For the last 5 or so years, the FDA has told applicants that they could likely submit an ANDA for a synthetic peptide product (40 amino acid chains or fewer) when the reference listed drug (RLD) was of rDNA origin but the guidance on which products, how, and what would be required was often sketchy.  Yesterday’s issuance of the document entitled “ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin” (here) cleared up some of the mystique around FDA expectations for such submissions.

The guidance specifically called out 5 rDNA RLD products, glucagon, liraglutide, nesiritide, teriparatide, and teduglutide for which the Agency would consider ANDA applications.  The bottom line is that FDA now believes that there are adequately sensitive advanced analytical methods available to characterize the impurity profile and the sequence of the amino acid chains.  Since impurity profile differences can lead to immunogenicity issues, FDA is paying particular attention to any differences between the impurity profile of the RLD and the proposed synthetic generic product.  The impurity profile should demonstrate that each impurity found in the synthetic version is at the same level or lower than that of the same impurity in the rDNA RLD, and that any new specified impurity found in the synthetic version is no more than 0.5% of the drug substance.  The applicant will be expected to characterize and justify any new specified impurity.

The guidance also provides scientific considerations for ANDAs for synthetic peptide products relative to active ingredient sameness, impurities, and the considerations relative to the submission of an ANDA for any of the 5 peptide RLDs of rDNA origin.  FDA has also provided a decision-tree to assist applicants in determining whether their proposed synthetic peptide may be suitable for submission as an ANDA.  There is also a section on requesting assistance from the FDA via a controlled correspondence for response to specific questions, as well as requesting a pre-ANDA meeting with OGD.  As OGD forges further into the peptide realm, the guidance hopefully makes the path clear for the ANDA sponsor.