阿斯利康印度工厂EU GMP检查未通过其原料药用于中国工厂制剂生产

albertchen

2015.12.11，阿斯特拉捷利康印度工厂获欧盟警告信
原因是在三轮缺陷回复之后工艺验证和数据完整性问题仍然存在
阿三问题比咱多!
咱不能与阿三看齐啊!

albertchen

CFDA的大手笔，已使得FDA和欧盟官方的动作波澜不惊了

自在飞花轻似梦

普遍存在，需要改变。

工作QQ

CFDA引发的惨案?

albertchen

欧盟官方和FDA已经把国际大公司的印度工厂玩得遍地菊花。

albertchen

工作QQ 发表于 2015-12-12 21:31
CFDA引发的惨案?

CFDA follows FDA and EU Authorities.

HelloWorld

感谢楼主分享！

albertchen

HelloWorld 发表于 2015-12-12 23:09
感谢楼主分享！

syhorchid

很牛的阿三

工作QQ

菊花残满地伤

julia朱玉姣

据EUGDMP数据库， AstraZeneca Pharma India Ltd.在2015年EU GMP检查未通过。
检查方：瑞典官方
检查日期：2015-1-19
产品：原料药TERBUTALINE SULPHATE（硫酸特布他林）
不符合事项：
Nature of non-compliance : The API manufacturing process was not acceptably validated and was not under control after the validation. The concerned batches have been sent to the EEA (Sweden) and to a third country (China). During the inspection, 24 deficiencies were found. None of the deficiencies was critical but 4 were major. The 4 major deficiencies were found in the areas of documentation routines and data integrity (2), design and maintenance (1), validation (1). After three CAPA responses from the company the major deficiency regarding validation still remains.
原料药生产工艺验证不能接受，验证后工艺不受控。相关批次已发往EEA（瑞典）和第三国（中国）。在检查期间，发现24个缺陷，没有关键缺陷，有4个主要缺陷。4个主要缺陷是关于文件记录日常管理和数据完整性（2个），设计和维护（1个），验证（1个）。公司的三个CAPA回复后，还有验证缺陷没有纠正。

Action taken/proposed by the NCA :
Recall of batches already released 已放行产品的召回
Risk assessment: The only API manufactured at the site is Terbutaline sulphate. The API is used for the manufacture of non-sterile and sterile finished products. In total five validation runs were executed between February and November 2014. The first four validation runs failed and included several OOS results, adjustments, test batches and inappropriate root cause analysis. After the fifth validation run the company stated that the process was successfully validated, despite a specification change (exclusion of a melting range) was necessary to approve the validation. After the validation the rejection rate was very high (approximately 40%) and for this reason the company stopped the production in December 2014.
风险评估：该工厂生产的原料药只有硫酸特布他林。原料药用于非无菌和无菌药品生产。2014年2月到11月间总共进行了五轮验证。前四轮均失败，其中有几个OOS结果、调整、检测批次和不恰当的根本原因分析。在第五轮验证后，公司声称工艺已验证成功，但为了批准验证，对质量标准进行了变更（包括一个熔点范围）。在验证完成后，不合格率非常之高（近40%），因此，公司于2014年停止生产。

On 2015-10-30 the company confirmed that a definite root cause has still not been identified and that no further manufacturing of the API is planned for this site. Eight API batches were released from the site in India without any restriction but they were retested and released a second time in Sweden. After this retest, one of the three validation batches was rejected but the validation was still not questioned by the company. According to the company seven batches have been sent to China and used for manufacturing finished products at the AstraZeneca site in Wuxi, China. The finished product (Bricanyl Tablets) has been declared to be intended for the Chinese market only. The issuance of this NCS is not expected to have a negative impact on the supply to the EEA.
在2015年10月30日，公司确认还有一个根本原因没有被识别，在此工厂没有生产更多的原料药。8批原料药在印度工厂没有任任何限制地被放行了，但是在瑞典进行了复测并再次放行。在此次复测后，三个验证批中的一批被判定不合格拒收（译者注：此处疑为原文错误，应该是8批中的1批合格，而不是3批中的1批），但该公司还是没有质疑其验证。根据公司的说法，7批已被发往中国，用于中国无锡的阿斯利康工厂生产制剂。公司声称成品（博利康尼片）只用于中国市场销售。该不符合项的问题被认为对EEA的供应没有不良影响。（译者注：此举甚为恶劣）

Risk Mitigating Actions: -In June 2015 the company was recommended to recall all Terbutaline Sulphate batches not supported by an acceptable validation. The batches have not been recalled but the further use of them has been stopped. All API batches manufactured during the year 2014 are concerned. This includes all batch numbers starting with TAIO and TABO. The O stands for year 2014. -Information about the NCS will be sent to the CFDA. A first information letter about the GMP deficiency was sent from the MPA to the CFDA in July 2015.  
风险降低措施：在2015年6月，公司被建议召回所有由不能接受的验证所支持的硫酸特布他林批次。这些批次没有被召回，但是其进一步使用被停止了。在2014年生产的所有原料药批次均受到影响，其中包括从TAIO和TABO开始的所有批号。0表示2014年。关于NCS的信息将被送达CFDA。在第一封信息函中，关于GMP缺陷已于2015年7月被送达CFDA的MPA。

-The concerned authority in India will be requested to recall the concerned written GMP confirmation.
印度相关政府部门将被要求召回其相关的书面GMP声明。

-Publication of this NCS is expected to prevent the API and finished product from being imported to the EEA from China.
此NCS公布期望能防止原料药和制剂从中国出口至EEA。

-The distribution and destruction records for any remaining API-batches will be followed-up.
所有现存的原料药批次的销售和销毁记录都将进行跟踪。

-It is recommended that the site is not approved in any new or ongoing applications before a re-inspection has confirmed GMP-compliance.
建议在对现场重新检查并确认其符合GMP要求之前，不要再行批准关于此工厂的任何新的或进行中的申报。

工作QQ

感谢朱斑竹分享。

julia朱玉姣

不要紧，慢慢玩，这是我们和阿三的主战场之一，相信我们会赢的

大呆子

真要认真学习一下

Ryan15

这个药很老了，医保品种，销量挺不错，价格比较便宜，主要靠走量

dml8888

感谢娇姐分享！！

dindin619

那个公司那些搞质量的哥们惨了

feige_gd

中国药品研发市场整肃后，期待新的秩序和转机

道路漫长黑暗

拿中国不当干部，这么高的风险CFDA不说引用结果吧，起码也评估下把有风险的制剂召回比较好。

王伟宁

谢谢分享，学习啦