News & Resources

Firm News

Compounding Confusion: Uncertainty Swirls in Compound Pharmacy Regulation

Five years after the New England Compounding Center tragedy led the FDA to step in as a primary regulator of compounding pharmacies, uncertainties and anxieties abound.

That was the thread running through a discussion led by Quarles & Brady partners Theodore Sullivan and Edward Rickert at Quarles & Brady's 3rd Annual Pharmacy Law Symposium on July 20 in Chicago.

Much of the confusion around compounding regulation emanates from 503B pharmacies, outsourcing facilities that were created by laws passed in wake of the New England Compounding contaminations. Those compounding pharmacies, Sullivan said, aren’t really compounding pharmacies at all, but rather federally registered manufacturing facilities that are allowed to make certain unapproved drugs and that must comply with current good manufacturing practice (CGMP) guidelines.

Sullivan, who advises clients in the food and drug industries on regulatory matters at the federal level, said while it’s clear that 503B facilities are completely under FDA jurisdiction, the law regarding them is otherwise scant and murky. The FDA has thus far been regulating 503Bs primarily through published guidance – which doesn’t have the force of law. And while the law on compounding pharmacies is abundant, none of its precedents apply.

“We can’t rely on traditional compounding case law because it exists at the state level,” Sullivan said. As a result, “it’s very hard to know when you’re in compliance.”

The confusion extends to 503A facilities, as well. The statute defines traditional compounding facilities as those that compound in response to patient-specific prescriptions, or in anticipation of prescriptions. They’re not allowed to compound in bulk or ship to doctors’ offices. And they remain under the primary regulatory jurisdiction of state boards of pharmacy.

That, however, has not stopped FDA inspectors from continuing to inspect 503A pharmacies, said Rickert, whose practice mostly consists of representing pharmacies on state-level regulatory matters. FDA has authority to inspect any place where FDA regulated products are stored, but should not be inspecting 503A pharmacies for compliance with FDA manufacturing regulations. They often do, however. He said that could be because of the fuzzy definition of “anticipatory compounding.” The statute says 503A facilities aren’t allowed to produce compounds in “inordinate amounts” but it doesn’t say how much that means.

According to a recent FDA guidance document, FDA has announced that it will not inspect 503A pharmacies to FDA standards, but will continue to inspect pharmacies to investigate whether it is in fact operating as a 503B. That creates deep apprehension among traditional pharmacists, who aren’t accustomed to having federal inspectors poking around their facilities. And because jurisdiction is unclear, it’s hard to know whether even to allow the agents in.

“It might be better to let them in, then be ready to fight the results if we don’t like them,” he said.

If the inspectors conclude that the facility is in fact operating as a 503A, they won’t have jurisdiction and won’t take any action unless they encounter what they perceive to be insanitary conditions or believe the compounding pharmacies products could be contaminated. They might also send a letter to the state board of pharmacy, detailing their findings.

“Those referral letters are usually very strongly worded,” Rickert said. “So just because you’re a 503A doesn’t mean you’re in the clear.”

It’s also important to remember that compounding inspections are new to many FDA and state pharmacy board inspectors. FDA inspectors are trained to, and experienced at, inspecting manufacturing facilities, not pharmacies. State pharmacy inspectors’ expertise generally lies in assessing traditional pharmacies for sanitary and other conditions. Now, pharmacy inspectors are expected to be experts on USP 797 compounding standards – but they’re not there yet.

“They’re all still trying to figure it out,” Rickert said.

Sullivan also touched on the dynamics in veterinary compounding, which isn’t mentioned in the law that created the 503B outsourcing facilities. And yet, the FDA’s published draft veterinary compounding guidance addressed the production of veterinary drugs in outsourcing facilities. The agency's legal basis for permitting manufacture of unapproved veterinary drugs at outsourcing facilities is not clear.

For now, FDA is taking little action against veterinary compounding pharmacies, and likely will not increase enforcement until it has promulgated regulations or issued a final guidance for veterinary compounding. In the past the courts have said that because the FDA has yet to issue valid guidance – let alone promulgated regulations – it lacks a clear enforceable standard for many aspects of veterinary compounding.

“Until we have proper guidance, we’ll have no enforceable standard,” Sullivan said. “And that means we’ll have a lot of manufacturing going on in the name of compounding.”