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With social media fueling the huge demand for drugs like Ozempic, Rybelsus, Wegovy, and Mounjaro, which are helping people to lose more weight than any previous weight loss medications, it’s no surprise that manufacturers have had trouble keeping up. And the recent approval of Eli Lilly’s Zepbound, which is the same drug, Mounjaro, approved already for diabetes, but renamed specifically for weight management, will only add to that demand. Novo Nordisk, which makes Ozempic, Wegovy, and Rybelsus, for example, has intentionally cut back on production of Wegovy in an effort to limit new prescriptions, to ensure that those who have already started on the weight loss drug can continue getting their injections despite the current limited availability and manufacturing schedules.

But as with many situations in which supply far exceeds demand, questionable versions of these drugs are making their way into desperate patients’ hands, and doctors are concerned about what exactly these versions contain. Some online sellers are exploiting the opportunity to cash in, selling knockoffs of Wegovy, whose active ingredient is semaglutide, that may not even contain semaglutide. Novo Nordisk, which still holds the patent on Ozempic and Wegovy, has also stepped in to address illicit versions of these drugs, suing medical spas, weight loss clinics, and compounding pharmacies in the U.S. that the company alleges are selling unapproved versions of its brand-name drugs, made with versions of semaglutide that the FDA does not sanction. (TIME reached out to the compounding pharmacies named in the suits, in Florida and Tennessee, and did not receive responses.)

Compounding pharmacies occupy a gray area in the current market for weight loss drugs. These pharmacies are licensed and regulated by state boards of pharmacy, and are legally allowed to make tailored versions of drugs that are customized to fit individual patients’ needs. For example, they can remove or substitute ingredients that might cause an allergic reaction. Or they might create a more palatable tasting medicine, reformulate a drug from a pill or tablet to a liquid for those who have difficulty swallowing, or mix up different doses of a drug that aren’t available with the branded version.

These drugs can be prescribed, made, and dispensed under Section 503A of the Federal Food, Drug, and Cosmetic Act, which permits compounding pharmacies to come up with their own recipes for copies of brand name drugs, much like the original apothecary pharmacists of centuries ago. But because they are producing customized versions of approved drugs, compounding pharmacists do not have to notify or receive authorization from the Food and Drug Administration (FDA) to make them, and the FDA does not review them for safety and efficacy. Compounding pharmacies are also allowed to produce more-or-less exact versions of branded drugs that are on the FDA’s drug shortage list, in order to address supply constraints. Semaglutide currently falls into that category, and Novo Nordisk says supplies of both semaglutide and the auto-injector pen device can’t keep up with the surge in demand for its drugs. While tirzepatide, the main ingredient in Mounjaro and Zepbound, is also listed in short supply for people with diabetes, Lilly executives say it’s now available, for people who need it for either diabetes or weight management, although it may take the FDA some time to verify how that supply compares to demand and remove it from the list.

Read more: Should We End Obesity?

While the practice of compounding is legal, some health experts, including the FDA, have raised concerns about how some compounding pharmacists are producing semaglutide. The branded—and FDA-approved—versions of Ozempic, Wegovy, and Rybelsus contain semaglutide made from a specific form of the compound, known as its base. But some compounding pharmacies have used the salt forms of semaglutide to meet the surge in demand, prompting the FDA to issue a warning on May 31. In its statement, the FDA said that compounders should only be using the base form of semaglutide, and that “the salt forms are different active ingredients than is used in the approved drugs.” In addition, the FDA said it is “not aware of any basis for compounding using the salt forms that would meet the [Food, Drug and Cosmetic Act] requirements for active ingredients that can be compounded.” Following the FDA’s lead, several state pharmacy boards of pharmacy, including those in Mississippi, Louisiana, and North Carolina have issued similar warnings to their pharmacies.

Some compounding pharmacists are pushing back, arguing that if the final product made with semaglutide salts does meet the FDA’s criteria for potency, sterility, and lack of endotoxins, it should be considered a legitimately compounded product. They point out that if semaglutide salts are dissolved, they form semaglutide base, so the end product is the same. They are also finding enough supply of both semaglutide base and salts from FDA-sanctioned facilities for compounding, which in their view means that the constrained supply of the branded drug may be more related to the availability of the sterile syringe in which the drug is given. They maintain that using the salt forms are a valid way to compound semaglutide. “I do think there is nuance there,” says one compounding pharmacist who asked not to be named. “The package insert [for the name-brand drug], which is where we start, says [it includes] semaglutide and two normal buffers that are commonly used in injectable medications.” In theory, that means a semaglutide salt-based version would match the FDA-approved drug.

The explosive demand for semaglutide-based weight loss drugs, fueled by their ability to help people shed 15% or more of body weight—more than any previously approved medication—has raised the visibility of compounding pharmacies and how they operate. It’s also placed an additional burden on patients of vetting the facilities that they turn to in order to fill prescriptions.

How does compounding work without a recipe for the drug

To make something like Wegovy, a compounding pharmacist begins by looking at the ingredient list on the drug’s package insert. All ingredients must come from FDA-registered manufacturers, which ensures their quality. From there, things become a little less rote, as the pharmacists come up with their own formula for reaching the right concentration of active ingredient to achieve the drug’s potency. ”It’s a lot like cooking,” says the compounding pharmacist who asked to not be identified. “You look at recipes but often don’t have every ingredient in the recipe, so you make modifications based on experience. It’s hard for people not in the industry to understand—it’s the old school way of making medicine where everything is customized. It’s not black and white.”

For semaglutide, the formula is relatively simple: “It’s semaglutide, the active ingredient, dissolved in solution,” says Scott Brunner, CEO of the Alliance for Pharmacy Compounding. “It’s not hard for a compounding pharmacist to make.”

In addition to potency, since semaglutide is an injected drug, the pharmacist must also ensure that it’s sterile and does not contain any contaminants such as bacteria-produced toxins. Once they come up with a product, compounding pharmacists then send their formulations to an independent lab—which generally follow similar standards for testing—to verify the potency, sterility, and safety of the drug.

Most compounded versions are legitimate copies of the branded drugs. “Compounding pharmacists are not a bunch of people making sketchy substances in their garage,” says Brunner.

But for now, much of the burden of ensuring that these compounded drugs are legitimate still rests on patients, with a system that relies too heavily on caveat emptor. Patients can ask compounding pharmacies for results of the testing from independent labs verifying the safety, sterility, and quality of the product they are purchasing. But compounding pharmacies don’t have to proactively report testing results of each product to their state boards; they are only required to keep logs of the sources of their raw ingredients and the process they used to make the drug.

States have varying levels of oversight over these pharmacies, so some may conduct more rigorous and frequent inspections of these records, while others perform them more sporadically. In addition, “inspections and investigations are typically done after the fact, after someone reports an adverse reaction or files a complaint,” says David Margraf, pharmaceutical research scientist at the Center for Infectious Disease Research and Policy at the University of Minnesota. “And state boards of pharmacy are typically not well-funded so they don’t have time to investigate everything.” Several pharmacy boards, including Nevada’s have launched investigations into products made by compounding pharmacies in their state. The Nevada board of pharmacy did not immediately respond to requests about the status of the investigation.

When Jess Holmes, a digital marketing entrepreneur living in Gilbert, Ariz., went to her naturopath to discuss using semaglutide to help with liver issues and other health concerns that could be alleviated with weight loss, he suggested getting a compounded version of the drug. Because access to branded versions of the drug was limited, he felt submitting a claim through Holmes’ insurance would take too long. “I had no idea what a compounding pharmacy was, or how it worked,” she says. Her naturopath recommended a specific compounding pharmacy, Strive, that he had used regularly. Holmes educated herself a little more about compounding and did some research on the facility herself, and “didn’t see anything shady that raised a red flag.”

When she went to pick up her first set of injections a few days later, she asked the pharmacist about the controversy over how compounded semaglutide is made, and asked him to confirm that the drug she was getting was indeed semaglutide. “They reassured me that it was, and I can only go by what they say,” she says. “For me that was all I needed.” Holmes has been injecting herself with compounded semaglutide for several months now, and only experienced side effects of nausea, diarrhea, and a headache the day after her first shot. Since then, she hasn’t had many adverse reactions to the drug, and it seems to be working; so far, she’s lost more than 23 pounds.

Compounding pharmacies are only one alternative source of branded semaglutide. Online retailers, many without proper licenses or any oversight at all, may be selling what they claim to be semaglutide, but are actually something else, says Al Carter, executive director of the National Association of Boards of Pharmacy. These sites often don’t even require a prescription—legitimate compounding pharmacies will require a prescription written specifically for compounded semaglutide. Carter says there are some other warning signs of illegitimate sites including promises of 24 hour delivery and enticingly lower prices. The FDA suggests patients consult BeSafeRx before purchasing medications from an online pharmacy, medical spa, wellness clinic, or other purported sellers. Patients can also find legitimate local compounding pharmacies through referrals from their prescriber, or by using resources such as the Alliance for Compounding Pharmacy.

Meanwhile, the demand for compounded forms of Wegovy and Ozempic has grown so much that it’s become exhausting, says the anonymous compounding pharmacist, noting that they dispense about 1,000 vials of semaglutide a week. “I honestly don’t know how doctors and patients find us. I understand that there is a lot of demand in the marketplace for patients with health problems like diabetes, and I want to help those people. But TikTok and Instagram ruined it for us. You can’t differentiate what the patients are using it for. We want to help the patients who need [the drug], but now it seems the majority of patients who are coming with prescriptions are moms who want to lose 10 pounds.”

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By: Alice Park
Title: What You Need to Know About Compounded Versions of Popular Weight Loss Drugs
Sourced From: time.com/6301552/weight-loss-drugs-compounding-pharmacies/
Published Date: Mon, 20 Nov 2023 17:36:14 +0000

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