FDA clashes with compounding pharmacies; lawmakers react

WASHINGTON-The U.S. Food and Drug Administration's (FDA) recent move against compounding drugs from bulk for use in nonfood animals has lured pharmacy groups and organized veterinary medicine to Washington in opposition.

Sen. Wayne Allard

On June 7, national compounding groups lobbied congressional members including veterinarian Sen. Wayne Allard, stressing the need to amend FDA's most recent interpretation of its Compliance Policy Guide (CPG). The issue: While compounders are opposed to a ban, manufacturers favor tighter regulation. Veterinarians just want access to non-veterinary drug equivalents for patients.

The CPG, designed as an internal reference for FDA agents, now bans the compounding of unapproved bulk products, which makes up a large part of an estimated $60 million to $75 million industry. In response, American Veterinary Medical Association (AVMA) officials met with the FDA Center for Veterinary Medicine (CVM) June 2 seeking clarification on the agency's new stance.

While FDA officials maintain their goal is to prevent the pirating of approved, manufactured drugs and the illegal sale of bulk product, discontent from some groups stems from the blanket ban. In an April 2 letter to state pharmacy boards, FDA says, "Compounding of drugs for use in animals, except in limited circumstances, is not permitted under federal law." With the practice deemed illegal, veterinarians have been stripped of the flexibility to prescribe medications such as potassium bromide and diethylstilbestrol.

Following the June 7 meeting, Allard chided FDA for failing to consult the profession. In a statement to DVM Newsmagazine, he says: "I am disappointed the FDA didn't seek any public comment before issuing this rule. I am hopeful the FDA will recognize its errors and will be taking the necessary steps to solicit public comment and make appropriate modifications to the guidelines."

Reaction from AVMA, profession

At presstime, AVMA leaders sent a private letter to FDA in an attempt to clarify the agency's stance. Dr. Gatz Riddell, who sat in on AVMA's June 2 meeting with CVM, says he hopes FDA reconsiders and allows compounding on a veterinarian-driven basis.

"The agency's sole purpose is to stop the illegal manufacturing of copycat drugs bypassing the FDA approval process, and we understand that," says Riddell, incoming chair of the AVMA Council on Biologic and Therapeutic Agents. "But FDA now offers a hard line on all compounding from bulk, and that puts veterinarians and pharmacists in a precarious position."

FDA spokeswoman Linda Grassie admits: "Vets have fluttered us with faxes, but we're basically not ready to say anything at this point. The pharmacists have gone to Congress, both houses. Now we've got to go down there and answer questions for them."

Opposition abounds

According to the April 2 letter, FDA's reinterpretation is an attempt to "determine the extent of illegal veterinary compounding activities" by controlling the business as well as the pirating of approved, manufactured drugs and their resale to the market. In the process, the agency harms legitimate users, says G.G. Davidson, director of clinical pharmacy at North Carolina State University's (NCSU) veterinary college.

"I think compounding is so incredibly essential to veterinary medicine, we have to protect it at all costs," says Davidson, who, like Riddell, attended the June 2 meeting. "This revision of the CPG is irrational and unreasonable. It hurts veterinarians; it hurts patients; it hurts compounders."

It could set veterinary medicine and the evolution of therapy back 15 years, says Dr. Dennis Feinberg, American Animal Hospital Association (AAHA) president and owner of Charles Towne Veterinary Clinic in Charleston, S.C.

"The truth of the matter is, yes, there needs to be some regulatory change, but the fact remains that some of these products are needed," Feinberg says, noting his opinion as a practitioner, not as an AAHA representative. "In a perfect world, manufacturers would make every product we need, but they don't. I think there has to be a joint effort between FDA, AVMA and the pharmacies to fix this."

Not all veterinary groups agree on the issue. As reported in DVM Newsmagazine, the American Association of Equine Practitioners (AAEP) formed a task force to confront the issue of compounding, and the American Association of Bovine Practitioners banned bulk drug compounders from exhibiting at its meeting.

History of regulation

FDA aims for more regulatory control of an industry Brakke Consulting, Inc., estimates is comprised of dozens of national veterinary compounding pharmacies and likely many more at local and regional levels. The Federal Food, Drug, and Cosmetic Act of 1938 (FDCA) grants FDA power to regulate and enforce drug manufacturing, marketing and distribution of any product approved by the agency.

But compounded drugs aren't FDA-approved, and although the agency generally left oversight of compounding to state pharmacy boards for the first 50 years of FDCA, regulators now are concerned some pharmacists are manufacturing and selling drugs under the guise of compounding, allegedly avoiding FDCA's drug approval requirements. In 1996, FDA responded, issuing its CPG, stating the agency would not ordinarily take action against bulk product compounding for nonfood animals if a medical need was identified and no market drug was approved to treat the condition.

FDA officials admit the CPG is not a decree but acts as a guide for investigators to interpret gray zones in federal statutes such as the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). The act permits extralabel use of human drugs and allows manufactured and approved FDA products to be used on nonfood animals.

In July 2003, the agency issued a more restrictive CPG, rescinding the bulk compounding permit of its predecessor. While compounders and veterinarians were concerned, it wasn't until the April 2 letter that FDA threatened enforcement, Riddell says.

"People were still compounding from bulk drugs, even after last year's CPG," he says. "The truth of the matter is FDA knows there needs to be change. In its strictest sense, it's against the law."

No jurisdiction

That's not true, says Howard Hoffmann, a Chicago attorney representing some of the nation's largest compounders. According to Hoffmann, any regulation FDA adopts is unenforceable against a compounding pharmacy because the agency has no power to enact it.

"FDA is not intended to govern compounding pharmacy; there is no law that gives them that authority," Hoffmann says. "In the absence of an act of Congress that would authorize the CPG as law, it has no enforcement value and is more like a wish list. As the FDA provides all this really bad propaganda about compounders, they sort of gloss over that very important fact."

FDA officials did not respond by presstime to DVM Newsmagazine inquiries seeking comment. Hoffmann speculates that the "sudden attention" FDA is giving to compounding pharmacies is disguising a turf war derived from the agency's desire to wrestle jurisdiction over the compounding market away from the states. If not, the issue is manufacturer derived, he says.

"Why go after compounding now?" Hoffmann asks. "There has never been one patent suit against compounders for making clones, and it's because it doesn't happen. It's possible that manufacturers believe compounding pharmacies are a threat to their business and put the buzz in the ear of FDA, but I don't believe that. To me, this looks like a power grab."

That's nothing but an argument in favor of illegal manufacturing, says Ron Phillips, spokesman for the Animal Health Institute (AHI), which represents pharmaceutical manufacturers.

"There are certainly people who believe there is widespread abuse by compounders," he says. "The veterinary community in general is concerned about safety and efficacy questions. Right now we have a regulated system and an unregulated system. That's not right. It cuts to the heart of why we even have an FDA."

Regulatory loopholes

Still, Riddell says he understands the agency's decision to come down on the manufacture and sale of compounded products. The products are not required to undergo safety and efficacy testing, and the manufacture and sale of copycat products does occur, he says, because copycat drugs are cheaper and practitioners can sell compounded versions for higher profit.

"It's shocking what some of these compounding pharmacies get away with, and right now, FDA's hands are just a little bit tied," he says. "In 1996, when FDA put out the previous CPG, they left the door a little too wide and that's where manufacturers got a foothold."

Officials with Wedgewood Pharmacy, the nation's largest veterinary compounder, resent FDA's attempted stronghold and accuse the agency of overstepping its bounds.

"I think they lack the jurisdiction to regulate a state-licensed pharmacy practicing in accordance with state law," Wedgewood Chief Executive Office George Malmberg says. "We hope FDA will get the message that the profession of pharmacy is very concerned with their recent stance on compounding, and legislators are curious as to what its motives are."

Taking the case to congress

To convey that message, L.D. King, executive director of the International Academy of Compounding Pharmacists (IACP), led the July 7 lobby in Washington. He says the issue stems from "a manufacturer-driven argument."

"At the heart of this issue are pharmaceutical companies that don't want compounders copycatting their drugs, and FDA, which doesn't want to see commercially generated drugs like potassium bromide," he says. "But working to ban compounded drugs leads to health consequences that are significant. That's where our frustration lies."

That's also why IACP and the American Pharmacists Association petitioned Washington, King adds. As a result, Sen. Lindsey Graham, an aggressive Republican from South Carolina, and Rep. Charles Bass, a New Hampshire Republican up for re-election this November, issued identical letters to FDA Acting Director Lester Crawford, DVM, requesting the agency withdraw its latest CPG. The letters also ask regulators to consult the public before drafting further policy changes.

"Should FDA demonstrate a compelling need to update the CPG, it should first articulate this need and then issue a revised CPG in draft form for public comment by stakeholders, allowing affected pharmacists and veterinarians to provide feedback on the policy before it is implemented," the letters state.

"We recognize the vital role compounding plays in animal health and believe that it is necessary to preserve access to compounded medication options for animal patients," the letters add.

Education key

According to Brakke Consulting, compounding has been part of veterinary medicine since people first began caring for animals. But NCSU pharmacist Davidson claims most veterinarians fail to understand the difference between generic and compounded drugs or what it means to use them in practice. The same goes for pharmacists, she says, who rarely train to compound animal drugs.

"What I think that would solve a huge percentage of this would be education, not only on the drugs, but on the laws that govern their dispense," she says.

To protect practitioners and patients, Davidson backs the creation of a new pharmacy compounding board, modeled after AAHA's accreditation program.

She's also heading a board certification initiative through the American College of Veterinary Pharmacists.

Practitioners could use the same type of education, Riddell says. "Veterinarians need to know that you can take two FDA approved drugs and mix them together and that's compounding, and compounding should not be a profit center for the veterinary profession."

In the meantime, he's hopeful the CPG will be amended favorably for the profession.