Closing The QC Gap For mAbs: Rapid Answers Without Compromising

By Selvakumar Dakshnamurthy, Thermo Fisher Scientific

Monoclonal antibodies (mAbs) have become essential therapies for treating cancer, autoimmune conditions, and other serious diseases. Yet their structural complexity presents ongoing challenges for developers and manufacturers. Unlike small-molecule drugs, mAbs are multi-domain biologics with inherent variability driven by factors such as post-translational modifications and higher-order structure. Even small changes during process development, scale-up, or early clinical manufacturing can affect product quality, consistency, and the strength of a regulatory submission. As a result, decisions made early in development often shape the analytical strategies that guide a program through later stages.

To ensure reliable production, developers must carefully define and monitor critical quality attributes (CQAs), including structural integrity, post-translational modifications, and functional activity. At the same time, process-related impurities such as residual host-cell DNA, host-cell proteins, and potential microbial contaminants must be tightly controlled to maintain product safety and regulatory compliance.

Molecular quality control assays play a critical role in this analytical framework. Techniques such as quantitative polymerase chain reaction (qPCR) enable highly sensitive detection and quantification of trace nucleic acids and microbial contaminants that may not be detectable through traditional biochemical testing. When implemented through well-designed, scalable workflows, these molecular tools help manufacturers maintain product integrity throughout development, supporting regulatory submissions, early clinical manufacturing, and future process scale-up.