Forced degradation of recombinant monoclonal antibodies: A practical guide

Abstract

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.

Keywords: Forced degradation; Recombinant monoclonal antibodies; Regulatory guidance.

Figure 1.

Major degradation pathways of recombinant monoclonal antibodies. Arrows indicate the main degradation sites. The commonly used methods to detect the degradation products are shown in the parenthesis.