3、过滤器完整性测试原理及在线完整性测试-密理博110428

Filter Integrity Test and SIP 过滤器完整性测试原理及在线完整性测试

Content 讲座目录
‹Why we do integrity test for sterile filter? ‹为什么要对除菌滤器进行完整性测试？ ‹Method for IT?完整性测试的方法有哪些？ ‹Why bubble point could replace bacterial retention test? ‹为什么可以用起泡点的方法代替细菌挑战试验？
‹When should we do IT? ‹什么时候进行完整性检测？ ‹Bubble point theory.起泡点测试原理是什么？ ‹Diffusion test theory.扩散流测试原理是什么？ ‹Automatic integrity tester自动完整性测试仪

What is filter integrity? 什么是滤膜完整性?
Integral membrane 完整滤膜
Contaminant 比膜孔大的污染物
Non-integral membrane 非完整滤膜
Contaminant比膜孔大的污染物
No contaminant in downstream 下游没有污染物
Contaminant in downstream
下游污染

Why Integrity Test? 为什么做完整性测试?
Common Sense 通常理解 „ Filtration is often the most critical step in an operation „ 过滤通常是操作的关键步骤 „ Confirmation of manufacturers specifications „ 确认制造规格 „ Detecting leaks due to o-rings, gaskets, seals „ 检测O形环,垫圈,密封垫的泄漏 „ Assuring the correct pore size filter „ 确认正确的过滤孔经 „ Assuring integrity before sterilization „ 确认灭菌前完整性 „ Assuring integrity after steaming or autoclaving „ 确认蒸汽和消毒锅灭菌后完整性
Business Practice 商业惯例 „ Government Guidelines & Regulations法规要求 „ Part of corporate standard operating procedure公司标准 操作规程 „ Auditing requirement审计需要

Regulations about integrity test 法规中对完整性测试的规定
FDA Guideline指南 (2003) ƒ Whatever filter or combination of filters is used, validation should include microbiological challenges to simulate worst-case production conditions…”
对于由一个或多个滤器组成的过滤系统，对它 的验证都应该包括在最差条件下进行的微生物挑 战试验。

Regulations about integrity test 法规中对完整性测试的规定
Revision of annex 1 to EC Guide to GMP for sterile medicinal products (1997) 欧盟对于无菌药品GMP指南的附件一(1997版)
ƒ “The integrity of the sterilized filter should be verified before use and should be confirmed immediately after use by an appropriate method such as a bubble point, diffusive flow or pressure hold test”
ƒ 除菌过滤膜应该在使用前及使用后立即采取合适的方法确认其完整性,可以采用 泡点,扩散流或压力保持的方法.
FDA Guideline on Sterile Drug Products Produced by Aseptic Processing (2004) FDA关于无菌工艺生产的无菌药品的指南(2004版)
ƒ Integrity testing of the filter(s) can be performed prior to processing, and should be routinely performed post-use. It is important that integrity testing be conducted after filtration to detect any filter leaks or perforations that might have occurred during the filtration. 完整性测试可以在过滤工艺前进行，并应当在过滤以后进行日常测试。过滤后 通过完整性测试检测过滤过程中可能出现的泄露或破损是非常重要的。
PDA Technical Report # 26 PDA技术报告26版
ƒ “It generally is regarded as a cGMP requirement that filters or filter systems routinely be integrity tested both prior to and after use.”
ƒ 现行的GMP要求过滤器及过滤系统在使用前及使用后均需要进行完整性测试