Uncertainty Looms Over Bulk Production Of Personalized GLP-1 Drugs

Compounding pharmacies are facing ongoing uncertainty over whether they can produce personalized weight-loss drugs in bulk at FDA-registered 503b compounding facilities once the FDA-approved drug is no longer on the agency’s drug shortage list, and FDA isn’t providing clear answers.

The question is a significant one for telehealth providers who are facing scrutiny for selling compounded versions of weight-loss drugs.

FDA officials provided a vague response to Inside Health Policy when asked whether companies can use 503b facilities to produce personalized copies of GLP-1 drugs once the drug is no longer in shortage.

“They can compound in large amounts if they have to comply with all provisions for 503b facilities,” an FDA official told IHP at the FDA compounding conference Thursday (Aug. 22).

With massive demand for GLP-1 drugs and many patients seeking cheaper versions, Hims & Hers Health Inc. (HIMS), a major telehealth company, announced in its earnings call that it has purchased an FDA-registered 503b compounding facility to help craft patient-specific prescriptions. HIMS, targeted at men, and HERS, targeted at women, offer treatments like mental health medications, erectile dysfunction drugs and birth control through direct shipping to patients, and both have begun offering personalized formulations of semaglutide, the active ingredient in Novo Nordisk’s Ozempic for diabetes and Wegovy for weight loss.

Compounders are advised to produce essential copies of drugs only when the approved drug is on FDA’s drug shortage list or when an FDA-approved drug is not suitable for specific patient

But Andrew Van Ostrand, vice president of policy, government and regulatory affairs at HIMS, told Inside Health Policy that the company is uncertain about whether it can continue using a 503b facility to produce personalized weight-loss drugs once the FDA's shortage designations end.

Currently semaglutide and tirzepatide, the active pharmaceutical ingredients (APIs) in Novo Nordisk and Eli Lilly’s GLP-1 drugs, are currently on FDA’s drug shortage list.

"We don't know exactly when the FDA shortage designations will end, but they will at some point. When that happens, we won't, as we have said publicly, be able to compound essential copies, and so we will have to adhere to existing, long-standing non-essential copy, personalized compounding rules and regulations," Van Ostrand said.

"What facilities we will utilize for those personalized treatments is yet to be decided for a range of reasons," Van Ostrand added.

On the Aug. 5 earnings call, HIMS’ CEO Andrew Dudum said that the telehealth company has been using the prescriber exception to determine individualized dosages, as the FDA-approved dose is not suitable for some patients.

“The compounding titration and dose customization exists and operates regardless of shortage,” Dudum said. “This is an exemption for which we operate the entire business under and have for the last six or seven years.”

The company’s chief financial officer said that more and more new users are opting for individualized options for weight loss drugs.

“We do see more and more users each quarter opt for personalized solutions,” Yemi Okupe, chief financial officer at HIMS, said. “That's coming from new users that increasingly are opting for those solutions as well as existing users making the switch as there's more and more value offered to our consumers.”

In under a year, HIMS has reached $100 million in annual revenue.

Compounding facilities are regulated under two sections in the Federal Food, Drug, and Cosmetic Act: 503a and 503b. 503a compounding facilities are overseen by state boards of pharmacy and follow FDA guidelines, while 503b compounding facilities are regulated directly by FDA.

As HIMS’ weight-loss business grows, the San-Francisco based telehealth company is facing some backlash from the brand-drug manufacturers of GLP-1 drugs.

Eli Lilly told IHP that FDA and state regulators must intervene to stop compounders from mass producing unapproved replicates of its weight-loss drugs, Mounjaro and Zepbound, and, without specifically naming HIMS, argued potential legal actions by brands against compounders are not enough.

Novo Nordisk also told IHP that it is pursuing additional lawsuits against compounders and that it does not supply HIMS bulk semaglutide for compounding purposes.

Pharmacies can only obtain APIs from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers, according to the Alliance for Pharmacy Compounding (APC).

Van Ostrand also told IHP that it is highly likely HIMS sources their APIs from the same suppliers as brand-name drug manufacturers.

Attempts to crack down on GLP-1 compounding by major companies, though, could draw backlash from smaller compounding pharmacies, with APC stressing the difference between online entities selling compounded GLP-1s and established compounding pharmacies.

Stuart Hinchen, CEO of QuVA Pharmacy, said at the conference guidance for 503b compounders is overly broad, since the category can encompass a variety of operations, from larger compounding facilities to much smaller in-house compounders for hospitals and health systems that compound drugs for those patients.

Hinchen said he supports the issue of a separate “503b-lite” guidance for compounders attached to hospitals and health systems, an idea he noted FDA has floated and then rejected in the past.

In 2017, FDA’s then-Commissioner Scott Gottlieb said FDA planned to issue a new policy he dubbed 503b-lite for smaller compounding pharmacies that registered with FDA. Gottlieb later told a House subcommittee FDA planned to apply currently good manufacturing practices “in a way that is tailored to the nature of specific compounding operations conducted by outsourcing facilitates, such as production in small batches,” rather than creating a new category or guidance.

Ken Jozefczyk, director of hospital system compounder BayCare Central Pharmacy, said he supports the idea of specific guidance for smaller or hospital-affiliated pharmacies, saying FDA needs to have a better understanding of the diversity of compounders that are currently all given the same guidance and all inspected and regulated in the same way.

Hinchen also it can be difficult for 503b compounders to keep up with FDA’s expectations for current good manufacturing practices, which can change frequently for compounders. He said it’s important for compounders to have frequent reviews from third-party, independent reviewers who are familiar with the latest industry trends and can provide updates.

Pallavi Badkar, vice president of operations at compounding pharmacy Medisource Rx, noted that smaller 503bs face a variety of challenges, including finding sources of APIs and managing quality practices with a smaller staff, as well as competing with larger 503bs.

Hinchen said 503b compounders get little credit for helping manage drug shortages despite being “one of the major resources for the health care supply chain.” He said compounders need to work on improving their public image, but also criticized FDA and lawmakers for adopting a negative attitude toward the industry, calling legislation that would encourage hospitals to stockpile large supplies of drugs in case of future shortages, rather than relying on compounders, “ludicrous.” -- Maaisha Osman (mosman@iwpnews.com), Jessica Karins (jkarins@iwpnews.com)