Manufacturing Science and Technology, Lonza Biologics Porriňo SL, A Relva s/n, 36410, Porriño, Pontevedra, Spain.
Biotechnol Bioeng. 2011 Jul;108(7):1494-508. doi: 10.1002/bit.23155. Epub 2011 Apr 20.
Monoclonal antibodies have proved to be a highly successful class of therapeutic products. Large-scale manufacturing of pharmaceutical antibodies is a complex activity that requires considerable effort in both process and analytical development. If a therapeutic protein cannot be stabilized adequately, it will lose partially or totally its therapeutic properties or even cause immunogenic reactions thus potentially further endangering the patients' health. The phenomenon of protein aggregation is a common issue that compromises the quality, safety, and efficacy of antibodies and can happen at different steps of the manufacturing process, including fermentation, purification, final formulation, and storage. Aggregate levels in drug substance and final drug product are a key factor when assessing quality attributes of the molecule, since aggregation might impact biological activity of the biopharmaceutical. In this review it is analyzed how aggregates are formed during monoclonal antibody industrial production, why they have to be removed and the manufacturing process steps that are designed to either minimize or remove aggregates in the final product.
单克隆抗体已被证明是一类非常成功的治疗产品。大规模生产药物抗体是一项复杂的活动，需要在工艺和分析开发方面付出大量努力。如果治疗蛋白不能得到充分稳定，它将部分或完全丧失其治疗特性，甚至会引起免疫反应，从而可能进一步危及患者的健康。蛋白聚集现象是一个常见问题，会影响抗体的质量、安全性和疗效，并且可能发生在制造过程的不同步骤中，包括发酵、纯化、最终配方和储存。在评估分子的质量属性时，药物物质和最终药物产品中的聚集物水平是一个关键因素，因为聚集物可能会影响生物制药的生物活性。在这篇综述中，分析了单克隆抗体工业生产过程中聚集物是如何形成的，为什么要去除它们，以及设计用于在最终产品中最小化或去除聚集物的制造工艺步骤。
