[Federal Register Volume 80, Number 96 (Tuesday, May 19, 2015)]
[Notices]
[Pages 28622-28624]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-11983]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-1196]


List of Bulk Drug Substances That May Be Used by an Outsourcing 
Facility To Compound Drugs for Use in Animals; Request for Nominations

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for nominations.

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SUMMARY: The Food and Drug Administration (FDA) intends to develop a 
list of bulk drug substances that may be used by outsourcing facilities 
registered under the Federal Food, Drug, and Cosmetic Act (the FD&C 
Act) to compound animal drugs, in accordance with FDA's draft guidance 
for industry #230, ``Compounding Animal Drugs from Bulk Drug 
Substances.'' You may nominate specific bulk drug substances for this 
list. This notice describes the information that should be provided to 
the Agency in support of each nomination.

DATES: To ensure that FDA considers your nominations for the initial 
version of the bulk drug substances list, submit either electronic or 
written nominations for the bulk drug substances list by August 17, 
2015.
    After the comment period is closed, nominations to add or remove 
bulk drug substances from the list may be submitted to FDA by citizen 
petition under Sec.  10.30 (21 CFR 10.30).

ADDRESSES: You may submit nominations by any of the following methods.

Electronic Submissions

    Submit electronic nominations in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written nominations in the following ways:
     Mail/Hand delivery/Courier (for paper submissions): 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

    Instructions: All submissions received must include the Docket No. 
FDA-2013-N-1524. All nominations received may be posted without change 
to http://www.regulations.gov, including any personal information 
provided. For additional information on submitting nominations, see the 
``Request for Nominations'' heading of the SUPPLEMENTARY INFORMATION 
section of this document.
    Docket: For access to the docket to read background documents or 
nominations received, go to http://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Neal Bataller, Center for Veterinary 
Medicine, Food and Drug Administration (HFV-210), 7519 Standish Pl., 
Rockville, MD 20855, 240-402-5745, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Sections 503A (21 U.S.C. 353a) and 503B (21 U.S.C. 353b) of the 
FD&C Act do not apply to the compounding of animal drugs. The FD&C Act 
does not distinguish between compounding animal drugs from bulk drug 
substances \1\ and any other manufacturing or processing of animal 
drugs. Except with respect to the limited exemption provided by the 
FD&C Act described in this document, statutory provisions applicable to 
manufactured animal drugs under the FD&C Act also apply to compounded 
animal drugs.
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    \1\ FDA regulations define ``bulk drug substance'' as ``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.'' 21 CFR 207.3(a)(4). ``Active ingredient'' is defined 
as ``any component that is intended to furnish pharmacological 
activity or other direct effect in the diagnosis, cure, mitigation, 
treatment, or prevention of disease, or to affect the structure or 
any function of the body of man or other animals. The term includes 
those components that may undergo chemical change in the manufacture 
of the drug product and be present in the drug product in a modified 
form intended to furnish the specified activity or effect.'' 21 CFR 
210.3(b)(7). Any component other than an active ingredient is an 
``inactive ingredient.'' See 21 CFR 210.3(b)(8). Inactive 
ingredients used in compounded drug products commonly include 
flavorings, dyes, diluents, or other excipients.
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    Section 512(a)(4) and (5) of the FD&C Act (21 U.S.C. 360b(a)(4) and 
(5)) provide a limited exemption from certain requirements for use for 
compounded animal drugs made from already approved animal or human 
drugs. Such use is considered an extra-label use and the FD&C Act 
provides that a compounded drug is exempt from the approval 
requirements and requirements of section 502(f)(1) (21 U.S.C. 
352(f)(1)) of the FD&C Act, if it meets the conditions set out in the 
statute and the extra-label use regulations at 21 CFR part 530.
    Elsewhere in this issue of the Federal Register, FDA is announcing 
the availability of a draft guidance for industry #230 entitled 
``Compounding Animal Drugs from Bulk Drug Substances'' (GFI #230).\2\ 
The draft guidance describes conditions under which FDA does not 
generally intend to initiate enforcement action against State-licensed 
pharmacies, licensed veterinarians, and facilities registered as 
outsourcing facilities under section 503B of the FD&C Act (outsourcing 
facilities) that compound animal drugs from bulk drug substances.
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    \2\ GFI #230 can be found at http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm042450.htm.
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    For pharmacies, these conditions include receipt of a valid 
prescription for a compounded drug from a licensed veterinarian for an 
individually identified animal patient before the

[[Page 28623]]

facility compounds the drug (with some limited compounding of an animal 
drug product in advance of receipt of a prescription in quantities 
based on a history of receipt of patient-specific prescriptions for 
that drug product). FDA recognizes that there may be some limited 
circumstances in which a drug compounded from one or more bulk drug 
substances should be available to a veterinarian for office use and is 
developing a list of such animal drug products and the bulk drug 
substances needed to make them applicable to drugs compounded by 
facilities registered as outsourcing facilities under section 503B of 
the FD&C Act. The draft guidance proposes that outsourcing facilities 
compound animal drugs only from bulk drug substances that will be 
listed in Appendix A of the final guidance, either pursuant to a 
veterinarian's order or pursuant to a patient-specific prescription. 
When a facility registered as an outsourcing facility under section 
503B of the FD&C Act uses the listed bulk drug substances to make the 
specified drug products pursuant to an order from a licensed 
veterinarian without a prescription for an individually identified 
animal, FDA does not intend to take action under sections 512(a), 
501(a)(5) (21 U.S.C. 351(a)(5)), 502(f), and 501(a)(2)(B) as long as 
such compounding is done in accordance with any associated conditions 
described in GFI #230. Although an outsourcing facility may fill a 
veterinarian's order for compounded animal drugs using bulk drug 
substances listed on Appendix A without obtaining prescriptions for 
individually identified animal patients, drugs produced by outsourcing 
facilities remain subject to the requirements in section 503(f) of the 
FD&C Act. Therefore, an outsourcing facility cannot dispense a 
compounded drug to the owner or caretaker of an animal patient without 
a prescription for that individually identified animal patient.
    This list only applies to outsourcing facilities. This list does 
not limit what bulk drug substances State-licensed pharmacies or 
licensed veterinarians can use in compounding drugs in accordance with 
the conditions set forth in the draft guidance, including the condition 
pertaining to obtaining a patient-specific prescription.
    FDA intends to include a bulk drug substance on Appendix A only 
when all of the following criteria are met:
     There is no marketed approved, conditionally approved, or 
index-listed animal drug that can be used as labeled to treat the 
condition;
     there is no marketed approved animal or human drug that 
could be used under section 512(a)(4) or (a)(5) of the FD&C Act and 
part 530 (addressing extra-label use of approved animal and human 
drugs) to treat the condition;
     the drug cannot be compounded from an approved animal or 
human drug;
     immediate treatment with the compounded drug is necessary 
to avoid animal suffering or death; and
     FDA has not identified a significant safety concern 
specific to the use of the bulk drug substance to compound animal drugs 
(under the listed conditions and limitations).
    Inactive ingredients need not appear on Appendix A to be used in 
compounding animal drug products.

II. Request for Nominations

A. Active Ingredients

    You may nominate specific bulk drug substances for inclusion on the 
list in Appendix A. Nominations will only be evaluated if they are for 
specific ingredients that meet the definition of a bulk drug substance 
in Sec.  207.3(a)(4) (21 CFR 207.3(a)(4)). Nominated substances that do 
not meet this definition will not be included on the list.
    To determine if a bulk drug substance should be included in 
Appendix A, FDA needs the following information about the bulk drug 
substance being nominated and the animal drug product(s) that will be 
compounded using such substance:
1. Confirmation That the Nominated Substance Is a Bulk Drug Substance
    A statement that the nominated substance is an active ingredient 
that meets the definition of ``bulk drug substance'' in Sec.  
207.3(a)(4), and an explanation of why the substance is considered an 
active ingredient when it is used in the identified compounded drug 
product(s), citing to specific sources that describe the active 
properties of the substance.
2. General Background on the Bulk Drug Substance
     Ingredient name;
     chemical name;
     common name(s); and
     identifying codes, as available, from FDA's Unique 
Ingredient Identifiers used in the FDA/U.S. Pharmacopeial Convention 
(USP) Substance Registration System, available at http://fdasis.nlm.nih.gov/srs/. Because substance names can vary, this code, 
where available, will be used by the Agency to confirm the exact 
substance nominated and to identify multiple nominations of the same 
substance so the information can be reviewed together.
     Chemical grade of the ingredient;
     description of the strength, quality, stability, and 
purity of the ingredient;
     information about how the ingredient is supplied (e.g., 
powder, liquid); and
     information about recognition of the substance in foreign 
pharmacopeias and the status of its registration(s) in other countries, 
including whether information has been submitted to USP for 
consideration of monograph development.

B. Information on the Animal Drug Products That Will Be Compounded With 
the Bulk Drug Substance

     Information about the dosage form(s) into which the bulk 
drug substance will be compounded;
     information about the strength(s) of the compounded 
product(s); and
     information about the anticipated route(s) of 
administration of the compounded product(s).

C. Need for the Animal Drug Products That Will Be Compounded With the 
Bulk Drug Substance

    For FDA to be able to meaningfully evaluate a substance, the 
information provided must be specific to the particular substance 
nominated and animal drug product to be compounded. A ``boilerplate'' 
or general explanation of need for compounding with bulk drug 
substances will not enable FDA to conduct an adequate review. Unless 
adequate supporting data are submitted for a bulk drug substance, FDA 
will be unable to consider it for inclusion in Appendix A.
    Prescribers of compounded animal drug products may be in the best 
position to explain why a particular bulk drug substance meets the 
criteria for including a bulk drug substance on Appendix A and are 
encouraged to provide data in support of a nomination. The following 
information about need is necessary to provide adequate support for 
nominations to the Appendix A list:
     A statement identifying the species and condition(s) that 
the drug product to be compounded with the nominated bulk drug 
substance is intended to treat;
     a bibliography of safety and efficacy data for the drug 
compounded using the nominated substance, if available,\3\ including 
any relevant peer-reviewed veterinary literature;
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    \3\ FDA recognizes that the available safety and efficacy data 
supporting consideration of a bulk drug substance for inclusion on 
the list may not be of the same type, amount, or quality as is 
required to support a new animal drug application.
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     a list of animal drug products, if any, that are approved, 
conditionally approved, or index listed for the

[[Page 28624]]

condition(s) in the species that the drug compounded with the nominated 
substance is intended to address;
     if there are FDA-approved or index listed drug products 
that address the same conditions in the same species, an explanation, 
supported by relevant veterinary literature, of why a compounded drug 
product is necessary (i.e., why the approved drug product is not 
suitable for a particular patient population);
     a review of the veterinary literature to determine whether 
there are FDA-approved animal or human drugs that could be prescribed 
as an extra-label use under section 512(a)(4) and (a)(5) of the FD&C 
Act and part 530 to treat the condition(s) in the species that the drug 
compounded with the nominated substance is intended to address;
     if the bulk drug substance is an active ingredient in an 
approved animal or human drug, an explanation, supported by appropriate 
scientific data, of why the animal drug product cannot be compounded 
from the approved drug under 21 CFR 530.13(b);
     an explanation, supported by relevant veterinary 
literature, of why the animal drug product to be compounded with the 
nominated bulk drug substance must be available to the veterinarian for 
immediate treatment to avoid animal suffering or death. Nominations 
should include specific information documenting that animal suffering 
or death will result if treatment is delayed until a compounded animal 
drug can be obtained pursuant to a prescription for an individually 
identified animal; and
     a discussion of any safety concerns associated with use of 
the nominated bulk drug substance or finished compounded product for 
the condition(s) in the species that the compounded drug is intended to 
address. If there are any safety concerns, an explanation, supported by 
veterinary literature, of why the concerns should not preclude 
inclusion of that bulk drug substance on Appendix A.

D. Nomination Process

    For efficient consolidation and review of nominations, nominators 
are encouraged to submit their nominations in a format that explicitly 
addresses each item previously listed in the order that they appear. To 
consider a bulk drug substance for inclusion in Appendix A, FDA must 
receive adequate supporting data for the substance. FDA cannot 
guarantee that all drugs nominated during the nomination period will be 
considered for inclusion on Appendix A prior to its initial 
publication. Nominations that are not evaluated during this first phase 
will receive consideration for later addition to Appendix A.
    Individuals and organization may petition FDA to make additional 
amendments to Appendix A after it is published, in accordance with 
Sec.  10.30.
    Interested persons may submit either electronic nominations to 
http://www.regulations.gov or written nominations to the Division of 
Dockets Management (see ADDRESSES). It is only necessary to send one 
set of nominations. Identify nominations with the docket number found 
in the brackets in the heading of this document. Received nominations 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

    Dated: May 12, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-11983 Filed 5-18-15; 8:45 am]
 BILLING CODE 4164-01-P