Access Services Considerations for Filter Validation ACCESS验证服务 过滤器验证要点验证服务 过滤器验证要点 Objectives目标目标 Why filter validation is important 过滤器验证的重要性何在 Who is responsible for validation 谁将对验证负责 What needs to be validated 需要验证哪些内容 How Merck Millipore can help 默克密理博将如何帮助您 Why is filter validation important 过滤器验证的重要性过滤器验证的重要性 Filter Validation is a Good Business Practice which ensures 过滤器验证是良好的生产实践 能保证 过滤器验证是良好的生产实践 能保证 Consistent 生产的连续稳定性生产的连续稳定性 reproducible results生产批次重复性好生产批次重复性好 It is a regulatory requirement 法规的要求法规的要求 Filter Validation is Required Worldwide by GMP 世界各国 法规要求进行过滤器验证世界各国 法规要求进行过滤器验证 US GMP 21 CFR Parts 210 211 美国GMP Appropriate written procedures shall be established and followed Such procedures shall include validation of any sterilization process 必须建立和跟进相应的证明性文件 这些文件中包括所有的除菌工艺的验证文件 EU GMP Annex 1 Sterile Medicinal Products 欧盟GMP 无菌药品附录 All sterilization processes should be validated 所有除菌工艺必须进行验证 Australian TGA GMP 澳大利亚 TGA GMP Filtration processes used as the sterilizing step for products should be validated 出于除菌目的过滤工艺应该验证 Health Canada GMP 加拿大GMP Documented evidence is available establishing validation and validity of each sterilization process 每步除菌工艺必须要有验证其有效性的证明性文件 Filter Validation in Regulatory and Industry Guidelines 法规及行业指南对过滤验证的要求法规及行业指南对过滤验证的要求 FDA Aseptic Processing Guidelines 1987 2004 www fda gov FDA无菌工 艺指南 Correlate filter performance with filter integrity testing Include microbiological challenges to simulate worst case production conditions 与过滤器完整性相关的性能测试应包括 模拟生产条件 在最苛刻生产环境下进行微生物挑战试验 PDA Technical Report 26 1998 www pda org Early careful screening of potential filter types and configuration can result in fewer technical and regulatory problems fewer delays more efficient product processing and greater sterility assurance 更早地 更细致地选用过滤器的规格和类型可减少技术和法规方面的问题 避免延误 更有效的生产 更好的无菌保障 ISO DIS 13408 2 Aseptic Processing 2003 www iso ch ISO DIS 无菌工艺 Filter Pre selection shall take into account chemical and physical characteristics of the filter as established by the filter manufacturer Bacterial retention performance of filters shall be validated in a fluid specific manner or for fluid groups under worst case conditions in production 选择过滤器前向生产商确认 仔细考虑过滤器的物理 化学性能 细菌截留性能验证 需要在生产过程中可能遇到的最差的条件下进行 使用产品或模拟液进行验证 Other Sources of Guidance 其它相关指南其它相关指南 FDA 483 and warning letters Show regulatory trend法规发展方向 Site Lack of Validation for缺陷常发生在 Filter Compatibility with product过滤器与产品间的兼容性 Filter Extractables过滤器的溶出物 Actual Filtration Process Conditions used实际过滤操作条件 Filter Integrity Testing Methods Fluids过滤器完整性测试方法 测试流体 Equivalency of alternate filters过滤器的一致性 Benefits of Filter Validation 过滤器验证的好处过滤器验证的好处 Validation Ensures 验证能够确保验证能够确保 Correct Filter Selection正确的过滤器选型 Chemically Compatible with product与产品的化学兼容性 Process Conditions such as temperature pressure are compatible 对生产条件 如温度 压力 耐受性 Verification of Sterilizing grade performance 无菌性能的验证 Optimized Filter Configuration优化过滤器的配置 Robust system design可靠的系统设计 Consistent Operation运行稳定 Validate Cleaning清洁验证 Validate Sterilization灭菌验证 Test Filter Integrity完整性测试 Trained Operators操作人员培训 Who is Responsible 谁对验证负责谁对验证负责 Filter User Responsibilities 用户的职责 用户的职责 Filter Selection w manufacturer s assistance 过滤器的选型 生产商协助 Filter Product Specific Validation Studies 过滤器 产品特性验证研究 Process Validation 生产工艺验证 Filter Vendor Responsibilities 生产商的职责 生产商的职责 Filter Design Qualification Filter Fabrication Qualification Filter Quality Testing 过滤器设计合理性确认 过滤器制造材料性能确认 过滤器本身质量测试 Filter User Responsibilities 用户的职责用户的职责 According to the guidelines the filter user is ultimately responsible for the filter validation 根据指南 用户应最终对过滤器的验证负责 When validating filter use be sure to 当过滤器选定后 必须 test in your drug product whenever possible 尽可能以产品进行验证 test your worst case process conditions 在最差条件下进行验证 测试最苛刻环境下过滤器性能 Using outside testing laboratories is acceptable according to 在经授权认定的实验机构进行相关实验是允许的 Aseptic Processing Guidelines 1987 2004无菌工艺指南无菌工艺指南 Data may be generated by outside labs filter suppliers or the user 数据可由第三方实验机构 过滤器生产商 或用户提供 Human Drug cGMP Notes December 1995 人类用药cGMP注释 1995年12月 The drug product manufacturer s ultimate responsibility is to ensure that worst case forumulation and processing parameters are adequately studied evaluated and documented 药品生产商应最终负责保证最差的条件下对过滤器性能充分的测试 评估 并有相应证明文件 Audit the outside laboratory 考核外部实验机构 Filter User Auditing审核审核 When auditing the outside laboratory evaluate the facility adequacy quality of the equipment documentation quality systems and training of operators 核查实验机构 仪器设备的齐备 仪器的性能可靠 证明文件 质量验证体系 及操作人 员的培训 Ensure each validation test has a protocol 保证每个验证测试均有相应实验方案 Review your protocols prior to testing 测试前核查实验方案 Ensure that protocols cover your process 保证实验方案能代表您的生产工艺过程 Meet guideline requirements满足指南要求 Signed prior to testing实验前签字确认 Responsibilities of the Filter Vendor 过滤器供应商职能过滤器供应商职能 Validate filter claims and manufacturing process 过滤器的验证证明及过滤器生产工艺 Establish specifications and operating limits 建立说明书及操作条件限制 Integrity specifications BP and diffusion 完整。