ECA新闻20150506：由于包装密闭完整性不充分引发的警告信

ECA新闻20150506：由于包装密闭完整性不充分引发的警告信

GMP News
06/05/2015

Warning letter due to insufficient container-/closure integrity

由于包装密闭完整性不充分引发的警告信

A site of the company Hospira in Italy received a comprehensive FDA Warning Letter at the end of March which criticises among others defects concerning the closure of vials and the related possible microbiological contaminations. Main problem for the FDA is that operators carried out operations over the vials that pose a microbiological risk for the product. Furthermore, the company did not perform smoke studies to demonstrate unidirectional airflow as protection for the product. This is aggravated by the fact that the FDA has criticised this already in 2013 and nothing has changed. According to the FDA this means that the sterility of the products produced since then is questioned. The FDA is clearly missing a video demonstrating the airflow and thus the protection of the product as well as a detailed assessment of the filling equipment design.

HOSPIRA公司的一个意大利工厂在3月底收到FDA警告信，其中批评了关于西林瓶的密闭问题，以及疑似微生物污染问题。FDA指出的主要问题是操作人员在对西林瓶操作过程中，对产品引入的微生物风险。另外，公司没有实施烟雾测试来证明非直流气流对产品的保护作用。上述问题已在2013年被FDA批评过，但现在还是一样的，并没有改变。根据FDA的说法，这表示从那时起所生产的产品的无菌性即受到质疑。FDA清楚指出缺失证明气流的录像，因此无法证明对产品的保证和对灌装设备设计的详细评估。

The FDA also criticised the approach as concerns the media fill, in other words the proof that the manufacturing process guarantees sufficient sterility. For example, several times numerous vials were rejected during the media fill and not assessed microbiologically (incubated) without sufficient explanation.

FDA还批评了其培养基灌装的方法，换句话说就是对生产工艺保证充分无菌性的证明。例如，有几次大量的西林瓶在培养基灌装过程中发现不合格，但并没有从微生物（培养后的）角度进行评估，没有充分的解释。

Another item in the Warning letter refers to the complaints processing that is handled inadequately according to the FDA. 103 complaints for discoloration of a sterile product have not been investigated adequately, for example.

警告信中的另一项内容是投诉处理不充分。例如，有103例关于无菌产品脱色的投诉未进行充分的调查。

Furthermore, the computerized systems in the QC laboratory were criticised because of insufficiency of the data integrity. The HPLC and GC systems did not have adequate controls to prevent the deletion or alteration of raw data files.

另外，在QC化验室的计算机系统也被批评，因为数据完整性不充分。HPLC和GC系统未进行充分控制以防止原始数据文件的删除和篡改。

The detailed FDA findings can be seen in the Warning Letter.

详细信息参见FDA官网警告信。