印度POLYDRUG未通过EUGMP检查被搁置全部7张CEP证书

julia朱玉姣

EUGDMP数据库增加新的不符合信息

受检公司：印度 POLYDRUG LABORATORIES PVT. LTD.

检查日期：2015-3-18

官方：斯洛文尼亚

不符合事项：

共发现17个缺陷，其中有5个为主要缺陷，包括以下方面

1.      故意不把客户投诉记录在正式登记本里

2.      质量文件存放在非受控区域，该区域有QC、QA、维保和生产人员

3.      纸质文件管理有缺陷

4.      计算机化系统管理有缺陷

5.      原料药送外磨微粉但没有说明交叉污染的风险

上述这些主要缺陷合起来代表一个关键缺陷，导致对患者的潜在风险。

要采取的措施：

上市许可持有人要提交变更更换原料药供应商

EDQM要搁置或吊销CEP，所有原料药的CEP均被吊销：

CEP2009-112(三氯叔丁醇半水合物)

CEP2009-152(酒石酸美托洛尔)

CEP2009-170(琥珀酸美托洛尔)

CEP2010-147（富马酸铁）

CEP2010-247(呋康唑)

CEP2011-304(酒石酸美托洛尔)

CEP2011-312(琥珀酸美托洛尔)

The manufacturer : POLYDRUGLABORATORIES PVT. LTD.

Site address :

Plot No. 37,  Anand Nagar, M.I.D.C., Ambernath (East), Maharashtra, IN - 421 506, India

Nature of non-compliance : Overall,17 deficiencies were found, of which 5 Major consisting in: - Customercomplaints deliberately unregistered in the official logbook - Storage ofquality documents in an uncontrolled location, involving staff from QC, QA,maintenance and production - Deficient management of paper documents -Deficient management of the computerised system - Failure to address risks ofcross contamination for APIs sent out to micronisation subcontractor. Thecombination of these major deficiencies represents a critical deficiencyleading to a potential risk for the patient.

Action taken/proposed by theNCA :

Requested Variation of the marketing authorisation(s)
change of API supplier

Suspension or voiding of CEP (action to be taken byEDQM)
All CEPs have been suspended: CEP 2009-112 (Chlorobutanol hemihydrate), CEP2009-152 (Metoprolol tartarate), CEP 2009-170 (Metoprolol Succinate), CEP2010-147 (Ferrous fumarate), CEP 2010-247 (Fluconazole), CEP 2011-304(Metoprolol tartarate), CEP 2011-312 (Metoprolol Succinate)

syhorchid

嘿嘿，这下够印度阿三喝一壶的。

北重楼

这个够厉害呀

beiwei5du

CEP suspend,withdraw和void之间有什么区别呢？？

beiwei5du

请问一下
1、EudraGMDP Non-Compliance Report 中都采取Part 1，Part 2, Part 3形式，主要是指什么呢(一层一层细化？？)那么在联邦制药中part2中提及的是Non-sterile products,而在part 3 都是提及的是aseptic manufacturing operation??
2、restricted GMP Certificate是指什么意思呢？？
3、 Directive 2001/83/EC as amended ， Directive 2001/82/EC as amended 后跟一个as amended是不是指最新版的意思？？

julia朱玉姣

beiwei5du 发表于 2015-6-21 22:20
CEP suspend,withdraw和void之间有什么区别呢？？

CEP suspend指搁置，即不能销售，但工厂可以整改，在2年内重新提出检查申请，再次检查通过可以恢复原CEP，再次检查不通过就是withdraw撤销了。
withdraw撤销，撤销后不能恢复，只能再次提交新的申请来获得CEP。
void不知道你说的是哪里来的

julia朱玉姣

beiwei5du 发表于 2015-6-21 23:04
请问一下
1、EudraGMDP Non-Compliance Report 中都采取Part 1，Part 2, Part 3形式，主要是指 ...

1、EU GDMP数据库里要求上传的报告采用相同的格式，part 1是检查对象、检查时间、检查结果、检查机构、检查依据，part 2是检查范围或不合格范围，part 3是缺陷内容，欧盟相关部门要采取的行动，NON-STERIAL是非无菌，看该报告的表述，应该此次检查包括了非无菌和无菌部分，结果是非无菌通过了，无菌没通过。不过这个报告貌似有点矛盾，part 2 的标题是不符合GMP项，但1.2项写的是非无菌，非无菌操作应该是符合GMP的。
2、受限GMP证书，只有部分操作或产品被许可销售入欧盟
3、是的，欧盟的法规修订不是全文发布修订版本，而是只签发修订增补的内容，不象我们的GMP说是哪年版本就OK，他们的法规要将原版本结合增补内容来看（当然官网也会发布consolide版本，就是整合版），这是他们的标准引用写法。

beiwei5du

julia朱玉姣 发表于 2015-6-23 11:01
CEP suspend指搁置，即不能销售，但工厂可以整改，在2年内重新提出检查申请，再次检查通过可以恢复原CEP， ...

Nature of non-compliance : The company was not operating its aseptic manufacture operations in compliance with EU GMP Annex 1. This was evident from by the high number of observations regarding the aseptic manufacturing facilities design, equipment, operations, environment monitoring and media fill validation. However, the QA system of the company failed to notice these problems and therefore was considered weak and inappropriately implemented. Detailed list of critical and major deficiencies is included in regulatory risk assessment
Action taken/proposed by the NCA :
Withdrawal, of current valid GMP certificate No. 004/2012/RO
current GMP certificate will be reissued to include only non-sterile products. A restricted GMP Certificate will be issued for sterile critical medicinal products for Romania, France, and UK

Requested Variation of the marketing authorisation(s)
change of API supplier

Prohibition of supply


Suspension or voiding of CEP (action to be taken by EDQM)
suspension of CEPs
void就是宣布其无效吧！但是withdraw后当然也就无效了啊！