WHO第961號技術(shù)報告 附件10 藥品的預(yù)認證程序 2011Procedure for prequalification of pharmaceutical products1. Introduction介紹2. Glossary術(shù)語3. Purpose and principles目的和原則4. Steps of the procedure程序步驟5. Invitation for expressions of interest表達興趣的6. Data and information to be submitted要提交的數(shù)據(jù)和信息7. Screening of dossiers submitted提交文件的篩選8. Dossier assessment文件評估9. Site inspection現(xiàn)場檢查10. Reporting and communication of the results of the evaluation評估結(jié)果的報告和溝通11. Outcome of the prequalification procedure預(yù)認證程序的結(jié)果12. Maintenance of prequalification status預(yù)認證狀態(tài)的維護13. Cost recovery成本回收14. Confidentiality undertaking保密義務(wù)15. Conflict of interest利益沖突Appendix 1附件1Flowchart of WHO prequalification of pharmaceutical products藥品WHO預(yù)認證流程圖Appendix 2附件2Characteristics of the prequalified pharmaceutical product to be made available for public access on the WHO web siteWHO官網(wǎng)上向公共開放的預(yù)認證藥品信息 1. Introduction介紹The World Health Organization (WHO) provides United Nations agencies with advice on the acceptability, in principle, of pharmaceutical products for procurement by such agencies.世界衛(wèi)生組織WHO向聯(lián)合國機構(gòu)提供根據(jù)該機構(gòu)所采購藥品是否可接受的建議。This activity of WHO aims to facilitate access to priority essential medicines that 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 facilities 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的本活動的目的使獲得符合WHO推薦質(zhì)量標準的優(yōu)先基本藥品的通道更方便。WHO負責(zé)基于產(chǎn)品生產(chǎn)商或其它申請人提交的信息，基于對相關(guān)生產(chǎn)場所和臨床試驗場所進行的檢查，對藥品的質(zhì)量進行綜合評估。這些活動都是根據(jù)WHO推薦質(zhì)量標準的標準程序來運作的。藥品質(zhì)量顯然對于這類藥品的安全性和有效性非常關(guān)鍵。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 procurement 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 guide 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.所有被發(fā)現(xiàn)符合WHO推薦質(zhì)量標準的藥品均包括在藥品清單中，包括其指定的生產(chǎn)場所，這些生產(chǎn)場所均被認為是可以接受的。這些清單中的藥品供聯(lián)合國機構(gòu)采購選用。通過預(yù)認證的產(chǎn)品的清單原則上來說是供聯(lián)合國機構(gòu)使用的-包括聯(lián)合國愛滋病規(guī)劃署（UNAIDS）、聯(lián)合國兒童基金（UNICEF）和聯(lián)合國人口基金（UNFPA）-指導(dǎo)其采購決策。逐漸增加的符合WHO推薦標準的藥品清單可能也會對其它組織和國家有益，這些國家可能會希望參與批量采購藥品。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, inclusion 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.藥品和生產(chǎn)場所包括在清單中并不意味著被WHO批準（那是國家藥監(jiān)機構(gòu)專有的權(quán)利）。并且，包括在清單中并不表示W(wǎng)HO保證其所有產(chǎn)品對特殊目的的適用性，包括其在治療特定疾病時的安全性和/或有效性。2. Glossary術(shù)語The definitions given below apply to the terms used in this procedure. They may have different meanings in other contexts.以下給出的定義適用于本程序中所用的術(shù)語。在其它上下文中可能有不同含義。active pharmaceutical ingredient (API)活性藥物成分A substance used in a finished pharmaceutical product (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.活性藥物成分：用于制劑成品的一種物質(zhì)，具有藥物活性，或?qū)υ\斷、治愈、緩解或預(yù)防疾病有直接影響，或?qū)謴?fù)、糾正或修復(fù)人類生理功能產(chǎn)生直接作用。Applicant申請人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 the required documentation on such product(s).在期限前，提交EOI表達想要參與產(chǎn)品預(yù)認證程序，并提交本程序所需的文件的人或?qū)嶓w。contract research organization (CRO)合同研發(fā)組織（CRO）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 studies with the product submitted to WHO for assessment under the current procedure.合同研發(fā)組織：接受申請人可能將要提交WHO作預(yù)認證的產(chǎn)品中，有些與臨床研究有關(guān)的任務(wù)或義務(wù)外包的組織（商業(yè)、學(xué)術(shù)或其它）。finished pharmaceutical product (FPP)制劑產(chǎn)品A finished dosage form of a pharmaceutical product, which has undergone all stages of manufacture, including packaging in its final container and labelling.制劑產(chǎn)品：已完成所有生產(chǎn)步驟，包括最終包裝和標簽的制劑成品。invitation for expressions of interest (EOIs) or invitation表達興趣的邀請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 the 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. 表達興趣的邀請：召集有興趣組織（例如，生產(chǎn)商或其它申請人），根據(jù)WHO列在邀請中的產(chǎn)品，在指定的期限前向WHO提交表示其興趣，以參與WHO預(yù)認證程序。該EOI應(yīng)與涉及產(chǎn)品所需的資料一起提交。Manufacturer生產(chǎn)商A company that produces, packages, repackages, labels and/or relabels pharmaceutical products.生產(chǎn)商：一個生產(chǎn)、包裝、再包裝、標簽和/或再標簽藥品的公司。pharmaceutical product藥品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 medical diagnosis in human beings, or to restoring, correcting or modifying physiological functions in human beings.藥品：所有銷售或生產(chǎn)準備銷售的物質(zhì)或物質(zhì)混合物，用于治療或防止人類疾病，或診斷人類疾病，或恢復(fù)、糾正或修復(fù)人類的生理功能。Prequalification預(yù)認證Standardized quality assessment procedure of WHO to evaluate the acceptability, in principle, of pharmaceutical 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 quantities, security of the supply chain, preshipment quality control and other related aspects.預(yù)認證：WHO的標準質(zhì)量評估程序，用于評價聯(lián)合國機構(gòu)所采購的藥品的可接受性。機構(gòu)在使用這些通過預(yù)認證收集的信息前，要另外采取一些確認措施，例如確認經(jīng)濟穩(wěn)定性、供應(yīng)商的立場、供應(yīng)所需數(shù)量的能力、供應(yīng)鏈的安全性、發(fā)貨前質(zhì)量控制和其它相關(guān)方面。stringent regulatory authority (SRA)For the purpose of this procedure, a stringent regulatory authority (SRA) is:嚴格法規(guī)機構(gòu)：本程序下，嚴格法規(guī)機構(gòu)指 the medicines regulatory authority in a country which is: (a) a member of the International Conference on Harmonisation (ICH) (European Union (EU) Japan and the United States of America); or (b) an ICH Observer, being the European Free Trade Association (EFTA) as represented by SwissMedic and Health Canada (as may be updated from time to time); or (c) a regulatory authority associated with an ICH member through a legally-binding, mutual recognition agreement including Australia, Iceland, Liechtenstein and Norway (as may be updated from time to time); and 國家藥品法規(guī)機構(gòu)是：（a）是ICH成員之一（歐盟、日期和美國），或（b）ICH觀察員，是歐洲自由貿(mào)易聯(lián)盟EFTA由瑞士藥監(jiān)和加拿大藥監(jiān)代表（可能會隨時更新），或（c）通過合法聯(lián)系、共認協(xié)議與ICH成員協(xié)作的藥監(jiān)局，包括澳大利亞、冰島、里茲本、挪威（可能會隨時更新），以及 only in relation to good manufacturing practices (GMP) inspections: a medicine regulatory authority that is a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) as specified at. 僅與GMP檢查相關(guān)：藥品法規(guī)當局是PIC/S組織的成員之一3. Purpose and principles目的和原則The purpose of this WHO procedure is to evaluate whether certain pharmaceutical products (considered by WHO to be vital for the prevention and treatment of human immunodeficiency virus/acquired immunodeficiency syndrome (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 practices (hereinafter referred to as GMP).本W(wǎng)HO程序的目的是評估特定的藥品（WHO認為治療艾滋病、肺結(jié)核、瘧疾和其它疾病，或生殖健康必須的藥物）是否符合由WHO推薦的要求，是否在符合GMP的條件下生產(chǎn)。This procedure established by WHO is based on the following principles:本程序由WHO建立，基于以下原則 the medicines eligible for prequalification are listed in invitations for EOI published on the WHO web site (/prequal/info_applicants/info_for_applicants_EOIs.htm); 適合預(yù)認證的藥品在WHO官網(wǎng)上公布的EOI邀請中列出 a general understanding of the production and quality control activities of the manufacturer; 對生產(chǎn)商的生產(chǎn)和質(zhì)量控制活動的共同了解 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; 對生產(chǎn)商提交的藥品安全、有效性和質(zhì)量的數(shù)據(jù)和信息進行評估，包括產(chǎn)品配方、生產(chǎn)和檢測數(shù)據(jù)和結(jié)果 inspection of finished pharmaceutical product (FPP) and active pharmaceutical ingredient (API) manufacturing site(s) for compliance with GMP; 對原料藥和制劑生產(chǎn)場所GMP符合性的檢查 inspection of clinical testing units or contract research organizations (CROs) performing clinical trials for compliance with current good clinical practices (hereinafter referred to as GCP) and current good laboratory practices (hereinafter referred to as GLP); 對實施臨床研究的臨床試驗單位或合同研究機構(gòu)（CROs）進行GCP和GLP符合性檢查 reliance on the information supplied by stringent national medicines regulatory authorities; 依賴由嚴格國家藥監(jiān)機構(gòu)提供的信息 random sampling and testing of pharmaceutical products supplied; 對供貨的藥品進行隨機抽樣和檢測 handling of complaints and recalls reported to WHO; and 處理報告至WHO的客訴和召回，以及 monitoring of complaints from agencies and countries. 藥監(jiān)機構(gòu)和國家對客訴的監(jiān)控WHO may collaborate with national medicines regulatory authorities (NMRAs) regarding dossier assessments and inspections. Subject to the terms of section 4 below, the prequalification of a product may also be based on approval by a stringent regulatory authority (SRA).WHO可能與國家藥監(jiān)局（NMRA）一起進行對產(chǎn)品資料的評審和現(xiàn)場檢查。根據(jù)以下第4部分的情況，產(chǎn)品預(yù)認證也可以基于嚴格法規(guī)機構(gòu)的批準。WHO recommends that applicants expressing interest in participation in the prequalification procedure inform the NMRAs in the country of manufacture of their intention and request them to collaborate with WHO in the quality assessment process. It is recommended that applicants provide the NMRAs 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).WHO推薦申請人將表達要參與預(yù)認證程序的情況通知其生產(chǎn)所在國的NMRA，要求他們與WHO合作進行質(zhì)量評審過程。建議申請人向NFRA提供必要的授權(quán)，在資料評審過程中與WHO代表討論相關(guān)產(chǎn)品資料，并參與現(xiàn)場檢查（必要時，服從適當?shù)谋Ｃ軛l款）。4. Steps of the procedure程序步驟WHO undertakes a comprehensive evaluation of the quality of pharmaceutical products, based on information submitted by the applicants, and inspection of the relevant manufacturing and clinical sites. (A flowchart showing the prequalification process is provided in Appendix 1.)基于申請人提交的資料，WHO對藥品的質(zhì)量進行綜合評估，對相關(guān)的生產(chǎn)和臨床試驗場所進行現(xiàn)場檢查。（預(yù)認證流程圖見附件1）At regular intervals, and also taking into consideration pertinent 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.WHO定期，同時考慮其所收到的來自相關(guān)聯(lián)合國機構(gòu)的信息，向有興趣的組織公布邀請，請求他們自愿參與本程序，進入邀請中提到產(chǎn)品的預(yù)認證程序。By submitting an EOI, the applicant undertakes 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 in the prescribed format, and other information as requested.申請人提交EOI，表示愿意與WHO共享所有與指定藥品相關(guān)的生產(chǎn)和控制的信息，以及做出的變更和/或計劃的變更。有興趣的申請人通過按指定的格式提交產(chǎn)品資料和其它要求的信息，向WHO提供必要的信息。The procedure will normally include:程序一般包括： assessment of product dossiers, which must include product data and information as specifi ed in the guidelines for submission, available on the WHO web site (/prequal/); 對產(chǎn)品資料的評估，資料中必須包括在申報指南中列出的產(chǎn)品數(shù)據(jù)和信息，在WHO官網(wǎng)上可以找到 inspection of manufacturing sites of FPPs and active pharmaceutical ingredients (APIs), to assess compliance with GMP; 對制劑和原料藥的生產(chǎn)場所進行檢查，以對其GMP符合性進行評估 inspection of clinical sites (if applicable), to assess compliance with GCP and GLP as appropriate. 對臨床試驗場所（如適用）進行檢查，評估GCP和GLP的符合性If the evaluation above demonstrates that a product and its corresponding manufacturing (and clinical) 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.如果上述評估證明產(chǎn)品和其相應(yīng)的生產(chǎn)（和臨床試驗）場所符合WHO推薦的標準，則該產(chǎn)品會被放入可以接受的藥品清單中，原則上，供聯(lián)合國機構(gòu)采購。WHO reserves the right to terminate the evaluation of a specific product if the applicant 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.如果申請人不能提供所要求的信息，和/或不能實施所有的WHO可能會要求在一定時間完成的糾正措施，或者提供的信息不充分，使得程序無法完成，WHO保留權(quán)利中止對該產(chǎn)品的評估。WHO recognizes the evaluation of relevant products by SRAs which apply 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 such 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 inspections conducted by the regulatory authority concerned, and the exchange of relevant information between the regulatory authority and WHO.WHO知道由SRA對相關(guān)產(chǎn)品進行的評估所適用的質(zhì)量標準與WHO推薦的其實是等同的，如果NMRA愿意與WHO分享所討論產(chǎn)品的特定信息，WHO會考慮將這些產(chǎn)品直接列入WHO預(yù)認證產(chǎn)品清單。如果WHO可以獲得這些信息，這類產(chǎn)品的法規(guī)批準持有人表達其想要WHO對這些產(chǎn)品進行預(yù)認證的興趣，則WHO就可以進行上述操作。在所在國家藥監(jiān)當局對該藥品進行科學(xué)性評審，實施現(xiàn)場檢查，并且該國家藥監(jiān)當局與WHO交換相關(guān)信息的基礎(chǔ)上，這些藥品會被加入WHO預(yù)認證的產(chǎn)品清單中。An inspection of a manufacturer or CRO may not be required if:如果滿足以下條件，可能不需要對生產(chǎn)商或CRO進行檢查1. There has been an inspection by an SRA; and由SRA檢查過，以及2. The inspection was conducted within the last three years; and檢查是在最近三年內(nèi)進行的，以及3. Information on the inspection (including inspection report and responses to any deficiencies) is available for review by WHO; andWHO可以審核檢查信息（包括檢查報告和對所有缺陷的回復(fù)），以及4. Based on this and other available information, it is determined1 that the site(s) in question meet(s) the applicable WHO-recommended standards.基于此和其它可以獲得的信息，決定所討論的工廠符合WHO推薦的適用標準。With a view to coordinating inspection activities, avoiding duplication and 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 well as to regulatory authorities that are members of the PIC/S.在協(xié)調(diào)檢查活動時，根據(jù)本程序的相關(guān)規(guī)定，為避免重復(fù)檢查，無偏見地共享信息，保護申請人和生產(chǎn)商的知識產(chǎn)權(quán)，WHO會將檢查相關(guān)的信息共享給WHO成員國藥監(jiān)機構(gòu)、是PIC/S成員的藥監(jiān)機構(gòu)。5. Invitation for expressions of interest表達興趣的邀請The pharmaceutical products listed in an invitation for EOIs are considered by WHO 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EOI邀請中列出的藥品是WHO認為對某些特定疾?。òò滩?、瘧疾和肺結(jié)核）或生殖健康進行治療和預(yù)防所必須的藥品。這些藥品一般包括在WHO基本藥物清單中，或者包括在WHO相關(guān)的治療指南和建議中（或兩者中均包括）。The products included in the WHO Model List of Essential Medicines are those that satisfy the priority health-care needs of a population. They are selected, among other criteria, on the basis of disease prevalence, evidence on efficacy and safety, and analysis of comparative cost-effectiveness. Products included in WHO treatment guidelines are selected on the basis of an assessment of the evidence for benefits, risks, costs and appropriateness for use in a variety of situations, taking into account the needs of special populations and the values and preferences of the groups (professional and patient) using them.包括在WHO基本藥物清單里的產(chǎn)品是滿足人口基本健康的藥品。它們是在疾病流行程度、有效性和安全性證據(jù)、性價比分析基礎(chǔ)上，從其它標準中選出來的。包括在WHO治療指南中的產(chǎn)品是在對利益、風(fēng)險、成本和不同情況下使用的適當性的證據(jù)評估基礎(chǔ)上選擇的，同時考慮了特殊人群的需要，價值和使用它們的專業(yè)人士和病人組的優(yōu)先情況。Each invitation will be open and transparent, inviting all relevant parties to submit an EOI for the pharmaceutical products listed. Such an invitation will normally be published on the WHO web site and possibly also through other media, such as the international press.每個邀請都是公開透明的，邀請所有相關(guān)方提交列出產(chǎn)品的EOI。這種邀請一般在WHO官網(wǎng)上公布，也可以通過其它媒體，例如國際出版物找到。In situations of high public health concern as determined by WHO, the Organization may also directly invite relevant parties to submit specified product dossiers for evaluation by WHO under this procedure without publication of an invitation for EOI.如果WHO認為情況為公眾健康相關(guān)性特別高，則組織也可能直接邀請相關(guān)方提交指定產(chǎn)品文件，由根據(jù)本程序WHO進行評估，而不公開EOI邀請。6. Data and information to be submitted要提交的數(shù)據(jù)和信息Interested parties are expected to submit documentation on the pharmaceutical products as called for in the invitation for EOIs. Applicants should submit their product dossiers with the required information to the WHO focal point, before the deadline specified in the invitati