【ICH之窗40】中间过程中的IPC不合格进行的重复操作是否算是返工？？

10. Q. If in-process nonconformance results are not documented as such prior to continuing the process, how will you know that a change is indeed required in the process? How many chances at reprocessing do you get to conform to specs prior to rejection of the lot?

问：如果中控中不符合的结果在继续生产前没有被记录，你如何知道在工艺中实际上是否需要变更？要返工多少次才可以在报废该批物料前获得符合质量标准的产品？

The purpose of the in-process test and the specification is to monitor the process and to make adjustments to the process.Take for example, a hypothetical case in which you might take a sample to measure pH against an in-process pH specification and it doesn't meet your in-process pH specification. Do you have to stop the process at that point and try to determine why it failed pH in the first place? Not necessarily, if it failed pH, it failed pH. It needs to be adjusted until the proper pH is achieved. This is not reprocessing, it is processing to a specification. Since this is not reprocessing, you would continue to monitor and adjust the pH as necessary in order to meet the specification for the Intermediate or API.

答：中控检验和中控质量标准的目的都是为了监控工艺而对工艺进行调整。例如，假设你可能取样进行pH值检测和你的中控pH值标准进行比较，它没有达到你中控pH值标准。你是不是要停止反应试图调查为什么pH值没有达到要求吗？不需要，如果你的pH值没有达到标准，就是没有达到。必须进行调整，直到pH值达到标准为止。这不是返工，是工艺操作到质量标准的要求。因为这不是返工，所以只要需要，你就可以继续监控或是调整pH来满足中间体或原料药的质量标准。

Regarding reprocess a batch, it actually makes little scientific sense to say you need to limit the number of times you can do it, at least from a product or material perspective. Generally, where synthetic chemistry is involved, reprocessing improves material quality sinceyou are doing multiple purifications. For someone to try to scientifically object to reprocessing something more than three times, or 10 times, or 100 times,makes no sense. Certainly for biological systems, further manipulations could lead to product quality degradation and multiple reprocessing could be undesirable.

对于一个批次的返工，要求你限制返工的次数，至少从产品或物料的角度来看没有多少科学的根据。一般来说，在合成化学中，返工将提高物料的质量因为你做了多次的纯化。一些人试图科学的反对返工3次，10次或是100次是没有意义的。当然，在生物系统中，多次的操作可能导致产品质量的降解，所以不希望返工。

The question becomes what knowledge is lacking that causes repeated reprocessing. Why this is potentially important it is not immediately nor should it be a GMP issue. It is an important economic issue.

问题就变成了缺乏什么知识将导致反复返工。为什么这个问题潜在重要不是因为它是GMP的问题，而是重要的经济问题。

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