Module 9 2021

22/03/2021

Do different assays/platforms generate the same data?

Same sensitivity? Same drug tolerance? Same titers? Same specificity? Same detected seroconversion time (onset of ADA)?  NO

ADA assay life cycle - Assays need to be fit-for-purpose and fully validated in support of phase 3

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Neutralisation assay

Determination of the neutralising potential of induced ADA is required by regulators - deviation needs a strong justification. Principle : if neutralising antibodies (NAb) directed against the therapeutic  biological activity induced by a known concentration of the therapeutic will be reduced or abolished. Neutralisation is therefore assessed by measuring the degree of inhibition induced by the sample. Two types of assays: Cell-based (bioassay) and non-cell-based (competitive ligand binding assay) MoA of the therapeutic will dictate the format to use, e.g.,: • Non-cell-based assay relevant when a therapeutic mAb acts by binding to a soluble ligand  blocking it from interacting with its receptor thus inhibiting the ligand’s biological activity. • Cell-based assays recommended for mAb where effector functions important for the clinical effect.

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