供应商确认、供应链、合同加工.pdf

GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 GMP compliance beyond the production GMP compliance beyond the production plantplant 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMPGMPGMP合规性合规性合规性合规性 Suppliers Qualification, Supply Chain, contract manufacturing 供应商确认，供应链，合同加工 Dr. Octavi Colomina 葛韬维 博士葛韬维 博士 Current scenario 当前状况当前状况 The management, evaluation and approvalof suppliers is a key process of a Quality System 供应商的管理，评估以及批准是质量系统中关键的程序供应商的管理，评估以及批准是质量系统中关键的程序 ISO 9001:2000 Product realisation 产品实现产品实现 GMP ICH Q10 Pharmaceutical Quality System 制药质量系统制药质量系统 Quality Manual 质量手册质量手册 In tough times, as we have now, its importance is even bigger for costs optimisation 正如我们现在处于的困难时期，供应商的管理其重要性对于成本优化显 得格外重要 正如我们现在处于的困难时期，供应商的管理其重要性对于成本优化显 得格外重要 GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 Supplier Qualification and GMP 供应商确认以及GMP供应商确认以及GMP Recent cases of deficiencies in the selection, approval and control of suppliers of raw materials have resulted in catastrophic results spread worldwide 最近的一些关于原料供应商选择，批准及控制缺失的案例，导致了世界范围内巨 大的灾难性结果 最近的一些关于原料供应商选择，批准及控制缺失的案例，导致了世界范围内巨 大的灾难性结果 Heparin 肝素钠肝素钠 Diethylene glycol 一缩乙二醇一缩乙二醇 Counterfeiting of drugs and APIs 假药及假的原料药假药及假的原料药 Special sensitivity and concern of regulatory authorities on the control of suppliers 药政官方对于供应商控制特别的敏感和关注药政官方对于供应商控制特别的敏感和关注 Many companies are developing or extending the internal policies for supplier qualification 很多公司针对供应商的确认，努力将其内部质量方针应用或扩展至其供应商很多公司针对供应商的确认，努力将其内部质量方针应用或扩展至其供应商 Understanding supplier qualification 理解供应商确认理解供应商确认 It is an interdisciplinary process where different areas in the organisation should be involved and coordinated 这是一个跨领域的过程，需要不同部门的参与与协调这是一个跨领域的过程，需要不同部门的参与与协调 Several concepts around qualification: Authorisation, Validation, Approval, 关于供应商确认的一些概念： 授权，验证，批准.关于供应商确认的一些概念： 授权，验证，批准. Qualification of suppliers supplier audit 供应商确认供应商确认供应商审计供应商审计 GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 Whats in the regulations ? 法规中的要求？ Whats in the regulations ? 法规中的要求？ GMP and supplier qualification GMP以及供应商确认GMP以及供应商确认 GMP of the World Health Organisation (WHO) (2003) 世界卫生组织（世界卫生组织（WHO）的）的GMP（ （2003） ） Cap. 7 - CONTRACT PRODUCTION AND ANALYSIS 合同加工与分析合同加工与分析 “in contractual situations, quality assurance also serves to generate confidence in the supplier” “.在合同情形下，同样需要质量保证部门的参与，以确认对供应商的信心” “The contract should permit the contract giver to audit the facilities of the contract accepter” “合同应该允许合同提供方对合同接受方的工厂进行审计” GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 GMP and supplier qualification GMP以及供应商确认GMP以及供应商确认 GMP of the World Health Organisation (WHO) (2003) 世界卫生组织（WHO）的GMP（2003）世界卫生组织（WHO）的GMP（2003） Cap. 8 - SELF-INSPECTION AND QUALITY AUDITS. Suppliers audits and approval 内部检查及质量审计。 供应商审计及批准内部检查及质量审计。 供应商审计及批准 “The person responsible for quality control should have responsibilitytogether with other relevant departments for approving suppliers who can reliably supply starting and packaging materials that meet established specifications” “负责质量控制的人员应该有责任与其它相关部门一起批准能够可靠地供应符合 质量标准起始原料和包装材料的供应商” “Before suppliers are approved and included in the approved suppliers list or specifications, they should be evaluated. The evaluation should take into account a suppliers history and the nature of the materials to be supplied. If an audit is required, it should determine the suppliers ability to conform with GMP standards” “在供应商被批准以及加入合格供应商名单之前，应该对其进行评估。评估应该 考虑供应商的历史以及产品的性质。如果需要进行审计，审计应该确定供应商 GMP标准的符合程度。” US GMP. 21 CFR 211 211.84 TESTING AND APPROVAL OR REJECTION OF COMPONENTS, DRUG PRODUCT CONTAINERS, AND CLOSURES 211.84 组分，药品包装箱和密封物的测试及批准/拒绝 211.84 组分，药品包装箱和密封物的测试及批准/拒绝 “In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the suppliers analyses through appropriate validation of the suppliers test results at appropriate intervals ” “假如生产商对该组分进行了至少一次同一性测试，并且假如生产商已经在 适当的时间段内对供应商测试结果进行了适当地验证对供应商测试结果进行了适当地验证从而确立了供应商分析 的可靠性，那么供应商供应商对一个组分的测试分析报告是可以接受的，从而这些 测试可以由供应商来进行以替代生产商测试。” GMP and supplier qualification GMP以及供应商确认GMP以及供应商确认 GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 CHINESE GMP (1998) 中国中国GMP1998 10 QUALITY MANAGEMENT 质量管理质量管理 Article 76: “Quality management department is required to evaluate the quality system of main materials providers with relevant departments” 第76条：“质量管理部门应该与其它相关部门一起评估主要原料供应商 的质量系统” GMP and supplier qualification GMP以及供应商确认GMP以及供应商确认 EU GMP 2 PERSONNEL 人员人员 “The heads of Production and Quality Control generally have some shared, or jointly exercised, responsibilities relating to quality” “: the approval and monitoring of suppliers of materials” “生产及质量控制主管一般具有一些共享的或者共同执行的关于质量的职责” “.: 批准以及监测供应商物料” 5 PRODUCTION 生产生产 “Special attention should be paid to a knowledge of the suppliers quality assurance system in assessing the suitability of a source and the extent of quality control testing required “ “应该特别注意对供应商质量保证系统的认识，以便评估物料来源的可靠性以及质量 控制部门需要测试的程度” GMP and supplier qualification GMP以及供应商确认GMP以及供应商确认 GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 EU GMP Annex 8. SAMPLING OF STARTING AND PACKAGING MATERIALS 附录8： 起始物料以及包装材料的取样附录8： 起始物料以及包装材料的取样 “validated procedure exempting identity testing of each incoming container of starting material could be accepted for: “.通过验证的程序以免除测试每一个起始物料的同一性测试是可以接受的：” starting materials coming from a single product manufacturer or plant; 起始物料来自一个专一的产品生产商或工厂 starting materials coming directly from a manufacturer or in the manufacturers sealed container where there is a history of reliability and regular audits of the manufacturers Quality Assurance system are conducted by the purchaser (the manufacturer of the medicinal product) or by an officially accredited body” 起始物料直接来自生产商或有生产商的密封标志，而该生产商的质量保证 系统是通过采购方（药品生产商）或正式授权机构的定期审计的，有可靠性 的历史记录 GMP and supplier qualification GMP以及供应商确认GMP以及供应商确认 Part II EU GMP / ICH Q7A 7 Materials Management 物料管理物料管理 “Manufacturers of intermediates and/or APIs should have a system for evaluating the suppliers of critical materials” “中间体或原料药的生产商应该拥有一个评估关键原料供应商评估关键原料供应商的系统” 7.3 SAMPLING AND TESTING OF INCOMING PRODUCTION MATERIALS 生产原料的取样及测试生产原料的取样及测试 7.31 ”Supplier approval should include an evaluation that provides adequate evidence (e.g., past quality history) that the manufacturer can consistently provide material meeting specifications” 7.31 “供应商批准应该包括一个评估，该评估提供足够的证据（比如过去的质 量历史记录）以表明该供应商能够持续地提供符合质量标准的原料” Directives 2004/27/EC and 2005/28/EC Obligation to Marketing Authorisation holders of using ONLY active ingredients manufactured under GMP. 市场准入持有者的义务，只能只能使用符合GMP生产的原料药 GMP and supplier qualification GMP以及供应商确认GMP以及供应商确认 GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 ICH Q9 II.5 Quality Risk Management as Part of Materials Management Assessment and evaluation of suppliers and contract manufacturers II.5 质量风险管理作为供应商及合同加工物料管理评估与评价的一部分质量风险管理作为供应商及合同加工物料管理评估与评价的一部分 “To provide a comprehensive evaluation of suppliers and contract manufacturers (e.g., auditing, supplier quality agreements)” “提供供应商及合同加工者的全面的评价（比如：审计，供应商质量协定）” ICH Q10 - 2 MANAGEMENT RESPONSIBILITY 管理职责管理职责 2.7 Management of Outsourced Activities and Purchased Materials 2.7 外包行为以及物料采购的管理外包行为以及物料采购的管理 “Assessing prior to outsourcing operations or selecting material suppliers, the suitability and competence of the other party to carry out the activity or provide the material using a defined supply chain (e.g., audits, material evaluations, qualification)” “在外包及选择物料供应商之前，评估其执行或通过指定的供应链提供物料的适当性 以及能力（比如：审计，物料评估，确认）” GMP and supplier qualification GMP以及供应商确认GMP以及供应商确认 The process of Supplier Qualification 供应商确认过程 The process of Supplier Qualification 供应商确认过程 Scope and elements 范围以及要点范围以及要点 GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 Scope of application 应用范围应用范围 Manufacturers of: 生产商生产商 Active ingredients 原料药原料药 Excipients 辅料辅料 Packaging materials 包装材料包装材料 Brokers and distributors 经纪人和分销商经纪人和分销商 Contract laboratories 合同实验室合同实验室 Logistic operators 物流操作员物流操作员 Software suppliers 软件供应商软件供应商 Transport companies 运输公司运输公司 supply chain供应链供应链 Responsibilities in the process 各个环节的职责各个环节的职责 Purchasing 采购采购 Production 生产生产 Quality Assurance 质量保证质量保证 Quality Control 质量控制质量控制 R & D 研发研发 GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 Qualification elements 确认要素确认要素 1. Initial evaluation 起始评估起始评估 Company profile 公司概况公司概况 Questionnaire 调查问卷调查问卷 Technical and legal capability to supply 技术及法规能力技术及法规能力 References from other customers 其它客户的参考意见其它客户的参考意见 2. Audit 审计审计 GMP + technical capability + manufacturing/control capability GMP + 技术能力技术能力 + 生产/控制能力生产/控制能力 Priority Risk Ranking (ICH Q9) 优先性优先性根据风险来排定（根据风险来排定（ICH Q9） ） Corrective actions and follow up 纠偏行动以及后续跟进纠偏行动以及后续跟进 Period of validity 有效时间有效时间 Follow up audits 审计跟进审计跟进 Qualification elements 确认要素确认要素 GMP compliance beyond the production plantGMP compliance beyond the production plant： Suppliers Qualification, Supply Chain, contract manufacturingSuppliers Qualification, Supply Chain, contract manufacturing 制药工厂外延的制药工厂外延的制药工厂外延的制药工厂外延的GMPGMP合规性合规性合规性合规性：供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工供应商确认，供应链，合同加工 CPHI Shanghai, June 24th, 2009 2009 3. Assessment of QC data 质量控制数据评估质量控制数据评估 Retrospective and prospective 回顾性以及前瞻性回顾性以及前瞻性 Trends 趋势趋势 Related to APR / PQR process 与年度质量回顾相关联与年度质量回顾相关联 4. Supplier approval 供应商批准供应商批准 Approved, authorised, validated, 批准的，授权的， 验证的.批准的，授权的， 验证的. Different levels of control 不同的控制等级不同的控制等级 Periodic reassessment 周期性的重新评估周期性的重新评估 Qualification elements 确认要素确认要素 xxx Production 生产 SUPPLIER APPROVALSUPPLIER APPROVAL 供应商批准供应商批准 Suppli