The FDA recently finalized regulatory guidance for compounded animal medications from bulk drug substances for use in non-food-producing animals, impacting the way compounded drugs can be used, documented, ordered, and prescribed. This new guidance, Guidance for Industry #256 (GFI 256), affects both office stock in veterinary practices and individual animal-patient prescriptions. The release of this new federal guidance is important and adherence is critical, but the explanations can be complex.
Let’s start with the basics. What’s the gist of GFI 256?
GFI 256 addresses two areas of compounded medication use, both dealing with compounding from bulk drug substances. Bulk drug substances are the raw active ingredients most compounded medications are made from. The two areas addressed by GFI 256 include:
- Office stock (aka “office use”): To obtain a drug for office stock from a 503A compounding pharmacy, the active ingredient, strength, dosage form, and species it is to be used in MUST be on the list provided by the FDA on their website found (here). In addition, the same information and the indication for the drug must be provided to the pharmacy with each order.
For example, Apomorphine 2.5mg/ml injection for use in dogs is on the list but no other strength can be compounded for office stock from a 503A compounding pharmacy.
- Individual patient prescriptions: This is not as restrictive but does put a documentation burden on veterinarians and pharmacists if the drug is a copy of an FDA-approved or indexed drug. If the drug is a copy, veterinarians MUST document what clinical difference is produced in the patient with the compounded product that is not produced with the FDA-approved or indexed product.
What is a drug copy?
A drug is a copy according to the guidance when it has the same active moiety and route of administration as an FDA-approved or indexed product. Pharmacists must document why an FDA-approved or indexed product is not being used to compound the medication. Dosage form availability could potentially be impacted by this portion of the guidance.
Why was GFI #256 released?
The FDA has long taken the position that the safest way to compound a drug is to start with an FDA-approved product because it is a known product following cGMP manufacturing standards.
cGMP Drugs = commercially manufactured and 503B medications.
The FDA is more concerned with the compounding of office stock medications because a mistake in large batches of drugs for widespread distribution can cause problems with many patients. For patient-specific prescriptions, the FDA wants veterinarians and pharmacies to use FDA-approved or indexed products whenever suitable, which is why documentation is required when those approved or indexed products are not being used.
So, what changes does your practice have to make? And how are your prescribing or inventory management methods going to be impacted? Below, our team takes a closer look at the top four points you and your veterinary staff need to know—and how to solve some of the challenges these changes present.
Top 4 GFI 256 Guidelines Veterinary Practices Need to Understand
1. The guidance does not include cGMP products from 503B outsourcing facilities. The GFI 256 Guidance is FDA policy regarding the compounding of animal drugs from bulk substances for patient-specific prescriptions and for office stock by or under the direction of veterinarians or pharmacists in state-licensed pharmacies. These entities are required to meet USP compounding standards or similar state laws and regulations. This would include traditional compounding pharmacies, such as Stokes Pharmacy, Epicur’s 503A sister division within the company.
In contrast, outsourcing facilities are registered with the FDA and must meet cGMP standards. Outsourcing facilities are typically licensed by states as manufacturers, wholesale distributors, or outsourcing facilities.
2. The FDA wants FDA-approved or indexed drugs to be the starting materials for compounded drugs [covered in AMDUCA], not bulk drug substances. Again, this is because the FDA believes that starting with an approved drug, manufactured to meet cGMP standards, provides at least some assurances of quality that bulk drug substances may not. GFI 256 is the FDA’s position on when it intends to take enforcement action against veterinarians and pharmacies for compounding animal drugs from bulk drug substances.
3. The restrictions around patient-specific prescriptions may change which drug you prescribe or what is allowed to be dispensed by a pharmacy. When prescribing a drug for an individual patient, you will need to consider:
- The finished compounded drug must not be a copy of a marketed FDA-approved or indexed drug, or it requires documentation from the veterinarian and the pharmacy.
- According to GFI 256, a drug is a copy if it has same active ingredient or same active moiety as a marketed FDA-approved or indexed drug AND it can be given by same route of administration as the marketed FDA-approved or indexed drug.
- If a drug is a copy of a marketed FDA-approved or indexed drug, FDA requires documentation of the veterinarian’s medical rationale with the prescription, describing the clinical difference the compounded drug produces in the patient when compared with the FDA-approved or indexed drug—so basically, an explanation of why the approved or indexed drug isn’t being used.
- Examples of FDA-allowed medical rationales: (1) “Patient is allergic to ingredient [X] in FDA-approved drug” (2)“Ingredient [X] in FDA-approved product is toxic to species” (3) “Patient cannot be pilled with FDA approved capsule”
- Examples of not-allowed rationales: (1) “The compounded drug is less expensive” (2) “Prefer compounded drug” (3) “Need half strength”
Solutions to these changes with patient-specific prescription:
Pharmacy ordering systems, such as Stokes Pharmacy’s iFill platform, will alert veterinarians when a compounded drug needs documentation. The system will then provide veterinarians with medical rationales that commonly apply. If a veterinarian instead orders by phone, the pharmacist will need to document the veterinarian’s clinical rationale for prescribing the copy of the FDA-approved or indexed drug.
4. Rules regarding office-stock for companion animals will change. If the office-use drug is being ordered from a traditional 503A compounding pharmacy, the active ingredient, strength, dosage form, and species it is to be used in must be on the FDA’s list, available on the FDA’s website (here). Veterinarians and pharmacies may nominate substances to be considered for the FDA’s list.
The veterinarian who stocks the drug cannot dispense or transfer it to anyone other than the owner or caretaker of the animal or another veterinarian in the same practice at the same physical location. This federal guidance may be more or less restrictive than current state laws or regulations, and veterinarians must follow the most restrictive law or regulation that applies. For example, if your state does not currently allow veterinary office-use, this guidance does not change that.
Solutions to office-stock requirement changes:
Outsourcing facilities – which can be thought of as 503B manufacturers – are not included in the guidance, which means veterinary practices needing compounded medications for office use will be able to order from an outsourcing facility without consulting the FDA list. GFI 256 is final and does not cover products manufactured at 503B facilities such as Epicur Pharma, which means Epicur will still be able to provide for all your office order needs. As mentioned earlier, outsourcing facilities are required to meet cGMP standards, while GFI 256 is concerned with facilities that meet USP standards.
FDA enforcement of the guidance will not start until April 2023, so your practice still has time to adjust to the changes and gain a better understanding of what GFI 256 means for you. The biggest changes to keep in mind are the increased documentation for patient-specific prescriptions and the limitations and changes to available office-stock drugs if you’re ordering from 503A compounding pharmacies.
GFI 256 brings changes to ordering and prescribing, but it also brings benefits. When you order cGMP drugs there are higher assurances of quality and safety than with USP drugs, leading to improved patient outcomes, more accurate dosing, and more time for you to focus on your business and your clients.
The iFill ordering system will streamline the process for veterinarians ordering both office-stock and patient-specific prescriptions. The iFill system will have listed what you can order for office-stock and will provide the usual documentation necessary for patient-specific orders if the guidance requires it.
More Ways to Learn About GFI #256
Upcoming Webinar: June 22 | 8-9pm ET
GFI #256 Part 2: What Every Inventory Manager Needs to Know About Compounded Medications
Presented by Nicole Clausen, CSSGB, CCFP
Still unsure you have a handle on what these changes mean to your practice? Our team is committed to helping you understand the new guidance. Watch our on-deman webinar with Lauren Forsythe, PharmD, DICVP and Mike Juliano, RPh, J.D. to:
- Understand the risks GFI #256 minimizes
- Review the requirements that will impact your practice
- Develop a practical plan that ensures compliance