Module 9 2024

03/09/2024

Considerations for Immunogenicity Assessment - Summary

Assessment of immunogenicity requires:

•

risk-based approach

• an optimal antibody testing strategy (tiered approach) • appropriate antibody controls •

validated methodologies (cut-off points - outliers, distribution, correction factors; intra & inter-assay precision; sensitivity; specificity; MRD; drug tolerance; matrix effect - disease state, haemolysed samples; pre-existing Abs; ...) Each assay has its own advantages and disadvantages (may be related to the characteristics of the therapeutic, the reagents and the repertoire of antibodies present in the samples). Bioassays or CLBA are necessary to distinguish between neutralising & non-neutralising antibodies. However, drive from industry to dispense with neutralisation assays in some cases and using a PK/PD/ADA integrated approach (need strong justifications for Health Agencies)

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Strategy for Immunogenicity Assessment

Patient samples taken at appropriate time-points

Screening Assay

negative samples - rejected

positive samples

Confirmatory Assay

Confirmed positive samples

Neutralisation Assay bioassay or CLBA

Titer & Characterisation

Assess correlation of ADAs with clinical responses

Clinical markers Clinical response of patients

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