1、Annex 3 附录三Procedure for prequalification of pharmaceutical Products 药品预认证程序1. Introduction 介绍2. Glossary 术语3. Purpose and principles 目的及原则4. Steps of the procedure 预认证步骤5. Invitation for expressions of interest 意向书邀请 6. Data and information to be submitted 提交日期和信息 7. Screening of dossiers submitted
2、 所申报品种技术资料的筛选 8. Dossier assessment 所申报品种技术资料评估9. Site inspection 现场检查10. Reporting and communication of results of the evaluation 评估结果报告及讨论11. Outcome of the prequalification procedure 预认证结果 12. Maintenance of prequalification status 预认证状态的维护13. Cost recovery 成本回收 14. Confidentiality undertaking 保密
3、措施 15. Conflict of interest 利益冲突References 参考资料Appendix 1 附录1 Flowchart of WHO prequalification of pharmaceutical products WHO药品预认证流程图Appendix 2 附录2Characteristics of the prequalified pharmaceutical product to be made available for public access on the WHO web site WHO官网上公布的预认证药品的特性 1. Introduction
4、介绍The World Health Organization (WHO) provides United Nations agencies with advice on the acceptability, in principle, of pharmaceutical products for procurement by such agencies.世界卫生组织给联合国相关药品采购机构提供了可供其采购的质量合格的备选药品。This activity of WHO aims to facilitate access to priority essential medicines that
5、meet WHO-recommended norms and standards of acceptable quality. WHO undertakes a comprehensive evaluation of the quality of pharmaceutical products, based on information submitted by the manufacturers of such products or other applicants, and on an inspection of the corresponding manufacturing facil
6、ities and clinical sites. This is done through a standardized procedure which is based on WHO-recommended quality standards. The quality of pharmaceutical products is obviously crucial for the safety and efficacy of such products.WHO的此项举措的目的在于使获得符合WHO推荐标准和规范的质量合格的必需药品更加容易。基于药品生产企业递交的产品资料以及相应生产场地和临床实
7、验场地的现场检查来综合的评估药品的质量，该过程是按照WHO的统一标准程序来完成的。药品的质量对于药品的安全性，有效性起着至关重要的作用。The pharmaceutical products found to meet the WHO-recommended quality standards are included in the list of medicines, as manufactured at the specified manufacturing sites, which are considered to be acceptable, in principle, for pr
8、ocurement by United Nations agencies. The list of prequalified pharmaceutical products is principally intended for use by United Nations agencies including the Joint United Nations Programme on HIV/AIDS (UNAIDS), United Nations Childrens Fund (UNICEF) and United Nations Population Fund (UNFPA) to gu
9、ide their procurement decisions. The growing list of pharmaceutical products that have been found to meet WHO-recommended standards may, however, also be of interest to other organizations and countries wishing to engage in the bulk procurement of pharmaceutical products.符合WHO统一标准的、在特定生产场地生产的药品涵括在一个
10、目录中，供联合国的一些机构参考使用，指导他们的药品采购。这些机构包括联合国艾滋病规划署，联合国儿童基金会，联合国人口基金会。然而符合WHO统一标准的越来越多的药品也引起了想要参与大规模药品采购其他组织或国家的兴趣。Inclusion in the list does not imply any approval by WHO of the pharmaceutical products and manufacturing sites in question (which is the sole prerogative of national authorities). Moreover, in
11、clusion in the list does not constitute an endorsement or warranty by WHO of the fitness of any product for a particular purpose, including its safety and/or efficacy in the treatment of specific diseases.列入目录的药品并不意味着世界卫生组织批准了上述药品和厂家，这些只能由国家当局决定。而且，列入名单的药品并不构成世界卫生组织对于任何药品适用于治疗某种疾病，包括治疗专门疾病的安全性和（或者）有
12、效性的背书或担保。2. Glossary 术语The definitions given below apply to the terms used in this procedure. They may have different meanings in other contexts. 以下定义适用于此程序中所用的术语。这些术语的含义可能与其他文件不同。active pharmaceutical ingredient (API) 原料Any substance or combination of substances used in a finished pharmaceutical pr
13、oduct (FPP), intended to furnish pharmacological activity or to otherwise have direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to have direct effect in restoring, correcting or modifying physiological functions in human beings.旨在用于药品制造中的任何一种物质或物质的混合物，而且在用于制药时
14、，成为药品的一种活性成分。此种物质在疾病的诊断，治疗，症状缓解，处理或疾病的预防中有药理活性或其他直接作用，或者能修复、纠正或改善机体的功能。 Applicant 申请人The person or entity who, by the deadline mentioned in the invitation, submits an expression of interest (EOI) to participate in this procedure in respect of the product(s) listed in the invitation, together with th
15、e required documentation on such product(s).在邀请函中规定的最后期限前提交参与意向函中列举的药品的预认证意向书以及所需文件的个人或实体。contract research organization (CRO)医药研发外包An organization (commercial, academic or other) to which an applicant may have transferred some of its tasks and obligations in relation to the conduct of clinical stud
16、ies with the product submitted to WHO for assessment under the current procedure.一种学术性或商业性的科学机构。申办者可委托其执行现阶段WHO预认证药品的临床试验中的某些工作和任务。finished pharmaceutical product (FPP)药品A finished dosage form of a pharmaceutical product, which has undergone all stages of manufacture, including packaging in its fina
17、l container and labeling.药品指经过了所有生产步骤，包括上市包装和标签的药品。invitation for expressions of interest or invitation意向书Invitation calling upon interested parties (e.g. manufacturers or other applicants) to submit an expression of interest (EOI) to WHO by a specified deadline for the purpose of participating in t
18、he WHO prequalification procedure in respect of the product(s) listed in the invitation. Such an EOI should be accompanied by the required documentation on the product(s) in question.意向书呼吁有兴趣的团体（如，生产商或其他申请者）为了参与世界卫生组织在意向书中列出的药品的预认证，在指定的最后期限前，向世界卫生组织提交意向书。内容需要包括上述产品所需的文件。Manufacturer 生产商A company tha
19、t produces, packages, repackages, labels and/or relabels pharmaceutical products.对药品进行生产，包装，再包装，贴标签，重新贴标签的公司。pharmaceutical product 药物产品Any substance or combination of substances marketed or manufactured to be marketed for treating or preventing disease in human beings, or with a view to making a me
20、dical diagnosis in human beings, or to restoring, correcting or modifying physiological functions in human beings.上市的或即将上市的一种物质或多种物质的混合物，用于治疗或预防人类疾病，或用于人类的医疗诊断，或者修复、纠正、改善人类的生理机能。Prequalification 预认证Standardized quality assessment procedure of WHO to evaluate the acceptability, in principle, of pharm
21、aceutical products for purchase by United Nations agencies. Agencies using information resulting from the prequalification procedure should perform additional steps of qualification prior to purchasing, such as ensuring financial stability and standing of the supplier, ability to supply the required
22、 quantities, security of the supply chain, preshipment quality control and other related aspects.大体上来说，是世界卫生组织用于衡量联合国药品采购机构所要采购药品质量的标准质量评估程序。使用预认证信息的这些机构在采购前还应该对供应商的其他资质进行验证，如:确保供应商经济的稳定性、资信等级、生产能力、供应链的安全性，装运前质量控制，以及其他相关方面。3. Purpose and principles 目的及原则The purpose of this WHO procedure is to evalua
23、te whether certain pharmaceutical products (considered by WHO to be vital for the prevention and treatment of HIV/AIDS, tuberculosis, malaria and other diseases, or for reproductive health) meet the requirements recommended by WHO and are manufactured in compliance with current good manufacturing pr
24、actices (hereinafter referred to as GMP). This procedure established by WHO is based on the following principles:12WHO此程序的目的是为了评估某些药品（WHO认为对预防和治疗艾滋病，肺结核，疟疾和其他疾病起着至关重要作用的药品，或者用于生殖健康的药品）是否能够符合WHO的要求以及现行GMP （以下用 GMP简称）。该程序是WHO 根据以下原则建立的： a general understanding of the production and quality control act
25、ivities of the manufacturer;对生产商的生产及质量控制的全面认识; assessment of pharmaceutical product data and information on safety, efficacy and quality submitted by the manufacturer, including product formulation, manufacture and test data and results;对生产商提交的药品的安全性、有效性和质量的数据和信息，包括产品处方，生产及检验结果进行评估; inspection of th
26、e manufacturing site(s) for consistency in production and quality control of starting materials (with specific emphasis on APIs) and finished products through compliance with GMP;对于原料（特别是APIs）以及成品的生产和质量控制在全过程中是否全程贯彻GMP的现场检查; inspection of clinical testing units or CROs performing clinical trials for
27、 compliance with current good clinical practices (hereinafter referred to as GCP) and current good laboratory practices (hereinafter referred to as GLP);对进行临床试验的的临床实验单位或医药研发外包机构是否符合现行的现行临床实验管理规范（以下简称GCP）以及现行良好实验室规范（以下简称GLP）进行的检查; reliance on the information supplied by the national medicines regulat
28、ory authority;国家药品管理局所提供的信息; random sampling and testing of pharmaceutical products supplied;所提供样品的随机抽样以及检验; handling of complaints and recalls; and投诉及召回的处理; monitoring of complaints from agencies and countries.国家和机构投诉的监管；WHO may also collaborate with national medicines regulatory authorities in the
29、 quality assessment. WHO recommends that applicants expressing interest in participation in the prequalification procedure inform the national medicines regulatory authorities in the country of manufacture of their intention and request them to collaborate with WHO in the quality assessment process.
30、 It is recommended that applicants provide the national medicines regulatory authorities with the necessary authorization to discuss the relevant product files with WHO representatives during dossier assessment and site inspections (subject to appropriate confidentiality provisions, if necessary).WH
31、O也可能会与国家药品管理局合作进行质量评估。世界卫生组织建议有兴趣参与预认证的申请者告知其所在国家的药品管理局其意图并要求他们与世界卫生组织合作进行质量评估。在所申报品种技术资料评估和现场检查期间，涉及到相应的保密条款时，在必要时WHO建议申请人赋予国家药品管理局与世界卫生组织的代表进行相关产品文件讨论的必要权限。1 The prequalification procedure may also be based on approval by certain stringent regulatory agencies, such as, but not limited to, the Unit
32、ed States Food and Drug Administration (USFDA) and the European Medicines Agency (EMEA), as described in section 4: Steps of the procedure.正如第四部分：预认证步骤中描述到的预认证也可能建立在通过某些权威管理机构的认证之上，这些机构有但不局限于：美国食品药品监督管理局（USFDA）和欧洲药品管理局（EMEA）。4. Steps of the procedure 预认证步骤WHO undertakes a comprehensive evaluation of
33、 the quality of pharmaceutical products, based on information submitted by the applicants, and inspection1 3of the relevant manufacturing and clinical sites. (A flowchart showing the prequalification process is provided in Appendix 1.) At regular intervals, and also taking into consideration pertine
34、nt input received from relevant United Nations agencies, WHO will publish an invitation to interested parties, requesting them to voluntarily participate in this procedure in respect of the products mentioned in the invitation. By submitting an expression of interest (EOI), the applicant undertakes
35、to share information with WHO on all relevant aspects of manufacture and control of the specified products along with changes made and/or planned. Interested applicants provide the necessary information to WHO by submitting a product dossier and other information as requested. The procedure will nor
36、mally include:世界卫生组织根据申请者所提交的材料以及相关生产场地和临床试验产地的检查对药品的质量进行综合评估。（附录1是预认证过程的流程图）。定期的，同时也考虑到从有关联合国机构收到的相关信息，世界卫生组织会对意向方发出邀请，要求他们自愿参加在意向函中提及的相关产品的预认证。通过提交意向函，申请人与世界卫生组织将共享特定产品的生产和控制的所有相关信息，也包括已经作出的和计划作出的变更。生产方面以及那些随着变化和进展的指定产品的控制信息。感兴趣的申请者通过提交产品资料和其他所要求的信息以提供给世界卫生组织其所必需的信息。此程序包括： assessment of product do
37、ssiers, which must include product data and information as specified in the guidelines for submission, available on the WHO web site (www.who.int/prequal);产品资料的评估，必需包括产品数据以及在世界卫生组织官网上可以看到的在提交指南中所规定的信息。(www.who.int/prequal) inspection of manufacturing sites of finished pharmaceutical products (FPPs)
38、and active pharmaceutical ingredients (APIs), which must adhere to GMP; and根据GMP 的要求检查药品和原料药的生产场地；若可能的话，根据GCP 和GLP检查临床试验基地。 inspection of clinical sites (if applicable), which must adhere to GCP and GLP. If the evaluation above demonstrates that a product and its corresponding manufacturing (and cli
39、nical) site(s) meet WHO-recommended standards, the product will be included in the list of pharmaceutical products that are considered to be acceptable, in principle, for procurement by United Nations agencies. WHO reserves the right to terminate the evaluation of a specific product if the applicant
40、 is not able to provide the required information, and/or is unable to implement any corrective actions which WHO may require within a specified time period, or when the information supplied is inadequate to complete this procedure. WHO recognizes the evaluation of relevant products by SRAs which app
41、ly standards for quality equivalent to those recommended by WHO. Provided that the NMRA is willing to share certain information with WHO on the products in question, WHO will consider such products for inclusion in the list of WHO-prequalified products. It will do so as and when information about su
42、ch products becomes available to WHO and when the holders of the regulatory approval of such products express their interest in having these products prequalified by WHO. These products will be added to the list of products prequalified by WHO, on the basis of the scientific assessment and inspectio
43、ns conducted by the regulatory authority concerned, and the exchange of relevant information between the regulatory authority and WHO. 如果上述的评估表明某项产品及其相应的生产（临床试验）基地符合世界卫生组织标准，该项产品原则上就会被列在供联合国相关机构采购的合格的药品目录内。如果出现下述情况，WHO有权终止某项产品的预认证：申请者不能提供所需资料，（或）申请者不能在WHO规定的时限内完成纠正措施，申请者提供的资料不够充分。某些权威药品管理机构执行的质量标准与W
44、HO的标准相当，WHO认可这些权威机构对于相关产品的认证。如果国家药品管理局愿意与WHO分享在预认证的产品的相关资料，WHO将考虑把该产品列入WHO预认证药品目录中。当相关的药品管理机构表达出对于WHO对这些产品预认证的兴趣，并且WHO得到相关产品的资料后，WHO会考虑该产品列入WHO预认证药品目录中。在这些相关的药品管理机构对于产品进行了科学的评估和检查以及与WHO进行相关资料的互换的基础之上，这些产品将被WHO列入预认证药品目录中。An inspection of a manufacturer or CRO may not be required if:1. There has been
45、an inspection by an SRA; and2. The inspection was conducted within the last three years; and3. Information on the inspection (including inspection report and responses to any deficiencies) is available for review by WHO; and4. Based on this and other available information, it is determined1 30 that
46、the site(s) in question meet(s) the applicable WHO-recommended standards. 如果有下列情况，可以不对药品的生产商或医药外包商进行检查：1. 已经有权威管理机构检查过了；2. 并且检查是在3年内进行的；3. 并且将检查的资料（包括检查报告和缺陷问题的回复）提供给WHO；4. 建立在上述资料以及其他WHO可以审查的资料之上，WHO才能认为上述生产商或医药外包商符合WHO的质量标准。With a view to coordinating inspection activities, avoiding duplication an
47、d promoting information sharing without prejudice to the protection of any confidential and or proprietary information of the applicants and manufacturers in accordance with the terms of this procedure, WHO may disclose inspection related information to regulatory authorities of WHO Member States as
48、 well as to regulatory authorities that are members of the PIC/S.根据预认证中的条款，WHO 秉持着合作的态度以及避免重复工作、提高申请者和生产商的机密资料和个人信息共享率，WHO 可能会向其成员国的管理机构和 PIC/S（药品生产检查相互承认公约）的成员管理机构提供检查的相关资料。5. Invitation for expressions of interest意向书The pharmaceutical products listed in an invitation for EOIs are considered by WHO
49、 to be vital for the effective treatment and prevention of the specified diseases (including HIV/AIDS, malaria and tuberculosis) or for reproductive health. These products are normally included in either the WHO Model List of Essential Medicines or the relevant WHO treatment guidelines and recommendations (or both). 在意向书中列出的药品是WHO认为对于治疗和预防特定疾病（包括艾滋病，疟疾和肺结核）或对生殖健康有着重要作用的药品。这些产品要么在
