Reframing Residual DNA Testing: What It Is--And What It Isn't

By Ilaria Scarfone and Shriya Sahu, Thermo Fisher Scientific

Residual host-cell DNA control is a central pillar of biologics quality and safety, requiring far more rigor than its long-standing presence in GMP workflows might suggest. Because biologics originate from living systems, the clearance and precise quantitation of nucleic acids from production cells remain regulatory expectations and key indicators of purification performance. Sensitive, validated workflows—encompassing efficient extraction, reliable amplification or detection methods, qualified standards, and compliant data analysis—are essential to ensure measured DNA levels accurately reflect true impurity burdens. Even small inefficiencies in lysis, recovery, or contamination control can distort results, complicate process understanding, or create inconsistencies across development and manufacturing sites.

The increasing diversity of therapeutic modalities, including viral vectors and plasmid-based systems, further heightens these demands by introducing new DNA species, challenging matrices, and modality-specific risks that legacy assays were not designed to accommodate. As a result, the industry is moving toward integrated, end-to-end solutions that minimize manual steps, reduce cross-vendor variability, and provide established controls and documentation aligned with global regulatory expectations. By adopting harmonized, lifecycle-ready workflows, manufacturers can improve analytical confidence, streamline validation, and enhance both in-process control and lot-release readiness—strengthening the overall reliability, reproducibility, and regulatory defensibility of their biologics programs.