【GMP缺陷】g009 2012年某公司无菌制剂欧盟GMP检查缺陷-中英对照

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Deficiencies

1、Samples for the release testing (vial filling process) have to be

traceable to the sampling time and should be representative for the

beginning, middle and end of the filling process. The samples taken have

to be tested individually

and not as a composite sample.

用于放行检测的样品（小瓶灌装工艺）必须追溯到取样时间，应该对灌装工艺的

开始、中间和结束时间点具有代表性。必须单独分别检测这些样品，而不能作为

组合样品进行检验。

2、During the validation of the newly established Turbometric Endotoxin

determination as per EP (Validation plan and report from 29.02.2012) USP

Endotoxin standards instead of EP standards were used. A comparison or

justification was not performed. During the reviewed Rubber Stopper

release testing the USP Endotoxin Standard was used.

在根据EP新建立的Turbometric内毒素检测方法验证过程中，采用了USP方法，

而不是EP方法。没有进行对比和论证。在审核胶塞放行测试中，采用了USP内

毒素测试方法。

3. In the master batch records some references to SOPs are needed e.g.

the performance of specific environmental monitoring activities were

missing.

在主批记录中，很多和SOP相关参考文件需要注明，例如特定环境监控活动的表

现没有注明。

4. The master batch records are offering in several cases (e.g. filling

record page 33 section “Equipment components and primary packaging

material check”) only one option – either Yes or No. Please ensure that

the operator has the possibility to choose Yes or No-

在主批记录中，在几个地方（例如33页灌装记录，设备部件和内包装检查），只

是提供了一种原则，或者是yes，或者是no。请确保操作者有可以选择yes或者no。

5. The disinfectant frequency for the scissor used for opening the PE bags

containing e.g. sterile rubber stopper or caps should be increased and

described in the related SOP.

用于打开PE袋，包括无菌胶塞或者铝盖的剪刀的消毒频率应该提高，并在相关SOP

里面注明。

6. The minimal required exposure time for settle plates (e.g. 1 hour as

per ISO or USP recommendation) is not defined in the related SOP.

沉降菌最少暴露时间（例如根据ISO标准或者USP建议，采用1小时）没有在相关

SOP上面注明。

【翻译者注释】如果审核意见是真实意思的表达，我认为制造商和检查官，都

对EU GMP太不熟悉了。这一点在EU GMP是白纸黑字注明的。

7. There was no written explanation or justification available explaining

why for the on-line particle counting (FMS) a deviation will be issued

only after an out of acceptance limits of 30 minutes.

没有书面解释或者论证来解释：对于在线粒子监控系统，为什么一个偏差只有在

超出限度30分钟才被处理？

8. On sterilisation printouts the concrete time has to be recorded to

calculate the maximal sterile validity period of the related materials.

关于灭菌法，要求必须记录具体时间来计算相关物料的最大有效灭菌周期。

9. The packed and transferred final finished product was not recorded in

the staging area inventory list.

包装完的转移的最后制剂产品，在集合储存区域，没有被记录在台账清单上。

10. The visual IPC checking of the filled vials should be performed while

the vials are rolling.

针对灌装完毕的小瓶的目视IPC检查，应该在小瓶旋转时进行检查。

11. The waste bin in the secondary packaging area is insufficient (e.g.

size and design) for the intended use.

外包装区域的废物桶（例如尺寸和设计）对于目的用途是不足够的。

12. A settle plate in the filling area class B was observed located under

an electric panel of the Bosch filling machine. This location seemed

unsuitable for the monitoring purpose.

在B级灌装区域，发现一个沉降菌测试碟放置在BS灌装机的电子仪表盘上。这个

位置对于监控目的是不合适的。

13. Due to the huge amount of personnel required in the secondary packaging

process (~ 10 to 12) a process optimization is requested.

因为在外包装工艺需要大量人员（10-12人），需要进行工艺优化。

14. The vial washing machine qualification (IQ, OQ & PQ) documentation

should be re-reviewed, restructured and required references / links

towards further reports included.

安瓿瓶洗涤机验证文件（IQOQPQ）应该被再次审核，再次安装并提供参考文献，

包括进一步的报告文件。

【翻译者注释】哪位负责这个文件，估计要倒霉了。

15. Please identify in the personnel monitoring form/ report the body or

hand side (right / left) from which the samples are taken.

请在人员监控表中注明，身体或者手（左手/右手）取样点，到底从哪个位置取

样。

16. The identification of the RRT for known impurity should be included

into the Related Substance Test Method.

对于已知杂质，RRT的鉴定项目，应该包括在有关物质测试方法中。

Recommendations

ꨠ The identification of the particle counter used for active air bourn

counting was not mentioned in the summary report attached to the batch

records used for batch release. The instrument number was traceable in

the related environmental monitoring raw data records. Please add the

number to the summary.

在用于支持批方形的批记录中汇总表中，没有提到用于测试浮游菌的例子计数

器。这个仪器编号要可以追溯到相关环境监控原始数据记录中。请在汇总表中加

上这个仪器编号。

ꨠ After IPC the powder from the controlled vials should be collected in

a more secure way e.g. in a flask to ensure that the powder won′t be

exposed to the packaging area.

IPC测试完毕，来自受控小瓶的粉末应该采用更安全的方式来收集，例如使用一

个烧瓶来确保粉末不会在包装区域暴露。

鯠 Review the individual sections of the Process Risk Assessment with

regard to further risk details / sub-sections.

结合进一步的风险细节和分支，审核工艺风险评估的单独部分。