PIC/S GMP对CCIT相关内容的最新要求汇总

以下是PIC/S GMP对CCIT的最新要求汇总，黄色突出显示的内容为更新内容。后续众林将对这些要求进行针对性地解读。

8.22 Where final containers are closed by fusion, e.g. Blow-Fill-Seal (BFS), Form-Fill-Seal (FFS), Small and Large Volume Parenteral (SVP & LVP) bags, glass or plastic ampoules, the critical parameters and variables that affect seal integrity should be evaluated, determined, effectively controlled and monitored during operations. Glass ampoules, BFS units and small volume containers (≤100 ml) closed by fusion should be subject to 100% integrity testing using validated methods. For large volume containers (>100 ml) closed by fusion, reduced sampling may be acceptable where scientifically justified and based on data demonstrating the consistency of the existing process, and a high level of process control. It should be noted that visual inspection is not considered as an acceptable integrity test method.如果最终容器采用熔封方式进行密封的，例如：BFS，FFS，小容量和大容量袋，玻璃或塑料安瓿，在操作过程中，影响密封完整性的关键参数和影响因素应当被评估、确定、有效控制和监测。玻璃安瓿、BFS和小容量容器（≤100mL）采用熔封进行密封的应当遭受100%完整性测试采用经验证的方法。对于大容量容器（＞100mL）采用熔封进行密封的，如果是科学合理的且基于数据证明现有工艺的一致性和高水平的过程控制，那么减少的取样量可能是可以接受的。应当注意的是，视觉检查不被认为是可接受的完整性测试方法。

8.23 Samples of products using systems other than fusion should be taken and checked for integrity using validated methods. The frequency of testing should be based on the knowledge and experience of the container and closure systems being used. A scientifically justified sampling plan should be used. The sample size should be based on information such as supplier management, packaging component specifications and process knowledge.采用熔封以外系统的产品样品应当被采集和采用经验证的方法检查完整性。测试频率应当基于所使用容器和密封系统的知识和经验。科学合理的取样计划应当被采用。样品量应当基于信息，例如：供应商管理、包装组件规格和工艺知识。

8.24 Containers sealed under vacuum should be tested for maintenance of vacuum after an appropriate pre-determined period prior to certification /release and during shelf life.在真空下密封的容器应当在认证/放行前和货架期过程中的合适的预定时间被测试真空度的保持。

8.25 The container closure integrity validation should take into consideration any transportation or shipping requirements that may negatively impact the integrity of the container (e.g. by decompression or extreme temperatures). 容器密封完整性验证应当考虑可能会负面影响容器完整性的任何运输需求（例如：减压或极端温度）。

8.28 Where capping of aseptically filled sterile product is conducted as a clean process with grade A air supply protection, vials with missing or displaced stoppers should be rejected prior to capping. Appropriately qualified, automated methods for stopper height detection should be in place.如果无菌灌装无菌产品的轧盖是在具有A级空气保护的洁净工艺下执行的，在轧盖前应当剔除使用缺失或胶塞移位的西林瓶。应采用适当合格的胶塞高度自动检测方法。

8.137 SUS should be designed to maintain integrity throughout processing under the intended operational conditions. Attention to the structural integrity of the single use components is necessary where these may be exposed to more extreme conditions (e.g. freezing and thawing processes) either during routine processing or transportation. This should include verification that intrinsic sterile connection devices (both heat sealed and mechanically sealed) remain integral under these conditions.SUS的设计应能在预期操作条件和持续时间内保持完整性。在日常加工或运输过程可能出现暴露于极端条件（例如冻融过程）的情况，有必要注意一次性组件的结构完整性。这应包括确认固有无菌连接装置（热密封和机械密封）在这些条件下保持完整。

4.21 The materials used for glove systems (for both isolators and RABS), should be demonstrated to have appropriate mechanical and chemical resistance. The frequency of glove replacement should be defined within the CCS.

i. Isolators:

a. For isolators, leak testing of the glove system should be performed using a methodology demonstrated to be suitable for the task and criticality. The testing should be performed at defined intervals. Generally glove integrity testing should be performed at a minimum

frequency of the beginning and end of each batch or campaign. Additional glove integrity testing may be necessary depending on the validated campaign length.Glove integrity monitoring should include a visual inspection associated with each use and following any manipulation that may affect the integrity of the system. For manual aseptic processing activities where single unit or small batch sizes are produced, the frequency of integrity verification may be based on other criteria, such as the beginning and end of each manufacturing session.

b. Integrity / leak testing of isolator systems should be performed at defined intervals.

用于手套系统（包括隔离器和RABS）的材料，应证明其具有适当的机械和化学耐受性。手套更换频率应在CCS中明确规定。

i.隔离器：

a. 对于隔离器，应采用已被证明适合该任务和关键性的方法对手套系统进行泄漏测试。测试应按规定间隔进行。通常，手套完整性测试的测试频率应至少在每批或每轮的开始和结束时进行测试。根据验证的频率时长，可能需要进行额外的手套完整性测试。手套完整性监测应包括每次使用以及任何可能影响系统完整性的操作后的目视检查。对于生产单个单元或小批量产品的手动无菌处理活动，完整性验证的频率可能基于其他标准，如每个制造环节的开始和结束。

b. 隔离系统的完整性/泄漏测试应按规定间隔进行。