What is GFI #256 and how does it impact my practice?

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Content submitted by Epicur Pharma, a dvm360® Strategic Alliance Partner

There has been significant discussion recently about GFI #256, but this discussion has often been met with confusion. Therefore, this article is written to clarify what this document is and is not, and how it is likely to affect your day-to-day practice. An important point to keep in mind when reading this, if the compound is prepared by manipulating a commercial product (e.g., crushing tablets to make a suspension), then nothing in this guidance applies. This guidance is only pertaining to compounds that are made from bulk chemicals.

To understand the impact of this document, it’s important to understand what Guidance for Industry (GFI) documents are. GFIs are written by the FDA to provide guidance on acts that the FDA has determined are illegal but necessary under certain circumstances or to provide clarification of FDA’s current thinking on a topic. In the case of compounding for animals, the Animal Medicinal Drug Use Clarification Act (AMDUCA) legalized compounding when done by manipulating approved products. Since AMDUCA didn’t address compounding from bulk chemicals, compounding from these technically remains illegal. However, there are circumstances where it’s necessary. Examples of when compounding from a bulk chemical is necessary include when a product isn’t commercially available (eg, cisapride) or the formulation quality is likely to be sacrificed due to the additional excipients in commercial products (eg, transdermals, and solutions).

GFI #256 is the latest in a series of documents since 1996 that have attempted to delineate what the FDA interprets is appropriate versus inappropriate bulk chemical compounding. GFIs are not laws and therefore don’t have the force of the law. However, the FDA utilizes these documents to guide their enforcement. GFI #256 was released in draft form in 2019 followed by an extended public comment period. The final version was released in spring 2022 with an expected enforcement date of April 2023. While this is a Federal-level guidance document, state regulatory boards often use FDA guidance documents to guide their regulatory decisions, so it’s important to monitor potential impacts to state-specific regulations.

It’s important to keep in mind that the guidance is written to guide those that are preparing the compounds (specifically pharmacists/pharmacies and veterinarians compounding in-house). If you do not fall into either of these categories, you are likely to notice minor changes in the information the pharmacy needs when filling compounded prescriptions. One such piece of information is the clinical justification for prescribing a compound. According to AMDUCA, approved products should be used, if possible, therefore, having a clinical reason for using a compounded medication isn’t new. The required documentation of that reason is what’s new. The guidance document provides several examples of acceptable and unacceptable reasons. It should be noted that cost is not an acceptable reason. What is considered a clinical difference to justify use of a compounded medication is often patient and medication specific; therefore, determination of a clinical difference is at the professional judgement of the prescriber as long as it falls within the requirements of the guidance document.

There are also additional documentation requirements for office stock compounds prepared by compounding pharmacies and the bulk chemicals that can be used must be accepted by the FDA for this purpose. Full requirements can be reviewed at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-256-compounding-animal-drugs-bulk-drug-substances. A list of bulk chemicals accepted or currently being considered for office stock compounding can be found at https://www.fda.gov/animal-veterinary/animal-drug-compounding/list-bulk-drug-substances-compounding-office-stock-drugs-use-nonfood-producing-animals.

The flow chart (see below) accompanying this article provides a quick assessment of what to expect the impact to be based on your specific circumstances. If you will be prescribing compounded medications, it’s suggested to review the guidance document for an understanding of the documentation requirements pharmacies must comply with. If compounding in-house using bulk chemicals, it’s important to review the guidance as several documentation requirements will apply to your in-house compounding including identifying why a formulation can’t be prepared from a commercially available product.