats--(i) Amount. 125 milligrams twice daily; in more acute
conditions three times daily.
(ii) Indications for use. Treatment of respiratory tract infections
(bacterial pneumonia) due to alpha and beta hemolytic streptococci,
hemolytic positive staphylococci, E. coli, and Proteus spp. In
infections associated with abscesses, lacerations, and wounds due to
Staphylococcus spp. and Streptococcus spp.
(iii) Limitations. Bacteriologic studies to determine the causative
organisms and their susceptibility to ampicillin should be performed.
Use of the drug is contraindicated in animals with a history of an
allergic reaction to any of the penicillins. Ampicillin is
contraindicated in infections caused by penicillinase-producing
organisms. Not for use in animals which are raised for food production.
Federal law restricts this drug to use by or on the order of a licensed
veterinarian.
[57 FR 37321, Aug. 18, 1992]
Sec. 520.90b Ampicillin trihydrate tablets.
(a) Specifications. Each tablet contains ampicillin trihydrate
equivalent to 50 or 100 milligrams of ampicillin.
(b) Sponsor. See No. 000069 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. 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
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. Not for use in animals which have shown
hypersensitivity to penicillin or for infections caused by
penicillinase-producing organisms. Not for use in animals which are
raised for food production. 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]
Sec. 520.90c Ampicillin trihydrate capsules.
(a) Specifications. Each capsule contains ampicillin trihydrate
equivalent
[[Page 133]]
to 125, 250, or 500 milligrams of ampicillin.
(b) Sponsor. See No. 055529 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. The drug may be given as an emergency measure;
however, in vitro sensitivity tests on samples collected prior to
treatment should be made. Ampicillin is contraindicated for use in
infections caused by penicillinase-producing organisms and for use in
animals known to be allergic to any of the penicillins. Not for use in
animals raised for food production. 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. The drug may be given as an emergency measure;
however, in vitro sensitivity tests on samples collected prior to
treatment should be made. Ampicillin is contraindicated for use in
infections caused by penicillinase-producing organisms and for use in
animals known to be allergic to any of the penicillins. Not for use in
animals raised for food production. 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]
Sec. 520.90d Ampicillin trihydrate 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. 5 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.
(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. 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. If no response
is obtained within 3 to 5 days, reevaluate diagnosis and treatment.
Appropriate laboratory tests should be conducted, including in vitro
culturing and susceptibility tests on samples collected prior to
treatment. 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
orally, 2 or 3 times daily, 1 to 2 hours prior to feeding.
(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) due to E.
coli, Staphylococcus spp.,
[[Page 134]]
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. 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. If no response
is obtained within 3 to 5 days, reevaluate diagnosis and treatment.
Appropriate laboratory tests should be conducted, including in vitro
culturing and susceptibility tests on samples collected prior to
treatment. 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]
Sec. 520.90e Ampicillin trihydrate 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. For use in swine only. Not for use in other animals
which are raised for food production. 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]
Sec. 520.90f Ampicillin trihydrate boluses.
(a) Specifications. Each bolus contains ampicillin trihydrate
equivalent to 400 milligrams of ampicillin.
(b) Sponsor. See No. 055529 in Sec. 510.600(c) of this chapter for
use as in paragraph (d)(1), 000069 for use as in paragraph (d)(2).
(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. Not for use
in other animals raised for food production. 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. Not for use in
other animals raised for food production. 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]
Sec. 520.100 Amprolium oral dosage forms.
Sec. 520.100a Amprolium drinking water.
(a) Chemical name. 1-(4-Amino-2-n-propyl-5-pyrimidinylmethyl)-2-
picolinium chloride hydrochloride.
(b) Sponsor. See No. 000006 in Sec. 510.600 (c) of this chapter.
(c) Related tolerances. See Sec. 556.50 of this chapter.
(d) Conditions of use. It is used in drinking water as follows:
(1) Chickens and turkeys--(i) Amount. 20 percent soluble powder.
[[Page 135]]
(ii) Indications for use. Treatment of coccidiosis.
(iii) Limitations. Administer at the 0.012 percent level in drinking
water as soon as coccidiosis is diagnosed and continue for from 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; no other source of drinking water should be available to
the birds during this time; as sole source of amprolium.
(2) Calves--(i) Amount. 9.6 percent solution or 20 percent soluble
powder.
(a) Indications for use. As an aid in the treatment of coccidiosis
caused by Eimeria bovis and E. zurnii.
(b) Limitations. Add 16 fluid ounces of the 9.6 percent solution to
each 100 gallons of drinking water; or 4 ounces of the soluble powder to
each 50 gallons of drinking water; at the usual rate of water
consumption, this will provide an intake of approximately 10 milligrams
per kilogram (2.2 pounds) of body weight; offer this solution as the
only source of water for 5 days; for a satisfactory diagnosis, a
microscopic examination of the feces should be done by a veterinarian or
diagnostic laboratory before treatment; when treating outbreaks, the
drug should be administered promptly after diagnosis is determined;
withdraw 24 hours before slaughter.
(ii) Amount. 9.6 percent solution or 20 percent soluble powder.
(a) Indications for use. As an aid in the prevention of coccidiosis
caused by Eimeria bovis and E. zurnii.
(b) Limitations. Add 8 fluid ounces of the 9.6 percent solution or 4
ounces of the 20 percent soluble powder to each 100 gallons of drinking
water; at the usual rate of water consumption, this will provide an
intake of approximately 5 milligrams per kilogram (2.2 pounds) of body
weight; offer this solution as the only source of water for 21 days
during periods of exposure or when experience indicates that coccidiosis
is likely to be a hazard; withdraw 24 hours before slaughter.
Sec. 520.100b Amprolium drench.
(a) Chemical name. 1-(4-Amino-2-n-propyl - 5 - pyrimidinylmethyl) -
2 - picolinium chloride hydrochloride.
(b) Sponsor. See No. 000006 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.50 of this chapter.
(d) Conditions of use. It is used for calves as follows:
(1) Amount. 9.6 percent solution or 20 percent soluble powder.
(i) Indications for use. As an aid in the treatment of coccidiosis
caused by Eimeria bovis and E. zurnii.
(ii) Limitations. Add 3 fluid ounces of the 9.6 percent solution to
1 pint of water or 3 ounces of the 20 percent soluble powder to each
quart of water and with a dose syringe administer 1 fluid ounce of this
solution for each 100 pounds of body weight; this will provide a dose of
approximately 10 milligrams per kilogram (2.2 pounds) of body weight;
administer daily for 5 days; for a satisfactory diagnosis, a microscopic
examination of the feces should be done by a veterinarian or diagnostic
laboratory before treatment; when treating outbreaks, the drug should be
administered promptly after diagnosis is determined; withdraw 24 hours
before slaughter.
(2) Amount. 9.6 percent solution or 20 percent soluble powder.
(i) Indications for use. As an aid in the prevention of coccidiosis
caused by Eimeria bovis and E. zurnii.
(ii) Limitations. Add 1\1/2\ fluid ounces of the 9.6 percent
solution to 1 pint of water or 1\1/2\ ounces of the 20 percent soluble
powder to each quart of water and with a dose syringe administer 1 fluid
ounce of this solution for each 100 pounds of body weight; this will
provide a dose of approximately 5 milligrams per kilogram (2.2 pounds)
of body weight; administer daily for 21 days during periods of exposure
or when experience indicates that coccidiosis is likely to be a hazard;
withdraw 24 hours before slaughter.
Sec. 520.100c Amprolium crumbles.
(a) Specifications. Amprolium crumbles contain 1.25 percent
amprolium.
(b) Sponsor. See No. 000006 in Sec. 510.600(c) of this chapter.
(c) Related tolerances. See Sec. 556.50 of this chapter.
(d) Conditions of use. It is top-dressed on or thoroughly mixed in
the daily feed ration of calves as follows:
[[Page 136]]
(1) Amount. 1.6 ounces of crumbles per 250 pounds of body weight per
day (5 milligrams per kilogram of body weight).
(i) Indications for use. As an aid in the prevention of coccidiosis
caused by Eimeria bovis and E. zurnii.
(ii) Limitations. Administer for 21 consecutive days during periods
of exposure or when experience indicates that coccidiosis is likely to
be a hazard. Withdraw 24 hours before slaughter. Use as sole source of
amprolium.
(2) Amount. 3.2 ounces of crumbles per 250 pounds of body weight per
day (10 milligrams per kilogram of body weight).
(i) Indications for use. As an aid in the treatment of coccidiosis
caused by Eimeria bovis and E. zurnii.
(ii) Limitations. Administer for 5 consecutive days. For
satisfactory diagnosis, a microscopic fecal examination should be done
by a veterinarian or diagnostic laboratory before treatment. When
treating outbreaks, the drug should be administered promptly after
diagnosis is determined. Withdraw 24 hours before slaughter. Use as sole
source of amprolium.
[42 FR 41855, Aug. 19, 1977]
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. (1) In swine for control of porcine
colibacillosis (weanling pig scours) caused by strains of E. coli
sensitive to apramycin.
(2) It is administered for 7 days in drinking water at the rate of
12.5 milligrams of apramycin per kilogram (5.7 milligrams per pound) of
body weight per day. Swine will normally consume 1 gallon per day of
medicated water containing 375 milligrams of apramycin for each 66
pounds of body weight. Water consumption should be monitored to
determine that the required amount of apramycin is being consumed. The
drug concentration should be adjusted according to water consumption
which varies depending on ambient temperature, humidity, and other
factors.
(3) Prepare fresh medicated water daily.
(4) 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]
Sec. 520.154 Bacitracin oral dosage forms.
Sec. 520.154a Soluble 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)(3) of this section.
(b) Sponsor. See No. 046573 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 per gallon 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 chickens--(i) Amount. 100 milligrams per gallon 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 milligrams per gallon in drinking water.
(A) Indications for use. Aid in the control of necrotic enteritis
caused by C. 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
[[Page 137]]
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.
[57 FR 37322, Aug. 18, 1992; 57 FR 42623, Sept. 15, 1992]
Sec. 520.154b Soluble bacitracin methylene disalicylate and streptomycin sulfate oral powder.
(a) Specifications. Each gram contains 200 units of soluble
bacitracin methylene disalicylate, streptomycin sulfate equivalent to 20
milligrams of streptomycin, and 850 milligrams of carob flour.
(b) Sponsor. See No. 011716 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. Dogs--(1) Amount. 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. 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. If no improvement is noted in 2 to 3 days,
diagnosis should be reevaluated. Federal law restricts this drug to use
by or on the order of a licensed veterinarian.
[57 FR 37322, Aug. 18, 1992]
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. 010042 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]
Sec. 520.182 Bicyclohexylammonium fumagillin.
(a) Specifications. The drug is a sol- uble powder containing
bicyclohexylammonium fumagillin and appropriate phosphate buffers.
(b) Sponsor. See No. 059620 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) The drug is used for the prevention of
nosema in honey bees.\1\
---------------------------------------------------------------------------
\1\ These conditions are NAS/NRC reviewed and deemed effective.
Applications for these uses need not include effectiveness data as
specified by Sec. 514.111 of this chapter, but may require
bioequivalency and safety information.
---------------------------------------------------------------------------
(2) It is administered usually in a 2:1 sugar sirup containing a
concentration of from 75 to 100 milligrams of fumagillin activity per
gallon of sugar sirup.1
(3) Colonies used for package production should be fed medicated
sirup as a principal food supply for a month prior to stocking nuclei or
shaking packages for market.1
(4) The medicated sirup should not be fed immediately before or
during the honey flow.
[40 FR 13838, Mar. 27, 1975, as amended at 42 FR 65151, Dec. 30, 1977;
56 FR 43699, Sept. 4, 1991; 58 FR 5608, Jan. 22, 1993]
Sec. 520.222 Bunamidine hydrochloride.
(a) Chemical name. N,N-Dibutyl-4-(hexyloxy)-1-naphthamidine
hydrochloride.
[[Page 138]]
(b) Specifications. The drug is an oral tablet containing 100, 200,
or 400 milligrams of bunamidine hydrochloride.
(c) Sponsor. See No. 011716 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 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]
Sec. 520.246 Butorphanol tartrate tablets.
(a) Specifications. Each tablet contains 1, 5, or 10 milligrams of
butorphanol base activity as butorphanol tartrate.
(b) Sponsor. See No. 000856 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. The drug is used for the treatment of dogs as
follows:
(1) Amount. 0.25 milligram of butorphanol base activity per pound of
body weight.
(2) Indications for use. For the relief of chronic nonproductive
cough associated with tracheo-bronchitis, tracheitis, tonsillitis,
laryngitis, and pharyngitis associated with inflammatory conditions of
the upper respiratory tract.
(3) Limitations. For oral use in dogs only. Repeat at intervals of 6
to 12 hours as required. If necessary, increase dose to a maximum of 0.5
milligram per pound of body weight. Treatment should not normally be
required for longer than 7 days. Federal law restricts this drug to use
by or on the order of a licensed veterinarian.
[47 FR l4702, Apr. 6, 1982, as amended at 53 FR 27851, July 25, 1988]
Sec. 520.260 n-Butyl chloride capsules.
(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
[[Page 139]]
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.1
---------------------------------------------------------------------------
1 These conditions are NAS/NRC reviewed and deemed effective.
Applications for these uses need not include effectiveness data as
specified by Sec. 514.111 of this chapter.
---------------------------------------------------------------------------
(2) Sponsors. See No. 023851 in Sec. 510.600(c) of this chapter for
221, 442, 884, or 1,768 milligram or 4.42 gram capsules; No. 000115 or
012983 for 884 or 1,768 milligram or 4.42 gram capsules; and No. 000069
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.
1
(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.1
(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.1
(iii) A veterinarian should be consulted before using in severely
debilitated dogs.1
(c)(1) Specifications. n-Butyl chloride capsules, veterinary contain
884 or 1,768 milligrams or 4.42 grams of n-butyl chloride in each
capsule.
(2) Sponsor. See No. 000115 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 (Ancyclostoma
caninum, Ancyclostoma 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 rations may be resumed 4 to 8 hours
after treatment.
(b) The drug is administered orally to dogs. Capsules containing 884
milligrams of n-butyl chloride are administered to dogs as follows:
weighing under 5 pounds, 1 capsule; weighing 5-10 pounds, 2 capsules;
weighing 10-20 pounds, 3 capsules; weighing 20-40 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 dogs
to dogs weighing 5-10 pounds and 2 capsules per dog to dogs weighing 20-
40 pounds. Capsules containing 4.42 grams of n-butyl chloride are
administered at dosage level of 1 capsule per dog to dogs 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]
[[Page 140]]
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. 000006 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) It is used in horses 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).
(2) It is administered 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).
(3) 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.
(4) Not for use in horses intended for food.
(5) Caution: Do not administer to pregnant mares during first 3
months of pregnancy.
(6) 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]
Sec. 520.300b Cambendazole pellets.
(a) Specifications. The drug is in feed pellets containing 5.3
percent cambendazole.
(b) Sponsor. No. 000006 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) It is used in horses 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).
(2) 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.
(3) 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.
(4) Not for use in horses intended for food.
(5) Caution: Do not administer to pregnant mares during first 3
months of pregnancy.
(6) 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]
Sec. 520.300c Cambendazole paste.
(a) Specifications. The drug is a paste containing 45 percent
cambendazole.
(b) Sponsor. No. 000006 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) It is used in horses 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).
(2) 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.
(3) 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.
(4) Not for use in horses intended for food.
(5) Caution: Do not administer to pregnant mares during first 3
months of pregnancy.
(6) 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]
[[Page 141]]
Sec. 520.310 Caramiphen ethanedisulfonate and ammonium chloride tablets.
(a) Specifications. Each tablet contains 10 milligrams of caramiphen
ethanedisulfonate and 80 milligrams of ammonium chloride.1
---------------------------------------------------------------------------
1 These conditions are NAS/NRC reviewed and deemed effective.
Applications for these uses need not include effectiveness data as
specified by Sec. 514.111 of this chapter, but may require
bioequivalency and safety information.
---------------------------------------------------------------------------
(b) Sponsor. See No. 000856 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.1
(2) Indications for use. For relief of cough.1
[43 FR 55385, Nov. 28, 1978]
Sec. 520.312 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]
Sec. 520.314 Cefadroxil tablets.
(a) Specifications. 50-, 100-, and 200-milligram tablets for dogs
and cats; 1 gram tablet for dogs.
(b) Sponsor. See No. 000856 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) For use in dogs as follows:
(i) Indications for use. 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
Staphylococcus aureus.
(ii) Amount. Ten milligrams per pound of body weight twice daily.
(iii) Limitations. The drug is administered orally. For skin and
soft tissue infections, treatment should be continued for a minimum of 3
days. For genitourinary tract infections, treatment should be continued
for a minimum of 7 days. Continue treatment at least 48 hours after the
dog has become afebrile or asymptomatic. If no response is seen after 3
days of treatment, therapy should be discontinued and the case
reevaluated. Do not treat for more than 30 days. Safety for use in
pregnant bitches and stud dogs has not been determined. Federal law
restricts this drug to use by or on the order of a licensed
veterinarian.
(2) For use in cats as follows:
(i) Indications for use. For the treatment of skin and soft tissue
infections including abscesses, wound infections, cellulitis, and
dermatitis caused by susceptible strains of Pasteurella multocida,
Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus
spp.
(ii) Amount. Ten milligrams per pound of body weight once daily.
(iii) Limitations. The drug is administered orally. Continue
treatment at least 48 hours after the cat has become afebrile or
asymptomatic. If no response is seen after 3 days of treatment, therapy
should be discontinued and the case reevaluated. Do not treat for more
than 21 days. Safety for use in pregnant cats and breeding male cats has
not been determined. Federal law restricts this drug to use by or on the
order of a licensed veterinarian.
[47 FR 41105, Sept. 17, 1982, as amended at 49 FR 43052, Oct. 26, 1984;
51 FR 4165, Feb. 3, 1986; 52 FR 11989, Apr. 14, 1987; 53 FR 27851, July
25, 1988]
Sec. 520.315 Cefadroxil powder for oral suspension.
(a) Specifications. Cefadroxil powder is reconstituted to form a 50
milligram-per-milliliter aqueous suspension.
(b) Sponsor. See No. 000856 in Sec. 510.600(c) of this chapter.
(c) Conditions of use. (1) For use in dogs as follows:
[[Page 142]]
(i) Indications for use. For treating genitourinary tract infections
(cystitis) caused by susceptible strains of Escherichia coli, Proteus
mirabilis, and Staphylococcus aureus; and skin and soft tissue
infections including cellulitis, pyoderma, dermatitis, wound infections,
and abscesses caused by susceptible strains of Staphylococcus aureus.
(ii) Amount. 10 milligrams per pound of body weight, twice daily.
(2) For use in cats as follows:
(i) Indications for use. For treating skin and soft tissue
infections including abscesses, wound infections, cellulitis, and
dermatitis caused by susceptible strains of Pasteurella multocida,
Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus
spp.
(ii) Amount. 10 milligrams per pound of body weight, once daily.
(3) Limitations. Discard unused portion of reconstituted product
after 14 days. Treatment should continue for 48 hours after animal is
afebrile or asymptomatic. If no response after 3 days, discontinue
treatment and reevaluate therapy. Not for use in animals raised for food
production. Safe use in pregnant or breeding animals has not been
established. Federal law restricts this drug to use by or on the order
of a licensed veterinarian.
[53 FR 27344, July 20, 1988]
Sec. 520.390 Chloramphenicol oral dosage forms.
Sec. 520.390a Chloramphenicol tablets.
(a)(1) Specifications. Each tablet contains 100, 250, or 500
milligrams, 1 or 2.5 grams of chloramphenicol.
(2) Sponsor. In Sec. 510.600(c) of this chapter: No. 000010 for 100-
, 250-, and 500-milligram and 1-gram tablets; No. 000856 for 100-, 250-.
and 500-milligram tablets; No. 017030 for 100-milligram tablets; No.
054273 for 100-, 250-, and 500-milligram and 1- and 2.5-gram tablets;
No. 000069 for 250-milligram tablets.
(3) Conditions of use. Dogs--(i) Amount. 25 milligrams per pound of
body weight every 6 hours.
(ii) Indications for use. Oral treatment of bacterial pulmonary
infections, bacterial infections of the urinary tract, bacterial
enteritis, and bacterial infections associated with canine distemper
caused by susceptible organisms.
(iii) Limitations. Laboratory tests should be conducted, including
in vitro culturing and susceptibility tests on samples collected prior
to treatment. If no response to chloramphenicol therapy is obtained in 3
to 5 days, discontinue its use and review diagnosis. Not for animals
which are raised for food production. Chloramphenicol products 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.
Because of potential antagonism, chloramphenicol should not be
administered simultaneously with penicillin or streptomycin. Federal law
restricts this drug to use by or on the order of a licensed
veterinarian.
(b)(1) Specifications. Each tablet contains 50, 100, 250, or 500
milligrams, or 1 gram of chloramphenicol.
(2) Sponsor. See No. 050604 in Sec. 510.600(c) of this chapter.
(3) Conditions of use. Dogs--(i) Amount. 25 milligrams per pound of
body weight every 6 hours.
(ii) Indications for use. Oral treatment of bacterial
gastroenteritis associated with bacterial diarrhea, bacterial pulmonary
infections, and bacterial infections of the urinary tract caused by
susceptible organisms.
(iii) Limitations. Laboratory tests should be conducted, including
in vitro culturing and susceptibility tests on samples collected prior
to treatment. If no response is obtained in 3 to 5 days, discontinue use
and reevaluate diagnosis. Not for animals that are raised for food
production. Chloramphenicol products should not be administered in
conjunction with or 2 hours prior to the induction of general anesthesia
with pentobarbital because of prolonged recovery. Chloramphenicol should
not be administered to dogs maintained for breeding purposes. Because of
potential antagonism, chloramphenicol should not be administered
simultaneously with penicillin or streptomycin. Federal law restricts
this drug to use by or on the order of a licensed veterinarian.
[57 FR 37323, Aug. 18, 1992]
[[Page 143]]
Sec. 520.390b Chloramphenicol capsules.
(a) Specifications. Each capsule contains 50, 100, 250, or 500
milligrams of chloramphenicol.
(b) Sponsor. (1) For chloramphenicol capsules containing 50, 100,
250, or 500 milligrams of chloramphenicol see Nos. 000069, 000172,
000185, and 027454 in Sec. 510.600(c) of this chapter.
(2) For chloramphenicol capsules containing 100 or 250 milligrams of
chloramphenicol see No. 058034 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.
(2) Indications for use. Oral 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. Laboratory tests should be conducted including in
vitro culturing and susceptibility tests on samples collected prior to
treatment. This product 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]
Sec. 520.390c Chloramphenicol palmitate oral suspension.
(a) Specifications. Each milliliter contains chloramphenicol
palmitate equivalent to 30 milligrams of chloramphenicol.
(b) Sponsor. See No. 000856 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]
Sec. 520.420 Chlorothiazide tablets and boluses.
(a)(1) Specifications. Each tablet contains 0.25 gram of
chlorothiazide.
(2) Sponsor. See No. 000006 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.