EUGMP最新不符合事件：波兰一家无菌制剂药企的缺陷项

lmqqwer

29条缺陷项，剂型：冻干制剂和小容量注射剂

Nature of non-compliance : 29 major deficiencies were found in Agila Specialties which pose a risk of microbial and particulate contamination and could not assure the sterility of the final product. Most of these are related to:
1.) design and qualification of HVAC, laminar air flow system and clean areas,空调系统，层流系统和洁净区的设计和确认
2.) cleaning and maintenance of clean areas.洁净区域的清洁和维护
3.) manufacturing and batch releasing in the conditions not complying with GMP requirements 生产和批放行不符CGMP要求
4.) change control. In December, 2014 HVAC system of vials and prefilled syringes lines was significantly modified. Since January till July 2015, 49 batches was manufactured in that area without qualification after the change. 变更控制方面：在2014年12月，该公司的空调系统和预灌装线经过大的改造，在没有经确认情况下，从2015年1月至7月，在该区域生产了49批产品。
During the inspection it was found that: 1) pressure differential between clean areas B and C grade were usually below 10 Pa (effective to < 0 Pa) and alarm (generated by electronic, non-validated after the change of the system) has triggered at 0 Pa and after reversing the flow; 在检查中，我们还发现：B/C区域之间的压差常低于10pa,小于0pa的报警也有触发。（电子报警，系统变更后无效）
2.) laminar air flow system did not fulfil with requirements given in Annex 1;层流系统满足附录1要求
3.) test of maximum permitted number of particles "in operation" does not performed properly; 微粒允许的最大值测试生效未能正确执行
4.) technical condition of clean areas and equipment show lack of proper and regular maintenance. In clean areas A/B grade contamination was found on the arm of the filling machine for prefilled syringes and difficult to clean equipment placed without proper SOP. In grade C e.g. crumbling insulation of pipes, peeling teflon on the ports of tanks and pumps, lack of labelling and mixed clean and dirty equipment, chipped glass accessories was found;洁净区和设备的技术规范缺乏适当的日常维护。在A/B发生过微生物污染，如在灌装设备的手套上。没有适当正确的SOP，设备清洁难以达到要求。在C级区，在罐和泵上出现管子的绝缘碎屑、聚四氟乙烯脱落物，设备缺少标识，存在交叉清洁，很脏，还出现玻璃碎屑。
5.) the filtration process was not fully validated and during routine process a pressure difference to be used across the filter was not recorded;过滤工序没有充分验证，在日常生产期间，滤芯测试出现异常也没有记录下来。
6.) lack of confirmation of A grade in a lyophilizer working in a nitrogen atmosphere;冻干机内（A级标准）充氮保护没有做确认。
7.) design, installation and use of nitrogen system not guarantee tightness and can cause contamination of the clean medium.
氮气系统设计、安装和使用不能保证密封，可引起洁净介质（氮气）污染。

没有做过无菌制剂，英语水平有限。仅供参考学习。

friendly521

国外的月亮也不那么圆呀

zysx01234

波兰可能水准没有那么高，德国会好一点

jacob3263313

起点高，标准低

Stilling

学习了，感觉很有用处。这个网站很有用，值得拥有。

北重楼

看得出这个企业问题不少，给了我们不少启发

ach成

问题谁都有，只能说看谁做的更好，主体还是人