Module 9 2024

03/09/2024

Factors Contributing to Immunogenicity

Nature of the protein (e.g., 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)

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Testing for Immunogenicity: Risk-Based Approach

Testing for ADA responses during product development is a regulatory requirement to ensure : • Clinical efficacy and safety of a biological therapeutic. • Product comparability: case of biosimilars All biotherapeutics need to be evaluated for immunogenicity and an appropriate strategy adopted, based on intended clinical use (case-by-case approach).

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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