A fit-for-purpose strategy for the risk-based immunogenicity testing of biotherapeutics: a European industry perspective

Here, we propose two pre-defined testing strategies for the detection and characterization of anti-drug antibody (ADA) responses where the different strategies are based on the phase of development for a biotherapeutic, a. without (category 1) and b. with (category 2) the expected potential to elicit ADA mediated severe clinical consequences. The harm of a potential ADA response determines which of the two testing strategies is adopted. Rather than replacing the overall risk assessment which is known to be challenging and multi-factorial, the testing strategy selection is a starting point for immunogenicity testing which adapts throughout drug development as more information becomes available. The scientific rationale on which the "case-by-case" approach advocated in white papers and guidance documents may be translated for each individual drug development program is provided and, underpins the recommendations made here.