Compounding pharmacies caught in counterfeit controversy

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Compounding pharmacies have increasingly been at the centre of safety concerns around the legitimacy and credibility of medications marketed and sold, especially obesity drugs. Novo Nordisk’s Ozempic (semaglutide), for example, has been making headlines worldwide, increasingly becoming synonymous with prompting significant weight loss.

Compounding is the practice of customising medications for individual patients, and it is subject to specific US Food and Drug Administration (FDA) regulations. Amid recent news relating to compounding pharmacy safety concerns, consumer concerns swirl as to whether the presence of obesity drugs like Ozempic in compounding pharmacies poses risks to patient health.

With Ozempic growing in prevalence not only in the pharma sphere, but also the broader zeitgeist, its presence has intensified the focus on medications released to address obesity and Type 2 diabetes. In 2024, the FDA responded and released guidance on medications containing semaglutide marketed for type 2 diabetes or weight loss.

Safety processes and regulations apply to custom-made medicines, which differ from traditional pharmacies. Now, however, compounded pharmacies and their risk of counterfeit medications entering the US market are evolving against the backdrop of regulatory changes, sparking new restrictions.

Earlier this year, the FDA proposed a new rule to address challenges in compounding certain drug products. On 20 March, the US FDA issued a proposed update to the FD&C Act, which follows increased attention on compounding semaglutide and related products. If implemented, it establishes criteria for listing drug products or categories of drug products that present clear challenges for compounding pharmacies.

Drugs that appear on the accompanying lists may not be compounded under Section 503A or 503B. As part of the new rule, the FDA suggests six criteria it would examine before adding drugs to a list: formulation, dosage form, compounding process, delivery system, bioavailability, and testing.

The FDA originally approved semaglutide as Ozempic to treat type 2 diabetes in adults in 2017. Since then, its use has been extended to help manage weight loss, where the drug is marketed as Wegovy.

Semaglutide is part of a family of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. The class of medications mimics the GLP-1 hormone, which enters the gastrointestinal tract after eating. As part of its function, GLP-1 instructs the body to produce more insulin, lowering blood glucose. When the GLP-1 hormone exists in the body in higher amounts, the FDA states it can interact with areas of the brain that can decrease appetite and prompt a feeling of fullness.

There are currently three FDA-approved semaglutide products on the US market to aid weight loss and manage Type 2 diabetes: Ozempic injection, Rybelsus tablets and Wegovy injection.

On 8 March, the FDA approved Wegovy to help lower the risk of cardiovascular death, heart attack and stroke in adults with heart disease who are obese or overweight.

Only available with a prescription, the FDA confirms there are no approved generic versions for the three medications. Semaglutide may be compounded and therefore available when there is a shortage of a particular medication. Since May 2023, Ozempic and Wegovy are listed on the FDA’s Drug Shortages list. 

Compounded pharmacies may prepare a compounded version of one of these three approved drugs. However, this is only possible if they meet specific requirements detailed in the Federal Food, Drug, and Cosmetic (FD&C) Act. “Patients should not use a compounded drug if an approved drug is available to treat a patient,” the FDA states.

Novo Nordisk—the company behind Ozempic, Rybelsus, and Wegovy—confirms it does not directly or indirectly provide or sell bulk semaglutide to compounding pharmacies or any other entity that compounds semaglutide products.

“We cannot validate the safety or effectiveness of compounded products claiming to contain semaglutide that are not one of our own branded products,” a spokesperson for Novo Nordisk told Pharmaceutical Technology. Novo Nordisk owns the registered trademarks for the FDA-approved Ozempic, Rybelsus and Wegovy drugs.

“Medical spas, weight loss or medical clinics, and compounding pharmacies claiming to offer or sell compounded products claiming to contain ‘semaglutide’ are sourcing their ingredients from entities other than Novo Nordisk,” the spokesperson said.

Aware of the current limited supply of certain drugs, the FDA urges patients to get their prescription drugs from state-licensed pharmacies in the US. In those cases, unlike counterfeit alternatives, the FDA and state authorities can ensure the quality of drug manufacturing, packaging, distribution, and labelling.

Some products marketed and sold as ‘semaglutide’ may not be formulated with the same active ingredient as FDA-approved semaglutide products. Instead, they may be made from salt formulations. “Products containing these salts, such as semaglutide sodium and semaglutide acetate, are not safe and effective,” the FDA says. On 27 April 2023, the FDA wrote to the National Association of Boards of Pharmacy detailing the agency’s concerns with using salt forms in compounded products. A few months later, the FDA sent additional letters to the National Association of Boards of Pharmacy and the Federation of State Medical Boards voicing similar worries.

Novo Nordisk has taken legal action against compounded products claiming to include the drug semaglutide. In June 2023, the Danish multinational pharmaceutical company announced it was taking multiple actions.

In November 2023, it revealed it was pursuing additional legal proceedings against two compounding pharmacies for selling adulterated and misbranded compounded drugs claiming to contain semaglutide. These claims brought its total proceedings to 12 legal actions, five of which were against compounding pharmacies.

Novo Nordisk confirmed that it had identified the presence of unknown impurities as high as 33%, which may pose potential safety risks to patients. The company also found lower levels of strength than labelled, including a sample with at least 19% less than what it claimed. The company states that this puts patients at risk of taking drug products that are less effective than expected based on their labeling.

Novo Nordisk shared a letter to healthcare professionals with information on compounded semaglutide. The company detailed that the FDA’s Adverse Event Reporting System (FAERS) database included 352 cases of adverse events associated with compounded “semaglutide” as of 31 December, 2023. Of those cases, 268 were classified as “serious” adverse events, 84 reported hospitalisation, and five involved deaths. It also stated that administration errors found patients had accidentally self-administered doses of compounded “semaglutide” that were up to ten times the intended amount.