Module 9 2021

22/03/2021

Testing for immunogenicity - timing

• The optimal time to design, develop, and validate ADA assays during therapeutic product development depends on the risk assessment of the product. • Fit-for-purpose assays to test phase 1 and phase 2 studies samples - screening, confirmatory, and in some instances neutralization assays. • Samples derived from pivotal clinical studies (phase 3) should be tested with fully validated assays. • When immunogenicity poses a high clinical risk and real-time data are required, assays suitable for their intended purpose might need to be developed before initiating clinical studies and testing performed in real time.

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Immunogenicity Testing – Assay strategy

Multi-tiered approach:

• Screening assay: identification of samples / patients potentially positive for ADA. • Confirmatory assays: elimination of false positives. Preferred approach: same assay format as screening assay but with therapeutic inhibition (competition using excess soluble drug). • Titration assay • Neutralisation assay: assessment of the neutralising capacity of the detected antibodies. • Further characterisation of induced antibodies (isotype, affinity)

The Organisation for Professionals in Regulatory Affairs

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