新加坡药品生商由于无菌包装泄露引发FDA警告信

31.05.2017

Warning Letter to Pharmaceutical Manufacturer in Singapore due to Leaking Sterile Containers新加坡药品生商由于无菌包装泄露引发FDA警告信

A manufacturer of sterile ophthalmics (preparations for use in the eye) has recently received a Warning Letter from the US FDA. Container leaks and the associated risk of microbial contamination were the main points of criticism.

一家无菌眼膏（眼用制剂）生产商最近收到了美国FDA签发的警告信。所批评的主要问题是容器泄露以及微生物污染相关风险。

During the inspection, the FDA had noticed numerous documented cases of leaking containers in the production area. The company changed process parameters in these cases and afterwards released the batches concerned. This led to market reclamations because of leaking containers. According to the FDA, leaking containers were also found in media fills. The FDA therefore questions the manufacturer's ability to safely produce sterile medicinal products.

在检查期间，FDA注意到生产区域里文件记录的大量容器泄露案例。公司在这些案例中改变了工艺参数，之后放行了相关的批次。这导致上市后由于容器泄露而引发产品回收。据FDA所言，在培养基灌装中也发现了泄露的容器。FDA因此质疑生产商安全生产无菌药品的能力。

The missing validation of production processes and the fact that the equipment had not been qualified are at least as serious. Furthermore, the FDA criticizes the missing root cause analysis of issues such as the leaks described above. When the findings of such cases are not considered when it comes to process design and validation, a continuing state of control is not possible according to the FDA.

生产工艺验证缺失，以及设备未经确认已经是严重缺陷；而FDA更进一步批评了对如上述泄露问题进行根本原因分析的缺失。FDA认为，如果在工艺设计和验证时未考虑此类问题，则不可能进行持续状态的控制。

Parts of the container/closure system are obtained from an external supplier. The FDA criticizes that the information on the supplier certificate were not verified. Moreover, there was no rationale for acceptance criteria. According to the FDA, this can lead to leaks in the packaging and result in loss of sterility.

容器/密闭系统的部件是来自于外部供应商的。FDA批评了供应商证书上的信息未经验证的问题。另外，对于可接受标准也不具有合理性。FDA认为，这可能会导致包装泄露，从而引发无菌性的丧失。

Another issue criticized by the FDA is the fact that the stability studies for at least two products were missing. Without stability studies, no reliable shelf life can be determined. The container tightness as well is addressed again, as it must be included in the stability study.

FDA批评的另一个问题是稳定性试验的问题，至少有2个产品的稳定性试验缺失。如果没有稳定性试验，则无法确定可靠的货架期。容器密闭性同样也提到了，因为这是必须包括在稳定性试验里的。

The FDA suggests that the manufacturer read FDA's Aseptic Guide and strongly recommends to hire an external consultant in order to become familiar with GMP requirements and compliance.

FDA建议生产商阅读FDA的无菌指南，并且强烈建议其聘请外部顾问以熟悉GMP要求和符合性。

Get more details in the Warning Letter of the FDA to Opto-Pharm Pte Ltd..

更多细节参见官网。