Immunogenicity testing constitutes a critical step in the development of therapeutic proteins.The immunogenicity data of an individual drug candidate is very important for internal and regulatory decision making, to compare e.g. biosimilars vs. originators or different therapeutic modalities and finally to select the optimal treatment option in clinical practice. Due to apparent performance differences, (e.g. sensitivity, drug tolerance), determined using different technologies and ADA positive controls, a comparison of immunogenicity data is deemed impossible. A valid comparison of technical performance parameters of ADA assays, would be a crucial step forward but requires an open discussion and consensus within the community, from industry to regulators. To initiate a discussion, we propose to use the “cut-point anti-drug antibody reagents complex” (CP-ARC) amount, as a clearly defined assay parameter that enables a technical assay comparison. The CP-ARC concept, based on commonly available bioanalytical assay information, will be introduced and illustrated by a case example. The feasibility and implementation in routine assay development will be discussed as well as the potential improvement of reporting of bioanalytical immunogenicity data. Scientific sound comparability of the bioanalytical methods enable comparability of clinical immunogenicity and consequently improve the treatment options for the sake of patients health.
...reflect on how the current (guideline recommended) way of ADA assay development limits our understanding of the true performance of ADA assays.
…realize what information might be the missing piece of the puzzle to fully exploit the information we could get from ADA assays
…understand how the application of the “CP-ARC” approach might improve immunogenicity testing, enable comparability of bioanalytical ADA methods and finally comparability of clinical immunogenicity of different compounds