Forced degradation studies have become integral to the development of recombinant monoclonal antibody therapeutics by serving a variety of objectives from early stage manufacturability evaluation to supporting comparability assessments both pre- and post- marketing approval. This review summarizes the regulatory guidance scattered throughout different documents to highlight the expectations from various agencies such as the Food and Drug Administration and European Medicines Agency. The various purposes for forced degradation studies, commonly used conditions and the major degradation pathways under each condition are also discussed.

Process changes are inevitable in the life cycle of recombinant monoclonal antibody therapeutics. Products made using pre- and post-change processes are required to be comparable as demonstrated by comparability studies to qualify for continuous development and commercial supply. Establishment of comparability is a systematic process of gathering and evaluating data based on scientific understanding and clinical experience of the relationship between product quality attributes and their impact on safety and efficacy. This review summarizes the current understanding of various modifications of recombinant monoclonal antibodies. It further outlines the critical steps in designing and executing successful comparability studies to support process changes at different stages of a product's lifecycle.

The robustness of good laboratory practice and clinical data is reliant upon a clear understanding of the bioanalytical assays. One of the most important components of ligand-binding based assays is critical reagents used to directly or indirectly measure biologic markers or signals. High quality, reproducible, sustainable critical reagents through the development lifecycle could avoid unnecessary rework, multiple validations, cross-validations, and ensure consistency of the data. Numerous analytical methods (UPLC-size exclusion chromatography, cation exchange chromatography, biacore/octet, and high-resolution mass spectrometry) have been evaluated by using current critical reagents. A comprehensive analytical toolbox of biochemical and biophysical methods has been employed to evaluate the quality of critical reagents and explore potential issues if there are any. Moving forward, this "tiered approach" of critical reagents characterization will be used not only to establish critical quality attributes for new reagents but also to evaluate stability in support of reagents recertification.

No abstract

No abstract