Facts About FDA's Guidance for Industry #256

Background

FDA’s Center for Veterinary Medicine (CVM) recently issued draft guidance (GFI #256) that, if finalized, threatens to have serious and damaging ramifications for your practice and your patients. You may recall in 2015, FDA introduced guidance (GFI #230) that was substantially similar on the compounding of animal drugs from bulk drug substances. Following significant pushback from the veterinary and pharmacy community and intervention from members of Congress, FDA formally withdrew that Guidance in 2017.

What is the New GFI #256?

GFI #256 is a draft guidance that would establish FDA’s policies about how and when they would seek enforcement action against veterinarians, state-licensed pharmacies, and federal facilities who compound animal drugs from bulk drug substances. FDA is creating both a positive and negative list for compounding from bulk ingredients. The positive list proposed contains a mere seven active pharmaceutical ingredients. We do not believe the process FDA proposes would allow the most common APIs to be added to the list.

If finalized, what repercussions might the GFI #256 have for my practice and patients?

FDA is taking this action, in the form of a supposed “non-binding” guidance document, that places veterinarians and veterinary compounding pharmacies under extremely burdensome restrictions that prohibit veterinarians and pharmacies from properly treating patients, when 99% of veterinarians report that access to compounded medication is important or very important to their practice. Especially important to note is that Congress has not passed legislation giving FDA authority to make such a substantial change in animal health. If finalized,

  • Your access to compounded medications would be severely restricted;
  • The quality and safety of compounded medications would suffer; 
  • The cost of your compounded medications would drastically increase; and
  • You and your practice would be burdened by additional FDA regulatory oversight.

Your Access: RESTRICTED

  • GFI #256 mandates the development of a positive list for bulk ingredients for office use, but there is no statutory basis for this requirement. This list contains only seven items (Apomorphine hydrochloride, Cisapride, Guaifenesin, Metronidazole benzoate, Miconazole nitrate, Potassium bromide, and Tacrolimus). Veterinarians utilize over 450+ active pharmaceutical ingredients to meet the needs of their patients—this is the standard of care. We do not believe the process FDA proposes would allow any additional APIs on the list.
  • GFI #256 severely restricts the ability of veterinarians to order any other compounded medication for office use, requiring a patient-specific prescription and burdensome, yet-to-be-defined, documentation of the clinical need and medical rationale.
  • Often, compounding is in response to FDA manufacturer backorders. Eliminating the ability to start from bulk ingredients will eliminate access during drug shortages.
  • GFI #256 contradicts existing state law - in most states, veterinarians may exercise their medical judgement to compound or order compounded medications for veterinary office use. 94% of veterinarians report that maintaining office stock of compounded medication is important or very important to medical outcomes. Additionally, 78% of veterinarians in the few states that do require patient-specific prescriptions report that patient-specific requirements have a negative impact on their ability to practice medicine.
  • GFI #256 mandates that compounding, other than the positive list of seven items, begin with FDA-approved drugs—this is not a requirement in human health.
  • GFI #256 limits compounding to drugs that “do not present a particular human or animal safety concern.” Some examples FDA gave include “superpotency leading to animal overdose, microbial contamination, and drug formulations that present safety risks for the treated animals or for the people handling or administering the animal drug.” This is vague but may lead to the elimination of sterile preparations and hazardous drugs, which currently make up a significant portion of compounding requests that get fulfilled. 
  • With no due process, FDA has also released a negative list, consisting of 11 bulk drug substances that may NOT be used for office use compounding. These currently include:
  • Amlodipine
  • Enrofloxacin
  • Budesonide
  • Gabapentin
  • Chloramphenicol
  • Idoxuridine
  • Dexamethasone
  • Itraconazole with DMSO
  • Dipyrone
  • Voriconazole
  • Doxycycline
 

Many FDA manufacturers will not permit sales of veterinary finished goods to compounding pharmacies, thus oftentimes preventing compounding from FDA-approved sources.

Quality and Safety: LOWER

Providing no scientific reason or rationale, FDA is taking the position that drugs compounded from bulk drug substances pose an increased risk to patient safety versus drugs compounded from commercially available dosage forms. This view is contrary to the views of many independent scientific experts in many respects. For example:

  • Pharmacy quality experts agree that starting with bulk powder ensures purity, consistency and appropriate potency of compounded medication. Quality standards for ingredients are written into state law, and USP monographs direct pharmacies to begin with bulk active pharmaceutical ingredients. Starting with FDA-finished goods may increase potency variability by as much as +/- 15%. 
  • Drugs intended for human use may contain ingredients that are toxic to some animal species. Even diluting FDA-approved medications to a lower concentration suitable for an animal could result in potentially deadly outcomes.

Cost: 300% HIGHER

  • Compounding from FDA finished goods will unnecessarily increase the price of your medication by an average of 300% due to the cost differential between finished goods and bulk API in addition to the added compounding effort. This will directly impact pet owners and veterinarians. You and your customers will have to pay for this unnecessary regulation.
  • GFI #256 will subject you and pharmacies to costly and time-consuming documentation requirements to justify your medical decisions.
  •  Increasing costs will negatively impact your practice and your patients, causing unnecessary suffering and death. As you are aware, owners may choose to put an animal down if the patient is difficult to medicate or they feel that they cannot afford treatment. It is horrendous that GFI #256 has the ability to cause more pain, suffering and death in patients than it proports to protect. 

FDA Regulation Over You: UNPRECEDENTED. GFI #256 would:

  • Give FDA new authority over veterinarians and pharmacies that provide compounded preparations. 
  • Hamper your ability to use your medical judgement to prescribe or order compounded medication that you believe is best for your patients regarding strength, dosage form and flavoring.
  •  Force you to use lower quality medication than what is available to human patients due to the requirement to begin most compounding with FDA-approved finished goods. 

What ido compounding pharmacies think about GFI #256?

Veterinarians compound and order compounded medication when, in their medical judgement, they deem this as the best solution for the unique needs of their patients. The interference from FDA that will result from GFI #256 is unnecessary and unwarranted. It does not serve to increase the safety of compounded medications. Instead, it would significantly decrease the access to and the quality of compounded medications, while increasing costs for consumers and veterinarians alike.

What actions are compounding pharmacies taking?

Our goal is to prevent FDA from severely restricting access for veterinarians and patients to compounded medication. We intend to ensure that patients benefit from the skills, experience and proven track record of compounding pharmacists when veterinarians believe a compounded medication is the right solution for the unique needs of their patients. To that end, Wedgewood Pharmacy will:

  • Provide detailed comments to FDA;
  • Keep you informed and engage you to ensure your access to compounded medication is secure;
  • Collaborate with a coalition of animal health pharmacies, as well as multiple industry associations, to align on feedback to FDA; and
  • Meet with lawmakers to inform them of the impact of this guidance on people and their pets, including increased pain, suffering and cost.

In response to significant concerns expressed by many groups, FDA has extended the comment period until at least June 17, 2020.

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