Microbiological Consulting, LLC, Rye, New York, USA.
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
J Clin Microbiol. 2023 Mar 23;61(3):e0165422. doi: 10.1128/jcm.01654-22. Epub 2023 Feb 27.
Over the last two decades, rapid technological advances have led to the wide adoption of cell and gene therapy products for the treatment of a variety of disease states. In this study, we reviewed the literature between 2003 and 2021 to provide a summary of overarching trends associated with microbial contamination in hematopoietic stem cells (HSCs) derived from peripheral blood, bone marrow, and cord blood. We provide a brief background on the regulatory context for human cells, tissues, and cellular and tissue-based products (HCT/Ps) as regulated by the US Food and Drug Administration (FDA), sterility testing expectations for autologous (Section 361) and allogeneic (Section 351) HSC products, and discuss clinical risks associated with the infusion of a contaminated HSC product. Finally, we discuss the expectations for current good tissue practices (cGTP) and current good manufacturing practices (cGMP) for the manufacturing and testing of HSC based on Section 361 and Section 351 categorization, respectively. We provide commentary on what is practiced in the field and discuss the critical need for updates to professional standards that keep pace with advancing technologies with an aim to clarify expectations for manufacturing and testing facilities to improve standardization across institutions.
在过去的二十年中，快速的技术进步导致细胞和基因治疗产品被广泛用于治疗各种疾病。在这项研究中，我们回顾了 2003 年至 2021 年的文献，总结了与外周血、骨髓和脐带血来源的造血干细胞（HSCs）中微生物污染相关的总体趋势。我们简要介绍了人类细胞、组织和细胞及组织基产品（HCT/Ps）的监管背景，这些产品由美国食品和药物管理局（FDA）监管，介绍了自体（第 361 节）和同种异体（第 351 节）HSC 产品的无菌检测预期，并讨论了输注污染的 HSC 产品相关的临床风险。最后，我们根据第 361 节和第 351 节的分类，分别讨论了当前良好组织规范（cGTP）和当前良好生产规范（cGMP）在 HSC 制造和检测方面的预期。我们对该领域的实践进行了评论，并讨论了更新专业标准的迫切需要，这些标准应跟上技术进步的步伐，旨在明确对制造和检测设施的期望，以提高各机构的标准化水平。
