Compounding Animal Drugs from Bulk Drug Substances - Part 5

This version of the guidance replaces the version made available April 2022. This revision provides the approved information collection OMB Control No. 0910-0904

The release of this FDA GUIDANCE has stimulated a lot of discussion. The FDA will receive comments on it as described below. To strengthen our voice, please join APC and participate in the educational programming offered on this topic and read and participate in the discussions on the IJPC Compounders' Network List.

This newsletter concludes the presentation of this FDA Guidance for Industry Document #256. The FDA will receive comments on it as described below. A complete copy of the Guidance with footnotes and comments may be downloaded at:

guidance-documents, or www.regulations.gov.

Compounding Animal Drugs from Bulk Drug Substances Guidance for Industry

Table of Contents

1. INTRODUCTION (Covered previously)
2. BACKGROUND (Covered previously)
   1. Legal Marketing Pathways for Animal Drugs
   2. Animal Drugs Compounded from Bulk Drug Substances
3. POLICY (Covered previously)
   1. Compounding for Nonfood-Producing Animals: Patient-Specific Prescriptions
   2. Compounding for Nonfood-Producing Animals: Without Patient-Specific Prescriptions (“Office Stock�)
   3. Compounding for Food-Producing Animals: Drugs for Use as Antidotes for Food-Producing Animals or Sedatives and Anesthetics for Free-Ranging Wildlife Species
4. PAPERWORK REDUCTION ACT OF 1995
   APPENDIX (Discussed in this newsletter)
   1. The List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals; or
   2. The List of Bulk Drug Substances for Compounding Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species

APPENDIX

Request for Nominations to:

1. The List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals; or
2. The List of Bulk Drug Substances for Compounding Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species

In a Federal Register notice published November 19, 2019, FDA established a public docket (FDA-2018-N-4626) so that interested parties could nominate bulk drug substances to a list of bulk drug substances for compounding office stock drugs for use in nonfood-producing animals or antidotes for food-producing animals (the List) and comment on nominated and evaluated bulk drug substances. In a Federal Register notice published April 8, 2022, FDA expanded nominations to include drugs compounded for use as sedatives or anesthetics for free-ranging wildlife species and also rearranged the List into two separate Lists as described above. This appendix incorporates information from the notices regarding the submission of nominations to these Lists.

Docket FDA-2018-N-4626 will remain open indefinitely to allow for nominations on a rolling basis.

Nominating a Bulk Drug Substance to a List:

When will FDA include a bulk drug substance on either of the Lists?
FDA intends to include a bulk drug substance on either of the Lists when:

1. There is no marketed FDA-approved, conditionally approved, or indexed animal drug(s) that can be used as labeled to treat the condition;
2. There is no marketed FDA-approved, conditionally approved, or indexed animal or human drug(s) with the same active ingredient(s) that could be used in an extralabel manner to treat the condition; and
3. FDA has not identified a significant safety concern specific to use of the bulk drug substance in animals.

For bulk drug substances used to compound drugs intended as office stock for nonfood-producing animals, in addition to 1-3 above:

1. Urgent treatment with the compounded drug is necessary to avoid animal suffering or death, or to protect public safety.

For bulk drug substances used to compound drugs intended for use as antidotes in food-producing animals or for use as sedatives or anesthetics for free-ranging wildlife species, in addition to 1-3 above:

1. There is sufficient scientific information for the prescribing veterinarian to determine appropriate withdrawal, withholding, or discard time(s) for meat, milk, eggs, or any food which might be derived from the treated animal(s).

How do I submit a nomination for one of the Lists?
You may submit nominations and comments to the docket through https://www.regulations.gov. The information to support nominations can be uploaded as attachments to your comment. The Docket No. is FDA-2018-N-4626.

You may submit written submissions to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All submissions must include the Docket No. FDA-2018-N-4626 for "Lists of Bulk Drug Substances for Compounding: Office Stock Drugs for Use in Nonfood-Producing Animals or Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species."

What information should I submit with the nomination?
You may nominate specific bulk drug substances for inclusion on either of the Lists. Each bulk drug substance should be submitted to the docket as its own, separate nomination. Submissions to the docket containing more than one bulk drug substance will not be considered an adequate nomination and will not be reviewed. Nominated substances that do not meet the definition of a bulk drug substance will not be evaluated for inclusion on a List.

For FDA to evaluate a bulk drug substance for inclusion on a List, you should submit the following information about the bulk drug substance and the compounded animal drug in the nomination:

1. Description of the Nominated Bulk Drug Substance:
   1. chemical name(s);
   2. common name(s);
2. Description of the Animal Drugs That Will be Compounded with the Nominated Bulk Drug Substance:
   1. dosage form(s) into which the nominated bulk drug substance will be compounded (e.g., capsule, tablet, suspension),
   2. strength(s) of the compounded drug(s), and
   3. intended route(s) of administration of the compounded drug(s) (e.g., oral, topical, injection, etc.).
3. Information Requested for FDA to Evaluate Nominated Bulk Drug Substances for Inclusion on a List:
   1. The species the drug to be compounded with the nominated bulk drug substance is intended to treat;
   2. The disease or condition(s) the drug to be compounded with the nominated bulk drug substance is intended to treat;
   3. If there is a marketed FDA-approved, conditionally approved, or indexed animal drug(s) that addresses the same condition(s) in the same species, an explanation of why a compounded drug is necessary (e.g., why the FDA-approved, conditionally approved, or indexed animal drug(s) is not suitable for a particular animal population);
   4. Confirmation that there is no marketed FDA-approved, conditionally approved, or indexed drug(s) that could be prescribed to treat the condition in the species that the drug compounded with the nominated substance is intended to address;
   5. If known by the nominator, if the nominated bulk drug substance is an active ingredient in a marketed FDA-approved, conditionally approved, or indexed animal or human drug(s), an explanation of why the animal drug cannot be compounded from the marketed FDA-approved, conditionally approved, or indexed animal or human drug;
   6. If known by the nominator, a description of any human user or animal safety concerns associated with use of the nominated bulk drug substance or finished compounded drug for the condition(s) in the species that the compounded drug is intended to address. If there are concerns, an explanation of why the concerns should not preclude inclusion of that nominated bulk drug substance on the List;
   7. For compounded drugs intended as office stock for nonfood-producing animals, an explanation of why the animal drug to be compounded with the nominated bulk drug substance is important to have available to the veterinarian for urgent treatment to avoid animal suffering or death, e.g., why 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
   8. For compounded drugs intended for use as antidotes to treat toxicoses in food-producing animals, or as sedatives or anesthetics for free-ranging wildlife species, relevant scientific literature or other evidence that demonstrates that the prescribing veterinarian has a basis for determining appropriate withdrawal, withholding, or discard time(s) for meat, milk, eggs, or any food which might be derived from the treated animal(s).
4. Contact information for FDA should there be follow-up questions regarding the nomination.

What about drugs that have been nominated for one of the Lists and are still under review?
FDA identifies those bulk drug substances that have been nominated and are under review at Nominated Bulk Drug Substances Currently Under Review. At this time, FDA generally intends to refrain from taking enforcement action when these bulk drug substances currently under review are used to compound a finished drug as described in the nomination. Bulk drug substances will remain on Nominated Bulk Drug Substances Currently Under Review only during FDA's review of their nomination. If FDA completes its review and declines to place the bulk drug substance on a List based on the information provided, FDA will continue to accept and review any adequate additional information submitted by any party that supports the previously reviewed nomination. Should adequate additional information be provided such that FDA can conduct further substantial review, the bulk drug substance will again be placed on Nominated Bulk Drug Substances Currently Under Review.

What happens when FDA approves or indexes a drug made with a bulk substance as described on one of the Lists?
FDA intends to remove a bulk substance from a List if a finished drug containing that substance in the appropriate dosage form and strength is approved or indexed. Please see Bulk Drug Substances Reviewed and Not Listed.

What happens when FDA reviews a bulk drug substance and determines that it cannot be placed on a List because of insufficient information or because of other reasons (e.g., safety concerns)?
Please see Bulk Drug Substances Reviewed and Not Listed for those bulk drug substances that have been reviewed by FDA but are not on either List.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition