制药业需求的质量管理人员

制药业需求的质量管理人员What Quality Professionals do the Pharmaceutical Industries Need?,2013.04.03,质量的重要性Why is Quality Important?,质量部门是制药公司的重要部门之一Quality unit is one of the important departments in pharma industries.PatientsPharma industries need good quality to survive.中国与国际市场接轨 One world药品出口 Exportation to other countries药品代工 Contract manufacturing organization合资药业 Joint venture就业机会（国内和国际）Find a good job,质量与国际市场,制药业,制药界现状的比较,工业结构：4800产品结构：价格产品研发和人员：投资，研发理念质量体系和人员：实施问题国内和国际制剂市场,中国药品出口现状,目前30个公司许可出口100种药品到发达国家，占药品出口量5%。So far, 30 companies received GMP certificates from developed markets, which export 100 finished products, or less than 5% of Chinas total pharma exports, 2015年的目标是80个公司出口200种药品。By 2015, the government aims to have 80 companies export 200 products to developed markets.,The Pink Sheet, 2/26/2013,对比一下 TEVA,149 个申报等待FDA审批149 product applications awaiting final FDA approval62个第一个申报在美国待批准62 first to file applications pending in the US在欧洲有1,103个已批准的仿制药1,103 generic approvals in Europe, as of December 2012在欧洲有2,131待批准的申请2,131 marketing authorization applications pending approval in 30 European countries.,对比一下：较小公司,Greenstone大约80个仿制药，450个SKUApotex大约108个仿制药， 410个SKU,国内药物市场,专利过期的国外药品仍比国内仿制药贵高达6倍。The price gap between off-patent originals and domestic generics can be as high as six times.专利过期的国外药品占跨国药业在中国收入的80%。Off-patent products contribute 80% of revenues for multinational pharmaceuticals companies.,虽然很多因素束缚制药界进入发达国家市场，例如研发方法，注册能力等，但质量是一个重要的因素,质量的代价？Cost of Quality？,是坚持质量增加的成本？还是不注意质量造成的损失？,他山之玉,TEVA仿制药的目标是：第一个投入市场高质量有竞争力的价格“TEVA aspires to be the first to market high quality, affordable, generic medicines.” -TEVA,质量体系,Current Good Manufacture Practice（CGMP）,质量是一个学科Quality Systems,不断发展的体系 It is ever-changing.自我完善的体系 It is self-improving.涵盖产品研发，生产，注册，销售等领域 It is a combination of product development, production, registration, and commercialization.越来越多的科学技术成分 It contains more and more sciences and technologies.,各种大同小异的GMP体系Various GMP systems,ICH：欧盟，美国，日本加拿大，澳大利亚，新西兰中国，印度，巴西，土耳其，俄国，韩国，新加坡，等等WHO：亚非拉,GMP六大体系,Quality system：质量管理体系Materials system：物料体系Facilities and equipment system：生产设施和设备体系Production system：生产体系Packaging and labeling system：包装和标签体系Laboratory controls：实验室控制体系,质量体系的主要工具Major tools,变更控制 Change control偏差 Non-conformance（包括 OOS, CAPA, PD）审计 Auditing（内审外审）验证 Validation and qualification（设施，工艺，方法，仪器，计算机等）程序和文件 Procedure and documentation 客户申诉 Complaint培训 Training年度总结 Annual review/report,质量部门的基本要求Basic Requirements for a Quality Organization,独立于生产部门 Independent of production承担产品质量法律责任 Legally responsible for product quality相应的权利 Empowered to make independent decision足够的人员和资源 Adequate resources,各个质量部门,QA, 质量保证QC, 质量控制（测试部门）Quality System, 质量体系部门Validation，验证部门Auditing，内审外审部门Intelligence，法规，药典，工业信息部门Quality engineering，质量统计部门Complaint，质量申诉和调查部门Documentation，文件部门Product quality，产品质量部门,质量管理人员,如何全面培养达到国际制药标准的,质量人员Quality Personnel,过去：来源于分析部门或生产部门基本是大学生现在：科研或研发部门人员硕士，博士注重研发/质量/药政交叉人员,质量部门（人员）的现状,缺少完整的药物研发经验知识更新跟不上技术和质量理念的发展对质量管理认识不到位，流于形式无法与国外客户，审计人员交流培训不到位人员配备不足配套资源不足,市场所需的质量管理人员What does the job market need?,原料药或制剂研发及生产经验分析方法研发和使用经验熟悉掌握 GMP 体系接待国外客户或药监部门审计书写注册文件，例如 IND, DMF, NDA 和 ANDA等,质量人员的培训方向Basic training for quality staff,质量体系的知识 Basic knowledge of quality system原料药和制剂的工艺开发，转移放大，生产验证，设备方面的知识和经验 Knowledge and experience of drug substance and drug product process development, transfer, scale-up, validation, and related equipment.分析方法（HPLC，GC，PSD，溶出度等）的建立，测试，质量标准建立和说明，稳定性 Analytical method development, testing; establishment of specification and justification; stability program, etc.,质量人员的培训方向Basic training for quality staff（续）,药典知识 Compendia（CP，USP，EP，JP 等等）统计知识 Statistics注册文件和注册程序DMF，ANDA，IND，NDA documents and procedures质量来源于设计 QbD风险评估 Risk Management,具体培训实例Real life examples,工艺开发，风险评估，关键工艺参数，正交试验，控制计划等方案和报告Technical report, risk assessment, critical process parameters, design of experiments, control strategies工艺验证计划和报告，样品计划，参数选择，可接受标准 Process validation protocols and reports, process parameter selection, acceptance criteria分析方法开发报告Analytical method development report,具体培训实例（续）Real life examples,分析方法验证计划和报告（HPLC, GC等），参数选择，可接受标准 Analytical method validation protocols and reports, parameter selection, acceptance criteria工艺和分析方法转移计划和报告 Process and method transfer protocols and reports稳定性试验，强解实验，运输条件实验计划和报告，数据统计分析 Stability, forced degradation, transportation study protocols and reports,具体培训实例（续）Real life examples,设备，仪器，厂房，计算机的 IQ，OQ，PQ 验证计划和报告 Equipment, instrument, facility, and computer validation protocols and reports软件的验证 Software and spread-sheet validation清洗验证 Cleaning validation空气，水系统，洁净区，压缩空气，氮气的验证 Utility validation,具体培训实例（续）Real life examples,年度产品报告Annual product review申报 IND，DMF，ANDA，NDA等等，年度 IND，DMF，ANDA 报告，更改和补充，或者 SFDA 的相关程序Registration procedures，annual regulatory filing reports审计和审计报告，答复客户审计报告，回答药监部门 483，警告信 Auditing report or answering customer or agencys auditing reports, observations, or warning letters,具体培训实例（续）Real life examples,偏差调查及报告 Non-conformance，OOS，CAPA变更报告 Change control产品放行 Batch release质量合同 Quality agreement基因毒性评估 Genotoxic impurities assessment生物等效性Bioequivalent,质量管理的趋势,New trend in quality management,近年新的趋势New trend,风险评估 Risk Management工艺分析技术 Process Analytical Technology (PAT)质量来源于设计 Quality by Design (QbD)QbD 注册QbD registration for AND