The messages were urgent and emphatic.
“Compounding for veterinary use is threatened again!” read the heading over one bulletin to pharmacists, exhorting them to send comments defending their work to the U.S. Food and Drug Administration (FDA).
Compounding pharmacists rallied to the cause, spreading word among their veterinary clients, who shared the news with fellow veterinarians and contacted the media
It turns out that the threat seen by leading organizations in the pharmaceutical compounding business is not quite what they perceived.
The FDA action that generated the tempest is a solicitation for public comments on how the agency should address the prevalence of animal drug products that have not been reviewed for safety and efficacy. The notice
, published in the Federal Register on Dec. 20, offers these examples of products the FDA has in mind:
“In general, the types of unapproved animal drugs being marketed include, but are not limited to, injectable vitamins, various topical solutions, shampoos and liniments, electrolyte and glucose solutions, and antidotes. In addition, there are a variety of anti-infective and other animal drug products marketed for use in a variety of animal species.”
Nowhere in the notice are compounded preparations specifically mentioned.
The American Veterinary Medical Association (AVMA) posted a blog entry
on its website Wednesday in an attempt to add some clarity to the issue. “... compounded drugs you prescribe for your individual patients are not believed to be part of this particular (FDA) initiative,” wrote Dr. Lynne White-Shim, an assistant director in the association’s Scientific Activities Division.
That and similar comments by other players in veterinary pharmacy left stakeholders bewildered.
“Are you confused?” asked David Miller, executive vice president and CEO of the International Academy of Compounding Pharmacists, when a reporter from the VIN News Service reached him by telephone. He acknowledged with a chuckle, “... I think I’m confused, too.”
To Miller’s eye, just because the FDA didn’t specify compounded preparations in the notice doesn’t mean compounded drugs are excluded. “Our concern as an organization is this,” he said: “The FDA, separate from this notice, has consistently and repeatedly stated that all compounded preparations are ‘unapproved new drugs.’ ... I’m looking at a document that says, ‘We want to know how to handle unapproved animal drugs.’ We fall into that category by past reference and past behavior.”
The relationship between veterinary pharmaceutical compounders and the FDA
is long and complicated.
Compounding is a time-honored tradition in pharmacy circles, hearkening back to the way medications were made in the old days: by hand for individual patients. The advent of machinery and mass production eclipsed compounding as the foremost method of producing drugs.
But compounding maintained a foothold in the market by catering to the custom requirements of particular populations; among them, special-needs children, menopausal women and veterinary patients — cats, dogs, horses and especially exotic pets.
The sector has been rising in popularity since the 1980s. It’s become big business, and that’s the rub.
As an activity of pharmacies, compounding comes under the purview of state boards of pharmacy. When applied to meet the specific needs of individual patients, no one objects to that system.
But compounding has become such a profitable pursuit that some compounding pharmacies appear to the FDA — and various other observers — to be manufacturing drugs en masse. If they’re acting as drug manufacturers, the federal agency’s thinking goes, they should be regulated as such. That would mean subjecting their products to the formal drug-approval process, a lengthy and expensive undertaking to demonstrate that the products are safe and perform as promised.
Here’s another wrinkle: The federal government's stance on compounding for veterinary medicine differs from its stance on compounding for human patients.
The difference lies in how a compound is made. Pharmacists preparing medications for humans are allowed under the Food and Drug Administration Modernization Act of 1997 to use “bulk ingredients” as raw materials.
But the veterinary counterpart to that law, the Animal Medicinal Drug Use Clarification Act of 1994, does not specifically allow bulk ingredients. Therefore, the official stance of the FDA is to require that veterinary compounders use finished, approved drugs as the basis of their compounds.
But the regulators realize that this isn’t entirely practical — chopping up pills to place in liquid suspension, for instance, is not an ideal way to create drinkable medicine. So the FDA published a “compliance policy guide” (CPG) describing the circumstances under which it would use “regulatory discretion” and look the other way when bulk ingredients were used.
However, the most recent version of the CPG, issued in 2003, was so restrictive that it drew an avalanche of protest. The agency announced in fall 2004 that it would rewrite the guide and post it for public comment.
That never happened. More than six years later, compounders are awaiting the revised guide.
Chris Simmons, a pharmacist and vice president of creative development at the Professional Compounding Centers of America (PCCA), a membership group for independent community pharmacists, heard buzz late last year that several members of Congress were prodding the FDA to produce the long-overdue CPG.
So when the agency issued a call for comments on unapproved animal drugs, Simmons thought it was the CPG.
“I put the word out,” he said. “I put it on my Facebook (page) that, 'Hey, there’s something going on.' ... I was just as confused as everybody else.”
Adding to the sense that the FDA is sharpening its focus on compounding is a court hearing scheduled Thursday in Jacksonville, Fla., that pits the agency against Franck’s Compounding Lab. The FDA took aim at Franck's
last spring, accusing the pharmacy of selling adulterated and misbranded drugs, and seeking to close the operation.
Government lawyers requested a permanent injunction against Franck’s but were turned down by the U.S. District Court for the Middle District of Florida. The hearing next week is another step in that case.
As to whether the call for comments on unapproved animal drugs involves compounding, an FDA spokeswoman, Laura Alvey in the Center for Veterinary Medicine, told the VIN News Service by e-mail:
“Unapproved new animal drugs are manufactured and distributed by a variety of firms, among them traditional drug manufacturers, compounding pharmacies, and supplement manufacturers.
“The notice does not reflect FDA concerns regarding any particular types of firms or unapproved new animal drug products. Rather FDA's goal is to increase the availability of approved, indexed, or otherwise legally marketed new animal drugs, with the assurances of safety, effectiveness, and quality that these processes provide. It's important to note that our intent is not to revise the current new animal drug approval process but to look for alternative approaches for certain products.”
To a follow-up question asking whether comments about veterinary compounding and the use of bulk ingredients are germane to the discussion, Alvey replied:
“While the public is free to submit any type of comment in response to a Federal Register notice, what would be particularly helpful in this instance are comments focused on how FDA can best achieve its goal of increasing the availability of approved, indexed or otherwise legally marketed new animal drugs.”
Some observers fear that discussing compounding under the umbrella of “unapproved animal drugs” could backfire on supporters of compounding.
In a message-board discussion
of the Veterinary Information Network (VIN), an online community for the profession, Gigi Davidson, director of clinical pharmacy services at North Carolina State University College of Veterinary Medicine and chair of the U.S. Pharmacopeia Compounding Pharmacy Expert Committee, raised that possibility.
“I do believe that the compounding pharmacy community has made a serious mistake by voluntarily associating ‘compounds’ with ‘unapproved drugs’ in this discussion,” Davidson wrote. “While the issues raised about compounding with medically necessary bulk chemicals are completely valid, these arguments should be saved for an appropriate comment period.
“Neither compounding pharmacists nor veterinarians want compounds lumped into the same framework that FDA will use to enforce regulatory discretion for unapproved manufactured
products. In my view, this is inviting FDA to regulate compounding, which is exactly what the compounding community has been adamantly opposed to for so long.”
Davidson said in an interview that she made similar comments on a compounding-pharmacy listserv. Demonstrating the tensions in the community, some readers lambasted Davidson for implying that they could be their own worst enemy.
The experience left Davidson, a highly knowledgeable and well-respected figure in veterinary pharmacy, doubting her own judgment. “It’s been a real eye-opener, this experience,” she said.
Davidson said that her initial interpretation of the Federal Register notice was that the FDA wished to deal with products such as potassium bromide (KBr), an old drug that’s never been formally approved but is the standard of care for epileptic dogs.
“I was 100-percent focused on that,” she said. “So I’m just as guilty as everybody else of myopia and selective reading.”
At the AVMA, White-Shim said in an interview by e-mail that she’s hopeful the FDA will clarify matters by sharing a list of drugs that comprise the focus of its unapproved-animal-drug initiative.
“FDA has been very open to discussing the topic with me,” she said, “and clearly, FDA’s looking closely at how it can most efficiently regulate and enforce the products under its jurisdiction, which is great.”
Today was the original deadline for comments on the topic, but in response to requests, the FDA extended the deadline
to April 19.
Ironically, in the view of Simmons at the PCCA, the importance of submitting comments — at least in defense of compounding — has subsided.
“I guess I’m still not 100-percent sure what they (the FDA) are doing with it,” he said. “... Because there’s so much confusion about it, I don’t know that we need to add more confusion to it by having more people comment.”