2009年1月28日
记录人: Dai Lu
Q20080134批记录查阅
特别看了此批地清洁记录，要求查看洁净区操作工人的培训记录， 包括GMP培训记录，与岗位有关的培训，以及与洁净区工作有关的培训。

2．一共查看了包括QA经理在内的12个人的培训记录

3．洁净区现场参观，没有发现问题。
需要提供一份洁净区人流物流示意图。

4．设备清洗验证，要求每个工段挑选一个设备。
非洁净区的设备我们只能清洁的SOP。
建议：所有关键设备（包括非洁净区）都需要作清洗验证。

5．虫害控制的措施/SOP
要求查看2008年7月/8月的检查记录。

6．要求查看以下仪器的校验和维护记录
IFP02-37 / TT03-12 / TT03-11 / TT03-13 / FM01-05

7．QA经理口述上次GMP自检发现的问题和整改方案。

8．Q20081109-02， Q20080621-02 批记录查阅

9．2008年水系统的监测记录 （自来水和纯化水）

10．化工生产区溶剂回收的问题
新的溶剂与回收的溶剂可以混用，但是溶剂回收的方法必须进行验证。
母液可以套用，关键是方法必须进行验证。

11．需要计算收率的工序
粗品 / 蒸馏 / 干燥 / 粉碎 / 内包

12．标签管理的SOP
到美国市场和其他市场的标签的差别
要求提供一份到美国市场的标签的复印件。
建议：下次工艺验证时加入标签的验证。

13．Q20080319偏差报告
有无预防措施：正在考虑设备的改造和选型。

14．要求提供生产中用到的所有仪器仪表的清单，附校验日期

15．查看20070103 （发往美国市场）的批记录

16．变更控制中，有很多原料供应商的变更，有无因为产品质量问题更换供应商的情况发生？
没有。

17．去年的原辅料有无不合格的。
有一批， 看过检测报告。

18．原料取样检测时，同一批产品从不同包装取样后，建议最多2-3个样品混合做红外检测。
欧盟的最新要求是必须每个包装取样必须单独做红外检测。


记录人: Phillip
FDA insection on 28 January, 200８
　2008-02-28

Stephen started from QC chemical analysis room on the 1st floor, Pan introduced him sample flow, Stephen checked calibration log on each instrument, found same problem of over calibration on balance PL203, current calibration is valid till 11 May, 2009, but last calibration was expired on 27 March, 2008. On IR room, the analyst introduced he repeats standard spectra once a month and keeps it with sample’s IR record. On stability study room, Stephen read stability study sample log, asked how to record chamber temperature and humility,, how to send alarm signal. On retention sample room, everything is good, checked expiry date of working standard sample and asked test items. He checked especially the test report generating process and electronic data backup SOP on QC lab.
Stephen从QC一楼理化室开始。潘向他介绍的取样流程，他检查每一台仪器的校验记录，在天平室检查天平的校验标签及记录。在红外室，分析人员介绍一个月做一次对照谱图，与样品谱图保存在一起。在稳定性实验室，Stephen看了样品稳定性研究记录，如果记录稳定性试验箱的温湿度，如何报警。留样室，查看工作对照品，并询问有效期及检测项目。特别检测电子备份及电子数据如何输出。
Went back to office, he wrote down analysis items of specification of all raw materials, intermediates and XXX on test methods list, asked how to identification of each raw material. He reviewed analysis records on annual report of 2008, reviewed stability study records of Q20070419, reviewed test reports of several raw materials.
On today’s closeout meeting, Marine gave 3 suggestions (will not appear on 483), label validation, test city water per month, sample for IR should be composed from no more than 2-3 packages.
Stephen said he is satisfied with the lab, the management system and control of lab. One thing to be discussed is the SOP of calibration of HPLC, QC, we should follow government’s rule, we also need to establish plan of vender calibration or in-house calibration to meet FDA requirement.
他记录原料的指标，并询问所有原料的鉴别方法。查看了2008年度报告中的批记录，查看验证批Q20070419的批检验记录

Sue 的记录：

1. Looked at process water teesting reports from government and Excel.
Noted that government tests for more heavy metals. 查看政府及公司的水的报告单。
2. Asked which water we use in process: we said for cleaning equipment use city water.
For clean room and lab use R/O water.工艺中所用的水。我们回答市政供水用来清洁设备，洁净区用工艺用水。
3. She asked for R/0 water testing data. 工艺用水的测试报告
4. Asked about which solvents are recovered? How are solvents recovered? Do we mix new solvent with recovered solvents?溶剂回收。溶剂如何回收，是否混合新鲜溶剂与回收溶剂

We explained for export to USA we use virgin solvent, exports to USA will have different batch no than other types as per our materials coding SOP. 发往美国的产品只用新鲜溶剂。
5. Asked what are yield check points? We said crude product, 2. distillation 3. drying.收率检查点，答：粗品，蒸馏品，干燥品
6. Asked for SOP on labelling.标签的SOP
7. ASked for deviation report and how some items could be prevented in the future?偏差报告和预防措施
8. Asked for drug listing information : we gave her file "drug listing" which I had prepared.NDC码资料
9. Asked where we print labels?, where do we keep lables? when label removed from cabinet do we keep a reord? What happens if you take out too many labes? Who is responsible for labels? Who issues labels (we said production but monitored by QA). On labels--how do we put on batch number? (we said batch no will be handwritten). What information is on label. 在哪印刷标签，保存标签，从柜中拿走标签时是否有记录。如果标签拿多如何处理。谁负责贴签。（生产部贴签，QA监督）。标签上的批号如何放上去（答：手写）标签上的信息。
10. Asked for package and labelling validation. We said is included in process validation, we do not have separate validation. Marie said this should be included in our next annual report (labelling validation). 贴签验证。
11. Marie asked for sample of our label. 美国标签的样本
12. Marie asked for batch record for 100kg sent to Invagen. 发往美国的批记录
13. Asked how we sample incoming raw materials?原料取样
14. Asked how many different packages we mixed together? 不同包装的如果混合。
15. For IR tests, asked how many different samples are mixed together (we said 10, she said this is too much) to make 5mg sample for IR test. Marie said we should change sop for IR testing for sampling to maximum 3 samples mixed together, not 10. IR取样
16. Asked how much of our production is for XXX (we said 2/3).
17. Asked for information on raw material lots. 原料批号的信息

Also for Steve:

1. Looked at training records. ASked about ability for person to move from one position to another position.培训记录，问换岗人员的能力证明
asked what items employee receives training for? 员工接受怎样的培训
2. Many questions on calibration of instruments in QA/QC and equipment calibration. Need better system to ensure that no one uses an instrument that has not been calibrated on time. 仪器校验
3. Asked about system to ensure that instruments would be calibrated on time. 如何确保仪器及时校验
4. REquested to talk to lady in charge of lab calibration.
5. checked records of dryier.
6. asked about hiring practices?
7. asked about who decides when employee needs training?
8. Asked about training schedule and records of training

Close out:

We need to do the following:

1. Need to add labelling validation.
2. Need to test city water on a monthly basis.
3. IR sampling SOP must be changed so only 2-3 samples are mixed to make 5gr IR sample.
4. Steve: Government required calibration is not up to FDA standards--we gave draft revised SOP which he accepted.

汇总：今天所复印带走的文件有：
文件编号    文件名称
R02-SOP-JY-113    2008年YYYY质检科超标结果汇总记录
SOP-JY-049-F    YYYYUSP检验操作规程
    液相超期校验期间生产批次清单
    质检科组织机构图
    物料编码操作规程SOP
    质检科仪器一览表
    工艺流程图
   

28日复印带走的东西
NDC 码注册资料
YYYY新的标签
洁净区人流物流图英文版
29日复印带走的东西
仓库一二三楼平面图英文版
2008年工艺验证上的仪表清单翻译版。

罗兴华
1.设备材质选择的原则
2.设备夹套的介质
3.贴签的过程。
关键设备变更后，如何考虑工艺验证，marie认为有三个关键设备变更，应工艺验证。工艺之后是否稳定性考察。
2008-020，答：材质变更，型号变更不做工艺验证。
查看：SOP-JY-111-A 水系统监控
ＧＭＰ自检的SOP，自检的频率，回答自检的情况。检查官不看自检报告。回答QC，仓库，车间发现问题进行自检。

包材库的消防等级，为什么灯没有灯罩。

公司所有产品的目录
Q20081109偏差

员工走了，培训记录也要保存2年以上。
仓库环境监控SOP
母液的处理
Q20070103批记录

Tim
1, Annual product review: Marie always starts with this documents and then expend to other areas from this document年度报告
2, OOS listOOS清单
3, Deviation investigation and corresponding records in the batch record偏差报告及对应的批记录
4, Training records of about 7-8 people培训记录
5, City water testing report (annually) by the government and by excel (quarterly), I noticed December testing was missing, but Marie did not notice it政府及公司的市政供水的报告单
6, 2008 Process validation 2008工艺验证
7, Floor plans of the warehouse, clean area..仓库及洁净区的平面图
8, List of production equipment生产设备清单
9, List of meters and measurement devices生产仪表清单
10, translated SOPs handed to them on the first day, OOS, method validation, training, supplier audit, etc OOs，方法验证，培训，供应商审计
11, Route of synthesis工艺路线
12, Process flow chart工艺流程图
13, Equipment validation protocol and report: the dryer, crystallization reactor, etc.设备验证方案及记录：干燥器，洁净锅
14, Insect lamp check and cleaning record灭蚊灯检查及清洁记录
15, Mouse pad check and replacement record粘鼠板检查及替换记录
16, Name list of the persons present会议人员清单
17, Presentation公司简介
18, Company brochure公司宣传册


FDA建议整改项及公司薄弱项

建议整改项：
物料的红外鉴别应分别取2、3个包装物料混样进行，原则上混样包装数不能超过3个；
质检科组织修改相关取样及红外检测SOP
工艺验证中应当增加帖签过程的验证；
编制验证方案；
生产03规格产品时安排进行验证；
市政供水应每月进行取样检测；
质检科安排修改相关文件；
QC计量仪器校验；
修改QC计量管理文件；
一般生产区设备应做清洁验证；
编制一般区设备清洁验证方案；
组织进行一般区设备清洁验证；

公司薄弱项：
计量系统；
修改计量相关文件；
将其它产品生产用计量设备纳入体系；
清洁验证；
检查现有清洁验证方案及报告，确定需再验证的项目；
组织进行再验证；
标签的管理；
修改标签管理SOP；
产品的最终标签应在相关记录上留档备查；
培训管理；
各部门检查本部门现有培训档案，对不完整项目进行完善；
严格按公司年度培训计划、部门年度度培训计划及岗位培训表的要求组织培训；
新纳入GMP体系的车间应建立岗位培训计划表、组织进行相关培训；
设备验证；
检查现有厂房设施验证方案及报告，确认需再验证项目；
组织进行再验证；
新纳入产品的设备验证应按要求组织进行；
新洁净区的验证应及时完成；
物料管理；
仓库重新规划（原辅料、成品）；
供应商审计；
合格供应商名录的建立；

这个是我一个朋友很不情愿给我的，希望大家对大家有帮助。

看来你的朋友是做GMP认证工作的。好好学习一下。谢谢。

是的，有几个朋友还是华海的。

应助达人

东风提出的问题，大多都有共性，值得厂家注意并改进。

个人认为主要厂家自检的程度和力度不够，所以就有这么多问题的。

应助工程师

最不喜欢写这些东东了！