Usually, every quarter, the FDA issues a series of new and revised product specific bioequivalence guidances designed to provide the industry with FDA’s current thinking on the appropriate methods to establish bioequivalence of certain products. Today, FDA issued a list (here) composed of only newly revised guidances and all of them are for injectable peptide products. These documents represent either the second or third revision to the original guidance for the product.

The guidances are very similar in nature and are broken down into the following format:

  • Recommendations to support active ingredient sameness and impurity assessment.
  • For meeting requests with OGD they recommend “For any inquiries regarding the use of non-clinical assays to assess risk in recombinant generic peptides, please submit pre-ANDA product development meeting requests”.
  • Waiver of in vivo bioequivalence studies on the basis that bioequivalence is self-evident under 21 CFR 320.22(b)(1).
  • Considerations for non-Q1/Q2 formulations citing the permissible difference in formulation allowed for injectable formulation.
  • Device considerations (if one is required), including user interface assessment.

 

The Federal Register pre-publication Notice (here) announcing the availability of the revised guidances also notes that “FDA is also withdrawing the guidance for industry entitled “ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin” (May 2021) as it no longer reflects FDA’s current scientific thinking. As noted in the Center for Drug Evaluation and Research guidance agenda, FDA plans to revise and reissue the guidance this year”.

It is clear that OGD is taking a play out of what was done with the advice in the biosimilar draft guidances that is reflective of its view that biosimilars that are found to be highly similar to their brand name counterparts will not need in vivo/clinical testing if there is adequate in vitro physicochemical characterization of the product, device, impurity profiles and user attributes.

FDA notes that “[T]hese revised draft PSGs provide FDA’s updated recommendations across five key areas for these peptide drug products: 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”.

FDA also notes that “[T]he recommendations set forth in these draft PSGs may also be applicable to the development of other generic peptide drug products. In those instances, applicants are encouraged to contact the Office of Generic Drugs (OGD) via a formal meeting request or in a controlled correspondence”.