European Bioanalysis Forum cross-industry perspective on emerging small-molecule modalities: bioanalytical challenges...

Emerging small molecule modalities, including oligonucleotides, peptides, lipid nanoparticles, covalent inhibitors and prodrugs, challenge conventional bioanalytical approaches. Recognizing this, the European Bioanalysis Forum convened a cross-industry working group to systematically identify and categorize bioanalytical challenges across seven modality types. Recurring issues include instability, poor recovery, matrix effects and anti-drug antibody interference. Beyond documenting these challenges, the group collected preliminary mitigation strategies based on cross-company experience and scientific discussion. These strategies represent potential approaches rather than formal recommendations. The findings highlight that emerging modalities require early cross-functional assessment and modality-specific analytical strategies, guided by the intended use of the data. This initial categorization provides a foundation for further scientific evaluation, community alignment and regulatory dialogue, supporting the development of science-driven, fit-for-purpose bioanalytical approaches as experience with these modalities evolves.