FDA警告信：可见颗粒和目视检查

17.05.2017

FDA Warning Letter: Visible Particles and Visual InspectionFDA警告信：可见颗粒和目视检查

During an FDA inspection at the Kansas-based company Hospira in mid 2016, the authority encountered several GMP violations which resulted in a Warning Letter.

在2016年年中FDA对HOSPIRA堪萨斯工厂的一次检查中，官方发现了几个严重的GMP问题，导致给该公司签发了一封警告信。

The GMP deficiencies concerning visual inspection as well as the handling of distributed batches which were contaminated with particles even lead to the assertion that the company's process of manufacturing injectable products was out of control. During the inspection, the FDA found numerous internal investigations concerning particulate matter in batches of parenteral products. In regards to visible particles in sterile lots of injectables, the FDA speaks of a "significant loss of control in the manufacturing process".

关于目视检查和已销售受颗粒污染批次处理的GMP缺陷甚至使得官方认为该公司的注射剂生产工艺不受控制。在检查期间，FDA发现大量关于注射剂中颗粒物的内部调查。在无菌注射剂批次可见颗粒方面，FDA说“生产工艺严重失控”。

A complaint was made for a batch because of visible particles, for example. This was confirmed; there were pieces of cardboard found in the respective retain samples. They were put down to the handling of vial stoppers, however the investigation was closed without a proper evaluation or corrective measures being taken. Even when another batch containing the same kind of particles was complained about at a later date, no further actions were instigated.

例如，该公司收到关于可见颗粒的一个批次投诉，投诉被确认。在对应的留样中发现了纸箱碎片。这些纸箱在安瓿瓶塞的处理过程中掉了进去，但调查没有进行适当评估，也没有采取纠正措施就关闭了，甚至还有另一个批次也有同类的颗粒物，也在迟些时候收到投诉，但并没有启动进一步措施。

The batch the cardboard particles had originally been found in hadn't been called back until four months after the complaint. An investigation confirmed this, 190 retain samples of the batch were also found contaminated. A subsequent investigation was found insufficient by the FDA. In their report, the FDA criticises the lacking scientific rationale for the chosen number of vials to be tested, as well as the missing description of the examination method.

最早发现纸箱颗粒的那个批次直到收到4次投诉之后才被召回。调查显示，该批次的190个留样同样发现有受到污染，而FDA还发现之后的调查也是不充分的。在报告中，FDA批评了该公司在选择测试安瓿瓶数量时缺乏科学合理性，也没有检查方法的描述。

The batch was distributed even though the found particulate matter had been detected in other batches before. It was claimed that the presence of particles was "intrinsic to the manufacturing process". The FDA further criticises the lack of a specific identification of the particles in question, that there was no investigation into other potentially affected batches and the missing corrective actions.

虽然之前在其它批次里已经发现了颗粒物，但该批次还是销售了。FDA认为颗粒物的出现是“因为生产工艺先天缺陷”。FDA进一步批评了公司缺乏对所讨论的颗粒物的具体识别，没有调查其它可能受影响批次，以及纠正措施缺失。

The visual inspection, semi- as well as fully-automatic, was also objected to by the FDA; there were no warning and action limits. The procedures for visual inspection instruct operators to ignore defect limits following changes to the inspection process.

半自动以及全自动目视检查都受到FDA的反对，其中没有警示限和行动限。在检查程序修订之后，目视检查程序要求操作人员忽略缺陷限制。

Source: FDA Warning Letter to Hospira Inc. from February 14, 2017

来源：2017年2月14日FDA对HOSPIRA公司的警告信。