Nonclinical Evaluation Strategies and Case Analyses for CMC Changes in Biological Products During Clinical Development

Pharmaceutical development of biological products during clinical trials is a continuous process in which manufacturing changes are inevitable. Chemistry, manufacturing and controls(CMC) changes may lead to changes in critical quality attributes, potentially impacting product safety and/or efficacy. Assessing the comparability of biological products before and after changes is therefore required to bridge existing nonclinical and/or clinical data. In some cases, dedicated nonclinical bridging studies are warranted. Integrating published technical paper with specific cases analyses, this paper delineates the fundamental rationale and pivotal considerations for the nonclinical assessment of CMC changes of biological products during clinical development, in order to provide reference for facilitating the efficient advancement of such changes.