Alliance for Pharmacy Compounding Issues Public Comment on FDA Notice

WASHINGTON, Oct. 26 -- Shawn Hodges, president with the Alexandria, Virginia-based Alliance for Pharmacy Compounding, has issued a public comment on the Food and Drug Administration notice entitled "Compounding Animal Drugs from Bulk Drug Substances; Guidance for Industry; Draft Guidance". The comment was written on Oct. 14, 2020, and posted on Oct. 23, 2020:

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I write today in my role as president of the Alliance for Pharmacy Compounding (APC), formerly the International Academy of Compounding Pharmacists (IACP). APC is the voice for pharmacy compounding, advocating for thousands of pharmacists, technicians, students, researchers and suppliers.

Our organization is driven by pharmacy compounders' passion for their patients and the medications they provide. We are focused on strategies to assure patients can continue to access those medications. Our commitment to the entire pharmacy compounding profession is to lead, to influence, to speak, and to serve so that the practice of pharmacy compounding is recognized as a key component of health care delivery for millions of patients across America. I appreciate the opportunity to enunciate APC's comments on draft GFI #256.

We're grateful to director Dr. Steven Solomon and the other professionals at the Center for Veterinary Medicine (CVM) for establishing an open line of communication with APC and other pharmacy stakeholders after it issued GFI #256 in November 2019. We appreciate the willingness of Dr. Solomon and his team to meet with us in person back in January. We also appreciate his presentation at our virtual educational conference in May. And we appreciate that CVM extended the comment period on GFI #256 to October 15, 2020, so that more stakeholders could provide input on this important guidance.

We recognize the expertise and experience that Dr. Solomon and CVM bring to matters of veterinarian medicine, and we do not doubt that he and his team have the best intentions in proposing draft GFI #256.

That said, APC has serious concerns with the legal authority cited by FDA to regulate animal drug compounding from bulk drug substances. We question the proposed establishment of an entirely new federal regulatory framework for animal drug compounding without notice and comment rulemaking and without any clear statutory authority granted by Congress to do so. More importantly, we are alarmed that FDA would consider finalizing a guidance document that, in its current form, would preempt state pharmacy and veterinary practice laws, interfere in the medical judgment of veterinarians, limit access to and decrease safety of animal drugs and would needlessly increase costs for pet owners, clinics and zoos. For these reasons, we respectfully request that FDA withdraw GFI #256.

Given the concerns we'll express here - concerns which are no doubt shared by other affected groups and individuals - we believe a better course would be to step back and engage stakeholders in developing policies that better balance the agency's stated goals of protecting animal safety and preventing the compounding of copies of FDA approved drugs with the needs of veterinarians to be able to prescribe and to have on hand for office administration the right drugs (FDA-approved or compounded) - those that in their medical judgment are essential to meet the needs of their animal patients.

Following is a discussion of our concerns with GFI #256.

GFI #256 Establishes a New Federal Regulatory Framework for Animal Drug Compounding from Bulk Substances Without Congressional Authorization:

Veterinary medicine and animal drug compounding have been historically and traditionally regulated by state boards of veterinary medicine and pharmacy pursuant to state laws passed by state legislatures and carried out by vets and pharmacists licensed by those state boards. This has been the case since at least 1938 when the Food, Drug and Cosmetic Act (FDCA) was originally passed. Congress has not passed any amendments to the FDCA that expressly preempt those state laws and create a new federal regulatory framework over the compounding of animal drugs. It is inappropriate for FDA to attempt to do so via non-binding guidance for industry without formal rulemaking and without any clear statutory authority from Congress to do so.

In draft GFI #256, FDA asserts regulatory authority over veterinary compounding by claiming that the Food, Drug and Cosmetic Act's (FDCA) definition of "new drugs" is expansive enough to cover all compounded animal drugs - meaning that they must go through the new drug approval (NDA) process, or be granted conditional approval, or be indexed. This means that FDA effectively considers all compounded animal drugs to be illegal, because by their very nature compounded drugs, human or animal, do not go through the drug approval process. The FDCA set up a federal regulatory framework for animal drug manufacturing, not animal drug compounding, and the subsequent amendments to the FDCA that carve out exemptions from the manufacturing requirements apply to human drug compounding, not animal drug compounding. The FDCA does not speak to animal drug compounding because Congress did not intend to give the FDA the power to regulate veterinary compounding, which would preempt state veterinary medicine and pharmacy laws and regulations and upend decades of professional practice and animal patient care.

Similarly, FDA appears in draft GFI #256 to be attempting to greatly expand the authority given to the agency in the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). Via this GFI, FDA asserts regulatory authority to limit bulk ingredient compounding of animal drugs. But AMDUCA doesn't speak directly to animal drug compounding either. AMDUCA simply allows vets to prescribe certain FDA- approved human or animal drugs for extra-label use when certain conditions are met. (see USC Secs. 360b(a)4 and (a)5). The implementing regulations (21 CFR Sec. 530 et. seq.) neither authorize nor prohibit bulk ingredient compounding for animals. Rather, they simply establish the requirements that must be met for prescribing extra-label use of FDA approved drugs, including drugs compounded from FDA-approved drugs for extra-label use. Those regulations also point parties to non-binding FDA guidance for information on compounding (see 21 CFR Sec. 530.13). Extra-label use is not bulk substance compounding. They are two completely unrelated activities that have nothing to do with each other. It is simply not plausible that Congress would have intended to give FDA broad regulatory authority over animal drug compounding in this section of the law related to a completely different subject.

Lastly, although the 2015 draft GFI on animal drug compounding inappropriately attempted to expressly apply section 503A and the amendments to the FDCA made by the Drug Quality and Security Act of 2013 (DQSA) to animal drug compounding - and GFI #256 does so more indirectly by applying many of the same requirements - those provisions of the law are clearly meant only to apply to human drug compounding, not to animal drug compounding. This attempt to apply the DQSA to animal drug compounding is especially evident through the GFI's establishment of a positive list of bulk ingredients for office stock compounding for animals, very similar to the list created under 503B of the FDCA for outsourcing facilities. It is completely inappropriate for FDA to apply that statutory language on human drug compounding to animal drug compounding through a non-binding GFI. Through GFI #256, FDA is saying to veterinarians and pharmacists that although they consider all animal drug compounding (even though authorized under state laws) to be illegal under federal law, the agency will exercise enforcement discretion if the conditions of the GFI are met. This puts vets and pharmacists in an untenable position and jeopardizes animal patient safety. Indeed, with a positive list tied to specific dosage forms, strengths and indications, the restrictions on bulk ingredient compounding for animals in GFI #256 are more restrictive, than those placed place on human drug compounding through the DQSA.

For these reasons, APC asserts that FDA does not currently have the legal authority through either the FDCA nor AMDUCA and its implementing regulations to regulate animal drug compounding from bulk ingredients. Animal drug compounding, like veterinary medicine, is appropriately regulated at the state level. FDA lacks the legal authority from Congress to create an entire federal regulatory framework over animal drug compounding through a non-binding guidance for industry citing statutes that relate to extra-label use of FDA approved products that do not apply to animal drug compounding from bulk substances. Until such time that Congress enacts law expressly granting FDA the authority to establish such a framework, the agency should continue to defer to state laws and regulations on veterinary medicine and animal drug compounding.

GFI #256 Interferes with the State Regulated Practice of Veterinary Medicine:

As stated above, the practice of veterinary medicine, like animal drug compounding, is a state licensed and regulated activity that is not within the jurisdiction of the FDA.

APC also takes issue with the GFI's requirement that veterinarians justify, in writing, the clinical need and "medical rationale" to prescribe a drug compounded from bulk ingredients. This unprecedented requirement is an inappropriate federal intrusion on veterinary medicine and beyond the scope of authority given to FDA by Congress. Additionally, the criteria listed in the GFI as to what constitutes a "copy" of an FDA approved human or animal drug and therefore requires the vet to justify the medical rationale is unreasonably expansive and will open vets and pharmacists to enforcement actions by FDA if the agency does not agree with the medical rationale cited by the veterinarian. FDA has documented their preference for fractional doses of manufactured products over compounded preparations of the appropriate dose in footnote 16 of the guidance despite having published a separate guidance document that speaks against this practice. Further, the guidance does not provide clarity as to how far veterinarians, pharmacists, and caregivers should have to go with attempting to break down manufactured drugs into fractional doses.

As discussed in more detail below, by so heavily favoring the use of FDA-approved animal drugs or even extra-label use of FDA-approved human drugs over animal drugs compounded from bulk ingredients in GFI #256, the FDA is inappropriately usurping the professional judgment of veterinarians and preempting state veterinary and pharmacy laws through a non-binding guidance document. This is also true in the way the GFI establishes positive and negative lists for bulk ingredients for compounding for office stock for veterinarians, something that is uniquely important in veterinary medicine because vet clinics very often serve as the emergency room and hospital for animal patients.

GFI #256 Will Limit Treatment Options and Decrease Animal Patient Safety:

Veterinary medicine involves the treatment of many different species of animals. They come in many different sizes and have many different health conditions that require varying types of medications in varying dosages and strengths and routes of administration. This is why FDA-approved products often do not meet the needs of a particular animal patient and why animal drug compounding from bulk substances is such an integral part of veterinary medicine. Unfortunately, GFI #256, if finalized, would limit the ability of veterinarians to prescribe animal drugs compounded from bulk substances and would drastically curtail their ability to order them for office stock for administration to their patients.

APC rejects the FDA's position in GFI #256 that FDA approved human or animal drugs are always a safer source of approved pharmaceutical ingredient (API) than bulk substances when compounding animal drugs because they have gone through the new drug approval process. This is unsupported by the scientific data, especially as it relates to FDA-approved human drugs, which are often made in dosage forms, routes of administration and contain ingredients not appropriate for the treatment of animals. Therefore, starting with an FDA approved human drug as the source of the API for compounding for an animal patient is often much more expensive, and can produce a lower quality compounded medication, than starting from bulk ingredients. The United States Pharmacopeia has published data showing formulations failed or could not be analyzed when using commercial products as the source of active ingredient.

Compounded medications prepared from bulk ingredients allow the compounder to produce a medication that meets the patient's exact requirements for dosage form and route of administration, as prescribed by the veterinarian, without containing any ingredients that may be in the FDA approved product that are unsafe for animals. Additionally, individual dosage units of FDA approved product can vary in purported strength across a legal range, often by as much as 10 percent or more =/-, which can lead to sub-potent or super-potent compounded drugs, compared to bulk ingredients with a known API potency as provided within a certificate of analysis from the FDA registered supplier of the bulk ingredients.

We are concerned about the provisions of GFI #256 that will limit bulk ingredient animal drug compounding needed by veterinarians, clinics and zoos to administer to their animal patients at the vet's office or clinic or remotely at the barn or zoo. Again, the veterinarian's office is often the emergency room and hospital for patients. Having a variety of compounded animal drugs in stock, many of which are compounded from bulk substances, is critical to veterinary medicine, which often requires the immediate treatment of animals and with no time to write and fill a prescription at a pharmacy or for the veterinarian to compound the drug. This is why most state pharmacy laws authorize some form of office-stock compounding for animal treatment. GFI #256, if finalized, would limit the bulk ingredients authorized for animal drug compounding for office stock to a list established by FDA of drugs where "immediate treatment with the compounded drug is necessary to avoid suffering or death." (see GFI #256 Appendix).

APC is also very concerned about the restrictive criteria FDA will consider under GFI #256 in deciding whether or not to put substances on the approved list for office stock compounding. By including only substances that cannot be compounded from an FDA-approved human or animal drug, the FDA is again substituting the agency's medical judgement for that of the veterinarian and limiting access to the drugs veterinarians need in stock to treat their animal patients in the office, clinic, zoo, or remotely.

It also ignores the very reason why bulk ingredient compounding is often necessary, to specialize the drug for the dosage form, route of administration, and/or indication to meet the needs of the veterinarian's patients.

We also object to the process prescribed in GFI #256 for nominating substances to the list. The volume of data and information required to be submitted rivals the new drug approval process and is unworkable and a poor fit for analyzing bulk ingredients used in animal drug compounding. And by what criteria will FDA evaluate nominated substances? Additionally, the negative list established by GFI #256 prohibits substances for specific indication, dosage form and route of administration. Again, this is appropriate under the new drug approval process, but inappropriate for evaluating bulk substances compounded to treat a variety of indications in differing dosage forms and routes of administration.

APC is also concerned that GFI #256 does not specify the process FDA will undertake when considering these positive and negative lists and does not require the involvement of any outside expert panel of veterinarians and animal drug compounding pharmacists. Lastly, APC strongly reiterates that it is inappropriate and well beyond any statutory authority given to FDA for the agency to establish a federal regulatory framework for animal drug compounding via GFI, especially the positive and negative lists for bulk substance compounding for office-stock, without any authorization from Congress to do so.

This GFI, if finalized, would unnecessarily restrict veterinarian access to the bulk ingredient compounded drugs they need, especially those for office stock, and would negatively impact the treatment of their animal patients.

GFI #256 Will Dramatically Increase the Cost of Animal Medicine:

In addition to interfering with the practice of veterinary medicine and greatly limiting the options that veterinarians have to treat their patients, GFI #256 will greatly increase health care costs for pet owners, clinics and zoos. As discussed above, compounding from the FDA-finished product cannot be shown to be safer compounding from bulk API and it is also much more expensive. This is due to the higher cost of FDA-approved drugs over API. Not only that, but the process of compounding from FDA-approved product is also much more expensive than compounding from bulk ingredients. The effect of the increased cost on animal owners will be amplified by the fact that pets and other animals rarely have health insurance, and their health care costs often must come second to human health. We are concerned that clinics, shelters and zoos would be particularly hard hit with the increased costs associated with GFI #256 and the stringent restrictions on bulk ingredient compounding for office stock. GFI #256 would needlessly drive up animal health care costs and lead to animals going without care, and could well result in animal patient deaths.

Conclusion:

In conclusion, APC again thanks Dr. Solomon and his team at CVM for the open dialogue on our concerns with GFI #256 and we appreciate the opportunity to provide further input with these comments. We believe this GFI is an inappropriate and dramatic expansion of the regulatory authority granted to FDA by the Congress. We believe it preempts state pharmacy and veterinary practice laws and negatively impacts animal health care in America. For the reasons we have enunciated here, we respectfully request that FDA rescind GFI #256 and continue discussions with stakeholders, including Congress, about whether new federal laws or regulations are needed to address compounding animal drugs from bulk substances.

Please feel free to contact me at [email protected] or APC's David Pore at [email protected] with any questions or concerns about this submission.

Sincerely,

Shawn Hodges, PharmD

President

Alliance for Pharmacy Compounding

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The notice can be viewed at: https://www.regulations.gov/document?D=FDA-2018-D-4533-0002

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