Compounding Animal Drugs from Bulk Substances - FDA Guidance GFI #256 Update
The US Food and Drug Administration (FDA) published Guidance for Industry #256: Compounding Animal Drugs from Bulk Drug Substances (GFI #256) after careful consideration and significant input from veterinarians, on August 2022.
GFI #256 guidance specifically addresses compounding from bulk drug substances for:
patient-specific prescriptions for nonfood-producing animals;
office stock for nonfood-producing animals;
antidotes for food-producing animals; and
sedatives and anesthetics for free-ranging wildlife species.
History of GFI #256 Updates and Concerns
In 2019, the FDA issued guidance on GFI #256, but after receiving feedback from veterinarians and compounders, they opted to make final modifications that would provide greater flexibility to veterinarians, allowing them to procure animal drugs compounded from bulk substances, which may be necessary for certain animals.
In 2020 the American Veterinary Medical Association, AVMA, submitted comments to the FDA, which was instrumental in communicating the challenges seen by veterinarians. At the time, the AVMA supported some provisions of the draft FGI #256 but opposed others.
Fast forward to 2022, when the Alliance for Pharmacy Compounding (APC) submitted a letter to the Center for Veterinary Medicine (CVM), which included an comprehensive list of questions from compounders and veterinarians in the industry.
Just shy of one year after the initial letter, CVM responded with their answers, giving compounding pharmacies further clarity on the FDAs GFI #256 - Compounding Animal Drugs from Bulk Drug Substances guidance.
Letter to APC From Center for Veterinary Medicine (CVM)
William T. Flynn, Deputy Director – Science Policy, Center for Veterinary Medicine (CVM) responded to President of the Alliance for Pharmacy Compounding (APC) Scott Brunner addressed in a letter dated February 15, 2023.
The letter from Flynn is a response to the APC’s letter from July 26, 2022.
In the letter, Flynn addresses questions and concerns from Brunner who was asking for “clarity on how the agency views the processes enumerated in the guidance document [GFI 256, “Compounding Animal Drugs from Bulk Drug Substances”].”
The response letter is 10 pages long and can be found here.
“There’s a good amount of helpful information in CVM’s response,” said APC Board Chair Anthony Grzib.
“It appears the agency took seriously our concerns about clarity in the GFI and has made a good-faith effort to describe its view of compliance. We’re grateful to Dr. Bill Flynn and his CVM team for that.”
As written by the APC article “CVM responds to GFI 256 questions”, below are the highlights of the Center for Veterinary Medicine’s answers to the APC’s questions from last year:
FDA does not intend to conduct inspections at 503B outsourcing facilities until it provides clarification on how GFI 256 applies to those facilities.
FDA does not expect compounding pharmacies to confirm a valid VCPR exists.
FDA will not question pharmacists’ professional judgment as to the documented reason a bulk ingredient was used instead of an FDA-approved drug.
FDA does not expect compounders to retroactively obtain medical rationale for prescriptions written prior to April 1, 2023.
CVM does not have a program to share with state licensing boards individual adverse events reports the agency receives.
FDA generally intends to refrain from taking enforcement action for bulk drug substances that are currently under review so that veterinary access to those compounded products is not restricted during the review process.
The APC and compounding pharmacies appreciate the answers from CVM and has shared the information and feedback with stakeholders, including the state boards of pharmacy.
As of February 24, 2023, the APC sent an updated briefing memo to all 50 state boards of pharmacy directors, and not the board members. The APC is encouraging that compounders share replies with the board of pharmacy members, and to help guide the state enforcements of GFI, so it is reasonably enforced across all states.
The briefing memo is 14 pages and is from APC’s leader Scott Brunner.
FDA GFI #256 Guidance - Aug 2022
In August 2022, the FDA released guidance addressing GFI #256 - Compounding Animal Drugs from Bulk Drug Substances – Guidance for Industry, which can be found here.
The agency made important changes to the final guidance to provide recommendations for veterinarians seeking to access animal drugs compounded from bulk drug substances for animals that need them.
Compounding an animal drug from bulk drug substances falls under the purview of the Federal Food, Drug, and Cosmetic Act (FD&C Act).
As per the Act, such compounding results in creating a "new animal drug," which must adhere to the FD&C Act's animal drug approval, conditional approval, or indexing regulations (detailed in sections 512, 517, and 572 of the FD&C Act).
All animal drugs must comply with current good manufacturing practice (cGMP) requirements (outlined in section 501(a)(2)(B) of the FD&C Act) and provide sufficient instructions for use (specified in section 502(f)(1) of the FD&C Act).
CLICK HERE TO DOWNLOAD GFI #256 GUIDANCE
The guidance will assist state-licensed pharmacies, veterinarians, and federal facilities who compound animal drugs from bulk drug substances for the purpose of administering the drugs to non-food-producing animals, using them as antidotes in food-producing animals, or employing them as sedatives or anesthetics in free-ranging wildlife.
These options should be considered only in limited circumstances when no other medically appropriate treatments are available.
An animal drug compounded from a bulk drug substance is not equivalent to an FDA-approved drug, even if they contain the same active ingredient.
However, the FDA has traditionally employed enforcement discretion in situations involving animal drug compounding from bulk drug substances under certain circumstances.
As described in the guidance, veterinarians can continue to prescribe animal drugs compounded from FDA-approved, conditionally approved, or indexed drugs.
The agency intends to focus on education and stakeholder engagement for the new animal drug compounding policies until April 2023 and will work flexibly and cooperatively with stakeholders during this period.
FDA will accept nominations of additional bulk drug substances at any time and continues to review nominations, update lists on a rolling basis, and prioritize office stock for enforcement action, as well as those products made under poor compounding practices.
Additional Links and Resources for GFI #265
CVM GFI #256 - Compounding Animal Drugs from Bulk Drug Substances
GFI #256 - Compounding Animal Drugs from Bulk Drug Substances
FDA Q&A: GFI #256 - Compounding Animal Drugs from Bulk Drug Substances
Bulk Drug Substances Links:
Bulk Drug Substances Reviewed and Not Listed (reviewed and not approved list)
Bulk Drug Substances Currently Under Review
For questions email AskCVM@fda.hhs.gov or submit electronic comments to https://www.regulations.gov.
Written comments should be mailed to: Dockets Management Staff (HFA305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Identify your comments with the docket number FDA-2018-D-4533.
You can also email the Center for Veterinary Medicine at CVMCompoundingNominations@fda.hhs.gov for questions about a specific nomination regarding the letter written by William Flynn to the APC in February 2023.
Where Does Your Facility Stand?
If you’re looking to become compliant with GFI # 256 or the new USP requirements, or if you wonder how you measure up, let consultants at Restore Health Consulting LLC perform a gap analysis to assess your pharmacy or hospital compliance status against the guidance & standards and lead remediation planning if needed.
Resources
Compounding Animal Drugs from Bulk Drug Substances Guidance for Industry
CVM GFI #256 - Compounding Animal Drugs from Bulk Drug Substances
CVM responds to GFI 256 questions
FDA updates compounding guidelines for vets (Webinar)
List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals
Q&A: GFI #256 - Compounding Animal Drugs from Bulk Drug Substances
Share CVM’s GFI 256 reply with your BOP
Veterinary Compounding Receives New Guidance From FDA
Video: Compounding Animal Drugs From Bulk Drug Substances - Key Points
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