Compounding from bulk drug substances

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In this article
  • Learn about the provisions of GFI #256.
  • Find information about nominating bulk drug substances to FDA lists.
  • See how AVMA influenced the development of GFI #256.
Gloved hands hold a mortar and pestle with white substance inside.

Understanding federal guidance: GFI #256

Veterinarians care for a wide variety of species with many different diseases and conditions, and we use multiple types of drugs to treat our patients. Drugs are approved, conditionally approved, or indexed by the U.S. Food and Drug Administration’s Center for Veterinary Medicine (FDA CVM) for use in specific species for particular diseases and conditions. Veterinarians also may prescribe drugs approved for human and animal use in an extralabel manner (in a way that differs from the label), and we may create or request from a pharmacist a product compounded from these drugs. When no such drug can be used to effectively treat our patients, veterinarians may need drugs compounded from bulk drug substances.

While drugs compounded from bulk substances are considered to be unapproved, the FDA CVM recognizes that veterinarians need these compounded drugs. On April 13, 2022, the agency published final guidance describing the conditions or situations under which the FDA does not intend to take enforcement action against entities compounding animal drugs from bulk drug substances.  

This guidance—Guidance for Industry #256 (GFI #256), Compounding Animal Drugs from Bulk Drug Substancesclarifies the parameters within which veterinarians may use compounded drugs that are prepared from bulk drug substances.  

The AVMA is actively working with FDA CVM and other stakeholders to ensure veterinarians’ access to these vital medications.

Spotlighting veterinary needs: AVMA's role

Compounding is a critical tool for veterinarians, including compounding from bulk drug substances. AVMA has made this clear to federal officials throughout the FDA's development and revision of GFI #256, and continues to communicate with FDA CVM about the guidance.

AVMA’s input and FDA CVM’s response

After withdrawing a previous draft guidance published in May 2015, based on feedback from the AVMA, state and allied veterinary organizations, individual veterinarians, the compounding industry, and other stakeholders, the FDA CVM published Draft GFI #256 in November 2019.

AVMA submitted written comments to FDA CVM on Draft GFI #256 on February 3, 2020, May 18, 2020, and October 8, 2020. These communications were instrumental in conveying to FDA CVM the many challenges veterinarians across the profession face in meeting the critical needs of our patients, why veterinarians must be able to maintain office stock of compounded products, and the need for clear guidance around the compounding that occurs daily in practice settings.

AVMA supported some provisions in Draft GFI #256, but opposed others. FDA CVM has taken AVMA’s feedback into consideration and responded with changes. Some examples include:

  • We expressed strong opposition to the use of lists to address office stock because of concerns that FDA might not be able to create and maintain them in a way to keep pace with clinical needs as well as the specific information that was being requested from those who wish to submit nominations. In response, FDA modified their approach to these lists to make the process of creating and reviewing them more dynamic and has indicated they will work with the profession to ensure the lists are robust. AVMA remains concerned about the potential professional and regulatory burden associated with these lists, but we appreciate FDA’s efforts to respond to our concerns and their agreement to work with us to make these lists work for the profession.
  • We conveyed concern that often, in cases of very large or small patients, use of available approved products may not always be feasible. In response, FDA indicated a clinical difference may include that too many tablets would be required or the tablet is not scored to accomplish the fractionated dose.
  • AVMA has consistently indicated that existing standards under USP Chapters 795 and 797 cannot be broadly applied to compounding for animals, particularly that occurring in a practice setting. In response, FDA CVM removed reference to USP Chapters 795 and 797 as a standard for compounding from the guidance
  • Clarification was requested around drugs listed in, and used in accordance with, AVMA’s euthanasia and depopulation guidelines that need to be compounded because FDA-approved drug(s) are not available or are not feasible to use in a particular situation. FDA CVM has indicated that it will be evaluating these on a case-by-case basis. AVMA will continue to work with FDA CVM to address the issues of products utilized for euthanasia and depopulation as questions remain regarding their approach to these products.
  • We shared that drugs used for immobilization or animal capture of free-ranging wildlife, that are also food-producing animals, often needed to be compounded for office stock, because FDA-approved drugs may not be available or may not be feasible to use in a given situation. FDA CVM has adjusted the scope of the list for food animals to include compounded drugs for use in free-ranging wildlife.  AVMA will be requesting clarification that such free ranging wildlife can be intended for consumption so long as appropriate provisions regarding withdrawal/withholding time are met. The list has also been adjusted so that it no longer applies to only products compounded for office stock but also to those compounded for use in patient specific prescriptions.

The AVMA has actively worked with FDA CVM regarding the agency’s approach to animal drug compounding from bulk drug substances as described in final GFI #256 and will continue to advocate for changes if implementation of the guidance does not meet veterinarians’ needs. FDA has indicated that it will focus on education and stakeholder engagement before shifting resources toward inspectional activities in Fiscal Year 2023 (October 2022).