Establishment of Limit of In Vitro Cell Age (LIVCA) for Biologics Manufacturing Process

This white paper explores current practices and industry experiences for establishing the Limit of In Vitro Cell Age (LIVCA) in biologics manufacturing. As per the International Council for Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), characterization and testing of banked cell substrate is a critical component of the control of biotechnological and biological products. Regulatory agencies require the establishment of LIVCA for the use of master cell bank (MCB) and working cell banks (WCBs) in commercial manufacturing of biologics to demonstrate that the maximum in vitro cell age of cells used in the production process has no impact on product quality and process consistency over the duration of cell culture expansion and manufacturing process. This white paper reviews the methodologies for genotypic, phenotypic, and product quality characterization for LIVCA while highlighting the necessity of aligning industry practices with regulatory expectations to expedite market approval. It discusses the strategies for implementing LIVCA, regulatory guidelines, expectations that shape different industry practices, and provides an overview of approval experiences including those based on data derived from production cells expanded under pilot plant scale or using representative scale-down models. Through a collaborative approach involving industry leaders based on an industry-wide survey coordinated by the BioPhorum Operations Group (BPOG), we aim to streamline and accelerate LIVCA timelines, while ensuring robust manufacturing processes and adherence to high compliance standards as companies design and implement their LIVCA strategies efficiently and effectively to support commercialization applications.