On May 19, 2021, the FDA finalized the guidance for industry entitled “ANDAs for Certain Highly Purified Synthetic Peptide Drug Products that Refer to Listed Drugs of rDNA Origin,” which was first published as a draft in October 2017. This guidance assists potential applicants in determining when an application for certain synthetic peptides (glucagon, liraglutide, nesiritide, teriparatide, and teduglutide) that refers to a reference listed drug (RLD) of rDNA origin should be submitted as an abbreviated new drug application (ANDA).
In December 2020, FDA approved the first generic of glucagon to treat severe hypoglycemia (very low blood sugar) in patients with diabetes. This approval of a complex, synthetic peptide drug was possible thanks to both the determinations made in this guidance and FDA research on analytical methods for peptides and immunogenicity testing for peptides.
A determination of whether an application for the synthetic peptide should be submitted as an ANDA depends largely on its impurity profile as compared to the impurity profile for the peptide of rDNA origin. Differences in impurities, particularly peptide-related impurities, may affect the safety or effectiveness of a peptide drug product. The guidance describes the circumstances under which submission of an ANDA for a synthetic peptide drug product that refers to a peptide drug product of rDNA origin generally would be appropriate.
Updates to the Guidance
Since its draft publication, the guidance has been updated as follows:
- Addition of Appendix 1, a flow chart that illustrates FDA’s recommendations for evaluating peptide-related impurities to determine whether submission of an ANDA for a synthetic peptide that references a peptide of rDNA origin is appropriate
- Incorporation of the FDA’s final rule on Definition of the Term “Biological Product”
- Expanded recommendations to ensure consistent impurity profiles between the RLD and the proposed generic
- Additional minor edits for clarification
Guidance can be downloaded from below link.