进入A/B级洁净区前的物料和设备的转移验证如何进行？

2023-12-08

前段时间瑞士药监局会发布了一份关于解释附录1的文件，该文件可以使用户更容易理解新的附录1。

该技术解释侧重于2022年修订版EU GMP附录1的一些最重要的主要变化，也涵盖了该指南以前版本中已经包含的、反复引起问题的方面。该技术解释旨在反映瑞士药监局对这些主题的一般意见，并在无菌药品生产商检查期间提供支持。

其中第3问如下：

Paragraph 4.12, point ii, states that only materials and equipment that are on an approved list and that have been assessed during validations of the transfer process, should be transferred into grade A or grade B areas via airlocks or pass-through hatches. What does “validation of the transfer process” mean, for example for the material transfer into an isolator?

第4.12段第ii点规定，只有在批准清单上并在转移过程验证中经过评估的物料和设备，才能通过气闸或传递窗转移到A级或B级区域。“转移过程的验证”是什么意思，例如物料转移到隔离器?

As mentioned in paragraph 4.10 of Annex 1, the transfer of materials, equipment or components into and out of a cleanroom (incl. the critical zone within a grade A environment), represents one of the greatest potential sources and risks of contamination.

如附录1第4.10段所述，进出洁净室(包括A级环境中的关键区域)的物料、设备或组分的转移是最大的潜在污染源和污染风险之一。

In order to minimise such risks, great care must be taken in particular when defining the technical and procedural measures associated with the transfer of materials/equipment into an aseptic processing area. Only in relatively rare cases it is possible to bring materials into an isolator before it is sealed and bio-decontaminate them together with the isolator using a validated VHP treatment (only possible for small batches and if materials are resistant to VHP). In the majority of cases, however, it is necessary to transfer materials to an isolator that has already been decontaminated. For this, all materials must first be sterilised and then moved through the physical barrier of the isolator in such a way that the sterility of the goods and the integrity of the isolator are maintained. Regardless of the technology used (e.g., usage of double-door sterilisers upstream of the isolator, use of transfer isolators or of rapid transfer port technology), the entire transfer process must be considered within detailed risk analysis and be part of the overall contamination control strategy. In addition, appropriate control mechanisms must be defined to monitor the maintenance of the integrity and functionality of the systems (e.g., measurement of differential pressure and control of door interlocks between adjacent zones of the transfer system). The technical solutions must be covered by appropriate equipment/system qualifications (incl. Smoke studies if applicable) and sterilisation validations and the suitability of the entire transfer process must be verified through APS (validations and also regular APS). Appropriate qualification measures and APS must also be used to demonstrate that the egress of materials from the isolator does not affect the maintenance of the grade A zone requirements. The arrangement of the installations, the processes carried out in it and the material movements must also be considered when defining the points to be sampled during PQ activities or during routine or event based environmental monitoring.

为了最大限度地降低此类风险，在确定与将物料/设备转移到无菌加工区域相关的技术和程序措施时，必须非常小心。只有在相对罕见的情况下，才有可能在密封之前将物料带入隔离器，并使用经过验证的VHP处理将其与隔离器一起进行生物净化(仅适用于小批量并且材料耐VHP)。然而，在大多数情况下，有必要将物料转移到已经被净化的隔离器中。为此，必须首先对所有物料进行灭菌，然后通过隔离器的物理屏障，以保持货物的无菌性和隔离器的完整性。无论使用何种技术(例如，在隔离器上游使用双门灭菌器，使用转移隔离器或快速转移端口技术)，必须在详细的风险分析中考虑整个转移过程，并将其作为整体污染控制策略的一部分。此外，必须确定适当的控制机制，以监测系统的完整性和功能的维护(例如，测量压差和控制传送系统相邻区域之间的门互锁)。技术解决方案必须包含适当的设备/系统确认(包括烟雾研究，如果适用)和灭菌验证，整个转移过程的适用性必须通过APS(验证和常规APS)进行验证。还必须使用适当的鉴定措施和APS来证明从隔离器流出的物料不影响A级区域要求的维护。在确定PQ活动或常规或基于事件的环境监测期间的采样点时，还必须考虑安装的安排、在其中进行的工艺和物料的移动。

点击“此处”可以查看原文PDF文件，文件名为“I-SMI.TI.25e Interpretation of GMP Annex 1 2022 (Rev. 1) (PDF, 336 kB, 31.10.2023)”

撰稿人 | 心作流云

责任编辑 | 胡静

审核人 | 何发