Module 9 2021
22/03/2021
Assessment of immunogenicity requires: • risk-based approach • an optimal antibody testing strategy (tiered approach) • appropriate antibody controls Considerations for immunogenicity assessment - summary
• validated methodologies (cut-off points - outliers, distribution, correction factors; intra & inter-assay precision; sensitivity; MRD; drug tolerance; matrix effect - disease state, haemolysed samples; pre-existing antibodies; ...) 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 (need strong justifications).
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Integrated 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 CLB assay
Characterisation titer, isotype, affinity
Assess correlation of ADAs with clinical responses
Assays for clinical markers Assessment of clinical response in patients
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