While Semaglutide (AKA Ozempic and Wegovy) is in Short Supply, Can Compounding Pharmacies Come to the Rescue?

The type 2 diabetes management and weight reduction medication, semaglutide, marketed under the brand names Ozempic and Wegovy, respectively, have been in limited supply at pharmacies all over the country.

The massive popularity of these drugs have led to supply shortages and were expected to be resolved in late 2022. While 503A compounding pharmacies step up to alleviate the shortage of these drugs, some question the quality, legality, and clinical equivalence of the compounds.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that was originally developed to help treat diabetes by injection under the brand name Ozempic, lowering blood glucose levels by stimulating insulin release. The FDA later approved semaglutide as a weight loss drug. Ozempic and Wegovy can be quite expensive.

With the high demand, lack of supply, and high price tag, consumers have turned to 503A compounding pharmacies for help during the shortage.

Pharmaceutical compounding facilities are providers of precision medicines having unique formulations to solve patient-specific issues and can also improve patient access to drugs currently on shortage. However, compounding semaglutide comes with warnings and potential legal issues.

Semaglutide (Wegovy) is in Short Supply Due to Unprecedented Demand

Physicians noted that the Novo Nordisk weight-management medicine semaglutide (Wegovy) has been in constant limited supply due to, "extraordinary demand," which has led to an increased and uncertain interest in compounded forms of the drug.

Wegovy, approved for weight loss, can carry price tags of more than $1,000 a month and is sometimes not covered under insurance plans. 

Novo Nordisk, the maker of both Wegovy and Ozempic, said that 81% of its patients on Wegovy are women. The company posted in an announcement in December of 2022 that they will increase production capacity in 2023, and will closely monitor the prescribing trends and demand.

Issues and Concerns with Compounding Semaglutide

Semaglutide is a polypeptide, containing fewer than 40 amino acids. Under section 503A and 503B of the Federal Food, Drug, and Cosmetic (FD&C) Act, peptide-based drugs containing over 40 amino acids in structure are considered biologics, which cannot be compounded.

The Alliance for Pharmacy Compounding (APC) noted that because semaglutide is not a "biologic" and is a component of an FDA-approved product, compounding pharmacies might be able to use semaglutide in compounded products.

A representative at FDA's Center for Drug Evaluation and Research said it was possible compounded semaglutide is exempt from normal FDA approval if it is, "made using a bulk drug substance (active ingredient) that is a component of an FDA-approved human drug product, provided all other conditions ... are met."

The drug is presently restricted by rules limiting the compounding of commercially accessible pharmaceuticals (Section 503A of the FD&C Act), which specifies that a pharmacy may only produce a compounded medication as needed and may not keep a supply on hand.

Replicating patented therapeutics is prohibited by regulations for compounding pharmacies.

Pharmacies Offer Lower Price and Easy Access to ‘Bootleg’ Compounded Semaglutide

A growing number of companies have begun selling compounded versions of the weight loss drug online, raising intellectual property questions. Certain experts warn against purchasing "bootleg" versions of semaglutide due to a lack of quality control.

Karl Nadolsky, an endocrinologist at Spectrum Health, voiced his opinion on compounding semaglutide, "nobody knows how [compounding pharmacies are] getting it. Who's making it? Novo's not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?"

The Alliance for Pharmacy Compounding notes on its website that pharmacies, "cannot compound a copy of a commercially available medication," but added, "if a patient needed semaglutide in a nasal spray, for example, it would be legal to compound it."

What is Semaglutide?

Semaglutide is an injectable glucagon-like peptide-1 (GLP-1) agonist that is administered once weekly.

Originally, semaglutide was approved in 2017 under the brand name Ozempic and at a lower dose than Wegovy. The drug claimed to help control blood sugar in type 2 diabetes patients, and found that patients taking Ozempic for blood sugar control tended to lose weight as an additional benefit.

In March 2021, the New England Journal of Medicine (NEJM) reported the results of their double-blind trial, which had 1,961 enrolled participants who were overweight and did not have diabetes. 

The results, as reported by the NEJM, “participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).”

Wegovy is prescribed specifically for weight loss. It contains semaglutide, just like Ozempic does, but Ozempic is indicated for the treatment of type 2 diabetes.

It is reported that a generic version of semaglutide cannot be released until 2031.

Drug Manufacturer Novo Nordisk Sends a Warning to Compounding Pharmacies

Novo Nordisk addresses compounding pharmacies on its official website, and says:

“We are aware that there are companies claiming to have availability of Wegovy® or semaglutide. We want consumers and healthcare providers to know and be very clear that Novo Nordisk does not sell Wegovy® (or its active ingredient, semaglutide) for the purposes of compounding with other products. We have not conducted studies to evaluate the safety and efficacy of Wegovy® when compounded with other ingredients. Novo Nordisk is the only company that has FDA approval to market Wegovy® and we supply it in a disposable single-use pen available by prescription only.”

Novo Nordisk is the only company with FDA approval related to Wegovy, which is offered as a prescription-based single-use pen.

The diabetic treatment drug Ozempic is protected by various patents held by Novo Nordisk, which warns that companies selling semaglutide products, "may be infringing Novo Nordisk's intellectual property rights and/or violating applicable law."

In order to safeguard its intellectual property rights, the corporation further stated that it, "would take such remedies as it considers necessary and appropriate."

Compounding with Semaglutide Sodium

Some chemical houses may be supplying the sodium salt form of semaglutide to compounding pharmacies. Semaglutide sodium compounding raises clinical questions, such as a potential reduction in bioavailability caused by the degradation of the formulation's absorption enhancer.

The FDA may consider dissimilar salts of APIs to be alternatives, not necessarily therapeutic equivalents. Today, only semaglutide (not its sodium salt) can be found in the FDA's Orange Book, with no therapeutic counterparts listed. Consequently, there is no FDA-backed assurance that the sodium salt form is as effective as the non-salt form.

The FDA has noted that it will send warning letters and may take action against companies illegally sourcing semaglutide and (possibly) the doctors and clinicians who prescribe it.

Where Does Your Facility Stand?

If you’re looking to become compliant with the new USP 797 and USP 795 requirements or if you wonder how you measure up against the semaglutide topic, let consultants at Restore Health Consulting LLC perform a gap analysis to assess your pharmacy or hospital compliance status against the new minimum standards and lead remediation planning if needed.

Amy Summers