PDA TR01 湿热灭菌程序的验证：灭菌程序的设计、开发、确认以及日常控制

关山难越

在PDA TR01的5.5.4 典型装载法 中“就最小装量而言，在确认时，可能只需要做腔室的最大加热和/或空气去除的挑战性试验。 ”和“对没有固定的加热及冷却速率/次数的灭菌程序而言， 最低装量通常需要进行低热量输入的确认试验 ”，这两句话怎么理解，麻烦大神解释一下，谢谢了

光风霁月

5.5.4 Load Bracketing 负载分组法（此处Bracketing中文翻译为括号法（分组法），关于这个专有名词的英文解释见下）
An approach for bracketing porous/hard goods loads requires the use of items that represent the greatest heat-up (mass) and/or air-removal challenges in the minimum and maximum load qualification. For the minimum load, the greatest heat-up and/or air-removal item(s) may be the only item(s) present in the chamber during qualification.
多孔/固体物品负载分组法要求使用可以代表最小和最大负载确认的最大加热（质量）和或空气移除挑战的物品。对于最小装载，确认过程中腔室可能只有最大加热和或空气移除物品。

In the event that load size is expected to vary for operational flexibility, minimum and maximum loads should be identified and qualified. At a minimum, three consecutive acceptable biological qualification runs should be achieved for maximum loads in each sterilizer. For sterilization cycles that do not have fixed heat-up and cool-down rates/times, the minimum load typically receives lower thermal heat input than maximum loads and should also be challenged. Where risk has been assessed and deemed to be acceptable, the number for replicate runs may be reduced.
在负载量因运行灵活性而期望不断变化的情况下，最小和最大装载必须确定且确认。每个灭菌器的最大装载最少完成连续3次可接受的生物确认测试。对于没有固定加热和冷却速率/次数的灭菌程序，相较于最大装载，最小装载通常吸收更低的热输入，这也应该进行挑战。当风险已做评估且被认为是可接受的，则可减少重复运行的次数。

In the event that load size is expected to vary for operational flexibility, minimum and maximum loads should be identified and qualified.在负载量因运行灵活性而期望不断变化的情况下，最小和最大装载必须确定且确认。最小装载不是一定要做的，如果你们日常是固定装载灭菌，且相关SOP也规定了规定装载，每次灭菌物品进行记录且与SOP中固定装载描述一致，可以不做最小装载确认。如果你们是做CDMO或者你们有因为运行灵活性装载量变化的需求，你们可以做最小装载。但说实话，国内药企中灭菌柜确认做这么细致的屈指可数。
Note:

Bracketing approach 括号法（分组法）

A science and risk based validation approach such that only batches on the extremes of certain predetermined and justified design factors, e.g. strength, batch size and/or pack size, are tested during process validation. The design assumes that validation of any intermediate levels is represented by validation of the extremes. Where a range of strengths is to be validated, bracketing could be applicable if the strengths are identical or very closed related in composition, e.g. for a tablet range made with different compression weights of a similar basic granulation or a capsule range made by filling different plug fill weights of the same basic composition into different size capsule shells. Bracketing can be applied to different container sizes or different fills in the same container closure system.

一种基于科学与风险的验证方法，其只分批处理工艺验证过程中考查的某些预先确定且合理的设计因素的极端条件（如剂量，批量和或包装规格）。该设计假定任何中间情况可由极端情况的验证来代表。如果要验证的是一个范围的剂量，这些剂量在组成上相同或非常相近，例如，基本制粒过程相似但片重不同的一系列片剂，或基本组成相同但将不同填充量装填到不同规格的一系列胶囊，就可以应用括号法（分组法）。括号法（分组法）可以应用于不同容量规格或相同容器密闭系统的不同填充物品。

Sanky

光风霁月 发表于 2021-1-5 16:10
5.5.4 Load Bracketing 负载分组法（此处Bracketing中文翻译为括号法（分组法），关于这个专有名词的英文 ...

求中英文对照版FDATR01

juanzi123

谢谢分享！向无私奉献者致敬！