含活性人体细胞的医疗产品.风险管理的应用和生产实践要求

[中文适用范围]： 本国际标准规定了对作为药品、生物制品、医疗器械和有源植入式医疗器械或上述各项组合进行监管的产品的活细胞成分的加工实践和风险管理的要求和指南。本标准涵盖从活体或已故捐献者获得的自体和同种异体的活细胞材料。对于含有人体活细胞的医疗产品制造商，本国际标准规定了在加工和处理中要使用的程序，以及在识别与此类细胞相关的危害和危险情况时要使用的程序，以便估计和评估由此产生的风险，控制这些风险并监测该控制的有效性。此外，本国际标准概述了剩余风险可接受性的决策过程，同时考虑到与可用替代方案相比的剩余风险和预期医疗效益的平衡。本国际标准提供了与利用活细胞材料制造的医疗产品的典型危害相关的风险管理要求和指南，例如：a) 细菌、霉菌、酵母或寄生虫的污染；b) 病毒的污染； c) 引起传染性海绵状脑病 (TSE) 的物质污染； d) 造成不良致热、免疫或毒理反应的污染物； e) 操作不当导致产品分解和降解产物； f) 与所用细胞类型的致瘤性相关的危害； g) 因非预期的生理和解剖后果（包括非预期的细胞迁移、激素和细胞因子等生物活性物质的非预期释放以及产品细胞和非细胞成分之间的非预期相互作用）导致的并发症； h) 无法追溯； i) 因材料引发非预期的免疫原性反应导致的并发症。 对于其他未分类致病实体污染的评估，可能适用类似的原则。 与基因改造相关的危害不在本国际标准的范围内，将在其他地方讨论。 注 1：“基因改造”的定义可在 ASTM F2312 中找到。注 2：本国际标准并未指定用于控制上述医疗产品生产所有阶段的质量管理体系。如果医疗产品使用国存在本国际标准定义以外的其他国家或地区标准，则这些标准也适用。注 3：地区要求可能比本国际标准中引用的要求更为严格，特别是在捐献者资格标准方面。本国际标准不适用于： — 来源于人体的非活性材料；1 — 非来源于非人体的活细胞； — 用于输血的血液及其成分、生殖细胞、用于移植的器官和骨髓，以及其他不符合“医疗产品”定义的组织； — 体外诊断器械。注 4：有关本国际标准应用的指导，见附件 A。 [外文原描述]： This International Standard specifies requirements and guidance for processing practices and managing risk associated with viable cellular components of products regulated as medicinal products, biologics, medical devices and active implantable medical devices, or combinations thereof. It covers viable human materials of autologous as well as allogeneic human origin, obtained from living or deceased donors. For manufacturers of medical products containing viable cells of human origin, this International Standard specifies procedures to be used in processing and handling, as well as those to be used in identifying the hazards and hazardous situations associated with such cells, in order to estimate and evaluate the resulting risks, to control these risks, and to monitor the effectiveness of that control. Furthermore, this International Standard outlines the decision process for the residual risk acceptability, taking into account the balance of residual risk and expected medical benefit as compared to available alternatives. This International Standard provides requirements and guidance on risk management related to the hazards typical of medical products manufactured utilizing viable human materials, such as: a) contamination by bacteria, moulds, yeasts or parasites; b) contamination by viruses; c) contamination by agents causing Transmissible Spongiform Encephalopathies (TSE); d) contaminating material responsible for undesired pyrogenic, immunological or toxicological reactions; e) decomposition of the product and degradation products caused by inadequate handling; f) hazards related to the tumorigenic potential of the cell types used; g) complications resulting from unintended physiological and anatomical consequences (this includes unintended migration of cells, unwanted release of biologically active substances such as hormones and cytokines, and unintended interactions between cellular and non‑cellular components of the product); h) failure of traceability; i) complications resulting from the material eliciting an unintended immunogenic reaction. For the evaluation of contamination with other unclassified pathogenic entities, similar principles might be applicable. Hazards related to genetic modification are outside the scope of this International Standard and are addressed elsewhere. NOTE 1 A definition of "genetically modified" can be found in ASTM F2312. NOTE 2 This International Standard does not specify a quality management system for the control of all stages of production of medical products as described above. If additional national or regional criteria beyond what is defined in this International Standard exist in the country where the medical product will be used, they are also applicable. NOTE 3 Regional requirements can be more stringent than requirements referenced in this International Standard, especially with regard to donor eligibility criteria. This International Standard is not applicable to: — non‑viable materials of human origin; — viable cells of non‑human origin; — blood and its components used for transfusion, germ cells, organs and bone marrow used for transplantation, and other tissues that do not meet the definition of "medical product"; — in vitro diagnostic devices. NOTE 4 For guidance on the application of this International Standard, see Annex A.