US FDA Regulatory Framework for Generic Peptides Referring to rDNA Origin Reference Products

Abstract

Peptides are polymeric molecules having 40 or less amino acids. Peptides have been used as therapeutic compounds for the treatment of various disorders since 1920s. Initially, these were isolated from animals. Currently, most of the therapeutic peptides are either synthetic or produced by recombinant DNA technology. Given the continuously improving synthesis technology and availability of robust characterization tools, it is now possible to synthesize a generic therapeutic peptide for a reference product which is of rDNA origin. The manufacturing of synthetic generic peptides is generally considered more advantageous than recombinant generic peptides due to low risk of immunogenicity and absence of host cell derived biomolecules.  This article compares the approval process of generic peptides for a reference product of recombinant DNA origin in the United States especially in light of US FDA guideline “ANDAs for certain highly purified synthetic peptide drug products that refer to listed drugs of recombinant DNA Origin”. This guideline provides recommendations for evaluating whether an Abbreviated New Drug Application submission is appropriate for a synthetic peptide referring to previously approved glucagon, liraglutide, nesiritide, teriparatide, and teduglutide of recombinant DNA origin. The requirements for Abbreviated New Drug Application submissions for synthetic generic peptides and 505(b) (2) submissions for generic peptides of recombinant DNA origin are compared.