番茄社区app

This story is part of a series called "Ozempic: Weighing the Risks and Benefits." It was produced in part through a grant from the .

Shortages of popular new weight-loss drugs have driven a compounding boom that has raised questions about how compounding pharmacies can create copies of drugs that are still protected by patents -- and how they produce these products in general.

Semaglutide (Ozempic, Wegovy) was added to FDA's drug shortage list in , and tirzepatide (Mounjaro, Zepbound) was added in . Both have a status of "currently in shortage" even though all doses -- with the exception of semaglutide 0.25 mg -- are listed as "available."

Those shortages -- driven by high demand; one in eight U.S. adults have taken a GLP-1 agonist like semaglutide and tirzepatide, according to a -- provide the reason why compounding pharmacies are allowed to produce these weight-loss drugs, despite patent protections. of the Food, Drug, and Cosmetic Act (FD&C Act) allow for compounding of a drug that's "currently in shortage" -- and they make no distinction for a patented drug.

"It's a little noteworthy in this case that these are blockbuster, brand-name drugs," Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists, told 番茄社区app. "Normally, we see shortages of generic drugs."

How Does Compounding Work?

Section 503A compounding pharmacies can sell patient-specific prescribed drugs, while 503B pharmacies can sell to both individual patients or healthcare facilities, such as a hospital. The latter group, linked to the New England Compounding Center, is required to follow stricter manufacturing requirements.

Tenille Davis, PharmD, chief advocacy officer for the Alliance for Pharmacy Compounding, told 番茄社区app that the process starts with compounding pharmacies purchasing the active pharmaceutical ingredient (API) from FDA-registered manufacturers, which must come with a valid certificate of analysis.

Those manufacturers, which can be based in the U.S. or abroad, usually also submit a drug master file to the FDA, which contains confidential, detailed information about the facilities and processes used in the manufacturing, processing, packaging, and storing of drugs, Davis said.

"Pharmacists take that API -- essentially powdered pure drug -- and turn it into finished dosage forms based on a prescriber's prescription order," Davis said. Essentially, compounders have to figure out the right formulation of the API plus the other ingredients.

Often, there's a from the U.S. Pharmacopeia (USP) that provides the "recipe" for that balance. However, these are usually only available for older, generic drugs, not for patented drugs like semaglutide or tirzepatide, Ganio said.

Other sources of that recipe include scientific journals such as the International Journal of Pharmaceutical Compounding, consulting companies like PCCA, or even academic labs, he added.

If those options are not available, compounding pharmacies have to figure out the formulation on their own, conducting a series of tests to determine the right potency and stability for the formulation.

"Of course the active ingredient you can figure out, but if there's stabilizers or something for a buffer for gaining the right pH, or preservative to make sure that there's an antimicrobial effectiveness there -- those would take some experimentation," Ganio said, adding that there "should be a lot of scientific rigor behind those different development processes."

Also, the lists the active and inactive ingredients and exact quantities in the "description" section, Davis said.

"They do have a patent on the product, but that doesn't mean that the ingredients are a secret," she added.

There are some key differences when a compounding pharmacy produces a batch of semaglutide or tirzepatide, including changing the solution used to dissolve the API or not including a preservative agent that might be found in the brand-name drug.

Even with those variations, Davis noted that GLP-1 drugs are "not complicated formulations."

After the compounding pharmacy produces a copy of semaglutide or tirzepatide, it tests the final product for impurities or other deviations. "In the case of GLP-1 injections, they mix with appropriate excipients under clean-room conditions and filter into sterile vials, then send samples of those vials to an independent third-party laboratory for a variety of tests," Davis said.

In short, Davis said compounding pharmacies that choose to offer these drugs are well-equipped to do so.

"The pharmacies that are doing sterile compounding are experts at it," Davis said. "They have built the space, hired the consultants, have the testing and training, and independent companies that come in and certify the space. It's not just something one pharmacist might decide to do one day."

Drugmakers Push Back

Semaglutide-maker Novo Nordisk and tirzepatide-maker Eli Lilly have been attempting to temper the flood of compounded versions of their drugs.

Eli Lilly released warning patients about the risks of using compounded tirzepatide, including claiming that it discovered some of these products contained "bacteria, high impurity levels, different colors (pink, instead of colorless), or a completely different chemical structure than Lilly's FDA-approved medicines."

The FDA said in June that some compounded forms of semaglutide may not use the same active ingredient as the branded products and warned more recently about reports of overdoses as a result of patient and physician confusion around compounded semaglutide.

In addition, against med spas, wellness centers, and other companies that have been attempting to sell compounded versions of its products. against similar companies. Of those lawsuits, five sellers were banned from continuing to sell their products.

A spokesperson for Eli Lilly told 番茄社区app in an email that the company "is deeply concerned that products fraudulently claimed by compounding pharmacies or counterfeiters to be FDA-approved tirzepatide, Mounjaro, or Zepbound may expose patients to serious health risks."

However, compounding pharmacies have pushed back against the negative characterization of their practices.

"Compounding always begins with a prescription," Scott Brunner, CEO of the Alliance for Pharmacy Compounding, told 番茄社区app. "It begins with a doctor, in whose judgment, the compounded medication is to be prepared, preferred for a patient over the FDA-approved drug."

Eli Lilly CEO David Ricks recently said the company expects tirzepatide soon, which would effectively end the compounding market for the drug; the same could be true for semaglutide.

Brunner agreed that news would be welcome, if true, but he noted that both semaglutide and tirzepatide remain listed as "currently in shortage" on FDA's website -- and it's up to the FDA to decide when there's sufficient supply.

"It's hopeful news that Lilly's Zepbound may soon be available again," Brunner said. "Whether that production is enough to satisfy demand for tirzepatide injection, which is what is on the shortage list, remains to be seen."

Comment