Module 9 2021
22/03/2021
Factors contributing to immunogenicity - interplay
Nature of the protein (immunomodulatory properties, target,...) Novel epitopes: primary sequence or post- translational modifications. e.g., glycosylation, oxidation Contaminants, formulation excipients, aggregates, storage conditions,…
Product- related
Treatment- related
Patient- related
Dose, frequency of administration, route of administration, duration of therapy
Age (e.g., adult vs paediatric), gender, ethnicity, immune status, medical history, pre-existing antibodies (e.g., HAMA, anti-PEG,..)
? Unknown factors
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Immunogenicity - Risk-based approach
Testing for Ab responses is a regulatory requirement during product development to ensure : • Clinical efficacy and safety of a biological therapeutic. • Product comparability: case of biosimilars Every product needs to be evaluated for immunogenicity (case-by-case approach) and an appropriate strategy adopted based on intended clinical use.
A risk assessment is to be considered early in the development process, as well as control and mitigation strategies (prior to clinical evaluation).
Risk assessment incorporates two elements: • evaluating the likelihood of inducing an immune response • evaluating the possible consequences of the immune response on safety and/or efficacy
Immunogenicity risk assessment is an iterative process.
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