FDA警告信_珠海联邦制药 2018年6月27日

kslam

FDA于2018年6月27日发出警告信给珠海联邦制药股份有限公司(广东省珠海市金湾区三灶镇安基路2428号)。

检查时间为2017年9月11日至15日。


1.未能根据程序充分调查和记录不合格的结果。


2.质量部门未能确保调查和解决关键偏差。


3. 与无菌工艺有关的其他问题。

beiwei5du

OOS Results for Residual Solvent
You initiated investigation P201611001 for an initial OOS result of (b)(4) parts per million (ppm) in your (b)(4)residual solvent test (specification: not more than (b)(4) ppm) for (b)(4) API batch (b)(4). The investigation did not reveal laboratory testing anomalies. You tested another sample preparation three times and obtained results very close to the specification upper limit ((b)(4), and (b)(4) ppm). You invalidated the initial failing result, stating that your statistical analysis showed a significant difference between the original value and the retest results. Your investigation lacked further assessment of the root cause of the failing result.

You released the batch to use as an intermediate in your in-house production of (b)(4) batches of (b)(4) API (batches (b)(4)).

It is not appropriate to use an “outlier test” to invalidate your API test results. Such statistical treatments do not identify the cause of an extreme observation and are only of informational use. In this case, your investigation included multiple retests that were near the upper limit of (b)(4) ppm, similar to the original OOS result.
Furthermore, your OOS investigation procedure, Q0100012.001, was inadequate because it did not adequately address the need to retest the original sample and specify when a new sample should be tested.

We acknowledge receipt of your revised OOS investigation procedure. However, your response is inadequate because it does not meet CGMP. Your response stated that you can use an outlier test in determining whether to “waive the requirement for conducting appropriate laboratory investigation to determine definitive or potential root cause(s) for the atypical result(s).” It is inappropriate for your procedure to permit waiver of this requirement. Your OOS procedure should specify that outlier tests cannot be used for anything other than auxiliary, informational purposes.

Your response also indicated that your firm was retrospectively assessing effects of previously-reported OOS results on your products. However, your response did not provide related records to document your review or summarize findings. It is unclear whether the retrospective review included an evaluation of your use of the statistical outlier test to invalidate OOS results.

这是典型的多次re-testing数据否认OOS数据啊！
outlier test的目的不能用于否定原先的OOS，因为其不能找出根本原因。outlier的目的是仅在于表征数据的特征以辅助此后的决定。
联邦不应该出现这个基本认识错误吧？？

beiwei5du

实验室和生产中都存在数据完整性问题，可能后期不是很好改。谁有483能否提供呢？？？

ztzhang

珠海联邦不是第一次被发警告信了吧。。。

Doitasyoulike

483不可能拿到吧

hlx

这个企业难过了

诗的远方

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mlao

PDF格式的是怎么下载的

小金库

感谢分享