To protect patients, pharmaceutical manufacturers must monitor any adverse events we hear about with respect to the drugs we produce and report those adverse events to the Food and Drug Administration, as required by law.
Developing and maintaining an accurate safety profile of a product is a joint responsibility between the manufacturer of the product, the FDA and consumers. This is particularly important in the post-approval period when the product is being used by a large number of patients in a “real world” setting rather than a controlled clinical trial setting. Collection and reporting of adverse events (i.e., any undesirable experience associated with use of a drug) to the FDA allows the agency and the manufacturer to evaluate such issues as whether drug label warnings sufficiently describe the associated risks or whether inappropriate manufacturing practices have contributed to the release of contaminated products. There are a number of “checks and balances” built into the system to ensure patient safety.
As noted, reporting of adverse events to the FDA is a critical component of the patient safety protection system in America. While some compounding pharmacy adverse events are now haphazardly reported — FDA just last week sent warning letters to drug compounding pharmacies in Tennessee and Virginia following reports — there is a giant gap in that system that may put patients at risk — adverse events with respect to drugs made by compounding pharmacies are generally not required to be reported to anyone.
Most readers will recall the New England Compounding Center fungal meningitis outbreak in 2012 where contaminated steroid injections sickened more than 800 people and resulted in 64 deaths. As investigators looked into that tragedy, it became clear that there were significant supervisory gaps with respect to compounding pharmacies. In response, Congress enacted the Compounding Quality Act as part of the Drug Quality and Security Act of 2013. That law divided compounding pharmacies into two categories: traditional compounding pharmacies (under section 503A of the Federal Food, Drug, and Cosmetic Act) and outsourcing facilities (under section 503B of that Act).
The key distinction between these two types of compounding pharmacies is whether they are permitted to make compounded drugs in advance of receiving a prescription for an individual patient. Section 503A states that traditional compounding pharmacies, which are not required to register with the FDA or comply with the “current good manufacturing practices” otherwise applicable to drug manufacturers, generally may make compounded drugs only for an identified individual patient based on the receipt of a valid prescription. It says they may compound “in limited quantities” before the receipt of a prescription based on prior orders from the individual patient or the prescribing practitioner. By contrast, Section 503B stipulates outsourcing facilities may compound without limitation in advance of receiving an individualized prescription, but they are required to register with the FDA, comply with current good manufacturing practices, and report adverse events.
The 2013 law gave the FDA primary responsibility for supervising outsourcing facilities while giving state boards of pharmacy primary responsibility for supervising traditional compounding pharmacies. It is questionable as to whether the division of responsibility intended by Congress is working. As of this writing, only 62 out of the thousands of compounding pharmacies in the country had registered with the FDA as outsourcing facilities. There is reason to believe that a substantial number of purported 503A compounding pharmacies should be registered as 503B outsourcing facilities but have evaded their responsibilities: In a July 2016 notice, the FDA wrote, “Our experience was that in the substantial majority of cases, inspected human drug compounders not registered as outsourcing facilities were compounding at least some of their drugs not in accordance with section 503A.” Since purported 503A traditional compounding pharmacies do not register with the FDA, the FDA has no way of routinely inspecting these compounders. Instead, the responsibility falls to the states — which in many cases do not appear to subjecting compounding pharmacies to comprehensive supervision. This may be as a result of not having appropriate resources.
Until recently, it was impossible to get a national overview of state practices in supervising sterile drug compounding. This has been remedied by the February 2016 report from the Pew Charitable Trusts, “National Assessment of State Oversight of Sterile Drug Compounding.”
The Pew report, which Congress, state boards of pharmacy, and state legislators should all study carefully, reveals a number of concerns with state oversight of drug compounding. The study states that to effectively oversee compounding activity, state regulators need reliable information about facilities that compound and their ability to meaningfully respond to any safety deficiencies.”
However, the numbers show a different story. Only 23 of 43 states reported tracking the number of pharmacies performing sterile compounding in their state, while even fewer – 19 percent – said their state tracked the number of out-of-state pharmacies shipping or dispensing compounded drugs into the state.
Further, Pew found that the majority of states responding (26 of 43, or 60 percent) do not require compounding pharmacies to report (to either the state or the FDA’s MedWatch) serious adverse events and reactions related to sterile compounding. This is a serious problem. Without a universal requirement that compounding pharmacies (and compounding physicians) report adverse events, there can be no effective oversight of their sterile compounding operations.
Regardless of how quickly states work to improve their oversight of sterile compounding, an immediate step should be to require reporting of adverse events. If states do not act to require this kind of reporting, Congress should step in and mandate it. Until then, patient safety is at risk.
Gavin Corcoran, M.D., FACP, is the chief medical officer of Allergan, plc.
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