On October 22, 2024, Novo Nordisk asked the FDA to add semaglutide to the demonstrably difficult to compound list.
The Food and Drug Administration is proposing to establish criteria for the lists of drug products or categories of drug products that present demonstrable difficulties for compounding (Demonstrable Difficulties for Compounding Lists or DDC Lists) under certain sections of the Federal Food, Drug, and Cosmetic Act. Additionally, the Agency is proposing to identify the first three categories of drug products on both DDC Lists. Drug products or categories of drug products that appear on the DDC Lists cannot qualify for certain statutory exemptions, and therefore may not be compounded under, either section 503A or section 503B, respectively.
Novo Nordisk has cited concerns about patient safety and drug effectiveness approximately two-and-a-half years into their semaglutide drug shortage. They assert that the process to compound semaglutide is demonstrably difficult because they utilize a recombinant DNA technology in lieu of using an API and they assert that a multitude of issues can stem from using the alternative process employed by compounding pharmacies.
Novo Nordisk states “It is well-established that changes in manufacturing techniques, such as a switch “from recombinant to peptide synthesis,” “can lead to the introduction of new or duplicated amino acids or side-chain modifications, resulting in impurities that are difficult to separate from the active pharmaceutical ingredient (API), which can change the clinical profile of the drug and contribute to immunogenicity” 1
Many compounding pharmacies are confusing the argument from Novo Nordisk by stating the use of an API makes it easier to compound with and not the the fact that the semaglutide molecule is demonstrably difficult to manufacture, which it is, and is precisely the argument Novo Nordisk is making. Novo Nordsik argues that for a semagltuide drug product to be both safe and effective it must be manufactured using the recombinant DNA technology exclusively.
Compounding pharmacies must recognize that it is true that synthetic manufacturing of peptide APIs may result in more impurities in the drug, it’s asserted that that those impurities are below 1%, well within acceptable industry ranges. Novo Nordisk will likely attempt to put the onus on the compounders to prove that the API produces an equivalent product that meets both safety and efficacy standards.
The compounding pharmacies have clearly gotten the attention of big Pharma, and how this plays out will likely have implications that reverberate across both industries.
https://www.fda.gov/media/107622/download
https://www.andersontriggs.com/wp-content/uploads/2024/10/FDA-2017-N-2562-0029_attachment_1.pdf
https://www.regulations.gov/document/FDA-2017-N-2562-0029
- Anne S De Groot et al., Immunogenicity Risk Assessment of Synthetic Peptide Drugs and Their Impurities, 28 DRUG DISCOVERY TODAY, at 2 (2023). ↩︎
0 Comments