Lawrence Moyra, Evans Amanda, Moreau Thomas, Bagnati Marta, Smart Matthew, Hassan Enas, Hasan Jahid, Pianella Monica, Kerby Julie, Ghevaert Cedric
Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge, UK.
Department of Haematology and NHS Blood and Transplant, University of Cambridge, Cambridge, UK.
NPJ Regen Med. 2021 May 26;6(1):27. doi: 10.1038/s41536-021-00138-y.
Quality, traceability and reproducibility are crucial factors in the reliable manufacture of cellular therapeutics, as part of the overall framework of Good Manufacturing Practice (GMP). As more and more cellular therapeutics progress towards the clinic and research protocols are adapted to comply with GMP standards, guidelines for safe and efficient adaptation have become increasingly relevant. In this paper, we describe the process analysis of megakaryocyte manufacture from induced pluripotent stem cells with a view to manufacturing in vitro platelets to European GMP for transfusion. This process analysis has allowed us an overview of the entire manufacturing process, enabling us to pinpoint the cause and severity of critical risks. Risk mitigations were then proposed for each risk, designed to be GMP compliant. These mitigations will be key in advancing this iPS-derived therapy towards the clinic and have broad applicability to other iPS-derived cellular therapeutics, many of which are currently advancing towards GMP-compliance. Taking these factors into account during protocol design could potentially save time and money, expediting the advent of safe, novel therapeutics from stem cells.
作为良好生产规范（GMP）总体框架的一部分，质量、可追溯性和可重复性是可靠生产细胞疗法的关键因素。随着越来越多的细胞疗法进入临床阶段，并且研究方案也在调整以符合GMP标准，安全高效调整的指南变得越来越重要。在本文中，我们描述了从诱导多能干细胞制造巨核细胞的过程分析，目的是按照欧洲GMP标准生产用于输血的体外血小板。该过程分析使我们能够全面了解整个制造过程，从而确定关键风险的原因和严重程度。然后针对每种风险提出了风险缓解措施，这些措施旨在符合GMP要求。这些缓解措施对于推动这种源自诱导多能干细胞的疗法进入临床至关重要，并且对其他源自诱导多能干细胞的细胞疗法具有广泛的适用性，其中许多疗法目前正在朝着符合GMP标准的方向发展。在方案设计过程中考虑这些因素可能会节省时间和金钱，加速安全、新型干细胞疗法的出现。
