Recently Distributed FDA Draft Guidance Highlights Importance of Immunogenicity Risk Assessment in Abbreviated New Drug Applications (ANDAs) of Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin

Protein drugs may be different sizes. Consider for example, monoclonal antibodies and peptide drugs. One likes green, the other likes red, but they both need to be assessed for potential immunogenicity. This is even true when your favorite pocket pooch or peptide biologic qualifies for an “Abbreviated New Drug Application” or ANDA. Pretty much everyone knows that big dogs (antibodies and other large proteins) require a careful immunogenicity risk assessment, before you cross the street (to the clinic). Now, as it turns out, peptides do too! Even if your dog has been around the block a few times as a well-known drug, a new version, subject to ANDA, requires scrutiny.

Are you planning to submit a proposed generic drug to the Food and Drug Administration (FDA) sometime soon? You may want to consider the draft FDA Guidance for Industry, ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin. This guidance discusses the necessary profile that your generic synthetic peptide, if using a reference listed drug (RLD) of rDNA origin, must fit to qualify under submission as a ANDA, rather than as a new drug application (NDA). The guidance specifically addresses ANDA for drug products: glucagon, liraglutide, nesiritide, teriparatide, and teduglutide.

What’s new? Well, to ensure the safety of the proposed generic drug, the impurity level of the synthetic peptide must also be evaluated.The FDA’s draft ANDA guidelines recommend that the peptide-related impurities in the synthetic, which can result from insertion, deletion, or modification of amino acid sequences or residues, must be equal to or less than that of the RLD (reference drug). Furthermore, if there are any new specified impurities found within the synthetic peptide, they must be characterized and justified as not affecting the safety or effectiveness of the proposed drug, with respect to immunogenicity. Read this tidbit from the FDA for yourself below or the entire guidance here.

ANDA requirements for peptide drugs

So, how can this be immunogenicity risk comparison of your generic synthetic peptide to the RLD be accomplished? The FDA suggests that these differences in impurity found in the synthetic peptide in comparison to the RLD be justified by data that reflects that the impurity does not contain T-cell epitopes, or sequences that have an increased affinity for MHC. Well, that’s where EpiVax can help you. We’ve been performing protein immunogenicity risk assessments by screening for T-cell effector epitopes for years!

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