验证主计划和验证计划之间的关联性

In a news item from 19 March 2025, we described deficiencies in microbiological tests of non-sterile products. However, the warning letter in question provides further information: on process validation. What was criticized?

在2025年3月19日的一篇新闻中（内容见文末），我们描述了非无菌产品的微生物检测缺陷。然而，有问题的警告信提供了进一步的信息：关于工艺验证，批评了什么？

The FDA found that although there were requirements in the Validation Master Plan for process validation and hold times, no operating conditions such as bulk hold times, process limits or acceptance criteria for process parameters were specified in the validation protocol itself.

FDA发现，虽然在验证主计划中对工艺验证和保持时间有要求，但在验证方案本身中没有规定操作条件，如批次保持时间、工艺限值或工艺参数的接受标准。

In response, the inspected company submitted an updated validation protocol which, according to the FDA, still failed to address hold times and other details, such as information on sampling and the batch report that is used for the first validation batch. Subsequently, the FDA refers to its process validation guideline and describes the content of the guideline in a short section of the warning letter. 

作为回复，被检查的公司提交了一份更新的验证方案，根据FDA的说法，该方案仍然没有说明保持时间和其他细节，例如取样信息和用于第一个验证批次的批次报告。随后，FDA引用了其工艺验证指南，并在警告信的一小部分中描述了指南的内容。

Another point of criticism was the equipment. Contrary to the intended use, the circulation of the (water) system was stopped when it was not in operation. There was also a lack of monitoring of both chemical and microbiological parameters in accordance with the US Pharmacopoeia (USP). The response of the inspected company to operate the system permanently in the future is not sufficient. The entire system design is still to be assessed and monitoring introduced. In addition, the FDA requires interim measures and an investigation into the impact of the incorrectly validated system on product quality.

另一个批评点是设备。与预期用途相反，（水）系统在不运行时停止循环。也缺乏根据美国药典（USP）对化学和微生物参数的监测。被检查的公司对未来永久运行该系统的回复是不够的。整个系统的设计还有待评估和监测。此外，FDA要求采取临时措施并调查错误验证系统对产品质量的影响