Compounding rules challenge practice norms
As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.
In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.
In the same position statement on compounding, the ACR said it also seeks a change to a Food and Drug Administration rule limiting practitioners’ access to quinacrine, a drug only available through compounding pharmacies that is sometimes used to treat lupus patients. Quinacrine is not on the FDA’s current list of bulk substances approved for compounding, except by special permission. The ACR has asked the agency to add quinacrine to the list, but no one knows when this will happen.
Rheumatologists may also be more restricted than before in terms of which compounding pharmacies they can turn to, as new federal standards divide them into two types – those that can provide medicines in larger quantities and those that can’t.
Steroid fiasco sparked rule revisions
The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.
More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.
The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.
As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.
“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.
“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.
In-office mixing a top concern
Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.
Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.
Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.
Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”
USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.
“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.
“There’s that law of unintended consequences where you snare things in a net that you really don’t want to,” Dr. Huffstutter said.
Marcus Snow, MD, a rheumatologist at the University of Nebraska, Omaha, who also worked on the statement, said that most rheumatologists are likely unaware that their ability to mix drugs in-office has been called into question.
“I brought it up at our division meeting with a group of 10 rheumatologists, and no one was aware that this was coming down the pike,” Dr. Snow said in an interview.
