On October 22, 2024, Novo Nordisk made a submission to the U.S. Food and Drug Administration (FDA) nominating Novo Nordisk’s semaglutide products (WEGOVY, OZEMPIC and RYBELUS) to be included in the FDA’s lists of drug products that present demonstrable difficulties for compounding (“DDC lists”), pursuant to the Federal Food, Drug, and Cosmetic Act (FDCA).[1]
Under Section 503A or 503B of the FDCA, qualified pharmacists, physicians, and outsourcing facilities may compound certain drugs without meeting all of the statutory requirements for conventionally manufactured drugs.[2] Compounders may not compound drugs that are “essentially a copy” of an FDA-approved drug if the approved drug is commercially available. An approved drug is not considered to be commercially available if it appears on the drug shortage list in effect under Section 506E of the FDCA (the “506E list”).[3] At least one of Novo Nordisk’s semaglutide products has been placed in the 506E list since 2022, allowing semaglutide compounding by qualified pharmacies and outsourcing facilities.[4]
In an attempt to prevent compounding of its drug products, Novo Nordisk has taken action against compounding pharmacies under federal trademark as well as state unfair competition causes of action.[5]
Novo Nordisk’s nomination of semaglutide to the DDC lists is another attempt by the drug maker to prevent compounding pharmacies and others from compounding semaglutide. Sections 503A and 503B provide that a compounded drug must be a drug product that does not present demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product.[6] The FDA has published proposed rules to establish criteria for the drug products or categories of drug products that would be included in the DDC lists, but has yet to select such drug products or categories of drug products.[7], [8] The proposed rule includes the following six criteria: 1. Complex formulation; 2. Complex drug delivery mechanism; 3. Complex dosage form; 4. Bioavailability achievement complexity; 5. Compounding process complexity; and 6. Physicochemical or analytical testing complexity. Further, the proposed rule would “consider these criteria individually and collectively,” and “take into account the risks and benefits to patients of the compounded drug product or categories of drug products.”[9]
In its submission, Novo Nordisk argues that its semaglutide products should be included in the DCC lists “due to the complexities associated with their formulations, delivery mechanisms, dosage forms, achievement of bioavailability, compounding processes, and physicochemical and analytical testing,” and because “the risks to patient safety presented by semaglutide products compounded under Section 503A or 503B far outweigh any actual or potential benefit.”[10] Novo Nordisk points to “serious immunogenicity risks” at least in part due to the use of chemical peptide synthesis by the compounders, in contrast to Novo Nordisk’s use of recombinant DNA technology to produce the drug product. Novo Nordisk also notes the absence of any identified actual or potential benefit that outweighs the risks.[11]
The FDA is expected to issue its final rule that includes the evaluation criteria and the list of products or categories of products that meet the criteria, but no guidance on the timeline for the final rule was provided.[12]
Editor: Brenden S. Gingrich, Ph.D.
[1] Nomination from Covington & Burling LLP on Behalf of Novo Nordisk Inc. Oct. 22, 2024. Available at https://www.regulations.gov/document/FDA-2017-N-2562-0029.
[2] https://www.fda.gov/drugs/human-drug-compounding/compounding-laws-and-policies.
[3] https://www.fda.gov/drugs/human-drug-compounding/compounding-when-drugs-are-fdas-drug-shortages-list.
[4] https://www.hcplive.com/view/semaglutide-shortage-prompts-fda-warning-to-patients-providers
[5] https://www.nbcnews.com/health/health-news/novo-nordisk-sues-two-pharmacies-allegedly-offering-contaminated-copyc-rcna127383
[6] 21 U.S.C. 353a [FDCA Section 503A] and 21 U.S.C.353b [FDCA Section 503B].
[7] Drug Products or Categories of Drug Products That Present Demonstrable Difficulties for Compounding Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act. 89 FR 19776. https://www.federalregister.gov/d/2024-05801.
[8] The FDCA requires that before implementing the provisions related to establishing the criteria for drug products or categories of drug products that would be included in the DDC lists, an advisory committee on compounding be convened and consulted. See id. at 19778. The Pharmacy Compounding Advisory Committee (PCAC) was established in 2000, but the FDA suspended its efforts to develop the DCC list following legal challenges to certain provisions of Section 503A. See Thompson v. Western States. Med. Ctr., 535 U.S. 357 (2002). Following changes to the statute in 2013 by the Drug Quality and Security Act, the FDA resumed consultation with the PCAC to establish the criteria for drug products or categories of drug products that would be included in the DDC lists.
[9] Id. at 19780.
[10] Nomination, supra.
[11] Id.
[12] Drug Products, supra at 19786.
