Niazi Sarfaraz K
College of Pharmacy, University of Illinois, Chicago, IL 60612, USA.
Pharmaceuticals (Basel). 2025 Aug 4;18(8):1157. doi: 10.3390/ph18081157.
The biopharmaceutical industry is undergoing a fundamental transformation from traditional batch manufacturing to continuous manufacturing (CM) for recombinant drugs and biosimilars, driven by regulatory support through the International Council for Harmonization (ICH) Q13 guidance and compelling economic advantages. This comprehensive review examines the technical, economic, and regulatory aspects of implementing continuous manufacturing specifically for recombinant protein production and biosimilar development, synthesizing validated data from peer-reviewed research, regulatory sources, and global implementation case studies. The analysis demonstrates that continuous manufacturing offers substantial benefits, including a reduced equipment footprint of up to 70%, a 3- to 5-fold increase in volumetric productivity, enhanced product quality consistency, and facility cost reductions of 30-50% compared to traditional batch processes. Leading biomanufacturers across North America, Europe, and the Asia-Pacific region are successfully integrating perfusion upstream processes with connected downstream bioprocesses, enabling the fully end-to-end continuous manufacture of biopharmaceuticals with demonstrated commercial viability. The regulatory framework has been comprehensively established through ICH Q13 guidance and region-specific implementations across the FDA, EMA, PMDA, and emerging market authorities. This review provides a critical analysis of advanced technologies, including single-use perfusion bioreactors, continuous chromatography systems, real-time process analytical technology, and Industry 4.0 integration strategies. The economic modeling presents favorable return-on-investment profiles, accompanied by a detailed analysis of global market dynamics, regional implementation patterns, and supply chain integration opportunities.
在国际协调理事会（ICH）Q13指南的监管支持以及引人注目的经济优势推动下，生物制药行业正经历从传统批量生产向重组药物和生物类似药连续制造（CM）的根本性转变。本全面综述探讨了专门针对重组蛋白生产和生物类似药开发实施连续制造的技术、经济和监管方面，综合了同行评审研究、监管来源和全球实施案例研究中的有效数据。分析表明，与传统批量工艺相比，连续制造具有诸多显著优势，包括设备占地面积减少多达70%、体积生产率提高3至5倍、产品质量一致性增强以及设施成本降低30 - 50%。北美、欧洲和亚太地区的领先生物制造商正在成功地将灌注上游工艺与相连的下游生物工艺整合，实现了具有商业可行性的生物制药全端到端连续制造。通过ICH Q13指南以及美国食品药品监督管理局（FDA）、欧洲药品管理局（EMA）、日本药品和医疗器械管理局（PMDA）及新兴市场当局的特定区域实施，监管框架已全面建立。本综述对先进技术进行了批判性分析，包括一次性灌注生物反应器、连续色谱系统、实时过程分析技术和工业4.0集成策略。经济模型呈现出有利的投资回报率概况，并对全球市场动态、区域实施模式和供应链整合机会进行了详细分析。
