疏水过滤器完整性测试

HydroCorr Testing Hydrocorr测试
– Force water under pressure onto the surface of the filter. 把水灌在膜表面 – Applied pressure is < integral filter intrusion pressure 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 – Pleated structure compacts 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,上游的压力不会太快 下降
0 Time (min.) 10
P atm
20
HydroCorr Test Results测试结果
After initial stabilization, “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
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Alternatives 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 – 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
Alcohol Testing Issues 采用酒精测试的问题
• Alcohol / Water mixtures are often used due to: 酒精/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 Secure areas and equipment needed 需要可靠的区域及设备 Can be difficult to perform in-situ 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
Hydrophobic Integrity Testing 疏水性过滤器完整性测试
过滤/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 it’s maximum advantage 如何及合适使用Hydrocorr方法更能体现其优点
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Aerosol Based - Non-destructive Test 气雾测试----非破坏性测试
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"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
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Filter remains dry and does not require drying between testing and use 在测试与使用中,过滤膜维持干燥也不需要干燥
1.0
Water Flow
ml/min
0.5 0.4 0.3 0.2 0.1 0 10
20 minutes
Time
– 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. – 水浸入压的定义为:把水挤入疏 水性膜最大孔的最小压力
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 cylinder 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 cylinder 水流的变化可通过圆柱管来读出
P1 Water
P2 Gas d
- 4 . k . . cos
IP = ------------------d
whereபைடு நூலகம் 其中 k = shape correction factor = surface tension = contact angle d = pore diameter
Integrity Tester
Air / N2
WFI
apply pressure and hold加压并保持
2.6 2.6
Measure pressure Decay测量压力衰减
2.6
2.6
0
bar
0
bar
0
bar
0
bar
P atm
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



Particle 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
Performing HydroCorr Tests 进行疏水性测试
• Manually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 – Use a pressure transducer to measure upstream gas pressure loss 使用压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 – 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
• 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
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Don't use 100% solvent, check gauges, set pressure accurately, check for correct test gas, look for distinctive change in gas flowrate 不要使用100%的溶剂.核实压力表.正确设定压力.核实正确的测 试气体.寻找在气体流速中特别的现象
• Water-Based Integrity Tests have been developed to overcome these issues 用水来测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
Traditional Testing Principles 传统测试原理
• Typical wetting liquids are Isopropyl Alcohol (I.P.A.), Methanol, Tert-butyl Alcohol, or a mixture 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
Particle Based Integrity Testing 测试所用的颗粒
Microorganism - Destructive Test 微生物测试---破坏性测试
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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)
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