From Complexity to Compliance: Regulatory and Validation Challenges for Biomarker Assays and Novel Modalities
Biomarker assays are playing a larger role than ever in modern drug development, supporting patient selection, dose optimization, and clinical decision-making. At the same time, new therapeutic modalities — such as gene therapies, oligonucleotides, and bispecific antibodies — introduce assay formats that regulators are still learning to evaluate. The result is a challenging but opportunity-rich landscape for developers.
Despite the release of ICH M10, many gray areas remain for nontraditional modalities. Biomarker assays often require ultra-high sensitivity, and they frequently suffer from matrix interference, cross-reactivity, or variable expression in diseased tissues. Cell- and gene-therapy assays bring even more complexity: viral vector quantification, potency measurements, and immunogenicity readouts that can vary widely between labs and patient populations.
Regulators are responding by raising expectations. Agencies increasingly expect “context-of-use” justification — a clear explanation of why a particular assay was chosen and how its performance supports a clinical or regulatory endpoint. Data-integrity requirements are also intensifying, with digital audit trails and automated workflows gradually becoming the norm.
For developers, success comes down to early planning and proactive risk mitigation. Building orthogonal confirmation into the validation package, establishing strong reference standards, and updating validation parameters as clinical understanding evolves are all essential.
Analytical consultants play a key role in navigating these complexities. They help teams design validation strategies that satisfy regulators, prepare clear documentation for submissions, evaluate assay risks, and ensure smooth technology transfer across internal and external sites. Consultants can also serve as the scientific interface during regulatory interactions — a major advantage for smaller companies without dedicated internal resources.
Biomarker assays will only grow more important as precision medicine expands. Understanding — and anticipating — the regulatory expectations behind them is now a core part of successful development.