Use of surrogate matrices in bioanalytical preclinical safety testing using immunoassay methods: a recommendation from the European Bioanalysis Forum

The use of blank authentic matrix for bioanalytical method validation and sample analysis has long been standard practice within the bioanalytical community and is considered a requirement under current guidelines for bioanalytical method validation. However, this practice has been increasingly challenged as there are scientifically valid alternatives to replace blank authentic matrices with surrogate matrices. The use of authentic matrices from preclinical animal species conflicts with the ethical 3Rs principles (Replacement, Reduction, and Refinement), a concern that the European Bioanalysis Forum has been addressing for years through data-driven advocacy. In this manuscript, the EBF presents experimental data supporting the use of surrogate matrices in preclinical assays for immunoassay formats. This approach significantly reduces the reliance on authentic matrices, while preserving the quality and integrity of bioanalytical data. The findings advocate for revisiting or clarifying regulatory guidelines, such as ICH M10, to more widely accept the use of surrogate matrices, ensuring alignment with ethical standards without compromising scientific rigor.