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# 参考法规/指南
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密理博课件
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美国GMP：US GMP 21 CFR Parts 210 &211
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欧盟GMP：EU GMP Annex 1 Sterile Medicinal Products
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FDA无菌工艺指南（2004版）： FDA Aseptic Processing Guidelines
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PDA技术报告26：PDA Technical Report 26
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ISO/DIS 13408-2 无菌工艺：ISO/DIS 13408-2 Aseptic Processing
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# 目的：为什么要进行除菌过滤器验证
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确保无菌工艺的稳定性及可重现性
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各国法规的要求
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# 职责
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## 滤器供应商
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过滤器设计确认
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过滤器制造确认
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过滤器质量检验
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批次细菌挑战试验，100%滤器完整性测试
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提供过滤器验证指南（产品的验证信息）
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## 滤器使用方
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根本上负责过滤器的验证，利用外部有测试资质的实验室进行过滤器验证测试是可被接受的
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审计过滤器供应商-生产设施及质量管理体系
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过滤器的选型（在滤器生产商的指导下进行）
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过滤器/产品特定的验证研究
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确定过滤器与产物之间的兼容性-通过适当的过滤器筛选，化学兼容性表及产物测试
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工艺验证：验证每一个过滤工艺
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验证过滤器灭菌次数（重复使用）
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验证清洁次数（重复使用）
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在过滤器的参数范围内进行操作
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确认操作员资质
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# 流程
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验证总计划→工艺调查表→验证方案→报告→验证总文件
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# 过滤器的无菌保证
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## 过滤设计
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过滤性研究
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加工
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## 过滤器的灭菌
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在线灭菌（SIP）验证
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## 过滤器的完整性测试
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产品规格参数
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检测仪的IQ、OQ
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## 过滤器性能
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细菌截留
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兼容性
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析出物
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吸附性
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## 生物负荷的降低
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取样设备IQ、OQ
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微生物方法验证PQ性能
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## 培训
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滤器操作者资格证书
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灭菌过程设计，SOP的执行
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# 除菌级过滤器验证的项目
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## 生物性质
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### 毒性试验
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### 微生物截留试验
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#### 菌种，安全性
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#### 浓度
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体积
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流速：2~4L/min，cm2
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压力：0.2mPa~30psi
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#### 产品细菌截留验证
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抑菌反应、裂菌反应
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阴性对照
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过程
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灭菌
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润湿：生理盐水
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完整性
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阴性对照
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挑战
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培养
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## 物理性质
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工艺参数的研究
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压力
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流速
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压力速度曲线
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温度
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## 化学性质
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析出物
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可能影响药品纯度
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化学兼容性
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吸附
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## 产品完整性测试方法（可选）
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