[Federal Register Volume 61, Number 97 (Friday, May 17, 1996)]
[Proposed Rules]
[Pages 25106-25118]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-12403]




[[Page 25105]]


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Part V





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



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21 CFR Part 530



Extralabel Drug Use in Animals; Propose Rule

  Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed 
Rules  

[[Page 25106]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 530

[Docket No. 96N-0081]

RIN 0910-AA47


Extralabel Drug Use in Animals

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of proposed rulemaking.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing to allow 
veterinarians to prescribe extralabel uses of certain approved animal 
drugs and approved human drugs for animals. This action implements the 
Animal Medicinal Drug Use Clarification Act of 1994 (the AMDUCA). This 
proposed rule will provide veterinarians greater flexibility for using 
approved drugs for animal use.

DATES: Written comments on the proposed rule by July 31, 1996. Written 
comments on the information collection requirements should be submitted 
by June 17, 1996.

ADDRESSES: Written comments on the proposed rule to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 12420 
Parklawn Dr., rm. 1-23, Rockville, MD 20857.

    -Submit written comments on the information collection requirements 
to the Office of Information and Regulatory Affairs, Office of 
Management and Budget (OMB), New Executive Office Building, 725 17th 
St. NW., rm. 10235, Washington, DC 20503, ATTN: Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Richard L. Arkin, Center for 
Veterinary Medicine (HFV-238), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-594-1737.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Background

    A. The Provisions of the AMDUCA

    B. FDA's Extralabel Drug Use Policies

II. Description of the Proposed Rule

    A. Scope and Purpose

    B. Definitions

    C. Specific Issues

    1. Extralabel use when approved drugs are available for intended 
therapeutic purposes

    2. Compounding

    3. Sponsor Records, Reports, and Adverse Events

    D. Advertising and Promotion Prohibited

    E. Access to Veterinarian Records

    F. Provision Permitting Extralabel Use of Animal Drugs

    G. Limitations

    H. Labeling

    I. Specific Provision for New Animal Drug Extralabel Use in Food 
Animals

    J. Prohibitions, Safe Levels, Analytical Methods

    K. Extralabel Drug Use in Nonfood Animals

III. Proposed Effective Dates

IV. Environmental Impact

 V. Analysis of Impacts

 VI. Paperwork Reduction Act of 1995

 VII. Federalism

VIII. Request for Comments

Appendix

I. Background

A. The Provisions of the AMDUCA

    FDA is proposing rules to implement the AMDUCA (Pub. L. 103-396) 
which was signed into law on October 22, 1994. Prior to enactment of 
the AMDUCA, section 512 of the act (21 U.S.C. 360b) provided that a new 
animal drug (NAD) is deemed unsafe unless it is subject to an approved 
application and the drug, its labeling and its use conform to such 
approved application. Therefore, use of an NAD without an approved 
application or in a manner different from that set out in an approved 
application resulted in the drug being unsafe under the act. Section 
501(a)(5) of the act (21 U.S.C. 351(a)(5)) provides that a drug deemed 
to be unsafe under section 512 is adulterated. The AMDUCA allows 
veterinarians to prescribe extralabel uses of approved animal drugs and 
approved human drugs for animals.

    The provisions of the AMDUCA relating to extralabel use of approved 
NAD's provide that such use must be in accordance with conditions 
specified by the Secretary of Health and Human Services (the Secretary) 
by regulations. The animal drug provisions also include several 
safeguards in allowing veterinarians to prescribe drugs for extralabel 
uses: (1) If the Secretary finds there is a reasonable probability that 
an extralabel use may present a risk to public health, the Secretary 
may establish a safe level for a residue for such extralabel use by 
regulation or order, and may require the development of analytical 
methods for residue detection; (2) the Secretary may, by general 
regulation, provide access to records of veterinarians to ascertain any 
use or intended use that the Secretary determines may present a risk to 
public health; and (3) if the Secretary finds, after affording an 
opportunity for public comment, that an extralabel animal drug use 
presents a risk to public health or that no acceptable analytical 
method has been developed and submitted, the Secretary may prohibit 
such extralabel use by order. In addition, the AMDUCA provides that an 
extralabel use of an approved NAD is not permitted if the label of 
another animal drug with the same active ingredient, dosage form, and 
concentration provides for that different use.

    The AMDUCA also allows veterinarians to prescribe approved human 
drugs for use in animals under conditions specified by the Secretary by 
regulations. The human drug provisions do not, however, contain the 
express conditions set out in the statute for extralabel use of 
approved NAD's.

    The AMDUCA adds a new section 301(u) to the act (21 U.S.C. 331(u)) 
which provides that failure to comply with the regulations or orders 
implementing the AMDUCA is a prohibited act. In addition, the AMDUCA 
amends section 512(l) of the act to require drug sponsors to keep 
records and make reports regarding extralabel uses.

    Neither the AMDUCA nor the implementing regulations are intended to 
lessen the responsibility of the manufacturer, the veterinarian, or the 
food producer with regard to violative drug residues or other adverse 
impact on human health. Under the act and this proposal, any amount of 
residue that may present a risk to public health resulting from an 
extralabel use would constitute a violation of the act subject to 
enforcement action, if a safe level or tolerance has not been 
established. Residue exceeding an established safe level would also 
constitute a violation of the act, as would residue resulting from an 
extralabel use where the residue exceeds an established tolerance.

    The AMDUCA requires that the Secretary issue final rules 
implementing the statute within 2 years of the enactment date. The 
provisions of the AMDUCA are effective upon adoption of the final 
rules.

B. FDA's Extralabel Drug Use Policies

    Under the current statute, extralabel use of drugs in animals is a 
violation of the act, therefore, FDA set out its enforcement policies 
regarding such use in two FDA Compliance Policy Guides (CPG's). The 
first of these was issued on March 9, 1984, as CPG 7125.06, 
``Extralabel Use of New Animal Drugs in Food-Producing Animals,'' and 
was revised most recently on July 20, 1992. In March 1995, CPG 7125.06 
was published as Section 615.100 of Chapter

[[Page 25107]]

6 in a new agency compilation of CPG's entitled the ``FDA Compliance 
Policy Guides Manual, first edition'' (Washington: Government Printing 
Office, publication 1995-386-982-3373, 1995). The second relevant CPG, 
``Human-Labeled Drugs Distributed and Used in Animal Medicine,'' was 
issued as CPG 7125.35 on March 19, 1991, and was last revised on July 
20, 1992. It has been published as Section 615.100 in Chapter 6 of the 
CPG Manual.
    -The extralabel CPG's were issued to provide information and 
direction to FDA personnel in the field about the circumstances in 
which FDA would take regulatory action against extralabel use of 
approved NAD's and human drugs in animals and the situation in which 
the agency would exercise its regulatory discretion and not take 
action. The scant legislative history of the AMDUCA includes some 
evidence that the AMDUCA is intended to codify policies similar to 
those in FDA's CPG's. While there are no committee reports on the 
AMDUCA, floor statements of individual members of Congress express this 
intent. For example, Senator Pressler said in debate on the bill, ``FDA 
has stated it will not institute regulatory action against licensed 
veterinarians for using or prescribing any drugs legally obtained. 
Thus, this bill codifies existing FDA practice.'' (140 Congressional 
Record S14072 (daily ed. October 4, 1994)). Senator Coats made a 
similar statement on the floor when he noted that the AMDUCA ``codifies 
the practices allowed under the current compliance policy guidelines'' 
regarding the extralabel use of veterinary pharmaceutical products. 
(140 Congressional Record S14272 (daily ed. October 5, 1994)).
    -Consistent with these congressional statements, FDA has generally 
followed policies similar to those in the existing CPG's in this 
proposed rule. For the public's convenience, the texts of the 
extralabel CPG's are included in this document in an appendix to the 
preamble. It-is anticipated that the CPG's will be withdrawn after a 
final rule based on this proposal has been published.

-II. Description of the Proposed Rule

--A. Scope and Purpose

    -The proposed rule would apply to the extralabel use in an animal 
of any approved NAD or approved human drug used by or on the lawful 
order of a veterinarian within the context of a veterinarian-client-
patient relationship. Human drugs include approved new human drugs, as 
well as over-the-counter (OTC) drugs marketed under OTC monographs as 
safe and effective and not misbranded within the meaning of 21 CFR part 
330. The proposal applies only to the extralabel use of approved NAD's 
and approved human drugs and not to the use of unapproved drugs.
    -Consistent with the policies in the CPG's, these proposed rules 
limit extralabel uses for food-producing animals to those that provide 
alternative treatment modalities when the health of an animal is 
threatened, or suffering or death may result from failure to treat an 
animal, i.e., therapeutic uses. FDA, however, has received increased 
requests to permit extralabel drug use for certain nontherapeutic uses 
such as uses related to enhanced animal reproduction. For example, 
representatives of the aquaculture industry have expressed a need for 
extralabel uses of drugs for spawning and gender reversal processes. 
Those representatives contended that certain aquaculture industries 
would not be able to survive economically without such extralabel uses, 
because approved drugs have not been available for those uses. Comments 
by members of the Veterinary Medicine Advisory Committee (VMAC) and 
others at the April 1995 VMAC meeting generally agreed that extralabel 
uses might be extended to some reproductive uses in terrestrial and, 
especially, aquatic animals.
    -The agency, in considering the appropriate scope of extralabel use 
under the statute, is concerned about the possible deterrent effect of 
such broad extralabel use on the widely-shared goal of increasing the 
number of approved drugs that are available for animal use. Therefore, 
the agency is interested in public comments as to nontherapeutic 
extralabel uses such as reproductive uses in terrestrial and, 
especially, aquatic animals and other possible uses. The agency also is 
interested in public comment as to appropriate ways to balance 
extralabel use with the need to preserve the goal of increased 
availability of new animal drugs approved for such uses under section 
512 of the act.

-B. Definitions

    -Proposed Sec. 530.3 includes definitions of relevant terms. The 
term ``extralabel use'' means the actual or intended use of a human or 
animal drug in an animal in a manner that is not in accordance with the 
approved labeling. This includes, but is not limited to, use in species 
or for indications (disease or other therapeutic conditions) not listed 
in the labeling, use at dosage levels, frequencies, or routes of 
administration other than those stated in the labeling, and deviation 
from the labeled withdrawal time. Any deviation from labeled withdrawal 
time based on these different uses must be supported by appropriate 
scientific information.
    -The proposed rule defines the term ``residue'' to mean any 
compound present in edible animal tissues that results from the use of 
a drug, and would include the drug, its metabolites, and any other 
substance formed in or on food because of the drug's use.
    -The proposal defines a ``safe level'' as a conservative estimate 
of a drug residue level in animal tissue derived from toxicology and 
metabolism data or other scientific information. This level would be 
established so that concentrations of residues in tissue below the safe 
level will not raise human food safety concerns.
    -Under the proposal, a safe level would not be either a safe 
concentration or a tolerance and would not indicate that an approval 
exists for the drug in that species or category of animals from which 
the food is derived. If FDA establishes a safe level and a tolerance is 
later established through an approval for a particular species or 
category of animals, the safe level would be superseded by the 
tolerance for that species or category of animals, and would be 
revoked. -
    -The term ``veterinarian'' is defined as a person licensed by a 
State or Territory to practice veterinary medicine, and who holds a 
degree of Doctor of Veterinary Medicine (D.V.M.), Veterinary Medical 
Doctor (V.M.D.), or the equivalent, from an accredited institution.
    -A ``valid veterinarian-client-patient relationship'' is defined as 
one in which: (1) A veterinarian has assumed the responsibility for 
making medical judgments regarding the health of an animal and the need 
for medical treatment, and the client (the owner or other caretaker of 
the animal or animals) has agreed to follow the instructions of the 
veterinarian; (2) there is sufficient knowledge of the animal(s) by the 
veterinarian to initiate at least a general or preliminary diagnosis of 
the medical condition of the animal(s); and (3) the veterinarian is 
readily available for followup in case of adverse reactions or failure 
of the regimen of therapy. Such a relationship can exist only when the 
veterinarian has recently seen and is personally acquainted with the 
keeping and care of the animal(s) by virtue of examination of the 
animal(s), and/or by medically appropriate and timely visits to the 
premises where the animal(s) are kept. This definition is consistent 
with the American Veterinary Medicine

[[Page 25108]]

Association's definition of a ``valid veterinarian-client-patient 
relationship.''
    The proposed rules, for purposes of establishing a safe level and 
requiring the development of analytical methods to detect residues, 
define the phrase ``a reasonable probability that a drug's use may 
present a risk to the public health''as a circumstance in which FDA has 
reason to believe that use of a drug may be likely to cause a potential 
adverse event. The proposal, for purposes of providing access to 
veterinarians' records, would define the phrase ``use of a drug may 
present a risk to the public health''to mean a circumstance in which 
FDA has information that indicates that use of a drug may cause an 
adverse event. In addition, under the proposal, the phrase ``use of a 
drug presents a risk to the public health,''for purposes of prohibiting 
an extralabel use, means a circumstance in which FDA has evidence that 
demonstrates that the use of a drug has caused or is likely to cause an 
adverse event.
    In defining these phrases regarding risk, the agency considered the 
common meaning of the words in these phrases, and other regulations in 
which FDA has defined similar concepts (e.g., 21 CFR 7.3(m), 7.41, and 
803.3(r). The statute provides for an increased level of FDA activity 
as evidence of public concern becomes more substantial, and as the 
connection between specific extralabel uses and effect on the public 
health becomes more apparent. The final step may be prohibition of 
specified extralabel uses.
    A finding that there is a reasonable probability that ``a drug's 
use may present a risk to the public health'' could be based on 
relevant information--assessed in the light of the education and 
experience of an agency staff member or other qualified person--that 
there may be a connection between a use and a potential adverse event. 
This would differ from a finding that ``use of a drug may present a 
risk to the public health,'' which would normally be based on some 
greater level of information that demonstrates that there may be some 
more concrete link between the use and an adverse event. In contrast, a 
finding that ``use of a drug presents a risk to the public health'' 
would require strong evidence of a direct link between the use and the 
risk.
    FDA intends that harm that results from chronic low level or repeat 
exposure that is not high enough to cause acute toxicity but that could 
cause toxicity over long periods of time is included within the meaning 
of ``adverse event.''
C. Specific Issues
1. Extralabel Use When Approved Drugs are Available For Intended 
Therapeutic Purposes.
    FDA's discretionary policies have precluded extralabel use of an 
animal or human drug in food-producing animals when an approved drug 
for the intended use exists. A similar limitation has not applied in 
the case of animal and human drugs used in animals not intended for 
human consumption; the agency has exercised broad enforcement 
discretion with regard to extralabel use in those species.
    The AMDUCA provides that an extralabel use of an approved animal 
drug is not permitted if an approved NAD with the same active 
ingredient in the same dosage form and concentration exists for that 
use. The statute does not limit this provision to food-producing 
animals as FDA did in its CPG. Therefore, proposed 
Sec. Sec. 530.20(a)(1) and 530.30(a) limit the extralabel use of 
approved animal drugs in all animals to circumstances in which there is 
no approved NAD in the needed dosage form and concentration. The CPG 
contains an exception that permits an extralabel use where the 
veterinarian finds, within the context of a valid veterinarian-client-
patient relationship, that an approved NAD is clinically ineffective 
for its intended use. The proposed rule does not include a similar 
provision. However, the agency invites comment as to whether the agency 
should permit such an exception.
    The AMDUCA does not restrict extralabel use of approved human drugs 
in a similar manner. However, these proposed rules include the same 
limitation for extralabel use of human drugs in food-producing animals. 
FDA believes that, because of the broad public health implications 
inherent in the treatment of animals that will become food, it is 
prudent to require the use of an approved NAD if one exists before the 
extralabel use of a human drug is appropriate.
2. Compounding
    FDA considers compounding from an approved drug to be an extralabel 
use. Thus, the agency views the language of the AMDUCA as giving 
statutory authorization to the compounding of finished drug products 
from approved human or approved animal drugs, within limits, under the 
same conditions as for any other extralabel use. FDA has certain 
concerns relative to compounding and the use of compounded drugs that 
can be distinguished from those issues associated with simple 
extralabel use of an approved finished drug product.
    In view of the above, the proposed rule includes several major 
factors in addition to the general criteria set forth elsewhere in this 
proposed rule applicable to the extralabel use by compounding from 
approved drugs. The proposal provides that such extralabel use is 
permissible if: (1) All relevant portions of proposed part 530 have 
been complied with; (2) there is no marketed or approved human or new 
animal drug that, when used as labeled or in conformity with criteria 
established in this part, will, in the available dosage form and 
concentration, appropriately treat the condition diagnosed; (3) 
compounding is performed by a licensed pharmacist or veterinarian 
within the scope of a professional practice; (4) adequate processes and 
procedures are followed that ensure the safety and effectiveness of the 
compounded products; (5) the scale of the compounding operation is 
commensurate with the established need for compounded products (e.g., 
similar to that of comparable practices); and (6) all relevant State 
laws relating to the compounding of drugs for use in animals are 
followed.
    The AMDUCA does not authorize compounding from bulk drugs or 
unapproved drugs. Compounding by or for veterinarians from bulk drugs 
or unapproved drugs results in the production of an unapproved NAD that 
may be subject to regulatory action. Accordingly, proposed Sec. 530.13 
provides that allowable extralabel use by compounding applies only to 
compounding of a product from approved drugs by a veterinarian or a 
pharmacist on the order of a veterinarian within the practice of 
veterinary medicine, and that nothing in proposed part 530 is to be 
construed as permitting compounding from bulk drugs or unapproved 
drugs.
    Additional guidance on the subject of compounding may be provided 
in guidance documents to be issued by FDA.
3. Sponsor Records, Reports, and Adverse Events
    FDA is concerned that the enactment of the AMDUCA could have the 
unintended effect of reducing the information that has heretofore been 
provided to the agency by sponsors regarding their products.
    Information that helps FDA assure the safe and effective use of 
approved drugs comes from two sources, among others. First, sponsors 
submit data and information on adverse events resulting from extralabel 
uses. Second, sponsors submit supplemental applications to extend the 
product labels to provide for new uses. The agency's concerns are

[[Page 25109]]

that under the AMDUCA the sponsors might have less incentive to submit 
supplemental applications, and might also be reluctant to report 
extralabel use adverse events that FDA could require to be stated in 
the labeling. FDA believes that neither result was intended by 
Congress. For example, the AMDUCA specifically requires the reporting 
of adverse events related to extralabel uses.
    -Section 512(l) of the act requires sponsors to maintain records of 
and report experiences ``and other data and information'' regarding a 
drug. Under 21 CFR 510.300  et seq., ``Records and Reports,'' adopted 
under section 512(l) of the act, sponsors are currently required to 
report on extralabel drug uses. Section 2 of the AMDUCA amended section 
512(l) of the act by adding new language specifically requiring 
maintenance of records and reports of experiences related to extralabel 
drug uses. Accordingly, the sponsor is required to maintain records of 
and report to the agency all information the sponsor has that pertains 
to extralabel drug uses, including adverse drug experiences.
    Data derived from such records and reports may be used in 
establishing a prohibition against the use of a drug in food-producing 
animals under Secs. 530.21 and 530.25, or safe levels and analytical 
methods under proposed Secs. 530.22, 530.23, and 530.24. In addition, 
Section 2 of the AMDUCA amended section 512(e) of the act by adding new 
language specifically giving authority to the agency to withdraw 
approval of a NAD based on records and reports of experience with 
extralabel uses, in addition to experience with an approved use.
    -FDA believes that it is important to publicize data it has 
received concerning adverse events resulting from all uses, including 
extralabel drug uses. This could be done through provision of this 
information to professional journals, the trade press, and others, 
through press releases, ``Dear Doctor letters,'' and similar documents. 
FDA would be interested in receiving comments from the public with 
respect to any policy that would allow or encourage sponsors to provide 
extralabel drug use information regarding significant adverse events on 
labeling.

-D. Advertising and Promotion Prohibited

    -While the AMDUCA and the proposed rule permit extralabel uses of 
approved drugs, neither the statute nor the proposed rule would permit 
advertising and promotion of extralabel uses. The act does not permit 
advertising and promotion of an unapproved use for a human or approved 
animal drug because scientific data supporting the safety and efficacy 
of a new drug use must be submitted by the sponsor and reviewed and 
approved by the agency in order to permit such use to be advertised, 
promoted, or included on the labeling. Advertising and promoting of any 
unapproved use for a drug would be inconsistent with the act and would 
subvert the entire system of drug approval and regulation because there 
would no longer be any incentive for a sponsor to submit data and go 
through the approval process for an unapproved use.
    -Accordingly, proposed Sec. 530.4 includes a statement that the 
rule shall not be construed as permitting advertising or promotion of 
extralabel uses of human or new animal drugs.

E. Access to Veterinarian Records-

    Section 2(a) of the AMDUCA adds a new section 512(a)(4)(C) to the 
act which provides that FDA may adopt regulations providing FDA the 
right of access to records maintained by veterinarians to ascertain any 
extralabel use or intended use of an approved animal drug authorized by 
the agency that may present a risk to the public health.
    -Proposed Sec. 530.5 provides that persons designated by FDA (i.e., 
FDA investigators) would be given access to the records of 
veterinarians, including records required to be maintained under the 
act, State veterinary practice acts, and State pharmacy acts. Any 
person who has custody of these records would be required to permit 
inspection at any reasonable times, permit copying, and verify such 
records.
    -While the AMDUCA does not include an explicit authority for FDA to 
require the creation and maintenance of records by veterinarians, the 
statute clearly allows the agency to specify the conditions for 
extralabel use. The agency believes that the maintenance of records is 
essential to the agency's ability to implement the statute and protect 
the public health and, as such, maintenance of records is a condition 
of allowable extralabel use. However, it is not FDA's intention to 
create new recordkeeping burdens on veterinarians who are required to 
keep records under State recordkeeping requirements.
    -FDA believes that these State required records will include the 
type of information FDA will need to carry out its statutory 
responsibilities. Records required by State veterinary practice acts or 
State pharmacy acts routinely document the existence of a valid 
veterinarian-client-patient relationship. These records also would 
provide relevant information concerning extralabel drug uses. 
Typically, these records include: (1) The name, address, and telephone 
number of the veterinarian; (2) the name, address, and telephone number 
of the client; (3) the complaint, or other reason for the provision of 
services, including information on the patient history, physical 
examination, and laboratory data; (4) the provisional or final 
diagnosis and date of diagnosis; (5) identification of the animal(s) 
treated (including species, breed, age, sex, color, brand, and tag or 
tattoo number); (6) the date of treatment, prescribing, or dispensing 
of the drug; (7) the established name of the drug and its active 
ingredient, or if formulated from more than one ingredient, the 
established name of each ingredient; the dosage form, strength, and 
quantity of the prescribed or dispensed drug, and the dates of 
administration; (8) any directions for use provided, including dose, 
route of administration, and length of therapy; (9) the number of 
refills authorized; (10) cautionary statements, if any; and (11) the 
veterinarian's specified withdrawal, withholding, or discard time(s), 
if applicable, for meat, milk, eggs, or any food that might be derived 
from any food animals treated.
    -Under the proposal, veterinarians would be required to maintain 
individual records for each nonfood animal treated as required by State 
veterinary practice and pharmacy acts. State veterinary practice acts 
generally require veterinarians in large animal practices to maintain 
records for food-producing animals that are adequate to substantiate 
the identification of the animals and the medical care provided. Such 
records in large animal practices can usually be maintained either as 
individual records or on a group, herd, flock, or per-client basis.
    -State veterinary practice and State pharmacy acts generally 
require veterinarians to maintain complete records of receipt and 
distribution of each veterinary drug. These records, which are 
maintained in the form required by the appropriate State acts, may 
include sales invoices, shipping records, prescription files, or 
records or logs established solely for this purpose. Receipt and 
distribution records usually are also required to include: (1) The name 
of the drug, (2) the name and address of the person or corporation from 
whom the drug was shipped, (3) the date and quantity received, and (4) 
the name and address of the person to whom the drug was distributed.

[[Page 25110]]

    -Under the proposed rule, drug distribution and use records would 
be required to be maintained for 2 years or as otherwise required by 
Federal or State law, whichever is greater.
    -The proposal would require that veterinarians maintain all records 
required by State veterinary practice and pharmacy acts in a legible 
form, document them in an accurate and timely manner, and keep them 
readily accessible to permit prompt retrieval of information.
    -Refusal to provide access to such required records is a prohibited 
act under section 301 of the act as amended by the AMDUCA.

-F. Provision Permitting Extralabel Use of Animal Drugs

    -Proposed Sec. 530.10 provides that extralabel use of an approved 
human or NAD is permitted by or under the lawful written or oral order 
of a veterinarian within the context of a veterinarian-client-patient 
relationship, if the extralabel use is otherwise in compliance with the 
regulation.

-G. Limitations

    - Proposed Sec. 530.11 sets out the following specific limitations 
on extralabel use. The following uses result in the drug being deemed 
to be unsafe within the meaning of the act: (1) Extralabel use in an 
animal of an approved new animal or human drug by a lay person (except 
under the supervision of a veterinarian), (2) extralabel use of an 
approved NAD or human drug in or on an animal feed, (3) extralabel use 
resulting in any residue which may present a risk to public health, and 
(4) extralabel use resulting in any residue above an established safe 
level or tolerance.

-H. Labeling

    -The proposal at Sec. 530.12 would require that any human or animal 
drug prescribed or dispensed for extralabel use by a veterinarian or a 
pharmacist on the order of a veterinarian bear or be accompanied by 
labeling information adequate to assure the safe and proper use of the 
product. The phrase ``be accompanied by'' is intended to permit 
shipment of drugs by a veterinarian or pharmacist on the order of a 
veterinarian in case quantities. The minimum information required under 
the proposal is the same as that currently required by CPG and 
includes: (a) The name and address of the veterinarian; (b) the 
established name of the drug, or if formulated from more than one 
active ingredient, the established name of each ingredient; (c) any 
directions for use specified by the veterinarian, including the class/
species or identification of the animal in which it is intended to be 
used; the dosage, frequency, and route of administration; and the 
duration of therapy; (d) any cautionary statements; and (e) the 
veterinarian's specified withdrawal, withholding, or discard time for 
meat, milk, eggs, or any food that might be derived from the treated 
animal.

-I. Specific Provision for New Animal Drug Extralabel Use in Food 
Animals

    -Proposed Sec. 530.20(a)(2) requires as a condition for extralabel 
use that a veterinarian be required to take a number of affirmative 
actions before prescribing or dispensing an animal or human drug for an 
extralabel use in food animals. The veterinarian must do the following: 
(1) Make a careful diagnosis and evaluation of the conditions for which 
the drug is to be used; (2) establish a substantially extended 
withdrawal period prior to marketing of milk, meat, or eggs supported 
by appropriate scientific information, if applicable; (3) institute 
procedures to assure that the identity of the treated animal or animals 
is carefully maintained; and (4) take appropriate measures to assure 
that assigned timeframes for withdrawal are met and no illegal drug 
residues occur in any food-producing animal subjected to extralabel 
treatment.
    -Because extralabel use of drugs in food-producing animals 
engenders an increased potential for illegal drug residues in meat, 
milk, and eggs, which are consumed in significant amounts by the 
American public, the proposed rule would also set forth additional 
conditions for extralabel drug use in food-producing animals.
    -One restriction, contained in proposed Sec. 530.20(b), applies to 
the extralabel use of either an approved human drug, or an animal drug 
approved only for use in animals not intended for human consumption. In 
such instances, records maintained by the veterinarian must reflect the 
medical rationale for such use. In addition, if there is no published 
scientific information on public health aspects of the use of the 
nonfood animal drug in food-producing animals, the veterinarian must 
determine that the animal and its food products will not enter the 
human food supply.
    -A second restriction would apply only to the use of human drugs in 
food animals. As discussed in section II.C. of this document, proposed 
Sec. 530.20(a)(1) would not allow such use if an approved animal drug 
is available for such use (with certain exceptions). Section 530.20(c) 
requires the additional step of consideration of extralabel use of 
approved food-animal drug before use of a human drug or drug approved 
for use in animals not intended for human consumption. In addition, 
records maintained by the veterinarian must reflect this consideration.

-J. Prohibitions, Safe Levels, Analytical Methods

    -Section 512(a)(4)(B) and (a)(4)(D) of the act as added by the 
AMDUCA grants FDA the authority to prohibit extralabel drug uses, 
establish safe levels and require the development of analytical 
methods. These provisions are included in section 512(a)(4) of the act 
which addresses approved NAD's and are not specified in section 
512(a)(5) which addresses approved human drugs. Nevertheless, FDA 
believes that, under the general authority in section 512(a)(5) of the 
act to set the conditions for extralabel use of approved human drugs in 
animals, the agency may also set safe levels, require development of 
analytical methods, and prohibit extralabel uses of human drugs when 
necessary to protect the public health. Thus, the proposed rule applies 
these safeguards to human drugs as well as animal drugs.
    -Proposed Sec. 530.21 addresses food-producing animals and states 
that FDA can prohibit the use of a drug or class of drugs in food-
producing animals if the agency determines that: (1) An acceptable 
analytical method needs to be established and such method has not been 
established or cannot be established, or (2) the use of the drug or 
class of drugs presents a risk to public health. Under the proposal, a 
prohibition may be a general ban on the use of the drug or class of 
drugs in all food-producing animals, or may be limited to a specific 
species, indication, dosage form, route of administration, or 
combination of factors.
    -Under proposed Sec. 530.22, FDA could establish a safe level for 
extralabel use of a drug upon a finding that there is a reasonable 
probability that an extralabel use may present a risk to the public 
health. To accomplish this, the agency may: (1) Establish a finite safe 
level based on residue and metabolism information (i.e., toxicological 
data) from available sources; (2) establish a safe level based on the 
lowest level that can be measured by a practical analytical method; or 
(3) establish a safe level based on other appropriate scientific, 
technical, or regulatory bases.
    -The proposal allows FDA to require the development of an 
acceptable analytical method for the quantification or detection of 
residues. If FDA requires such a method, the agency would

[[Page 25111]]

announce that requirement in the Federal Register. If development of an 
acceptable analytical method is required and a method is not developed, 
submitted, and accepted, the agency could, under the proposal, prohibit 
the extralabel use of the drug in food-producing animals.
     -The proposed rule provides, however, that if the agency 
establishes a safe level and a tolerance is later established through 
an approval for a particular species or category of animals, the safe 
level is superseded by the tolerance for that species or category of 
animals.
    -The proposed rule contemplates that FDA: (1) Will establish safe 
levels and publish them in the Federal Register, and (2) may establish 
specific analytical methods for drug residue detection for those drugs 
for which safe levels have been established. The safe levels and the 
availability of an analytical method will be codified at proposed 
Sec. 530.40.
    -Proposed Sec. 530.23 states that FDA will publish a document 
establishing a safe level in the Federal Register. This document would 
include a statement setting forth the agency's finding that there is a 
reasonable probability that extralabel use in animals of the human drug 
or animal drug may present a risk to public health, and would request 
public comments.
    -Under the proposed rule, FDA would codify in proposed Sec. 530.40 
the following: (1) A current listing of those drugs for which a safe 
level for extralabel drug use in food-producing animals has been set, 
and (2) the specific safe levels, and the availability, when one has 
been developed, of a specific analytical method or methods for drug 
residue detection.
    -Proposed Sec. 530.24 provides that copies of analytical methods 
would be made available upon request from the Center for Veterinary 
Medicine's Communications and Education Branch (HFV-12), 7500 Standish 
Pl., Rockville, MD 20855, and that acceptable analytical methods will 
be incorporated by reference.
    -While the agency does not intend to engage in prior notice and 
comment rulemaking for the establishment or acceptance of analytical 
methods or safe levels, interested persons will have the opportunity to 
make public comment to the agency as these actions are announced and 
published that could, if appropriate, result in modifications to the 
actions.
    -Proposed Sec. 530.25 provides that FDA could issue an order 
prohibiting extralabel use of a drug in food-producing animals if the 
agency finds, after providing an opportunity for public comment, that: 
(1) An acceptable analytical method has not been developed, submitted, 
and found to be acceptable by FDA; or (2) an extralabel use in animals 
of a particular human drug or animal drug presents a risk to the public 
health.
    -After making a preliminary determination that a required 
analytical method has not been developed and submitted, or an 
extralabel use in food-producing animals of a particular human drug or 
animal drug presents a risk to the public health, FDA would, under the 
proposal, publish an order of prohibition with a 90-day delayed 
effective date in the Federal Register. Such order would specify the 
nature and extent of the order of prohibition and the reasons for the 
prohibition, and provide a period of not less than 60 days for 
comments.
    -The order of prohibition would become effective 90 days after the 
date of publication of the order of prohibition unless FDA publishes a 
Federal Register document before that date revoking the order of 
prohibition, modifying it, or extending the period of public comment.
    -The proposed rule would permit the agency to publish an order of 
prohibition with an abbreviated comment period and/or delayed effective 
date in exceptional circumstances (e.g., where there is immediate risk 
to the public health), provided that the order of prohibition states 
that the comment period and/or effective date have been abbreviated 
because there are exceptional circumstances, and sets forth the 
exceptional circumstances and the agency's rationale for taking such 
action.
    -Under the proposal, a current listing of drugs prohibited for 
extralabel use in food-producing animals would be codified in new 
Sec. 530.41.
    -The proposed rule would also note that the agency could, after 
publishing a Federal Register document, remove a drug from the 
prohibited list after the submission of appropriate information, such 
as adequate safety and effectiveness data, an acceptable method, 
approval of a new animal drug application for the prohibited drug and 
use, or information demonstrating that the prohibition was based on 
incorrect data.

-K. Extralabel Drug Use in Nonfood Animals

    -Because the same public health implications do not exist in the 
treatment of nonfood animals as for food animals, the proposed rule 
does not include the same level of detail for such extralabel use. 
Specifically, proposed Sec. 530.30 provides that veterinarians can make 
extralabel use or dispensing of drug products in nonfood-producing 
animal practice except when such use may threaten the public health. 
One other limitation, as discussed earlier in the preamble, is that, if 
an approved NAD for such use exists, an extralabel use of an approved 
animal or human drug is not permitted. (See proposed Sec. 530.30(a).)
    -The proposal adds that the agency may publish a document in the 
Federal Register prohibiting a particular extralabel drug use in 
nonfood animals if the agency determines that it presents a risk to the 
public health. This provision is consistent with the agency's authority 
to establish conditions for extralabel use of human drugs under the 
AMDUCA.

-III. Proposed Effective Dates

    -Under Section 2(d) of the AMDUCA, the amendments to the act 
permitting the extralabel use of certain approved animal drugs and 
approved human drugs for animals become effective upon the adoption of 
final rules implementing the amendments. FDA intends that any final 
rule that may issue based on this proposal become effective 30 days 
after the date of publication in the Federal Register.

-IV. Environmental Impact

    -The agency has determined under 21 CFR 25.24(a)(8) that this 
action is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

-V. Analysis of Impacts

    -FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354). 
Executive Order 12866 directs agencies to assess all costs and benefits 
of available regulatory alternatives and, when regulation is necessary, 
to select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this proposed rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the proposed 
rule is not a significant regulatory action as defined by the Executive 
Order.
    -Most of the requirements in this proposed rule have already been 
implemented by regulated industry,

[[Page 25112]]

veterinarians, and pharmacists in response to the existing Compliance 
Policy Guides relating to extralabel drug use in animals and the 
passage of the AMDUCA, FDA guidance, and industry trade associations' 
recommendations, as well as the requirements of State veterinary 
practice acts and as customary elements of good veterinary medical 
practice.
    -The actual cost to industry and the public associated with this 
proposal will be quite minimal. The AMDUCA was enacted to decriminalize 
extralabel use of most approved new human and animal drugs in 
veterinary medicine, and to provide FDA with specific regulatory tools 
to assure food safety. Congress intended that the new legislation 
codify FDA's discretionary enforcement policies that have permitted 
extralabel use of approved new human and animal drugs by veterinarians 
in specified circumstances.
    -FDA is likely to require the establishment of a safe level for one 
to two drugs per year after the proposed rule is finalized. An 
analytical methodology for drug residue detection will be required for 
each of these drugs. The sponsor may be willing to provide the 
methodology in some cases, while in others, FDA, the sponsor, and, 
perhaps, a third party, may negotiate a cooperative arrangement for 
methodology development. The range of costs for development of 
methodologies is likely to range from about $90,000 for a drug for 
which there are few problems in developing a procedure, upward to about 
$350,000 for a drug which presents significant problems in methodology 
development, with an additional $100,000 required for a drug metabolism 
study. Methodology development costs for a drug presenting an 
intermediate level of difficulty would be about $170,000. The agency 
estimates that the average year would see the development of two drug 
methodologies presenting an intermediate level of development 
difficulty, with one of those drugs requiring a metabolism study, for 
an annual cost impact of about $440,000. The proposal does not impose 
any new extralabel drug use recordkeeping and reporting requirements 
for sponsors or veterinarians which are not currently required under 
other sections of the act or under State veterinary practice acts.
    -The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a 
proposed rule on small entities. Because the proposed rule clarifies 
existing FDA policy, and because most of the requirements in this 
proposed rule have already been implemented by regulated industry, 
veterinarians, and pharmacists in response to the existing Compliance 
Policy Guides relating to extralabel drug use in animals and the 
passage of the AMDUCA, FDA guidance, and industry trade associations' 
recommendations, the agency certifies, in accordance with section 
605(b) of the Regulatory Flexibility Act, that the proposed rule will 
not have a significant economic impact on a substantial number of small 
entities. Therefore, under the Regulatory Flexibility Act, no further 
analysis is required.

-VI. Paperwork Reduction Act of 1995

    -This proposed rule contains reporting requirements that are 
subject to public comment and to review by OMB under the Paperwork 
Reduction Act of 1995 (Pub. L. 104-13). Therefore, in accordance with 5 
CFR 1320, a description of reporting requirements is given below with 
an estimate of the annual collection of information burden. Included in 
the estimate is the time for reviewing instructions, gathering and 
maintaining the data needed, and completing and reviewing the 
collection of information.
    -With respect to the following collection of information, FDA is 
soliciting comments on: (1) Whether the proposed collection of 
information is necessary for proper performance of FDA's functions, 
including whether the information will have practical utility; (2) the 
accuracy of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection of information on respondents, including through the use of 
automated collection techniques, when appropriate, and other forms of 
information technology.
    -Title: Extralabel Drug Use in Animals.
    -Description: This proposed rule provides that FDA may require the 
development of an acceptable analytical method for the quantification 
of residues above an established safe level. FDA estimates that it will 
likely establish safe levels for one to two drugs per year if the rule 
is finalized, and that an analytical methodology for drug residue 
detection will be required for each of these drugs. If no method is 
provided, the Secretary may prohibit the extralabel use. This 
requirement may be fulfilled by any interested person. FDA believes 
that the sponsor may be willing to provide the methodology in some 
cases, while in others, FDA, the sponsor, and perhaps a third party may 
negotiate a cooperative arrangement for method development.
    -Description of Respondents: Persons, sponsors, States, or Federal 
Government.

                                        ESTIMATED ANNUAL REPORTING BURDEN                                       
----------------------------------------------------------------------------------------------------------------
                                                      Annual                                                    
         21 CFR Section               No. Of       Frequency per   Total Annual      Hours per      Total Hours 
                                    Respondents      Response        Responses       Response                   
----------------------------------------------------------------------------------------------------------------
21 CFR 530.22(b)                        2               1               2           4,160           8,320       
----------------------------------------------------------------------------------------------------------------

There are no operating and maintenance or capital costs associated with 
this information collection. The agency recognizes that the time and 
expense of method development is highly variable dependent on the 
difficulty of the development. The agency estimates that two methods of 
intermediate difficulty would be developed and these methods may take 
up to 2 person-years to develop.
    -The agency has submitted a copy of this proposed rule to OMB for 
its review and approval of this information collection. Interested 
persons are requested to send comments regarding this information 
collection, including suggestions for reducing this burden to the 
Office of Information and Regulatory Affairs, OMB, New Executive Office 
Building, 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: Desk 
Officer for FDA. Written comments on the information collection should 
be submitted by June 17, 1996.

-VII. Federalism

     -FDA has analyzed this proposal in accordance with the principles 
and criteria set forth in Executive Order 12612 and has determined that 
this

[[Page 25113]]

proposal does not have sufficient federalism implications to warrant 
the preparation of a federalism assessment.

-VIII. Request for Comments

    -Interested persons may, on or before July 31, 1996, submit to the 
Dockets Management Branch (HFA-305), Food and Drug Administration, 
12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857, written comments 
regarding this proposal. Two copies of any comments are to be 
submitted, except that individuals may submit one copy. Comments are to 
be identified with the docket number found in brackets in the heading 
of this document. Received comments may be seen in the office above 
between 9 a.m. and 4 p.m., Monday through Friday.

List of Subjects in 21 CFR Part 530

    -Administrative practice and procedures, Advertising, Animal drugs, 
Animal feeds, Human drugs, Labeling, Prescription drugs, Promotion, 
Reporting and recordkeeping requirements.
    -Therefore, under the Federal Food, Drug, and Cosmetic Act, and 
under authority delegated to the Commissioner of Food and Drugs, it is 
proposed that Title 21 of the Code of Federal Regulations be amended to 
add a new part 530 to read as follows:

PART 530--EXTRALABEL DRUG USE IN ANIMALS

Subpart A--General Provisions

Sec. 530.1 Scope.
Sec. 530.2 Purpose.
Sec. 530.3 Definitions.
Sec. 530.4 Advertising and promotion.
Sec. 530.5 Veterinary records.

Subpart B--Rules and Provisions for Extralabel Uses of Drugs in Animals

Sec. 530.10 Provision permitting extralabel use of animal drugs.
Sec. 530.11 Limitations.
Sec. 530.12 Labeling.
Sec. 530.13 Extralabel use from compounding approved new animal and 
approved human drugs.

Subpart C--Specific Provisions Relating to Extralabel Uses of Animal 
and Human Drugs in Food-Producing Animals

Sec. 530.20 Conditions for permitted extralabel animal and human 
drug use in food-producing animals.
Sec. 530.21 Prohibitions for food-producing animals.
Sec. 530.22 Safe levels and analytical methods for food-producing 
animals.
Sec. 530.23 Procedure for setting and announcing safe levels.
Sec. 530.24 Procedure for announcing analytical methods for drug 
residue quantification.
Sec. 530.25 Orders prohibiting extralabel uses for drugs in food-
producing animals.

Subpart D--Extralabel Use of Human and Animal Drugs in Animals Not 
Intended for Human Consumption

Sec. 530.30 Extralabel drug use in nonfood animals.

Subpart E--Safe Levels for Extralabel Use in Animals and Drugs 
Prohibited for Extralabel Use in Animals

Sec. 530.40 Safe levels and availability of analytical methods.
Sec. 530.41 Drugs prohibited for extralabel use in animals.
    -Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act 
(15 U.S.C. 1453, 1454, 1455); Secs. 201, 301, 501, 502, 503, 505, 
507, 512, 701, and 721 of the Federal Food, Drug, and Cosmetic Act 
(21 U.S.C. 321, 331, 351, 352, 353, 355, 357, 360b, 371, 379e).

-Subpart A--General Provisions


Sec. 530.1   Scope.

    -This part applies to the extralabel use in an animal of any 
approved new animal drug or approved new human drug by or on the lawful 
order of a veterinarian within the context of a valid veterinarian-
client-patient relationship.


Sec. 530.2   Purpose.

    -The purpose of this part is to establish conditions for extralabel 
use or intended extralabel use in animals by or on the lawful order of 
veterinarians of approved new animal drugs and approved new human 
drugs. Such use is limited to treatment modalities when the health of 
an animal is threatened or suffering or death may result from failure 
to treat. This section implements the Animal Medicinal Drug Use 
Clarification Act of 1994 (the AMDUCA) (Pub. L. 103-396).


Sec. 530.3   Definitions.

    -(a)  Extralabel use means actual use or intended use of a drug in 
an animal in a manner that is not in accordance with the approved 
labeling. This includes, but is not limited to, use in species not 
listed in the labeling, use for indications (disease or other 
conditions) not listed in the labeling, use at dosage levels, 
frequencies, or routes of administration other than those stated in the 
labeling, and deviation from the labeled withdrawal time based on these 
different uses.
    -(b)  FDA  means the U.S. Food and Drug Administration.
    -(c) The phrase  a reasonable probability that a drug's use may 
present a risk to the public health means that FDA has reason to 
believe that use of a drug may be likely to cause a potential adverse 
event.
    -(d) The phrase  use of a drug may present a risk to the public 
health  means that FDA has information that indicates that use of a 
drug may cause an adverse event.
    -(e) The phrase  use of a drug presents a risk to the public health 
means that FDA has evidence that demonstrates that the use of a drug 
has caused or likely will cause an adverse event.
    -(f) A  residue  means any compound present in edible tissues that 
results from the use of a drug, and includes the drug, its metabolites, 
and any other substance formed in or on food because of the drug's use.
    -(g) A  safe level is a conservative estimate of a drug residue 
level in animal tissue derived from food safety data or other 
scientific information. Concentrations of residues in tissue below the 
safe level will not raise human food safety concerns. A safe level is 
not a safe concentration or a tolerance and does not indicate that an 
approval exists for the drug in that species or category of animal from 
which the food is derived.
    -(h) Veterinarian means a person licensed by a State or Territory 
to practice veterinary medicine.
     -(i) A valid veterinarian-client-patient relationship is one in 
which:
    (1) A veterinarian has assumed the responsibility for making 
medical judgments regarding the health of (an) animal(s) and the need 
for medical treatment, and the client (the owner of the animal or 
animals or other caretaker) has agreed to follow the instructions of 
the veterinarian;
    (2) There is sufficient knowledge of the animal(s) by the 
veterinarian to initiate at least a general or preliminary diagnosis of 
the medical condition of the animal(s); and
    (3) The practicing veterinarian is readily available for followup 
in case of adverse reactions or failure of the regimen of therapy. Such 
a relationship can exist only when the veterinarian has recently seen 
and is personally acquainted with the keeping and care of the animal(s) 
by virtue of examination of the animal(s), and/or by medically 
appropriate and timely visits to the premises where the animal(s) are 
kept.


Sec.  530.4   Advertising and promotion.

    -Nothing in this part shall be construed as permitting the 
advertising or promotion of extralabel uses in animals of approved new 
animal drugs or approved human drugs.


Sec. 530.5   Veterinary records.

    -(a) Persons designated by FDA shall have access to the records of 
veterinarians, including records

[[Page 25114]]

required to be maintained under the act, State veterinary practice 
acts, and State pharmacy acts, to ascertain any extralabel use or 
intended extralabel use of drugs that the agency has determined may 
present a risk to the public health. -
    -(b) As a condition of extralabel use permitted under this part, 
veterinarians shall maintain records as required by State veterinary 
practice and pharmacy acts. Such records shall be legible, documented 
in an accurate and timely manner, and be readily accessible to permit 
prompt retrieval of information. Such records shall be adequate to 
substantiate the identification of the animals and the medical care 
provided and shall be maintained either as individual records or, in 
large animal practices, on a group, herd, flock, or per-client basis. 
As required by the State, such records will typically include, but not 
be limited to, the following information:
    -(1) The name, address, and telephone number of the veterinarian;
    -(2) The name, address, and telephone number of the client; -
    (3) The complaint, or other reason for the provision of services, 
including information on the patient history, physical examination, and 
laboratory data;
    -(4) The provisional or final diagnosis and date of diagnosis;
    -(5) Adequate identification of the animal(s) treated;
    -(6) The date or dates of treatment, prescribing, or dispensing of 
the drug;
    -(7) The established name of the drug and its active ingredient, or 
if formulated from more than one ingredient, the established name of 
each ingredient; the dosage form, strength, and quantity of the 
prescribed or dispensed drug, and the dates of administration;
    -(8) Any directions for use provided, including dose, route of 
administration, and length of therapy;
    -(9) The number of refills authorized;
    -(10) Cautionary statements, if any; and
    -(11) The veterinarian's specified withdrawal, withholding, or 
discard time(s), if applicable, for meat, milk, eggs, or any food which 
might be derived from any food animals treated.
    -(c) A veterinarian shall keep all required drug distribution and 
use records for 2 years or as otherwise required by Federal or State 
law, whichever is greater.
    -(d) Any person who is in charge, control, or custody of such 
records shall, upon request of a person designated by FDA, permit such 
person designated by FDA to, at all reasonable times, have access to, 
permit copying, and verify such records.

Subpart B--Rules and Provisions for Extralabel Uses of Drugs in Animals


Sec. 530.10   Provision permitting extralabel use of animal drugs.

    -An approved new animal drug or human drug intended to be used for 
an extralabel purpose in an animal is not unsafe under section 512 of 
the act and is exempt from the labeling requirements of section 502(f) 
of the act if such use is:
    -(a) By or on the lawful written or oral order of a veterinarian 
within the context of a valid veterinarian-client-patient relationship; 
and
    -(b) In compliance with this part.


Sec. 530.11   Limitations.

    -In addition to uses which do not comply with the provision set 
forth in Sec. 530.10, the following specific extralabel uses are not 
permitted and result in the drug being deemed unsafe within the meaning 
of section 512 of the act:
    -(a) Extralabel use in an animal of an approved new animal drug or 
human drug by a lay person (except when under the supervision of a 
veterinarian); -
    (b) Extralabel use of an approved new animal drug or human drug in 
or on an animal feed;
    -(c) Extralabel use resulting in any residue which may present a 
risk to public health; and
    -(d) Extralabel use resulting in any residue above an established 
safe level or tolerance.


Sec. 530.12   Labeling.

    -Any human or animal drug prescribed and dispensed for extralabel 
use by a veterinarian or dispensed by a pharmacist on the order of a 
veterinarian shall bear or be accompanied by labeling information 
adequate to assure the safe and proper use of the product. Such 
information shall include the following:
    -(a) The name and address of the veterinarian;
    -(b) The established name of the drug, or if formulated from more 
than one active ingredient, the established name of each ingredient;
    -(c) Any directions for use specified by the veterinarian, 
including the class/species or identification of the animal in which it 
is intended to be used; the dosage, frequency, and route of 
administration; and the duration of therapy;
    -(d) Any cautionary statements; and
    -(e) The veterinarian's specified withdrawal, withholding, or 
discard time for meat, milk, eggs, or any food which might be derived 
from the treated animal.


Sec. 530.13   Extralabel use from compounding of approved new animal -
and approved human drugs.

    -(a) This part applies to compounding of a product from approved 
animal or human drugs by a veterinarian or a pharmacist on the order of 
a veterinarian within the practice of veterinary medicine. Nothing in 
this part shall be construed as permitting compounding from bulk drugs.
    -(b) Extralabel use from compounding of approved new animal or 
human drugs is permitted if:
    -(1) All relevant portions of this part have been complied with;
    -(2) There is no approved new animal or approved new human drug 
that, when used as labeled or in conformity with criteria established 
in this part, will, in the available dosage form and concentration, 
appropriately treat the condition diagnosed;
    -(3) The compounding is performed by a licensed pharmacist or 
veterinarian within the scope of a professional practice;
    -(4) Adequate procedures and processes are followed that ensure the 
safety and effectiveness of the compounded product;
    -(5) The scale of the compounding operation is commensurate with 
the established need for compounded products (e.g., similar to that of 
comparable practices); and
    -(6) All relevant State laws relating to the compounding of drugs 
for use in animals are followed.
    -(c) Guidance on the subject of compounding may be provided in 
guidance documents issued by FDA.

Subpart C--Specific Provisions Relating to Extralabel Use of Animal and 
Human Drugs in Food-Producing Animals


Sec. 530.20   Conditions for permitted extralabel animal and human -
drug use in food-producing animals.

    -(a) The following conditions must be met for a permitted 
extralabel use in food-producing animals of approved new animal and 
human drugs:
    -(1) There is no approved new animal drug that is labeled for such 
use and that contains the same active ingredient which is in the 
required dosage form and concentration.
    -(2) Prior to prescribing or dispensing an approved new animal or 
human drug for an extralabel use in food animals, the veterinarian 
must:
    -(i) Make a careful diagnosis and evaluation of the conditions for 
which the drug is to be used;
    -(ii) Establish a substantially extended withdrawal period prior to 
marketing of

[[Page 25115]]

milk, meat, or eggs supported by appropriate scientific information, if 
applicable;
    -(iii) Institute procedures to assure that the identity of the 
treated animal or animals is carefully maintained; and
    -(iv) Take appropriate measures to assure that assigned timeframes 
for withdrawal are met and no illegal drug residues occur in any food-
producing animal subjected to extralabel treatment.
    -(b) The following additional conditions must be met for a 
permitted extralabel use of an approved human drug, or of an animal 
drug approved only for use in animals not intended for human 
consumption, in food-producing animals:
    -(1) Records maintained by the veterinarian must reflect the 
medical rationale; and
    -(2) If there is no published scientific information on the public 
health aspect of the use of the drug in food-producing animals, the 
veterinarian must determine that the animal and its food products will 
not enter the human food supply.
    -(c) Extralabel use of an approved human drug in food-producing 
animals will not be permitted unless the veterinarian first considers 
the extralabel use of an approved animal drug for use in food-producing 
animals under the provisions of this part. Such consideration must be 
documented in the veterinarians' records.


Sec. 530.21   Prohibitions for food-producing animals.

    -(a) FDA may prohibit the use of an approved new animal or human 
drug or class of drugs in food-producing animals if FDA determines 
that:
    (1) An acceptable analytical method needs to be established and 
such method has not been established or cannot be established, or
    (2) The use of the drug or class of drugs presents a risk to public 
health.
    -(b) A prohibition may be a general ban on the use of the drug or 
class of drugs or may be limited to a specific species, indication, 
dosage form, route of administration, or combination of factors.


Sec. 530.22   Safe levels and analytical methods for food-producing -
animals.

    -(a) FDA may establish a safe level for extralabel use of an 
approved human drug or an approved new animal drug when the agency 
finds that there is a reasonable probability that an extralabel use may 
present a risk to the public health. FDA may:
     -(1) Establish a finite safe level based on residue and metabolism 
information from available sources;
    -(2) Establish a safe level based on the lowest level that can be 
measured by a practical analytical method; or
    -(3) Establish a safe level based on other appropriate scientific, 
technical, or regulatory bases.
     -(b) FDA may require the development of an acceptable analytical 
method for the quantification of residues above any safe level 
established under this part. If FDA requires the development of such an 
acceptable analytical method, the agency will publish notice of that 
requirement in the Federal Register.
     -(c) The extralabel use of an animal drug or human drug that 
results in residues exceeding a safe level established under this part 
is an unsafe use of such drug.
    -(d) If the agency establishes a safe level and a tolerance is 
later established through an approval for a particular species or 
category of animals, for a particular species or category of animals, 
the safe level is superseded by the tolerance for that species or 
category of animals.


Sec. 530.23   Procedure for setting and announcing safe levels.

    -(a) FDA may issue an order establishing a safe level for a residue 
of an extralabel use of an approved human drug or an approved animal 
drug. The agency will publish in the Federal Register a notice of the 
order. The notice will include:
    -(1) A statement setting forth the agency's finding that there is a 
reasonable probability that extralabel use in animals of the human drug 
or animal drug may present a risk to public health, and
    -(2) A request for public comments.
    -(b) A current listing of those drugs for which a safe level for 
extralabel drug use in food-producing animals has been set, the 
specific safe levels, and the availability, if any, of a specific 
analytical method or methods for drug residue detection will be 
codified in Sec. 530.40.


Sec. 530.24   Procedure for announcing analytical methods for drug -
residue quantification.

    -Copies of analytical methods for the quantification of extralabel 
use drug residues above the safe levels established under Sec. 530.22 
will be available upon request from the Communications and Education 
Branch (HFV-12), Division of Program Communication and Administrative 
Management, Center for Veterinary Medicine, 7500 Standish Pl., 
Rockville, MD 20855. When an analytical method for the detection of 
extralabel use drug residues above the safe levels established under 
Sec. 530.22 is developed, and that method is acceptable to the agency, 
FDA will incorporate that method by reference.


Sec. 530.25   Orders prohibiting extralabel uses for drugs in -food-
producing animals.

    -(a) FDA may issue an order prohibiting extralabel use of an 
approved new animal or human drug in food-producing animals if the 
agency finds, after providing an opportunity for public comment, that:
    -(1) An acceptable analytical method required under Sec. 530.22 of 
this part has not been developed, submitted, and found to be acceptable 
by FDA; or
    -(2) The extralabel use in animals presents a risk to the public 
health.
    -(b) After making a determination that the analytical method 
required under Sec. 530.22 has not been developed and submitted, or 
that an extralabel use in animals of a particular human drug or animal 
drug presents a risk to the public health, FDA will publish in the 
Federal Register, with a 90 day delayed effective date, an order of 
prohibition for an extralabel use of a drug in food-producing animals. 
Such order will:
    -(1) Specify the nature and extent of the order of prohibition and 
the reasons for the prohibition, and
    -(2) Request public comments, and
    -(3) Provide a period of not less than 60 days for comments.
    -(c) The order of prohibition will become effective 90 days after 
date of publication of the order unless FDA publishes a notice in the 
Federal Register prior to that date, that revokes the order of 
prohibition, modifies it, or extends the period of public comment.
    -(d) The agency may publish an order of prohibition with a shorter 
comment period and/or delayed effective date than specified in 
paragraph (b) in exceptional circumstances (e.g., where there is 
immediate risk to the public health), provided that the order of 
prohibition states that the comment period and/or effective date have 
been abbreviated because there are exceptional circumstances, and the 
order of prohibition sets forth the agency's rationale for taking such 
action.
    -(e) If FDA publishes a notice in the Federal Register modifying an 
order of prohibition, the agency will specify in the modified order of 
prohibition the nature and extent of the modified prohibition, the 
reasons for it, and the agency's response to any comments on the 
original order of prohibition.
    -(f) A current listing of drugs prohibited for extralabel use in 
animals will be codified in Sec. 530.41.
    -(g) After the submission of appropriate information (i.e., 
adequate

[[Page 25116]]

data, an acceptable method, approval of a new animal drug application 
for the prohibited drug and use, or information demonstrating that the 
prohibition was based on incorrect data), FDA may, by publication of an 
appropriate notice in the Federal Register, remove a drug from the list 
of human and animal drugs prohibited for extralabel use in animals, or 
may modify a prohibition.
    -(h) FDA may prohibit extralabel use of a drug in food-producing 
animals without establishing a safe level.

Subpart D--Extralabel Use of Human and Animal Drugs in Animals Not 
Intended for Human Consumption


Sec. 530.30   Extralabel drug use in nonfood animals.

    -(a) Because extralabel use of animal and human drugs in nonfood-
producing animals does not ordinarily pose a threat to public health, 
extralabel use of animal and human drugs is permitted in nonfood-
producing animal practice except when the public health is threatened. 
In addition, the provisions of Sec. 530.20(a)(1) will apply to the use 
of an approved animal drug.
    -(b) If FDA determines that an extralabel drug use in animals not 
intended for human consumption presents a risk to the public health, 
the agency may publish in the Federal Register a notice prohibiting 
such use following the procedures in Sec. 530.25. The prohibited drug 
use will be codified in Sec. 530.41.

Subpart E--Safe Levels for Extralabel Use in Animals and Drugs 
Prohibited for Extralabel Use in Animals


Sec. 530.40   Safe levels and availability of analytical methods.

    -In accordance with Sec. 530.22, when the agency finds that there 
is a reasonable probability than an extralabel use may present a risk 
to the public health, FDA may establish by order a safe level for an 
extralabel use in animals of an approved human drug or an approved 
animal drug, and may establish a specific analytical method or methods 
for drug residue detection. FDA will publish in the Federal Register a 
notice of the order and the availability, if any, of an analytical 
method or methods for drug residue detection and will codify them in 
this section. This section will include the following: A current 
listing of those drugs for which a safe level for extralabel drug use 
in food-producing animals has been set, and the specific safe levels, 
and the availability, when one has been developed, of a specific 
analytical method or methods for drug residue detection.


Sec. 530.41  Drugs prohibited for extralabel use in animals. -

    -In accordance with Sec. 530.25, the following drugs are prohibited 
for extralabel use in animals:

    Dated: May 8, 1996.
William B. Schultz,
Deputy Commissioner for Policy.

    Note: The following appendix will not appear in the Code of 
Federal Regulations.

Appendix

Compliance Policy Guides

Chapter 6--Veterinary Medicine

Sec. 608.100 Human-Labeled Drugs Distributed and Used in Animal ---
Medicine (CPG 7125.35)

Background

    -This Compliance Policy Guide explains how FDA will exercise its 
enforcement discretion with respect to distribution and use of 
human-labeled drug products for use in animals. It is FDA's intent 
to:
    --eliminate promotion by manufacturers, distributors, and 
pharmacies;
    --ensure that distribution and dispensing are made only in 
response to requests by veterinary practitioners (practitioner 
driven);
    --refrain in ordinary circumstances from enforcement actions 
when human drugs are used or dispensed by veterinarians in treating 
non-food-producing animals;
    --take enforcement action against veterinarians who cause 
illegal residues in food-producing animals;
    --limit use of human-labeled drugs in treating food-producing 
animals to very narrow circumstances; and
    --prohibit use except by or on the order of a licensed 
veterinarian in the course of his or her practice.
    The key regulatory elements under this policy are determination 
of whether or not (1) the distribution and dispensing are 
practitioner driven and (2) the veterinary practitioners limit their 
uses of human-labeled drug products to treating non-food animals, 
with certain narrow exceptions. Because distribution and dispensing 
are to be veterinary practitioner driven, and because distributors 
and pharmacists, after properly distributing the drug, ordinarily 
cannot control end uses, this policy places primary responsibility 
on the veterinarian. This policy is not intended to permit the 
distribution of human-labeled drug products to veterinarians where 
prohibited or limited by State laws.
    -FDA is aware that human-labeled drug products have been 
promoted and distributed by manufacturers, distributors, and 
pharmacies for use in animals and that such drugs are being 
prescribed, dispensed, and administered by veterinarians for animal 
use.
    -Promotion of human-labeled drug products for veterinary use by 
these sources has included acts such as advertising animal use in 
veterinary publications; distribution of labeling and promotional 
materials suggesting or recommending use of these products in 
animals; or oral statements from sales personnel describing or 
recommending use in animals. Such promotion causes the drugs to be 
misbranded under Section 502(f)(1), or adulterated new animal drugs 
under Section 501(a)(5), or both. Furthermore, such promotion may 
subvert the New animal drug approval process by creating a 
disincentive for drug manufacturers to seek such approvals.
    -Most veterinary use of human-labeled drug products occurs in 
non-food animal practice (companion, sporting, exotic, etc.). Many 
of the maladies of pets and other non-food animals cannot be treated 
in accordance with current standards of veterinary practice without 
the use of human-labeled drugs since appropriate drug products 
bearing veterinary labeling often do not exist. Because of this, FDA 
has generally refrained from taking enforcement actions in this area 
because there is no expected adverse impact upon the public health.
    -FDA is very concerned about the use of human-labeled drugs in 
food-producing animals because of the increased potential for 
illegal drug residues in meat, milk, and eggs. Human-labeled drug 
products have not, among other things, undergone testing for residue 
depletion from edible tissues. Appropriate withdrawal times to avoid 
illegal residues in food can only be estimated.
    -Nevertheless, there are legitimate and important veterinary 
needs for human-labeled drugs in the treatment of disease or to 
prevent pain in food-producing animals in instances where there 
simply are no animal drug products available that would avoid animal 
suffering or death. Examples include, but are not necessarily 
limited to analgesics and anesthetics for pain, sedation, and 
surgery, insulin for ketosis, and antidotes for poisonings.

Policy

    A. Distribution and Dispensing
    -Labeling, advertising, oral representations, or any other act 
by a manufacturer, distributor, or pharmacy which establishes an 
intended use of human-labeled drugs for animal use is subject to 
regulatory action. However, the simple listing of human-labeled drug 
products in price sheets and catalogues distributed to veterinarians 
will not ordinarily be subject to such action. Dispensing 
pharmacists are required by Section 503(f) to label dispensed drugs 
in accordance with the prescribing veterinarian's instructions, 
including the name and address of the dispenser, the serial number 
and date of the order or of its filing, the name of the licensed 
veterinarian, and directions for use and any cautionary statements. 
Providing this information does not constitute promotion against 
which the agency is prepared to take action.
    -High priority will be placed on actions against manufacturers, 
distributors, and pharmacies who promote the substitution of human-
labeled drug products for animal drugs for economic reasons.
    B. Use of human drugs by veterinarians in professional practice
    -(i) Use in non-food-producing animals; e.g., dogs, cats, 
horses.
    Under usual circumstances, veterinary practitioners may consider

[[Page 25117]]

the use of human-labeled drug products in non-food-producing animal 
practice without the threat of FDA enforcement actions. In rare 
circumstances, for example, when the health of the treated animals is 
harmed, regulatory attention by FDA would be considered or, preferably, 
referred to the State veterinary licensing authority for investigation.
    (ii) Use in food-producing animals; e.g., cattle, swine, 
poultry.
    Use of human-labeled drug products in food-producing animals should 
be extremely limited, primarily because of the increased potential for 
illegal drug residues in meat, milk, and eggs. For example, it is 
ordinarily unacceptable to use a human-labeled product for common 
disease conditions in food animals because approved veterinary-labeled 
drug products; e.g., antibacterials, anti-inflammatory agents, etc. are 
available. The food animal veterinarian assumes greater responsibility 
when he or she uses a human drug rather than a veterinary drug. Use of 
human-labeled drugs may be considered by food animal veterinarians only 
when they have:
    --made a careful and definitive diagnosis and evaluation of the 
condition for which the drug is to be used, and are otherwise 
operating within the confines of a veterinarian/client/patient 
relationship;
    --made a deliberate determination that there is no other 
appropriate veterinary-labeled therapy; i.e., there is no marketed 
veterinary labeled drug product specifically labeled for the disease 
condition to be treated or the veterinary drug has been found 
clinically ineffective by the veterinarian in the animals to be 
treated; and
    --taken adequate steps to prevent the occurrence of illegal 
residues in edible animal products. This should include a review of 
the best available toxicological and tissue distribution and tissue 
residue depletion data and establishment of an extra long drug 
withdrawal period prior to marketing meat, milk, or eggs. The animal 
owner or manager should be given explicit written withdrawal 
instructions. The practitioner should have a high degree of 
confidence that the client will follow the drug withdrawal 
instruction.
    -Regulatory action should be considered when an illegal residue 
occurs even if the veterinarian followed the foregoing precautions. 
The enforcement discretion that might be accorded to veterinarians 
will not be extended to lay persons; e.g., owners, who administer 
human-labeled drugs either to food-producing or nonfood animals 
without the supervision of a licensed veterinarian operating within 
the framework of a valid veterinarian/client/patient relationship.
    -Veterinarians are expected to follow cautionary handling and 
disposal provisions, if any, specified in human drug labeling to 
protect handlers and the environment.

Regulatory Action Guidance

    -The highest priority for regulatory attention is for follow-up 
on reports of illegal tissue residues from human-labeled drugs. 
Follow the instructions in Compliance Program 7371.006,  Illegal 
Drug Residues in Meat and Poultry and Compliance Program 7371.008,  
National Drug Residue Milk Monitoring Program. Consultation with 
Case Guidance Branch for guidance under this policy is indicated 
when encountering other suspected violations, especially where there 
is substitution of human-labeled drugs for treatment of common 
disease conditions in food animals.
    -The initial enforcement action of choice is ordinarily a 
Warning Letter. Center concurrence is required prior to issuance. 
Depending on the circumstances, one or more of the following charges 
would be appropriate.
    --402(a)(2)(D)-food adulterated by illegal residue from a new 
animal drug;
    --402(a)(2)(A)-food adulterated by illegal residue from a human-
labeled drug;
    --501(a)(5)-adulterated drug (labeled for human use which is 
accompanied by labeling indicating it for animal use which causes it 
to be unsafe under Section 512(a) as an unapproved new animal drug);
    --502(f)(1)-misbranded human drug when not used as labeled; 
misbranded human drug promoted for animal use in ways other than by 
labeling (see 21 CFR 201.128).

Issued: 3/19/91

Revised: 7/20/92

Sec. 615.100 Extralabel Use of New Animal Drugs in Food-Producing 
Animals (CPG 7125.06)

Background

    -Concern over the extralabel use of drugs in treating food-
producing animals and the possibility that human food may become 
adulterated with illegal drug residues from such misuse has prompted 
a revision in the Center for Veterinary Medicine (CVM) extralabel 
drug use policy. Under the revised policy, a finding of illegal drug 
residues no longer will be a prerequisite for initiating regulatory 
action based on extralabel drug use of drugs in food-producing 
animals.
    -For the purpose of this policy, ``extralabel use'' refers to 
the actual or intended use of a new animal drug in a food-producing 
animal in a manner that is not in accordance with the drug labeling. 
This includes, but is not limited to, use in species or for 
indications (disease or other conditions) not listed in the 
labeling, use at dosage levels higher than those stated in the 
labeling, and failure to observe the stated withdrawal time.
    -FDA in the past has not sanctioned extralabel uses of drugs in 
food-producing animals, but the agency has stated that it would 
refrain from instituting regulatory action against licensed 
veterinarians for using or prescribing in their practices any drugs 
they could legally obtain. Nevertheless, it has been FDA's position 
that veterinarians may be subject to regulatory action for any 
violative drug residues in human food resulting from their 
prescriptions, recommendations, or treatments contrary to label 
instructions. Similarly, anyone in the producing or marketing chain 
who could be shown to have caused illegal drug residues through 
extralabel use of drugs in food-producing animals has been subject 
to regulatory action.
    -In contrast, under usual circumstances veterinary practitioners 
may consider the extralabel use of drug products in non-food-
producing animal practice without being subject to FDA enforcement 
actions. In rare circumstances, for example when the health of the 
treated animals is harmed, regulatory attention by FDA would be 
considered or, preferably, referred to the State veterinary 
licensing authority for investigation.

Policy

    -The use or intended use of new animal drugs in treating food-
producing animals in any manner other than in accord with the 
approved labeling causes the drugs to be adulterated under the 
Federal Food, Drug, and Cosmetic Act (the Act) (sections 501(a)(5) 
and (6), 512(a)(1)(A) and (B), 512(a)(2)). The agency will consider 
regulatory action when such use or intended use is found, whether by 
a veterinarian, producer, or other person. Regulatory actions will 
also be considered against distributors and others who might cause 
adulteration of approved new animal drugs. Nevertheless, extralabel 
drug use in treating food-producing animals may be considered by a 
veterinarian when the health of animals is immediately threatened 
and suffering or death would result from failure to treat the 
affected animals. In instances of this nature, regulatory action 
would not ordinarily be considered provided all [at] the following 
criteria are met and precautions observed:
    -1. A careful medical diagnosis is made by an attending 
veterinarian within the context of a valid veterinarian-client-
patient relationship;* * *
    -2. A determination is made that (a) there is no marketed drug 
specifically labeled to treat the condition diagnosed, or drug 
therapy at the dosage recommended by the labeling has been found 
clinically ineffective by the veterinarian in the animals to be 
treated;
    -3. Procedures are instituted to assure that identity of the 
treated animals is carefully maintained;
    -4. Significantly extended time period is assigned for drug 
withdrawal prior to marketing meat, milk, or eggs; steps are taken 
to assure that the assigned time frames are met, and no illegal 
residues occur; and
    -5. The prescribed or dispensed extralabel drug (prescription 
legend or over the counter) bears labeling information which is 
adequate to assure the safe and proper use of the product. At a 
minimum, the following label information is recommended:
    -a. The name and address of the veterinary practitioner.
    -b.-The established name of the drug (active ingredient), or if 
formulated from more than one ingredient, the established name of 
each ingredient.
    -c. Any directions for use specified by the practitioner 
(including the class/species or identification of the animals; and 
the dosage, frequency, route of administration, and duration of 
therapy).

[[Page 25118]]

    -d. Any cautionary statements specified by the veterinarian.
    -e. The veterinarian's specified withdrawal/discard time(s) for 
meat, milk, eggs, or any food which might be derived from the 
treated animal(s).
    -Extra-label use of drugs in treating food-producing animals may 
under this policy, therefore, be considered only in special 
circumstances. The ``exempting'' criteria do not include drug use in 
treating food-producing animals by the layman. Lay persons cannot be 
expected to have sufficient knowledge and understanding concerning 
animal diseases, pharmacology, toxicology, drug interactions, and 
other scientific parameters to use drugs in treating food-producing 
animals in any way other than as labeled.
    -Certain drugs may not be used in treating food-producing 
animals even under the cited criteria. This includes 
chloramphenicol. Extralabel uses of drugs in treating food-producing 
animals for improving rate of weight gain, feed efficiency, or other 
producing purposes, or for routine disease prevention are 
inappropriate as is use for therapeutic purposes other than under 
the circumstances described above. Also, the criteria cited above do 
not sanction the sale and use, for any purpose, of new animal drugs 
that are not approved, such as diethylstilbestrol (DES). 
Furthermore, a drug (including a bulk drug) may not be mixed into 
feed for any use or at a potency level not specifically permitted by 
the regulations in 21 CFR Part 558, even if prescribed or ordered by 
a veterinarian.

Regulatory Guidance

    -The highest priorities for regulatory attention regarding 
extra-label use are:
    1. Instances where illegal residues occur.
    2. In all food-producing animals:
    -Chloramphenicol
    -Clenbuterol
    -Diethylstilbestrol (DES)
    -Dimetridazole
    -Ipronidazole
    -Other nitroimidazoles
    -Furazolidone (Except for approved topical use)
    -Nitrofurazone (Except for approved topical use)
    3. In lactating dairy cattle:
    -Sulfonamide drugs (except approved use of sulfa-dimethoxine, 
sulfabromomethazine and sulfaethoxy-pyridazine)
    4. Manufacturers and distributors who promote extra-label use of 
drugs.
    5. The mixing of drugs into medicated feeds intended for extra-
label use.
    6. Extra-label use by laymen at their own initiative.
    * * *A valid veterinarian-client-patient relationship, as 
defined by the American Veterinary Medical Association is the 
following: An appropriate veterinarian-client-patient relationship 
will exist when: (1) the veterinarian has assumed the responsibility 
for making medical judgements regarding the health of the animal(s) 
and the need for medical treatment, and the client (owner or other 
caretaker) has agreed to follow the instructions of the 
veterinarian; and when (2) there is sufficient knowledge of the 
animal(s) by the veterinarian to initiate at least a general or 
preliminary diagnosis of the medical condition of the animal(s). 
This means that the veterinarian has recently seen and is personally 
acquainted with the keeping and care of the animal(s) by virtue of 
an examination of the animal(s), and/or by medically appropriate and 
timely visits to the premises where the animal(s) are kept; and when 
(3) the practicing veterinarian is readily available for follow-up 
in case of adverse reactions or failure of the regimen of therapy.

Issued: 3/9/84

Revised: 5/1/84, 8/1/86, 11/1/86, 7/20/92

[FR Doc. 96-12403 Filed 5-16-96; 8:45 am]
BILLING CODE 4160-01-F