Lately, varied federal companies, together with the Division of Well being and Human Companies Workplace of the Inspector Basic and the U.S. Meals and Drug Administration (FDA), have more and more scrutinized compounded prescribed drugs because the demand for compounded medication continues to develop in response to affected person demand for specialty prescribed drugs and nationwide drug shortages.
Learn on for extra info concerning (1) why federal companies proceed to focus appreciable assets on compounded prescribed drugs, (2) the present restrictions on compounding pharmacies and outsourcing services, (3) why compounded injectable Ozempic® (with the energetic ingredient semaglutide) poses potential points for compounding pharmacies, and (5) how the marketplace for compounded Ozempic® is likely to be impacted as soon as the energetic ingredient in Ozempic® is taken off the FDA drug shortages checklist. (FDA’s drug shortages checklist contains semaglutide with two variations “at present obtainable” and one other variation with “restricted availability via mid-August 2023.”)
Federal Companies Stay Targeted on Compounded Prescribed drugs
Not like FDA-approved, commercially obtainable medication, compounded drug merchandise aren’t topic to the identical formal approval course of. Though the energetic substances in compounded medication are FDA-approved, the protection and efficacy of compounded preparations aren’t verified by the FDA. Relatively, preparation of compounded merchandise is ruled by FDA guidelines below Part 503A (Pharmacy Compounding) and Part 503B (Outsourcing Services) of the Federal Meals, Drug, and Beauty Act (FD&C Act), in addition to state statutes and rules enforced by state boards of pharmacy.
Compounded medication could profit sure sufferers whose wants require personalization, or could treatment drug shortages, however they’ll pose security dangers, equivalent to efficiency issues or contamination, and are meant for affected person use solely when commercially obtainable, FDA-approved medication don’t meet patient-specific wants. (FDA’s Compounding Incidents Program is meant to establish and forestall outbreaks via surveillance of hostile occasions and product high quality incidents. Infrequently, the FDA points Compounding Danger Alerts to tell healthcare professionals, compounders and customers about dangers related to compounded medication, together with info on hostile occasions, outbreaks or product high quality.)
As well as, sufferers may have compounded medication if they’re allergic to an ingredient in available medication or if the commercially obtainable drug poses a bodily barrier to the affected person (i.e., the drug is out there solely as a tablet, however the affected person requires the drug in liquid type).
Compounders Should Navigate FDA’s “Primarily a Copy” Steering
Sections 503A and 503B of the FD&C Act prohibit compounding pharmacies and outsourcing services, respectively, from compounding merchandise which are “basically a duplicate” of FDA-approved medication, which means the merchandise are an identical or basically an identical (the “basically a duplicate” provision). However this prohibition, compounding pharmacies and outsourcing services could compound medication that (i) seem on the FDA drug shortages checklist or (ii) have been discontinued and are not “commercially” obtainable. (For added info, see FDA’s overview of federal compounding necessities and FDA steerage concerning Medicines Containing Semaglutide Marketed for Sort 2 Diabetes or Weight Loss.)
In January 2018, the FDA issued its ”basically a duplicate” steerage to make clear its insurance policies. Notably, this steerage reveals that FDA considers a compounded drug to be “an identical or practically an identical” to an accredited drug if the 2 have the identical (i) energetic ingredient(s), (ii) route of administration, (iii) dosage type, (iv) dosage energy, and (v) excipients (which means inactive substances that function automobiles, equivalent to fillers or preservatives). Compliance with the FDA’s “basically a duplicate” steerage is a frequent level of rivalry with 503A compounding pharmacies and 503B outsourcing services. These services should be capable to efficiently navigate the FDA’s steerage and exhibit that their merchandise aren’t basically a duplicate of some other merchandise which are obtainable available in the market except such merchandise are experiencing an industrywide drug scarcity.
Present State of Affairs: Compounded Ozempic® for Weight Loss
Ozempic®, an injection accredited to deal with Sort 2 diabetes, has gained reputation for off-label use as a weight-loss drug attributable to its skill to gradual the emptying of the abdomen and suppress starvation hormones. Now that semaglutide has been added to the FDA drug shortages checklist, compounding pharmacies are ready to make use of semaglutide to create “generic” Ozempic®. Semaglutide is accredited in its “base type,” which should be acquired from Novo Nordisk, the patent holder of Ozempic®.
With out entry to the bottom type of the drug, compounding pharmacies are making generic Ozempic® via a course of of blending different variations of semaglutide — for instance, salt varieties equivalent to semaglutide sodium and semaglutide acetate — with different substances. In accordance with the boards of pharmacy in North Carolina, West Virginia and Mississippi, such salt types of the drug are for “analysis use solely.” The manager director of the Louisiana Board of Pharmacy went additional, stating that the salt types of semaglutide are additionally not meant to be used in people. This echoes statements made by the FDA indicating that salt types of semaglutide “haven’t been proven to be secure and efficient.”
Pharmacies are struggling to maintain tempo with the demand for semaglutide, as are weight-loss clinics. Elevated demand and semaglutide’s place on the FDA drug shortages checklist have inspired on-line retailers, physicians and telehealth firms to promote salt types of semaglutide to sufferers. Moreover, off-label use of Ozempic® for weight reduction has made entry to the drug tougher for sufferers who depend on Ozempic® to deal with their Sort 2 diabetes.
The FDA despatched a letter to the Nationwide Affiliation of Boards of Pharmacy on April 27, 2023, stating that, whereas Ozempic® and Wegovy® (a drug with the identical energetic ingredient as Ozempic®) stay on the FDA drug shortages checklist, salt varieties don’t meet federal legislation necessities to be used in compounded medication. On Could 30, 2023, the FDA revealed a security warning concerning the salt types of semaglutide, stating that there is no such thing as a foundation for utilizing the salt types of semaglutide in compounded medication and that there is no such thing as a FDA-approved generic of semaglutide. The FDA warned that there are identified circumstances of sufferers being harmed by the salt types of semaglutide and supplied a hyperlink to its MedWatch hostile occasion reporting program.
Whereas the FDA has but to take motion towards compounding pharmacies for utilizing salt types of semaglutide, the FDA’s security warning makes it clear that it’s keen to research reviews of such prohibited use of semaglutide. On the identical time, state boards of pharmacy in North Carolina, West Virginia and Mississippi have issued statements outright banning using salt types of semaglutide. Additional, these three state boards of pharmacy have clarified that they’re keen to take motion towards compounding pharmacies that use prohibited salt types of semaglutide, and additional, that pharmaceutical producers can take authorized motion towards prescribers and compounders who illegally compound semaglutide.
What’s Subsequent for Compounded Ozempic®?
As soon as Ozempic® is faraway from the FDA’s drug shortages checklist, compounding pharmacies and outsourcing services won’t be permitted to make the most of the shortages checklist exception and could be prohibited from compounding semaglutide injections except they can fulfill one of many different exceptions of the “basically a duplicate” provision. Moreover, weight-loss clinics and different healthcare suppliers might be required to manage and prescribe brand-name Ozempic®, which comes at a steeper value than its compounded counterparts. It will place a higher monetary burden on sufferers, who can anticipate to pay considerably extra per 30 days for the drug, which prices round a number of hundred {dollars} in compounded type however runs over a thousand {dollars} per 30 days below the model identify.
When Ozempic® is faraway from the drug shortages checklist, compounding pharmacies might want to depend on one of many different exceptions to the “basically a duplicate” provision. Many compounding pharmacies already add substances (equivalent to Vitamin B-12) to distinguish their merchandise from commercially obtainable varieties. The FDA has but to offer steerage on whether or not these compounded variations of Ozempic® could also be thought-about novel and never “basically copies” of brand-name Ozempic®. Regardless, the FDA has made it clear that it intends to research cases and reviews of harmful or illicit compounding of semaglutide.