Document ID: FDA-2003-D-0202-0003
Agency: fda
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-07-14T04:00Z

Guidance for FDA Staff and 

Industry

Compliance Policy Guides Manual

Sec. 608.400

Compounding of Drugs for Use in Animals 

Submit written comments regarding this guidance document identified with
Docket No. 2003D-0290 to the Dockets Management Branch (HFA-305), 5630
Fishers Lane, rm. 1061, Rockville, MD 20852.

Additional copies of this document may be obtained by sending a request
to the Division of Compliance Policy (HFC-230, Food and Drug
Administration, 5600 Fishers Lane, Rockville, MD 20857, or from the
Internet at:   HYPERLINK
"http://www.fda.gov/ora/compliance_ref/cpg/default.htm" 
http://www.fda.gov/ora/compliance_ref/cpg/default.htm   or     HYPERLINK
"http://www.fda.gov/OHRMS/DOCKETS/98fr/03d-0290-gdl0001.pdf" 
http://www.fda.gov/OHRMS/DOCKETS/98fr/03d-0290-gdl0001.pdf   

U.S. Department of Health and Human Services

Food and Drug Administration

Office of Regulatory Affairs

Center for Veterinary Medicine

July 2003

Compliance Policy Guide

Compliance Policy Guidance for FDA Staff and Industry

CHAPTER – 6

SUBCHAPTER - 600

Sec. 608.400 - Compounding of Drugs for Use in Animals

This compliance policy guidance is intended to provide guidance and
instructions to FDA staff, industry, and the public for obtaining
information to help fulfill the Agency’s plans regarding the
compounding of drugs for use in animals.  The compliance policy guidance
does not create or confer any rights for or on any person and does not
operate to bind the Food and Drug Administration (FDA) or the public. 
An alternative approach may be used if such approach satisfies the
requirements of the applicable statute and regulations.  It is intended
for FDA personnel, industry, and the public and is available
electronically to the public.

INTRODUCTION

This document provides guidance to drug compounders, veterinarians, and
the staff of the Food and Drug Administration (FDA) on how the Agency
intends to address compounding of drugs intended for use in animals. 
This guidance describes FDA’s current thinking on what types of
compounding might be subject to enforcement action.

BACKGROUND

FDA announced the availability of Compliance Policy Guide (CPG) section
608.400 entitled “Compounding of Drugs for Use in Animals” on July
3, 1996 (61 FR 34849), to provide guidance to FDA’s field and
headquarters staff with regard to the compounding of animal drugs by
veterinarians and pharmacists for use in animals.  There is a potential
for causing harm to public health and to animals when drug products are
compounded, distributed, and used in the absence of adequate and
well-controlled safety and effectiveness data or adherence to the
principles of contemporary pharmaceutical chemistry and current good
manufacturing practices.  Use of compounded drugs in animals can result
in adverse reactions and animal deaths.  Furthermore, because the
pharmacokinetics and depletion times for residues from compounded
products intended for use in food-producing animals are not known, the
assignment of an extemporaneous withdrawal time may result in
potentially harmful residues in food.  Inactive ingredients, such as
excipients and vehicles, from unapproved or unknown origins may also
pose additional risk (e.g., Freunds adjuvant, a carcinogen).  

FDA is updating this guidance to be consistent, to the extent
practicable, with the scope of compounding permitted under regulations
implementing the Animal Medicinal Drug Use Clarification Act of 1994, to
describe what factors FDA will consider in exercising its enforcement
discretion regarding compounding of drugs intended for use in animals,
and to ensure the consistency of its policies with regard to compounding
of drugs intended for use in humans and in animals.

DISCUSSION

The Federal Food, Drug, and Cosmetic Act (the Act) does not distinguish
compounding from manufacturing or other processing of drugs for use in
animals.  FDA acknowledges the use of compounding within certain areas
of veterinary practice.  The current state of veterinary medicine
requires products to treat many conditions in a number of different
species, some of which are known to have unique physiological
characteristics.  Furthermore, FDA regulations specifically permit the
compounding of products from approved animal or human drugs under the
conditions set forth in 21 CFR 530.13.  This activity is not the subject
of this guidance.  

However, FDA is greatly concerned about veterinarians and pharmacies
that are engaged in manufacturing and distributing unapproved new animal
drugs in a manner that is clearly outside the bounds of traditional
pharmacy practice and that violates the Act (e.g., compounding that is
intended to circumvent the drug approval process and provide for the
mass marketing of products that have been produced with little or no
quality control or manufacturing standards to ensure the purity,
potency, and stability of the product).  These activities are the focus
of this guidance.  Pharmacies and veterinarians who engage in activities
analogous to manufacturing and distributing drugs for use in animals may
be held to the same provisions of the Act as manufacturers.

With regard to compounding from bulk drug substances, two Federal
Appeals Court decisions, United States v. Algon Chemical Inc., 879 F.2d
1154 (3d Cir. 1989) and United States v. 9/1 Kg. Containers, 854 F.2d
173 (7th Cir. 1988), affirmed the FDA position that the Act does not
permit veterinarians to compound unapproved finished drug products from
bulk drug substances, unless the finished drug is not a new animal drug.
 The principle established by the court applies equally to compounding
by pharmacists. 

Neither the Act nor its implementing regulations exempt veterinarians or
pharmacists from the approval requirements in the new animal drug
provisions of the Act, 21 U.S.C. Section 360b.  In the absence of an
approved new animal drug application, the compounding of a new animal
drug from any unapproved drug or from bulk drug substances results in an
adulterated new animal drug in violation of section 21 U.S.C. Section
351(a)(5).  The compounding of a new animal drug from an approved human
or animal drug also results in an adulterated new animal drug in
violation of 21 U.S.C. Section 351(a)(5), unless the conditions set
forth in 21 CFR 530.13(b) are met.

DEFINITIONS

“Bulk drug substance,” as defined in 21 CFR 207.3(a)(4), means any
substance that is represented for use in a drug and that, when used in
the manufacturing, processing, or packaging of a drug, becomes an active
ingredient or a finished dosage form of the drug, but the term does not
include intermediates used in the synthesis of such substances.

“Compounding” does not include mixing, reconstituting, or other such
acts that are performed in accordance with directions contained in
approved labeling provided by the product's manufacturer and other
manufacturer directions consistent with that labeling

A “valid veterinarian-client-patient relationship” (valid VCPR), as
defined in 21 CFR 530.3(i), is one in which:

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;

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

The practicing veterinarian is readily available for follow-up 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.

POLICY: 

Generally, FDA will defer to state authorities regarding the day-to-day
regulation of compounding by veterinarians and pharmacists of animal and
human drugs that are intended for use in animals.  FDA anticipates that,
in such cases, cooperative efforts between the states and the Agency
will result in coordinated investigations, referrals, and follow-up
actions by the states. 

However, when the scope and nature of activities of veterinarians and
pharmacists raise the kinds of concerns normally associated with a drug
manufacturer and result in significant violations of the new animal
drug, adulteration, or misbranding provisions of the Act, FDA has
determined that it will seriously consider enforcement action.  In
determining whether to initiate such an action, the Agency will consider
whether the veterinarian or pharmacist engages in any of the following
acts:

Compounding of drugs for use in situations (a) where the health of the
animal is not threatened; and (b) where suffering or death of the animal
is not likely to result from failure to treat.

Compounding of drugs in anticipation of receiving prescriptions, except
in very limited quantities in relation to the amounts of drugs
compounded after receiving prescriptions issued within the confines of a
valid VCPR.

Compounding of drugs that are prohibited for extralabel use in
food-producing or nonfood-producing animals, under 21 CFR 530.41(a) and
(b) respectively, because the drugs present a risk to the public health.

Compounding finished drugs from human or animal drugs that are not the
subject of an approved application, or from bulk drug substances, other
than those specifically addressed for regulatory discretion by the FDA,
Center for Veterinary Medicine, e.g., antidotes (see Appendix A). 
Inquiries about compounding from unapproved drugs or bulk drug
substances should be directed to CVM, Division of Compliance,
301-827-1168.  

Compounding from approved human drugs for which FDA has implemented a
restricted distribution system. 

Using commercial scale manufacturing equipment for compounding drug
products. 

Compounding drugs for third parties who resell to individual patients,
or offering compounded drug products at wholesale to other state
licensed persons or commercial entities for resale. 

Failing to operate in conformance with applicable state law regulating
the practice of pharmacy. 

Compounding of drugs for use in animals where an approved new animal
drug or approved new human drug used as labeled or in conformity with 21
CFR Part 530 will, in the available dosage form and concentration,
appropriately treat the condition diagnosed. 

Compounding from a human drug for use in food-producing animals if an
approved animal drug can be used for the compounding.

Instances where illegal residues occur in meat, milk, eggs, honey,
aquaculture, or other food-producing animal products, and such residues
were caused by the use of a compounded drug.

Labeling a compounded drug with a withdrawal time established by the
pharmacist instead of the prescribing veterinarian. 

Labeling of compounded drugs without sufficient information, such as
withdrawal times for drugs for food-producing animals or other
categories of information that are described in 21 CFR 530.12.

The foregoing list of factors is not intended to be all inclusive. 
Other factors may be appropriate for consideration in a particular case.

REGULATORY ACTION GUIDANCE: 

District offices are encouraged to consult with state regulatory
authorities to assure coherent application of this guidance to
establishments that are operating outside of the traditional practice of
pharmacy.

Follow FDA’s laws and procedures prior to sharing non-public
information with the public, or federal, state, local, and foreign
government officials.

 

FDA-initiated regulatory action may include issuing a warning letter,
seizure, injunction, and/or prosecution. Charges may include, but need
not be limited to, violations of 21 U.S.C. Sections 351(a)(2)(B),
351(a)(5), 352(a), 352(f)(1), and 352(o) of the Act.  Tissue residue
violations are covered under 21 U.S.C. Section 342(a)(2)(C)(ii) of the
Act.

Issued: 6/26/1996 (7/3/1996 Federal Register) 

Revised:  7/8/2003 (7/14/2003 FR)

 APPENDIX A	

LIST OF BULK DRUG SUBSTANCES FOR COMPOUNDING AND SUBSEQUENT USE IN
ANIMALS TO WHICH CVM WOULD NOT ORDINARILY OBJECT 

Ammonium molybdate

Ammonium tetrathiomolybdate

Ferric ferrocyanide

Methylene blue

Picrotoxin

Pilocarpine

Sodium nitrite

Sodium thiosulfate

Tannic acid

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