25106 Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules

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
Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules 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. Itis 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-thecounter (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 widelyshared 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 § 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
25108 Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules

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 § § 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 § 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
Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules 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 §§ 530.21

and 530.25, or safe levels and analytical

methods under proposed §§ 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 § 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 § 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 foodproducing 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.
25110 Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules

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 § 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 veterinarianclient-patient relationship, if the

extralabel use is otherwise in

compliance with the regulation.

G. Limitations

Proposed § 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 § 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 § 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 § 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 § 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 § 530.21 addresses foodproducing 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 § 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
Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules 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 foodproducing 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 § 530.40.

Proposed § 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 § 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 § 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 § 530.25 provides that FDA

could issue an order prohibiting

extralabel use of a drug in foodproducing 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 foodproducing 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 § 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

§ 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

§ 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,
25112 Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules

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

21 CFR Section No. Of Respondents

Annual Frequency per Response

Total Annual

Responses

Hours per Response Total Hours

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

§ 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.

§ 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).

§ 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.

§ 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.

§ 530.5 Veterinary records.

(a) Persons designated by FDA shall

have access to the records of

veterinarians, including records
25114 Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules

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 perclient 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

§ 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-clientpatient relationship; and

(b) In compliance with this part.

§ 530.11 Limitations.

In addition to uses which do not

comply with the provision set forth in

§ 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.

§ 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.

§ 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

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

§ 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.

§ 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.

§ 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

§ 530.40.

§ 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 § 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 § 530.22 is developed,

and that method is acceptable to the

agency, FDA will incorporate that

method by reference.

§ 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 § 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

§ 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 foodproducing 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 § 530.41.

(g) After the submission of

appropriate information (i.e., adequate
25116 Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules

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

§ 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 § 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 § 530.25.

The prohibited drug use will be codified

in § 530.41.

Subpart E—Safe Levels for Extralabel Use

in Animals and Drugs Prohibited for

Extralabel Use in Animals

§ 530.40 Safe levels and availability of

analytical methods.

In accordance with § 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.

§ 530.41 Drugs prohibited for extralabel

use in animals.

In accordance with § 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 humanlabeled 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 humanlabeled 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
Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules 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 veterinarylabeled 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 veterinarylabeled 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 foodproducing animals has been subject to

regulatory action.

In contrast, under usual circumstances

veterinary practitioners may consider the

extralabel use of drug products in non-foodproducing 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 foodproducing 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).
25118 Federal Register / Vol. 61, No. 97 / Friday, May 17, 1996 / Proposed Rules

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 foodproducing animals may under this policy,

therefore, be considered only in special

circumstances. The ‘‘exempting’’ criteria do

not include drug use in treating foodproducing 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 foodproducing 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 foodproducing 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 veterinarianclient-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