药物研发至2016中国和印度原料药生产商欺诈和主要GMP违规
20160302 ECA新闻：中国和印度原料药生产商欺诈和主要GMP违规
GMP News
02/03/2016
Fraud and Major GMP Violations at API Manufacturers in India and China 中国和印度原料药生产商欺诈和主要GMP违规
The Non-Compliance reports in the Eudra-GMDP database of the European Medicines Agency (EMA)are - to a certain extent - the European counterpart of FDA's Warning Letters. These reports are first drawn up then put in the database after a GMP inspection performed by a representative of the European national competent authorities at an API or medicinal product manufacturer showed serious GMP deficiencies. Similar to Warning Letters, the consequences of Non-Compliance reports are for the companies concerned critical, e.g. withdrawal of the GMP certificate or product recalls. EMA的欧盟GMDP数据库里的不符合报告是----某种程度上----欧洲版的FDA 警告信。这些报告在欧洲国家药监局对原料药或制剂生产商的GMP检查中发现严重GMP缺陷后先写就，然后放进数据库。与警告信相似，不符合报告的对于公司来说是关键的，例如，吊销GMP证书或召回产品。
Two Non-Compliance reports issued at the end of last year concerned API production sites in China and India.
中国和印度有2份不符合报告在去年年底公布。
Regarding the Chinese manufacturer "Minsheng Group Shaoxing Pharmaceutical Co. Ltd", GMP inspectors from the French competent authority found 2 critical and 4 "major" deficiencies. Those deficiencies are summarised below:
关于中国的生产商“民生集团绍兴药业有限公司”，来自法国药监的GMP检查员发现2个关键4个主要缺陷。这些缺陷总结如下：
?Falsification of source of starting materials: the starting materials supposed to have been manufactured in-house actually came from an
external non GMP-compliant supplier and have been repackaged and
relabelled accordingly (critical deficiency).
?原料药来源做假：起始物料应该是公司内部自己生产的，而实际是来自外部非GMP符合的供应商，并且进行了相应的重新包装和重新标签（关键缺陷）
?The API manufactured according to the Chinese Pharmacopoeia was wrongly and intentionally released as USP quality; there was no
traceability of the testing activities (critical deficiency).
?根据中国药典生产的原料药错误地有意作为USP质量放行，没有检测活动可供追溯。（关键缺陷）
?The cleaning and maintenance operations of the manufacturing line were insufficient (major).
?生产线的清洁和维护不充分（主要缺陷）
?Deficient equipment design (pipelines); non-compliant transfer of the intermediate solution using nitrogen; non-compliant change
management with regard to equipment (major).
?设备设计有缺陷（管线）、中间体溶液使用氮气传送不合规、设备变更管理不合规（主要缺陷）
?Hoses were lying on a dirty floor of an area not mentioned in the general layout of the site. Those hoses were unidentified and their cleaning
status was unclear (major).
?软管放在脏的地面上，该区域在工厂总平图上没有提到。这些软管没有标识，其清洁状态不清楚（主要缺陷）
?Audit trail function in the chromatographic system was deactivated; there was no procedure in place for audit trail (major).
?色谱系统的审计追踪功能没有激活，没有审计追踪程序（主要缺陷）
By the way, the inspection of the Chinese manufacturer performed by the French authority was part of the prequalification programme of the WHO which means that it had been initiated by the manufacturer himself within the framework of his application for the inclusion of his products in the list of prequalified pharmaceutical APIs of the WHO.
顺便说一下，法国药监对中国生产商的检查是WHO预确认程序的一部分，这表示该检查是由生产商自己激活的，意在将其产品包括在WHO的预确认原料药清单上。
Secondly, the inspection of the Indian company "AstraZeneca Pharma India Ltd." was carried our by inspectors of the Swedish competent authority. The GMP deviations observed are summarised below:
第二个是由瑞典药监对印度公司“阿斯利康药业印度公司”的检查。发现的GMP 偏差总结如下：
?The manufacturing process of the API was not sufficiently validated (major).
?原料药生产工艺未经过充分验证（主要缺陷）
?The documentation routine was not GMP-compliant (major).
?文件记录常规做法不合规（主要缺陷）
?Data integrity wasn't assured (major).
?未保证数据完整性（主要缺陷）
?Design and maintenance of the equipment was insufficient (major).
?设备的设计和维护不充分（主要缺陷）
The GMP deficiencies discovered in both production sites concern essential GMP requirements for the manufacture of APIs as laid down in the ICH Q7 Guideline and in the EG GMP Guide Part II since already 16 years. Unfortunately, GMP inspectors from European authorities, the EDQM and the FDA are - again and again - confronted to such GMP deficiencies, mainly in Indian and Chinese manufacturing sites.
在两个生产工厂里发现的GMP缺陷关系到基本的GMP要求，是ICH Q7指南和EU GMP指南第二部分16年之前就制订的原料药生产要求。不幸的是，欧洲药监GMP检查员，EDQM和FDA一而再，再而三地面对这样的GMP缺陷，主要是在印度和中国生产工厂。