《疏水过滤器完整性测试.pdf》由会员分享，可在线阅读，更多相关《疏水过滤器完整性测试.pdf（17页珍藏版）》请在三一文库上搜索。
1、Hydrophobic Integrity Testing 疏水性过滤器完整性测试 过滤过滤/完整性测试培训课程完整性测试培训课程 What you will learn 主要内容 The types of particles and microorganisms used for testing hydrophobic filters 测试疏水性滤膜所用的颗粒及微生物的种类 How we can test hydrophobic filters with the same liquid properties we used to test hydrophilic filters 如何利用测试
2、亲水性滤膜的液体来测试疏水性滤膜 What new tests are available to address the limitations of alcohol based testing HydroCorr 新的测试方法可以去除使用酒精-Hydrocorr How and when to use HydroCorr to its maximum advantage 如何及合适使用Hydrocorr方法更能体现其优点 Particle Based Integrity Testing 测试所用的颗粒 Microorganism - Destructive Test 微生物测试微生物测试-破
3、坏性测试破坏性测试 Aerosol microorganisms or liquid bacterial challenge 气雾型微生物或者使用液状细菌进行挑战 Phage (T1, T3, phiX)噬菌体 Bacteria (B. diminuta) 细菌(缺陷型假单孢杆菌) Aerosol Based - Non-destructive Test 气雾测试气雾测试-非破坏性测试非破坏性测试 Smoke (D.O.P., Glycerol, Corn oil, etc) 烟雾 Methylene Blue, Sodium Flame 亚甲基蓝,钠火焰 Issues注意点 Particle
4、 Distribution must be uniform颗粒分布必须是均一的 Must have correlation of particles vs microorganisms 颗粒与微生物之间需要有相关性 High equipment cost设备成本高 Difficult to perform in-situ很难在线测试 Traditional Testing Principles 传统测试原理 Typical wetting liquids are Isopropyl Alcohol (I.P.A.), Methanol, Tert-butyl Alcohol, or a mix
5、ture of one of these and water 典型的润湿液是异丙醇,甲 醇或他们与水的混合物 Uses same principles as a hydrophilic test 使用与亲水性滤膜测试相同 的原理 compressed air Alcohol / Water Gas Flow Curve 酒精/水 气体流速曲线 Dont use 100% solvent, check gauges, set pressure accurately, check for correct test gas, look for distinctive change in gas fl
6、owrate 不要使用不要使用100%的溶剂的溶剂.核实压力表核实压力表.正确设定压力正确设定压力.核实正确的测核实正确的测 试气体试气体.寻找在气体流速中特别的现象寻找在气体流速中特别的现象 Alcohol Testing Advantages 用酒精测试的优点 No special equipment required 不需特定的设备 Follows similar procedures to hydrophilic membranes. Operator training time is reduced 可以采用与亲水性滤膜相同的步骤.操作者培训时间可以省去. Traditional 是
7、传统的方法 Widely accepted 广泛被接受 Well understood 很好理解 Correlated to bacterial challenge与细菌挑战有相关性 Can be performed easily & quickly 能非常容易及快速的进行测试 Alcohol Testing Issues 采用酒精测试的问题 Alcohol / Water mixtures are often used due to: 酒精酒精/水的混合物使用经常会导致水的混合物使用经常会导致 Cost成本高 Flammability有燃烧的危险 high diffusion高的扩散流 Se
8、cure areas and equipment needed 需要可靠的区域及设备需要可靠的区域及设备 Can be difficult to perform in-situ 很难在线操作很难在线操作 Some concerns with residual test solution remaining in filter holder / pipework after testing 在测试后,测试液体会残存在过滤器/管路中 Residual solution should be removed before filter sterilization 灭菌前需要去除残存的液体 Altern
9、atives to Alcohol Based Integrity Testing 代替酒精进行完整性测试 Needed primarily due to: 改变的主要原因是改变的主要原因是 Issues with alcohol contamination of processes residues 酒精残留的问题 Risks inherent with the use of solvents 使用有机溶剂的问题 Water-Based Integrity Tests have been developed to overcome these issues 用水来测试可以克服以上问题用水来测
10、试可以克服以上问题 Ease of validation容易验证 Water-Based Integrity Test Theory 用水作完整性测试的原理 Hydrophobic polymers repel water 疏水膜抗拒水 Pleated structures compact under pressure 在压力下,折叠式结构进一步压 缩 Water Intrusion Pressure is the minimum pressure necessary to force water into the largest pores of a hydrophobic membrane
11、. 水浸入压的定义为水浸入压的定义为:把水挤入疏把水挤入疏 水性膜最大孔的最小压力水性膜最大孔的最小压力 P1 P2 Water Gas d - 4 . k . . cos IP = - d where: 其中 k = shape correction factor = surface tension = contact angle d = pore diameter HydroCorr Testing Hydrocorr测试 Force water under pressure onto the surface of the filter. 把水灌在膜表面把水灌在膜表面 Applied pr
12、essure is integral filter intrusion pressure 加压至小于膜的水浸入压加压至小于膜的水浸入压 The water pressure is maintained but not increased. 压力维持但不再加压压力维持但不再加压 Pleated structure compacts 折叠式结构进一步压缩折叠式结构进一步压缩 If integral, the upstream pressure will not drop below a preset value. 膜如果是完整的膜如果是完整的,上游的压力不会太快上游的压力不会太快 下降下降 Int
13、egrity Tester Air / N2 WFI 0 2.6 bar 0 2.6 bar P atm P atm 0 2.6 bar 0 2.6 bar 0 10 20 Time (min.) apply pressure and hold加压并保持 Measure pressure Decay测量压力衰减 Pressure causes pleats to compact - resulting in apparent water flow 压力导致折叠式滤膜进一步压缩现 象是有一定的水流 HydroCorr Test Results测试结果测试结果 After initial stab
14、ilization, “apparent” water flow for an integral filter is very low 在最初的稳定后,对于完整膜来说,水流是非常小的 Specifications are correlated to bacterial challenge 水流指标是与细菌挑战有关 For integral filter there is no “actual” water flow 实际上完整膜,没有实际的水流 Filter remains dry and does not require drying between testing and use 在测试与
15、使用中,过滤膜维持干燥也不需要干燥 Water Flow ml/min Time 20 minutes 0.1 0.2 0.3 0.4 0.5 1.0 0 10 Performing HydroCorr Tests 进行疏水性测试 Manually手动操作手动操作 Use a flow meter to measure actual upstream water displacement 使用流量计来测量上游水的水流 Automatically自动操作自动操作 Use a pressure transducer to measure upstream gas pressure loss 使用压
16、力传感器来测量上游气体压力的损失 Both need long stabilization & test time 都需要长时间的稳定及测试时间都需要长时间的稳定及测试时间 Typically 10 minute stabilization & 10 minute test 一般需要10分种的稳定时间及10分钟的测试时间 Manual HydroCorr Test 手动测试 Clear cylinder with pipette inside is attached to the top of the filter housing 把洗干净的圆柱管与过滤器上游相连 Housing and cy
17、linder are filled with water 过滤器外壳及圆管中加满水 Air pressure below the expected intrusion pressure is applied 缓慢加压,不超过水浸入测试压力 After stabilization, valve is closed so all water flow into housing is through the pipette 稳定好后,关闭阀门以使水通过管路流至外 壳中 Changes in water level in the pipette can be read through the cyli
18、nder 水流的变化可通过圆柱管来读出 Automated HydroCorr Test自动化测试 As pleats compress water level drops 由于折叠式结构压缩,水平面下降 Upstream air volume increases 上游气体流增加 Instrument determines volume change by measuring the corresponding pressure drop 通过测量相应的压力降来得出体积变化 Po * Vo = P1 * V1 The rate of change in volume equals the fl
19、ow rate 体积改变的速率相当与 流速 o o P P P P f f tt ttf f o o f f HydroCorr Test Considerations 测试的注意点 Must have a leak-free system 必须在一密闭系统内进行 Filters must be dry and clean 过滤芯必须干燥且干净 It is relatively easy to Hydrocorr test “very hydrophobic” membranes such as PTFE 对于疏水性很强的滤芯,例PTFE材质的膜,水浸入法是相当容易 Successfully
20、testing “less hydrophobic” membranes such as PVDF requires ideal conditions that can be difficult to achieve in actual biopharmaceutical processes 在实际的生物制药工艺中,测试一些疏水性不强的滤膜,例PVDF膜是 比较困难的 Temperature changes should be minimized 尽量减少温度的变化 Reference testing is important 相关的参考比较重要 Must have a complete va
21、lidation package 必须有一完整的验证文本 Values must be comprehensively correlated to microorganism challenge 数据必须与细菌挑战相关 Conclusion 结论 Non-destructive integrity testing of hydrophobic filters follows the same principles as hydrophilic filters. 疏水性膜的非破坏性测试与亲 水性膜是相同的原理 All based on capillary forces 所有的测试原理基础均是毛 细管张力 Alcohol based bubble point 用酒精来测起泡点 Water based HydroCorr 水浸入法测试 WFI 注射 用水