一次性使用工艺组件 | ASME BPE-2022 新增内容解读
时间：2023-07-07 阅读：1016
一次性使用技术应用于制药领域已有30余年历史。凭借其聚合物材料可塑性强、便于运输和使用的优势，在质量可控的前提下，一次性使用系统已经广泛应用于液体储存、液体转移、无菌过滤、超滤和透析换液，以及病人使用的输液系统等。近年来，随着单抗药物和细胞治疗药物的成功发展，相关技术迅速升级，一次性使用技术在制药领域的应用不断拓展。目前一次性使用技术几乎可以涵盖整个生物制药工艺过程的各个单元操作。
ASME BPE 2022已发布，本次版本升级，增加了一次性使用部件和组件的要求，分为三个章节，分别是第七章一次性使用设计、第八章一次性使用工艺组件和第九章一次性使用的制造、组装和安装。本文继续介绍第八章一次性使用工艺组件。
蒸汽直通和蒸汽直通连接器设计用于将一次性系统连接至多次使用（金属）系统。蒸汽直通和蒸汽直通连接器应：
(a)形成符合DT和MC部分要求的卫生夹紧接头
(b)保持密封（见MC-4）
(c)可排水（见SD部分）
(d)可灭菌（参见SU-9）
(e)与SIP兼容，灭菌后（例如，伽马辐照）在266°F（130°C）下持续1小时（暴露表面）
(f)符合PM-3.1的生物相容性要求
(g)符合表PM-2.2.1-1的符合性证书要求。
无菌连接器允许连接一次性组件，同时在连接之前、期间和之后保持工艺接触表面无菌，而不考虑制造环境。
2.1制造商责任
制造商应：
(a)进行微生物侵入试验，以确认连接后无菌液路不会受到损害
(b)定义连接器是干连接器还是湿连接器
(1)干燥意味着液体不能进入连接器。使用前，必须使用夹钳或其他合适的技术将液体与连接器隔离。
(2)湿意味着连接器中可以有液体进行连接。
(c)提供产品规格，包括但不限于以下内容：
(1)温度额定值
(2)压力额定值
(3)灭菌方法的兼容性（例如，伽马灭菌，高压灭菌）
(4)产品流路清洁度（微粒、内毒素、生物负载）
(5)流速
(d)定义连接器两半部分的性别
(1)独。特的阳半部分和阴半部分
(2)没有性别，每一半都是一样的
(e)定义连接是设计用于一次性连接还是多个连接
(1)设计用于一次性连接的连接器应具有不可逆的锁定机制，除非其专门设计用于无菌断开。
(2)设计用于多重连接和断开的连接器应具有规定的最大连接数。
(f)提供装配说明，以确保正确连接
2.2 所有者/用户责任
所有者/用户应
(a)根据所有适用过程和灭菌条件的服务要求，审查制造商的质量标准
(b)确保由经过适当培训的操作员按照合格程序进行连接，以保持系统完整性
柔性生物处理容器，也称为一次性袋，可在2D或3D格式中以不同的配置和体积容量获得。这些一次性袋用于生物工艺流体或粉末的制备、储存、取样、转移和运输组件中。一次性袋具有连接端口，并与管路或管路支路结合使用，以实现灌装、分配、取样和其他工艺功能。本节提供了对一次性袋结构材料和鉴定的要求。
3.1材料
多层膜通常用于制造一次性袋。制造商应确定袋的所有薄膜和连接层的构造材料。对于预期用于过程接触的袋，制造商应识别所有材料（例如，主要材料、粘结层和添加剂），这些材料可能会掺杂袋内产品。
3.2确认
制造商应提供一次性袋的工作温度和压力限值。制造商应规定适当的灭菌方法，包括暴露范围、灭菌后有效期和其他限制。制造商应提供处理和安全使用程序，包括悬挂限制、填充限制和二次密封建议。
参见PM-4.4。
- 原文参考 -
CHAPTER 8 PROCESS COMPONENTS FOR SINGLE-USE
PART SC COMPONENTS FOR SINGLE-USE
SC-1 STEAM-THROUGH AND STEAM-TO CONNECTORS
Steam-through and steam-to connectors are designed to connect single-use systems to multiuse (metallic) systems. Steam-through and steam-to connections shall:
(a) form a hygienic clamp union, meeting the requirements of Parts DT and MC
(b) maintain a seal (see MC-4)
(c) be drainable (see Part SD)
(d) be sterilizable (see SU-9)
(e) be compatible with SIP, poststerilization (e.g., gamma irradiation) at 266°F (130°C) for 1 hr (exposed surfaces)
(f) meet the biocompatibility requirements of PM-3.1
(g) meet the Certificate of Conformance requirements of Table PM-2.2.1-1.
SC-2 ASEPTIC CONNECTORS
Aseptic connectors allow single-use assemblies to be joined while maintaining a sterile process contact surface before, during, and after connection, without regard to the manufacturing environment.
SC-2.1 Manufacturer Responsibilities
The manufacturer shall
(a) conduct microbial ingress testing to qualify that a sterile fluid path postconnection is not compromised
(b) define whether the connectors are dry connectors or wet connectors
(1) Dry means liquid cannot be in the connector. Pinch clamps or another suitable technique must be used to isolate the liquid from the connector prior to use.
(2) Wet means the connection can be made with liquid in the connector.
(c) provide product specifications including, but not limited to, the following:
(1) temperature ratings
(2) pressure ratings
(3) sterilization method compatibility (e.g., gamma, autoclave)
(4) product flow path cleanliness (particulates, endotoxins, bioburden)
(5) flow rates
(d) define the gender of the connector halves
(1) unique male and female halves
(2) genderless, where each half is identical
(e) define whether the connection is designed for onetime connection or multiple connections
(1) Connectors designed for a one-time connection shall incorporate an irreversible locking mechanism, unless it is specifically designed for aseptic disconnect.
(2) Connectors designed for multiple connections and disconnections shall have the maximum number of connections specified.
(f) provide assembly instructions to ensure proper connection
SC-2.2 Owner/User Responsibilities
The owner/user should
(a) review the manufacturer’s specifications against the service requirements for all applicable process and sterilization conditions
(b) ensure the connection will be performed to a qualified procedure by a properly trained operator to maintain system integrity
SC-3 FLEXIBLE BIOPROCESSCONTAINERS (BAGS)
Flexible bioprocessing containers, also referred to as single-use bags, are available in 2D or 3D format, in different configurations and volume capacities. These bags are used in assemblies for preparation, storage, sampling, transfer, and transport of bioprocess fluids or powders. The bags have connection ports and are used in conjunction with tubing or tubing manifolds to allow for filling, dispensing, sampling, and other process functions. This section provides requirements on materials of construction and qualification.
SC-3.1 Materials
Multilayer films are often used to manufacture single-use bags. The manufacturer should identify the material of construction of all film and tie layers of the bag. For bags intended for process contact, the manufacturer shall identify all materials (e.g., primary materials, tie layers, and additives) that have the potential to adulterate the bag contents.
SC-3.2 Qualifications
The manufacturer shall provide the operating temperature and pressure limits of the single-use bag. The manufacturer shall specify appropriate sterilization methods, including range of exposure, poststerilization shelf life, and other limitations. The manufacturer should provide handling and safe use procedures, including hanging restrictions, filling limitations, and secondary containment recommendations.
SC-4 POLYMERIC HYGIENIC UNIONS
See PM-4.4.