欧盟GMP及卫生消毒研讨会课件

Minimum one of the disinfectants should be sporicidal 基于经验/微生物效力考虑：至少一种 消毒液应为杀孢子剂
standard
sporicide
Active substances 有效成分
Why two different disinfectants? 为何需要两种消毒液？ • Prevent development of new resistance? 防止新的耐受性？ -> not the case 不是 Disinfectants have broad biocidal properties (different from specific antibiotics) 消毒剂具有广谱杀菌性（不同于特定抗生素）
Disinfection
EU-GMP:
Selection of disinfectants 消毒剂的选择
enveloped viruses 包膜病毒
gram + bacteria 革兰氏阳性菌
Yeast 酵母菌
gram – bacteria 革兰氏阴性菌
non-enveloped viruses 无包膜病毒
Active substances 有效成分
EU GMP Guidelines
Annex 1, Sanitation 61. Where disinfectants are used, more than one type should be employed. Monitoring should be undertaken regularly in order to detect the development of resistant strains.
• Combination of different active substances improves efficiency 将两种不同的有效成分复配能增加其效力 Examples: Ethanol + Propanol / Quat + Biguanide / Quat + Amine 如：乙醇+正丙醇 / 季铵盐+双胍 / 季铵盐+胺
EU-GMP Guidelines on Hygiene 欧盟GMP卫生和消毒相关条例
Key Guidelines & Regulations 主要法规&规范
Other important regulations 其他重要的法规、规范
EU GMP Guidelines
1 Pharmaceutical Quality System 药品质量体系 2 Personnel 人员 3 Premises and Equipment 房屋和设备 4 Documentation 文件 5 Production 生产 6 Quality Control 质控 7 Outsourced activities 外包 8 Complaints and Product Recall 投诉和召回 4 Self Inspection 自查 Annex 1 – 19 附录 ISO Standards ISO标准 European Norm (EN) 欧盟标准 European Pharmacopoeia 欧洲药典
病毒
Yeasts
酵母菌
Fungal spores
霉菌孢子
Bacterial spores
细菌芽孢
Example
Ethanol Isopropanol
Benzalkonium chloride
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++ ++ +++ +++
++ ++ + ++
++ +++ +++ ++
++ ++ + ++
Disinfection消毒
Removal of contaminants 去除污染
Sampling采样
Monitoring监测
Detection of contaminants 检测污染来自Overview 交流主题
Selection of disinfectants 消毒剂的选择 • Active substances 有效成分 • Rotation 轮换 • Sterility 灭菌性 Hygiene plan 卫生计划 • Concept / SOPs 理念/ SOPs • Sample hygiene plans 卫生计划样例 Validation of disinfectants 消毒液验证 • Methods / norms 方法/依据的标准 • Selection of strains & surfaces 菌株&载体的选择 Personnel hygiene 个人卫生 • Key areas • Hand disinfection 手消毒 Audit findings & Case studies 案例分析
Annex 1, Sanitation 62. Disinfectants and detergents should be monitored for microbial contamination; dilutions should be kept in previously cleaned containers and should only be stored for defined periods unless sterilised. Disinfectants and detergents used in Grades A and B areas should be sterile prior to use. 清洁剂和消毒剂必须监测其污染情况；稀释液 应存放于预先清洁的容器内，如果未经无菌处 理，稀释液的存放时间只能是经过验证的那段 时间。A/B级洁净间使用的清洁剂和消毒剂使 用前必须经过无菌处理。
Product selection 产品选择
Standard EU-GMP disinfectant selection 标准的欧盟GMP消毒液轮换 Routine disinfection 常规消毒剂 Active substances 有效成分
Quaternary ammonium compounds, Biguanides, Amines, Aldehydes 季铵盐、双胍、胺、醛 Cost effective Acceptable cleaning efficiency Excellent material compatibility Good user acceptance 便宜、有清洁功效、 很好的材料相容性、用户友好 Daily 每天
• To fight already resistant microbes? 对抗已有的耐受菌？ -> this is the relevant risk 这才是关键！
• Most routine disinfectants not effective against all microorganisms 大多数常规消毒液不能对所有微生物都有效 Using the correct combination of two DIFFERENT disinfectants is very important 使用正确组合的两种（有效成分的）消毒液尤其重要
fungi 霉菌
bacterial endospores 细菌芽孢
Increasing resistance to disinfectants 对消毒剂耐受性逐渐增强 Selection of the right / effective disinfectants is key 选择正确/有效的消毒剂是关键
Oxidising agents 活性氧
+++ +++
+++ +++
+++ +++
+++ +++
+++ +++
+++ +++
Hypochlorite
Peracetic acid Active Oxygen
Quats = quaternary ammonium compounds
Active substances 有效成分
Key Areas for GMP Hygiene GMP卫生关键
Raw Materials原材料 Air & Water 空气&水 Personnel人员
Entry of contaminants 污染源
Facility设施
Machinery机器
Equipment设备
Spreading of contaminants 扩大污染
Sporicidal disinfection 杀孢子剂
Peracetic acid, Active oxygen, Hydrogen peroxide, Hypochloric acid, Aldehydes 过氧乙酸、活性氧、过氧化氢、次氯酸、醛
Key features 主要原因
Excellent efficiency Acceptable material compatibility 出色的效力，可接受的材料相容性
EU-GMP regulations on Hygiene and Disinfection
欧盟GMP卫生和消毒相关条例
Dr. Christian Wippo International Business Development Life Sciences & Foodtec
European GMP
Intervals 使用频率
(Cleanroom Grade A/B)
Once a week 一周一次 More often if necessary 如有需要增加频率 Daily during „outbreak“ 每天换班时
Sterile Disinfectants 无菌消毒剂
EU GMP Guidelines
Quats = quaternary ammonium compounds
Only an overview 上表仅为参考 • Efficiency depends on formulation (specific active substance, concentration, helper substances….) 实际效力取决于配方（特定的有效成分、浓度、添加剂等）
Pharmaceutical Inspection Convention Scheme PIC/S 药品检查合作组织
International Conference on Harmonisation […] ICH Guidelines
国际（药品注册）协调会议
Key points on Hygiene & Disinfection 与卫生消毒相关的关键点
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p-tertiary amylphenol
N-(3-aminopropyl)N-dodecylpropane1,3-diamine
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+++
+++
++
++
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++
++
++
++
Polyhexamethyle nbiguanid
Formaldehyde Glutaraldehyde
Halogens 卤素
PIC/S Recommendation
PIC/S, PI007-6 药品检查合作组织 9.4.2 Sporicidal agents should be used wherever possible but particularly […] in aseptic areas. 无菌区域应当使用杀孢子剂 + Microbiologic limits (EU GMP)
More than one type = more than one active substance! 一种以上消毒液 = 一种以上有效成分 的消毒液 = 消毒液的轮换
active substance A active substance B
必须使用一种以上消毒液，必须定期监测以了解 耐受菌株的情况
Active substances 有效成分
Gram + bacteria
格兰氏阳性菌
Substance group Alcohols 醇类 Quats 季铵盐 Phenols 酚类 Amines 胺类 Biguanides 双胍 Aldehydes 醛
Gram – bacteria
革兰氏阴性菌
Viruses