On July 28, 2026, the U.S. Food and Drug Administration published 17 revised draft product-specific guidances (PSGs) for generic peptide drugs. The list covers nine active ingredients, including semaglutide, tirzepatide, liraglutide, teriparatide, and calcitonin salmon. On the same day, the agency withdrew its May 2021 guidance on ANDAs for synthetic peptides referencing products of rDNA origin, stating that the document no longer reflects current scientific thinking. For generic developers and their API suppliers, this is the most concrete signal so far of how the FDA will assess peptide ANDAs going forward.
What the FDA Published
The 17 revised draft PSGs map to 17 approved reference products (NDAs) across nine molecules:
- GLP-1/GIP class: semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro, Zepbound), liraglutide (Victoza, Saxenda)
- Other metabolic and endocrine peptides: glucagon (three NDAs), dasiglucagon hydrochloride (Zegalogue), teriparatide (Forteo and one additional NDA), calcitonin salmon (Calcimar, Miacalcin)
- Specialty peptides: pegcetacoplan (Syfovre, Empaveli), vosoritide (Voxzogo)
Each PSG gives the agency's updated recommendations in five areas: submission of recombinantly, synthetically, or semi-synthetically produced peptides as ANDAs; innate immune response testing; impurity thresholds; higher order structure assessment; and biological activity assessment. The documents are drafts. The FDA will review public comments before finalizing them.
Why the Impurity and Characterization Requirements Matter
For peptide ANDAs, the hardest technical questions are rarely about the active ingredient itself. They concern what else is in the product. Peptide-related impurities—deletion sequences, truncated forms, oxidation and deamidation products—must be identified, quantified, and held below the thresholds the FDA sets for each molecule. The revised PSGs put impurity control at the center of the sameness argument a generic applicant has to make.
This has a direct supply-chain consequence. Developers now need well-characterized drug peptide impurities as reference standards to validate their analytical methods against the PSG thresholds. Higher order structure assessment and biological activity testing add two more layers of method development, and both depend on accurate, traceable reference materials for the parent drug peptides and their degradation products.
The 2021 rDNA Guidance Is Withdrawn
Alongside the new drafts, the FDA withdrew the guidance ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin (May 2021). That guidance had set the framework for filing synthetic versions of recombinantly produced peptides—such as glucagon and liraglutide—as ANDAs. The agency says it no longer reflects current scientific thinking and plans to issue a revision this year, as noted in the CDER 2026 Guidance Agenda. Until a replacement is finalized, the revised PSGs are the most current statement of the FDA's expectations for these products.
What Generic Developers Should Do Now
Three practical steps follow from this announcement. First, review the PSG for each target molecule and map its five recommendation areas against your current development plan. Second, audit your impurity strategy early: synthesis route, degradation pathways, and the availability of reference standards all feed the impurity profile the FDA will compare against the reference listed drug. Third, use the comment period. PSGs change between draft and final versions, and the FDA explicitly invites controlled correspondence with the Office of Generic Drugs for peptides not covered by these 17 documents.
Key Takeaways for the Industry
What did the FDA publish on July 28, 2026?
Seventeen revised draft product-specific guidances for generic peptide drugs covering nine active ingredients, including semaglutide, tirzepatide, and liraglutide. The PSGs update recommendations on ANDA submission routes, innate immune response testing, impurity thresholds, higher order structure, and biological activity. They are drafts open to public comment, not final rules.
Does this mean generic semaglutide is approved?
No. A PSG is a development roadmap, not an approval. It tells applicants what evidence an ANDA for that molecule should contain. Any generic version still has to go through full ANDA review before it can be marketed.
Why was the 2021 synthetic peptide guidance withdrawn?
The FDA states it no longer reflects current scientific thinking. The framework for submitting synthetic versions of rDNA-origin peptides as ANDAs will be revised, with an updated guidance expected in 2026 according to the CDER Guidance Agenda.
Sources
- FDA: FDA Publishes Revised Draft Product-Specific Guidances for Certain Generic Peptide Products (July 28, 2026). https://www.fda.gov/drugs/drug-alerts-and-statements/fda-publishes-revised-draft-product-specific-guidances-certain-generic-peptide-products
- FDA: Product-Specific Guidances for Generic Drug Development. https://www.accessdata.fda.gov/scripts/cder/psg/index.cfm
- FDA: ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin — Guidance for Industry (May 2021, withdrawn July 28, 2026). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/andas-certain-highly-purified-synthetic-peptide-drug-products-refer-listed-drugs-rdna-origin
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