The FDA’s approval of the drug Aduhelm as a treatment for Alzheimer’s disease — despite the recommendation of its own advisory committee against approval — came as a surprise to many. But to me, that decision is the latest in an ongoing pattern of FDA keeping its own counsel and doing things its own way.
I’ve seen this firsthand in its oversight of pharmacy compounding, where the agency has a track record of cutting corners, manipulating processes, and even defying Congress to implement its own agenda.
Compounding means creating a customized medication, most often from raw ingredients, for an individual patient pursuant to a prescription. Pharmacists’ ability to compound medications from pure ingredients is authorized in federal law and for good reasons: Manufactured drugs don’t come in strengths and dosage forms that are right for everyone, and physicians need to be able to prescribe customized medications when, in their judgment, a manufactured drug is not the best course of therapy for a patient.
Yet the FDA impugns pharmacy compounding by insinuating that because each of the millions of individually compounded preparations are not FDA-approved (which is true) they are therefore unsafe (which is a logical fallacy). Never mind that Congress specifically and intentionally exempted compounded medications from FDA approval via Section 503A of the Federal Food, Drug, and Cosmetic Act.
From the simple addition of grape flavoring for a child’s medication to the compounding of critical medications in shortage — as the FDA has temporarily allowed during the Covid-19 pandemic — compounding pharmacies must adhere to high standards of quality and compliance. Every one of the ingredients that compounding pharmacies use must come from FDA-registered facilities and manufacturers. Compounding labs and the equipment in them are subject to exacting regulation and are inspected by state boards of pharmacy and by the FDA.
Of course, there have been bad actors in compounding, just as in medicine or drug manufacturing or any other industry. That’s why a strong regulatory framework is essential. But that framework must also be practical and avoid creating impediments to patients’ access to physician-prescribed therapies.
The FDA doesn’t seem terribly concerned about patient access. Under its mantra that compounded preparations are by their very nature “unsafe,” the FDA has mounted a yearslong campaign to marginalize compounding that often ignores patient outcomes data, legal protocol, or stipulations in the law.
Here are just four examples:
Stacking the deck. In 2019, the FDA commissioned the National Academies of Sciences, Engineering, and Medicine to undertake what the FDA said would be an objective review of the safety and effectiveness of compounded hormones. After the National Academies released the final report on July 1, 2020 — which included a recommendation for across-the-board restrictions on compounded hormones — the FDA said in an email to FDA stakeholders on that day it would be “reviewing NASEM’s findings to inform our next steps regarding cBHT [compounded bioidentical hormone therapy].”
What the FDA did not say — but which is demonstrated in a Freedom of Information Act request made by the Reed Smith law firm — was that the agency exerted inappropriate influence and bias in almost every phase of that commissioned report, even recommending appointees to the study committee who had no expertise in prescribing or compounding hormones, all with the intention of steering the study’s findings to support its previously held opposition to compounded hormones. An independent analysis of the NASEM report, commissioned by the Pharmacy Compounding Foundation, shows it to be tainted by potential bias, conflicts of interest, and bad science.
Defying Congress. In 1997, Congress instructed the FDA to promulgate, via the formal notice-and-comment rule-making process, a memorandum of understanding with state boards of pharmacy that would allow states to provide the FDA information on compounding pharmacies that distributed “inordinate quantities” of compounded preparations out of state. Twenty-three years later, the FDA finally announced an overreaching version of that memorandum of understanding — one that gives it authority over certain aspects of traditionally state-regulated pharmacy dispensing.
Not only did the FDA award itself new authority, it didn’t even follow the prescribed notice-and-comment rule-making process. Had it done what Congress directed, the statutory comment period would surely have brought to light the fact that many states are not authorized to sign such a memorandum of understanding without their state legislatures amending state laws so boards can comply with the reporting requirements. Why does it matter? In states that don’t sign the memorandum of understanding, the law imposes on compounding pharmacies a 5% cap on shipping compounded medications out of state, a threat to patient access to compounded medications that might have been avoided had FDA followed the instructions in the statute.
Skirting the law. In finalizing the memorandum of understanding, the FDA was required under the Paperwork Reduction Act to survey state boards of pharmacy to estimate the additional administrative costs — technology, staffing, and the like — that signing the memorandum would impose on states. But the FDA didn’t do that. Instead, it relied on outdated data from the National Association of Boards of Pharmacy that was based on an earlier iteration of the memorandum of understanding.
Overreaching. In November 2019, the FDA proposed for comment a guidance document on veterinary compounding that would, among other things, make compounding drugs for animals subject to certain restrictions contained in the Drug Quality and Security Act, a statute that is explicitly related to human compounding only. That proposed guidance would also limit pure ingredient compounding for animals to special instances in which a veterinarian would be required to document why a manufactured drug is not suited to his or her animal patient — something not required of other prescribers. But the biggest head-scratcher? The FDA’s authorization to promulgate such guidance was unclear at best.
All of that is why, when the FDA ignored its advisory committee and approved Aduhelm, pharmacy compounders hardly blinked. The FDA we know is one that marches to the beat of its own biases. The question now is whether the next FDA commissioner will be willing to establish a new rhythm.
Scott Brunner is the chief executive officer for the Alliance for Pharmacy Compounding.