By Karla L. Palmer –
The Food and Drug Administration (FDA) announced earlier this week that it is seeking nominations for bulk substances that may be used by outsourcing facilities to compound drugs for use in animals. FDA will ultimately include the listed substances in Appendix A to FDA’s guidance for “Compounding Animal Drugs from Bulk Substances.” The draft of that guidance was released earlier this week (and blogged about here). Bulk substance nominations should be submitted within 90 days after publication of the notice (or by August 17, 2015) to ensure FDA’s consideration (but FDA noted it cannot guarantee that all drugs nominated during the nomination process will be considered prior to initial publication of Appendix A). After the comment period is closed, nominations to add or remove substances from the list may be submitted by citizen petition.
FDA’s request for nominations notes there are “limited circumstances” where a drug compounded from bulk substances should be available for office use; FDA is proposing in its related draft guidance that outsourcing facilities compound animal drugs only from the bulk substances listed in Appendix A. FDA will exercise enforcement discretion for those facilities that compound animal drugs using Appendix A’s listed bulk substances. Although an outsourcing facility may fill an order for compounded animal drugs from bulk substances without obtaining an individually identified patient prescription, “outsourcing facilities cannot dispense a compounded drug to the owner or caretaker of an animal without a prescription for that individually identified animal patient.” FDA specifically notes that Appendix A only applies to outsourcing facilities, and does not limit what bulk drug substances state-licensed pharmacies and veterinarians can use in compounding in accordance with the draft guidance. In addition, the underlying draft guidance only addresses compounding from bulk substances; it does not apply to the compounding from approved animal or human drugs.
The list will be limited to bulk substances (but not inactive ingredients) that address all of the following criteria:
- 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 FDCA section 512(a)(4) or (a)(5) and 21 CFR 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).
Concerning active ingredients, nominations must be for specific bulk substances that meet FDA’s definition of a bulk substance in 21 C.F.R. §207.3(a)(4). As set forth in further detail in the notice, nominations must also include the following:
- “Confirmation” that the nominated substance is a bulk substance including an explanation of why the substance is considered an active ingredient when it is used in the compounded product, citing to “specific sources that describe the active properties of the substance”;
- A general background on the bulk drug substance;
- Information on the animal drug products that will be compounded with the bulk drug substance (including dosage form, route of administration, strengths, etc.);
- Information detailing the need for the animal drug products that will be compounded with the bulk drug substance. FDA states that to be able to meaningful evaluate and review the substance, it needs more than a general explanation.
FDA adds that following information about “need” is necessary:
- A statement identifying the species and condition the drug is intended to treat;
- Bibliography of safety and efficacy data if available including peer reviewed literature;
- List of approved/index listed/conditionally approved animal drug products for the condition that the compounded drug is intended to address;
- If there are approved drugs for the condition, why the compounded drug from the bulk substance is necessary, supported by relevant literature;
- Review of veterinary literature to determine whether there are any approved or extralabel uses of the drug that could treat the condition in the species that the compounded drug is intended to address;
- If the bulk substance is an active ingredient in an approved animal or human drug, an explanation (with appropriate supporting scientific data) of why it cannot be compounded from the approved drug;
- An explanation (supported by relevant veterinary literature) of why the animal drug product must be available to the veterinarian for immediate treatment to avoid animal suffering or death. Nominations should include information documenting that “animal suffering or death will result if treatment is delayed until a compounded animal drug product can be obtained pursuant to a prescription for an individually identified patient”; and
- A discussion of safety concerning, including relevant literature. Safety concerns must include an explanation with supporting literature of why those concerns should not preclude inclusion on the list.
FDA warns that it will be unable to consider the bulk substance for Appendix A unless adequate information is submitted. FDA encourages submission of nominations in a format that “explicitly addresses each item ... listed in the order that they appear” in the notice.