Host-Cell Protein Risk Management and Control During Bioprocess Development:A Consolidated Biotech Industry Review, Part 1

摘要

Host-cell proteins (HCPs) constitute a significant class of process-related impurities during biologies manufacturing. Due to their potential impact on product quality and efficacy as well as patient safety, the total amount of residual HCP in a biological drug substance generally is considered a critical quality attribute (CQA) that usually needs to be tested for during batch release (l, 2). It is both an "industrywide" common understanding and a regulatory requirement to remove HCPs from biologiesto acceptably low levels that will not affect product quality, compromise expected product efficacy, or jeopardize patient safety (3,4). However, the complexity and diversity of residual HCP composition in drug substances and limited knowledge publicly available on the biological, physiological, pharmacological, and toxicological effect of individual HCPs detected in biologies create significant challenges. The main difficulty is in effectively determining at what level — and more important, for whichspecific HCPs — they could be considered safe or low risk. The industry applies HCP specification limits based on experience, process capabilities, clinical development stages, and HCP testing results from sensitive immunoassays supplementedwith HCP characterization by orthogonal methods (5-7). However, little to no guidance is available on how to manage HCP-related risks throughout drug substance development.