一家中国公司EU GMP检查失败

julia朱玉姣

公司名称：Dongying TiandongPharmaceutical Co., Ltd.  东营天东

检查日期：2015-12-9

检查地址：No. 1236, Nan-erRoad, Dongying City, Shandong Provice, China

检查方：法国药监

产品：原料药ENOXAPARIN SODIUM依诺肝素钠

原料药HEPARIN SODIUM肝素钠

Nature of non-compliance : 不符合情况

Overall, 10 deficiencieswere observed during the inspection, 2 Critical and 3 Major deficiencies:

检查期间总共发现10个缺陷，其中2个关键缺陷，3个主要缺陷：

[Critical 1] PCR results ofCrude Heparin showing the presence of ruminant DNA received from approvedsuppliers were manipulated. There was no evidence that the samples retestedcame from the same batch tested initially;

【关键缺陷1】肝素粗品PCR结果显示从批准的供应商处接收的反刍动物类DNA是伪造的。没有证据证明复测样品与初测样品来自同一批次；

[Critical 2] The qualitysystem implemented by the company for ensuring the full traceability of crudeHeparin was identified as very weak : e.g., the traceability fromslaughterhouses/abattoirs was not available and not assessed during the auditsof the suppliers (lack of supporting documents for the received lots) ;

【关键缺陷2】公司执行的确保肝素粗品可追溯性的质量体系很差，例如，从屠宰场开始的可追溯性没有，对供应商审计期间并没有进行评估（接收批次缺乏支持性文件）；

[Major 1] Misunderstandingof the basic GMP principles for handling of out of specification (OOS) resultsand deviations (e.g., 7 batches of crude Heparin received in 2014 and 2015 wereobtained OOS for potency and used for the manufacturing of finished APIs withoutany OOS investigation);

【主要缺陷1】对处理OOS结果和偏差的基本GMP原则有误解（例如，2014年至2015年接收到的7批肝素粗品效价结果为OOS，没有进行任何OOS调查即用于原料药成品的生产）；

[Major 2] The evaluation ofthe new suppliers of crude Heparin was deficient: the procedure was notfollowed, no delivery documents were available, the testing was notsystematically recorded in the equipment logbook, the samples from approvedsuppliers were contaminated during the sampling operation, etc. ;

【主要缺陷2】肝素粗品新供应商的评估有缺陷：未遵守程序，没有送货资料，检测仪器日志没有系统记录检测，从批准的供应商处送来的样品在取样操作中受到污染等。

[Major 3] The assessment of1 H NMR spectrum (Heparin Sodium) and 13 C NMR (Enoxaparin Sodium) used foridentification test were deficient (e.g., the presence of an additional peak atthe C13 NMR obtained by a subcontracted laboratory was not identified andinvestigated)

【主要缺陷3】用于鉴别测试的1H NMR图（肝素钠）和13C NMR图（依诺肝素钠）评估有缺陷（例如，在合同化验室做的C13 NMR图中有多余的峰出现，没有鉴别没有调查）。

措施：

1.   吊销现有EU GMP证书

2.   要求上市许可提交变更

3.   已放行批准要求召回

4.   禁止销售

5.   搁置CEP2005-258

Actiontaken/proposed by the NCA :

Withdrawal,of current valid GMP certificate No. GIF-IW-N-4022/68/13
Using QRMprinciples, consideration of withdrawal of current valid EU GMP certificateissued by the Main Pharmaceutical Inspectorate of Poland (GIF-IW-N-4022/68/13).

RequestedVariation of the marketing authorisation(s)
Using QRMprinciples, the removal of the site from MAs should be considered.

Recallof batches already released
Considerationof a recall of product should be given due to the critical findings observed.Using QRM principles, National supply situation and clinical requirementsshould be taken into account when making this decision.

Prohibitionof supply
The sitehas been issued a statement of non compliance and should not be named on anymarketing authorisations whilst this statement remains in place.

Suspensionor voiding of CEP (action to be taken by EDQM)
Suspensionof CEP 2005-258 (Enoxaparin sodium).

小杨7788

首次检查失败，多累几点经验，以后回好的

大呆子

首次申报检查确实有一定困难，失败是成功的妈妈，继续努力

syhorchid

可惜了

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qqqq111

只是一次审计而已，没什么大不了的。跌倒了再爬起来照样是英雄！