Immunogenicity, or the potential to trigger immune responses, is a critical concern for peptide drugs like Teriparatide. Impurities, aggregates, or contaminants in peptide-based generics could lead to unwanted immune reactions. Thus, the FDA recommends evaluating both the innate and adaptive immune responses when developing a generic peptide.
Innate Immune Response:
- The innate immune system reacts immediately to foreign substances, including contaminants or aggregates in the drug. Manufacturers must ensure that the final product does not contain impurities that could activate this response. Comparative testing against the RLD helps minimize this risk.
Adaptive Immune Response:
- Over time, repeated exposure to impurities can cause the adaptive immune system to produce antibodies against the drug, reducing its effectiveness or causing adverse reactions. Thus, any new impurities or higher levels of known impurities should be carefully evaluated for potential immunogenicity risks.
Comparative Studies for Impurity Profiling
Generic drugs, especially peptides like Teriparatide, must undergo thorough impurity profiling to ensure that no harmful impurities are present in higher concentrations than those found in the RLD. The FDA’s ANDA guidance sets strict limits for impurities:
- Impurities ≥ 0.10%must be identified and characterized.
- Impurities > 0.5% should not be present unless a valid scientific justification is provided, particularly concerning immunogenicity risks.
Using Ultra-High-Performance Liquid Chromatography (UHPLC) combined with High-Resolution Mass Spectrometry (HRMS/MS), impurities are detected, and their potential impact on safety is assessed. This high level of scrutiny ensures that generics do not introduce unexpected risks to patients.
Read also:
- Biological Molecules Notes for Bachelor Students
- Understanding Patent Length and Generic Competition in Pharmaceuticals
Resource Person: Shubham Sonu