清洗验证方案模板.docx

1、清洗验证方案模板XXX MachineCleaning Validation ProtocolXXX机清洗验证方案Protocol Approval 方案批准Company/Title公司/职务Name姓名Signature签名Date日期Written by起草Reviewed by审核Approved by批准Resivion 版本Issued Date 颁布日期Reason For New Issue 颁布原因Rev. 00Initial Issue首次颁布Index 目录1. Purpose目的The purpose of this cleaning validation study

2、is to verify and document that the standard cleaning programs for the equipment, systems or facilities in direct contact with the product can ensure that the residual active ingredients and the residues from the former batch of product, or the potential microbial contaminations are within the predef

3、ined acceptance criteria, so as to prevent any contaminations (related to the product or the cleaning process) that can cause any adverse effects to the safety or the quality of the products produced the next time, and the selection of product residual limit, the microbial contamination degree and t

4、he hold time are also determined at the same time. The set limit shall be practical and testable. The analytical methods used for the detection of residues or contaminants during the cleaning validation shall be validated. The validation results are obtained through the evaluation of the amounts of

5、the residues of the major active ingredients on the equipment surfaces and in the rinse water. 本清洁验证研究的目的是为了确认和记录与产品直接接触的设备、系统或设施的标准清洗程序能够保证活性成分和上一批产品可能的残留物，或潜在的微生物污染在预先所定义的可接受范围内，以防止出现能够对下一次生产产品的安全性和质量带来不利影响的污染（与产品或清洁工艺相关的），同时对产品残留物限度的选择、微生物污染程度和保留时间进行确定。设定的限度应是切合实际和可检查的。清洗验证中检测残留物或污染物的分析方法，应该得到验证。

6、验证的结果，通过评估设备表面和清洗水的主要活性残留物的量而得。2. Scope范围This protocol is XXX cleaning validation protocol, the equipment which it mainly contains is XXX machine at the XXX plant.本方案为XXX清洗验证方案，主要涉及的设备为XXX车间的XXX机。Responsibility职责Austar responsibilities奥星的职责 Protocol compilation方案的编写 Supervision of protocol execution

7、 and data collection监督方案的实施，数据的收集 Review of final report最终报告的审核XXX responsibilities XXX职责 Review and approval of this protocol before execution执行前审核和批准本方案 Supply of all procedures, data, manuals, drawings and documentation necessary for the generation and execution of this protocol and the completio

8、n of the final report提供为方案编写、方案执行和报告编写所需要的所有的规程、数据、手册、图纸和文件 Assure all punchlist items and prerequisites for execution are satisfied保证在执行前所有的未完成项和先决条件得到满足 Provide personnel, when necessary, to assist in the operation of utility system在需要的时候，提供必要的人员协助进行公用系统的运行 Protocol execution and data collection方案

9、的实施，数据的收集 Provide personnel, when necessary, to calibrate critical and non-critical measuring, recording, and/or controlling instrumentation在需要的时候，提供必要的人员进行关键和非关键的测量、记录和控制仪表的校准 Define solution for non conformity针对不一致项，界定解决方法 Review and approval of the report after successful execution.审核和批准报告Regulat

10、ion and Guidance 法规和指南 (SFDA) Good Manufacturing Practice 1998(SFDA) GMP 1998版 (SFDA) Good Manufacturing Practice(Draft for comment, Dec 2009)(SFDA) GMP（2009年12月征求意见稿） EudraLex - Volume 4 Good Manufacturing Practice (GMP) GuidelinesEudraLex-卷4 GMP指南 China Pharmacopoeia 2010 Edition中国药典 2010版 (FDA) G

11、uide to Inspections Validation of Cleaning Process （July 1993）清洗工艺验证检查指南(1993年7月) Guide to drug manufacture validation 2003药品生产验证指南2003年版 Part 211: Current Good Manufacturing Practices for Finished Pharmaceuticals第211部分：现行药品生产质量管理规范Abbreviations缩略语Abbreviations缩略语Definition定义IQInstallation Qualifica

12、tion安装确认OQOperational Qualification运行确认PQPerformance Qualification性能确认GMPGood Manufacturing Practice 药品生产质量管理规范SOPStandard Operation Procedure标准操作程序CVCleaning Validation清洗验证COPCleaning out of Place离线清洗MTDDMinimum Therapeutic Daily Dosage最低日治疗剂量MARMaximum Allowable Residue最大残留量BSSBatch size of the su

13、bsequent product下批次产品的批量PWPurified Water纯化水WFIWater for Injection注射用水 System Description 系统描述2.1 Equipment Description 设备描述XXX fills powder with equal volume principle. At filling station, the powder is absorbed in a hole by vacuum and blow up into vial by cleaning air. The system is controlled by P

14、LC and droved by servo motor. The advanced automatic weighing system can ensure the accuracy of the filling volume.XXX采用等容积分装原理。在分装工位，系统使用真空吸附一定量的药粉，再用洁净压缩空气将药粉吹入小瓶。分装机采用PLC控制，伺服电机驱动。先进的自动称量系统能够保证装量的准确性。2.2 COP Description COP描述After the production, disassemble the equipment component in order accor

15、ding to the regulations, then put them in the appropriate container. Let them through the passbox besides the autoclave to the decontamination room. Supply the powder pipe which the components are larger should through the passbox alone to the decontamination room. The cleaning methods of the specif

16、ic parts are as follows.生产结束后，按规定依次拆下设备相关部件，放在相应容器内，通过传递窗，传递到洗消间，供粉管等较大的物件，需单独通过传递窗，传递到洗消间。具体部件清洗方法如下：Parts to be Cleaned 清洁部位Cleaning Method清 洁 方 法Method No.方法序号12345Good Documentation Practice文件管理规范Recording pens 记录用笔- Archive proof ink pens or marker pens shall be used. Blue pens are recommended.

17、 使用不消退的墨水笔和记号笔，推荐使用蓝色笔记录。Signature 签名- Only authorized persons can sign on any documents. 被授权的人员才能签署文件。- Unless otherwise specified, the full name shall be used as the signature应签全名，除非文件另有规定。- The signature shall be readable. 签名应该是可辨认的。- The signatures shall be consistent. 签名应始终一致Column filling 填写栏目

18、- All the columns shall be filled. 所有栏目必须填写- The full text shall be filled if it is the same as that in the field above. 填写内容与上面栏目相同应重新填写- If there is nothing to be filled in to an individual field, N/A (abbreviation for not applicable) shall be written in this field. 若有单个栏目不需要填入内容，则在空白处填写英文字母“不适用”的

19、简写“N/A”，以表示无此项内容- If there is nothing to be filled in more than one neighboring fields, such fields shall be crossed with a diagonal line, with “N/A” noted above the line and the signature and the date noted below the line. The signature and the date shall be written along the line on the same side

20、as much as possible. 填写记录时，若有多个栏目不需要填入内容，应用斜线划掉，斜线上方填写“N/A，下方签名和注明日期。签名及日期应尽量沿斜线同侧填写N/A 签名 日期Signature dateCorrection of mistakes 更改错误- When any mistakes are to be corrected immediately after the document has been completed, the correct record shall be entered and signed and dated. The original info

21、rmation shall be left clearly readable 文件刚完成，立即更改的在错误处划线，填入正确的，签名和注明更改日期，确保原先信息仍清晰可识别For example: January 1, 2010, signature and date如：2010年01月01日 签字，日期- When any mistakes are to be corrected afterwards, besides conforming to the above requirements, the reasons for the correction must be noted and t

22、he possible influences shall also be assessed and noted事后更改的，除非立即更改的要求外，还应注明更改的原因，检查和注释可能的影响Date Recording Format 记录日期- Four digits shall be used for the indication of the year, two digits for the month and another two for the date. 年用4位数表示，日和月用2位数表示For example: 2009年09月01日 如：2009年09月01日Use of Abbre

23、viations 使用缩略语- An abbreviation shall be noted in brackets immediately after the full name before it can be used in the rest of the document. 在术语全称后的括号内注明缩写，然后才可以使用缩写Written Words and Names 书面语及名称- Standard written words and names shall be used. 使用规范的书面语及名称。- The names shall be consistent all throug

24、h the document. 文件前后名称要一致Sampling procedures取样程序2.3 Sampling principles 取样原则The sample location should select the most difficult cleaning location, when use swab sampling, the biological swab samples and chemical rinse samples could not sample on the same location. For easy to reach places by hand i

25、t should use a cotton swab sampling method and for large containers such as pipes and hard to reach places, use of rinse sampling method. The component which sample area is not enough should according to the cotton swab area calculating.取样位置的选择应该选用设备最难清洁的部位，棉签取样时，微生物取样和化学取样不能对同一位置进行取样。对于用手容易达到的地方，用棉

26、签法进行取样，对于管路及较大的容器等难以达到的地方，采用冲淋法进行取样。不足规定取样面积的部件按照棉签擦拭的范围进行计算。2.4 Active pharmaceutical ingredient residues sampling procedures 活性成分残留取样程序2.4.1 Swab sample 棉签法取样Swab the equipment surface after washing with a cotton swab using a 1010cm2 Surface of stainless steel plate with PTFE frame to help definin

27、g the sampling area. During the swabbing process, dip the cotton swab with a small amount of the water for injection and swab horizontally first. Then turn the cotton swab over and swab vertically. Attention shall be paid to follow the same direction during the swabbing process. Do not swab back and

28、 forth. All the area defined by the PTFE frame shall be swabbed (please see the following drawing). After the swabbing, put the cotton swab into a volumetric flask with a stopper, dissolve the sample with 2ml of the washing solution and perform the test. 用棉签在清洗后的设备表面进行擦拭，用1010cm2不锈钢表面，用聚四氟乙烯框作为取样范围，

29、在擦拭过程中用棉签蘸少量注射用水首先横向擦拭，然后翻转棉签再纵向擦拭，注意在擦拭时棉签一定沿一个方向擦拭，不可来回擦拭。擦拭过程中要求聚乙烯四氟框范围内都要擦到（见下图）。擦完后棉签放入具塞量筒中用2ml的清洗溶液溶解测试。2.4.2 Rinse sample冲淋法取样For Curved supply of powder pipe, after finishing the normal washing process, rinse it with 200ml WFI, take the rinse solution. Take 10ml the rinse solution and perf

30、orm the test. 对于弯供粉管，正常清洗完毕后，再采用200ml注射用水反复冲洗，并接取淋洗液。取10ml进行测试。2.5 Microbiological sampling procedures微生物取样程序2.5.1 Swab sample棉签法取样Swab the equipment surface after cleaning with a cotton swab using a 1010cm2 Surface of stainless steel plate with PTFE frame to help defining the sampling area. During

31、the swabbing process, dip the cotton swab with a small amount of physiological saline and swab horizontally first. Then turn the cotton swab over and swab vertically. Attention shall be paid to follow the same direction during the swabbing process. Do not swab back and forth. All the area defined by the PTFE frame shall be swabbed. After the swabbing, put the cotton swab into a conical flask with a stopper, dissolve the samp