Cleaning validation(CV) protocol 清洁验证方案

Cleaning validation(CV) protocol of

Mixing tank、Storage tank、Transfer vehicle and Pipeline 配液罐、储液罐、移液车及其管道清洁验证方案

Prepared by起草：Date日期：

Reviewed by审阅：Date日期：

Approved by批准：Date日期：

Table of contents

目录

1.0 Summarize概述 (3)

2.0 Purpose验证目的 (3)

3.0 Responsibility验证职责 (3)

3.1 Validation team验证小组 (3)

3.2 Production department生产部 (4)

3.3 Equipment department设备部 (4)

3.4 Quality department质量部 (5)

4.0 Validation scope验证范围 (5)

5.0 Validation content验证内容 (5)

5.1 Cleaning procedure清洗规程 (5)

5.2 Sample Plan取样计划 (5)

5.3 Test and Evaluation 测试和评估 (8)

5.4 Re-validation and re-validation period拟定再验证及验证周期 (9)

5.5 Conclusion 验证方案结论 (10)

6.0 Approval of validation protocol验证方案最终批准 (10)

1.0 Summarize概述: Mixing tank, storage tank, transfer vehicle and pipeline were used in alcohol wipe workshop for the 70% Isopropyl alcohol solution's storage and transporting. Because this system cleaning effect may affects the quality of the product, so we will perform a cleaning validation(CV) for this system. 配液罐、储液罐、移液车及其管道用于酒精擦片车间的药液配料、储存及药液运送，该系统的清洗效果直接影响到产品的质量，因此我们将对本系统进行一个清洁验证。

2.0 Purpose验证目的: Confirm cleaning procedure of mixing tank, storage tank, transfer vehicle and pipeline was reliability, to perform the cleaning procedure, right after a number of chemical pollution 确认配液罐、储液罐、移液车及其管道的清洗规程的可靠性，执行清洁程序后，不对后一批药液产生污染。

3.0 Responsibility验证职责：

3.1 Validation team验证小组：

3.1.1 Responsible for approval of protocol负责验证方案审批。

3.1.2 Responsible to coordinate the work of validation, ensure the implement of this protocol effectively.负责验证的协调工作以保证本验证方案规定项目的顺利实施。

3.1.3 Responsible for approval of validation report.负责验证报告的审批。

3.1.4 Responsible for signing and issue the certification of validation负责验证证书的发放。

3.1.5 Responsible for affirmed the period of validation负责验证周期的确认。

3.2 Production department生产部：

3.2.1 Responsible for draft the protocol负责验证方案的起草。

3.2.2 Responsible for collected all validation data and submitted to the validation team. 负责收集各项验证记录，报验证小组。

3.2.3 If this protocol need to change because of specific cause, Equipment department should be responsible to fill 'the application and approval form of protocol change.若因特殊原因需变更原验证方案时，应负责填写“验证方案变更申请及批准书”，报验证小组批准。

3.2.4 Responsible for operation、cleaning and maintenance of equipment.负责设备的操作、清洗和维护保养。

3.2.5 Responsible for implement of this protocol.负责验证方案的实施。

3.2.6 Responsible for identified the re-validation period and protocol.负责拟定再验证方案及周期。

3.3 Equipment department设备部：

3.3.1 Responsible for installing, adjusting the equipment and recording.负责设备的安装、调试并作好相应记录。

3.3.2 Responsible for the calibration of equipment and meter.负责仪器仪表的校正。

3.3.3 Responsible for providing mainly parameter of equipment.负责提供与设备有关的主要参数。

3.3.4 Responsible for assisting implement of this protocol.负责协助验证

方案的实施。

3.4 Quality department质量部：

3.4.1 The representative of Quality department should be involved in the approval of validation protocol and report.质量部负责人参与验证方案、验证报告的审阅。

3.4.2 Responsible for assisting the calibration of equipment and meter.负责协助仪器仪表的校正。

3.4.3 QA was responsible to supervise the validation process.QA对验证的过程实施监督。

4.0 Validation scope验证范围:Mixing tank, storage tank, transfer vehicle and pipeline 配液罐、储液罐、移液车及其管道清洗消毒验证.

5.0 Validation content验证内容：

5.1 Cleaning procedure清洗规程：

5.1.1 According to YJ / SMP-PR-005 Daily cleaning procedure of Production equipment.按YJ/SMP-PR-005生产设备日常清洁和清洗指南操作。

Validate three continued lots.连续进行三个批次的验证。

5.1.2 The equipment operators should be trained and the training record should be finished and archived before they performed this procedure.在设备的操作人员执行清洁程序之前应该接受培训并完成培训记录及归档。

5.2 Sample Plan取样计划：

5.2.1 Swab samples擦拭取样：

5.2.1.1 sketch map of cotton棉签擦拭图：

5.2.1.2 Worst case and sampling location最差条件和取样位置:

Those location as following were not easy to be cleaned, so we will sample in those location.易进行清洗，因此在下列位置取样：

Total 6 Sampling locations总共6个取样点:

Table1表1:

Part Name 部件名称Sample location

取样位置

Sample No.

取样点编号

Sample area

取样面积(cm2)

Mixing tank配液罐顶部喷淋装置后方 1 200

底面搅拌浆遮挡处 2 200

中部内表面 3 200 Storage tank储液罐顶部内表面 4 200

中部内表面 5 200

底部内表面 6 200

Transfer vehicle移液车顶部内表面7 200 中部内表面8 200 底部内表面9 200

5.2.2 Final Rinse samples淋洗水取样：Total 3 Sampling locations总共3个取样点:

Part Name 部件名称Sample location

取样位置

Sample No.

取样点编号

Sample Volume

取样体积(cm2)

Mixing tank

配液罐

液体管道出口10 500（250*2）

Storage tank

储液罐

液体管道出口11 500（250*2）

Transfer vehicle

移液车

液体管道出口12 500（250*2）

5.2.3 Hold time of cleaning 清洁保持时间：Conduct sample and test

according to 5.2.1 at 1 week, 2 weeks, 3 weeks, 4 weeks after cleaning

mixing tank, storage tank, transfer vehicle and pipeline placed in normal

workshop conditions. Because the concentration of Isopropyl alcohol will decrease as the storage time pass, the residue of isopropyl alcohol in first time is the highest; so microbial test was enough for this validation. Finally, we can determine the hold time of cleaned equipment according to the test results. 将清洁以后的配液罐、储液罐、移液车及其管道放置在车间正常环境中，至1周、2周、3周、4周。分别按5.2.1再次取样进行测试，因为随着储存时间推移，对于异丙醇残留量来说只会减少，第一次测试的异丙醇残留量是最高的；因此只需进行微生物测试。根据检测结果确定设备清洁后的保持期。

5.2.4 Sampling record 取样记录

Sampling record

取样记录

Product Name产品名称: ____________________________

Equipment设备:___________________________________

Batch No批号: ____________________________________

Part Name Visual Inspection Sampled for

部件名称目检取样

清洁不清洁

1. ???

2. ???

3. ???

4. ???

5. ???

6. ???

7. ???

8. ???

9. ???

10. ???

11. ???

12. ???

Remarks: __________________________________________________________________

备注

Sampled by/date取样人/日期：Reviewed by/date复核人/日期：

5.3 Test and Evaluation 测试和评估：

5.3.1 Appearance inspection 外观检测

5.3.1.1 Test method检查方法: Visual inspect the inside and outside surface of those equipment .目测设备内外表面洁净情况。

5.3.1.2 Acceptance criteria认可标准: The inside and outside surface were clear, no dirt. 设备内外表面光洁、无污物。

5.3.1.3 Appearance inspection record外观检查记录表格

Date

清洗日期Clean Status of inside/outside surface

(visual) 设备内外壁洁净情况(目测)

Inspected by/date

检查人/日期

QA Review/date

QA 复核/日期

5.3.2 Chemical test化学检测:

5.3.2.1 Method检测方法: Because Isopropyl alcohol was easy to be cleaned by water, the residue of the Rinse samples was more than that of the surface samples. So we need test the residue of the final rinse samples only. To 250mL of water sample in 5.2.2 in a suitable flask, observe if it is clear, and test the residue of isopropyl alcohol by GC(Gas chromatography) .由于异丙醇易于被水清洁，由最终管道排除的液体的浓度远远大于表面残留的浓度，因此只需对罐管道出口的样品进行化学检测。分别取5.2.2项下水样250mL，观察性状是否为澄明液体，并用气相色谱法测定异丙醇残留量。

5.3.2.2 Acceptance criteria认可标准: The residue of isopropyl alcohol was not more than 10ppm.异丙醇残余量不得大于10ppm。

5.3.2.3 Chemical test record化学检测记录表格

LOT 批号Clean Date

清洗日期

Appearance

性状

Residue

异丙醇残余量

Tested by/date

检测人/日期

Evaluation 评价

Qualification 确认Reviewed by/date

复核人/日期:

Validation team/date

验证小组/日期:

5.3.3 Microbiological test微生物检测

5.3.3.1 Method检测方法: Take the sample in 5.2.1and 5.2.2 ,Carry out Microbiological test 取5.2.1及5.2.2项下样品,做微生物检测。

5.3.3.2 Acceptance criteria认可标准: Total bacteria count≤10CFU/ml 清洗水微生物菌落数≤10CFU/ml。

5.3.3.3 Microbiological test record微生物检测记录表格

LOT 批号Clean Date

清洗日期

Total count

菌落数（CFU/ml）

Residue

异丙醇残余量

Tested by/date

检测人/日期

Evaluation 评价

Qualification 确认Reviewed by/date

复核人/日期:

Validation team/date

验证小组/日期:

5.4 Re-validation and re-validation period拟定再验证及验证周期：

Re-validation will be performed as this protocol or supplement protocol drafted per actual Situation when there were major changes or maintenance in this equipment, and any exception in manufacture process, and any trouble in the utilities etc to ensure applicability and repeatability of this equipment.

当设备和装置发生较大变更或做大检修后，在日常验证中发现重要的工艺特性出现异常，公用工程发现故障以等情况下，应按照其前验证采用的方法对清洁程序进行再验证，或根据实际情况修订补充验证方案后进行“再验证”，以确认清洁程序的适应性和重现性。

Re-validation period should be identified per the requirement of process and operation status of this equipment by Production Department (See the Validation master plan). 设备部根据工艺要求、设备运行情况拟定验证周期(见“验证主计划”)。

5.5 Conclusion 验证方案结论：

Conclusion should be decided per validation results. If applicable, Analysis and summarize this problem occurred in validation process. 根据验证结果，做出验证是否通过的结论，如适用，对验证中发生的问题进行分析总结。

Conclusion see the validation report验证结论见验证报告。

6.0 Approval of validation protocol验证方案最终批准：

This validation protocol is effectively after approved by relatively department manager, Quality Director. 验证方案最终由相关部门经理，质量总监批准后生效。