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WHO第937号技术报告 附件4 GMP补充指南：验证 2006（中英文8/8）
2014-01-26 13:05:15| 分类： WHO |
7. Performance qualification 性能确认
Note: see also “Supplementary guidelines on good manufacturing practices (GMP): validation”. 注：也请参见“GMP补充指南：验证” 7.1 Systems and equipment should consistently perform in accordance with design specifications. The performance should be verified in accordance with a performance qualification protocol. 系统和设备的性能应持续满足设计标准。性能表现应根据性能确认方案进行确认。 7.2 There should be documented records for the verification of performance (performance qualification report) to indicate the satisfactory performance over a period of time. Manufacturers should justify the selected period over which performance qualification is done. 性能确认应有书面记录（性能确认报告），证明在一段时间内满足性能要求。生产商应论述其所选择的性能确认所持续的时间长度。 Format for a performance qualification protocol Validation protocol Performance Qualification Pageof TitleName of facility: | Validation Protocol #Performance Qualification Title Protocol written by Departmental Approval by Date QA Approval byDate | Objective To determine that the systems/equipment perform as intended by repeatedly running the system on its intended schedules and recording all relevant information and data. Results must demonstrate that performance consistently meets pre-determined specifications under normal conditions, and where appropriate for worst case situations. | Scope To be performed after the Installation and Operational Qualification have been completed and approved. To be performed after installation, modification or relocation and for re-validation at appropriate intervals. Each piece of equipment must be validated before it serves another piece of equipment/system during validation of the latter (e.g. water system before steam generator; steam generator before autoclave). |
*This format is used for training purposes and reflects some of the possible contents for a performance qualification protocol. Format for a performance qualification protocol (continued) Validation protocol Performance Qualification Pageof TitleName of facility: | Responsibility Person responsible for operating the system or equipment will perform the qualification and record the information. The supervisor will supervise the study, verify the completion of the records and write the Deviation Report and the Performance Qualification Report. Quality Assurance will review and approve the Performance Qualification Protocol and Report. | Materials, Equipment, Documents SOPs for normal operations of the equipment or system under test (including data record forms, charts, diagrams materials and equipment needed). Attach copies. SOP list: SOPs specific for performance tests (including data record forms, charts, diagrams, materials and equipment needed, calculations and statistical analyses to be performed, and pre-determined specifications and acceptance criteria). Attach copies. SOP list: |
*This format is used for training purposes and reflects some of the possible contents for a performance qualification protocol. Format for a performance qualification protocol (continued) Validation protocol Performance Qualification Pageof TitleName of facility: | Procedure Equipment: Run normal procedure three times for each use (configuration or load) and record all required data and any deviations to the procedure. Systems: Run for 20 consecutive working days, recording all required data and any deviations to the procedure. Prepare the Summary Data Record Form (Chart 1). | Evaluation Attach all completed, signed data record forms. Complete the Summary Data Record Form (Chart 1). Perform all required calculations and statistical analyses (Chart 2). Compare to acceptance criteria (Chart 3). Prepare Deviation Report including the justification of acceptance and impact on the performance. Prepare a Performance Qualification Report: This should include: date study initiated; date completed; observations made; problems encountered; completeness of information collected; summary of deviation report; results of any test; do results meet acceptance criteria; location of original data; other information relevant to the study; and conclusions on the validity of the equipment/system. Submit Performance Qualification Document to QA for review and approval. |
* This format is used for training purposes and reflects some of the possible contents for a performance qualification protocol. Format for a performance qualification protocol (continued) Validation protocol Performance Qualification Pageof TitleName of facility: | Chart 1: Summary Data Record (To be prepared for the specific procedure being tested) | Performed by ate Verified byate |
* This format is used for training purposes and reflects some of the possible contents for a performance qualification protocol.
Format for a performance qualification protocol (continued) Validation protocol Performance Qualification Pageof TitleName of facility: | Chart 2: Calculations and Statistical Analyses | Performed byate Verified byate |
* This format is used for training purposes and reflects some of the possible contents for a performance qualification protocol.
Format for a performance qualification protocol (continued) Validation protocol Performance Qualification Pageof TitleName of facility: | Chart 3: Acceptance Criteria vs. Performance Test results Criteria Results Pass/Fail
| | Performed byate Verified byate |
* This format is used for training purposes and reflects some of the possible contents for a performance qualification protocol.
Format for a performance qualification protocol (continued) Validation protocol Performance Qualification Pageof TitleName of facility: | Deviation report Deviation(s): Justification for acceptance: Impact on operation, function or process | Written byate Verified byate |
* This format is used for training purposes and reflects some of the possible contents for a performance qualification protocol.
Format for a performance qualification protocol (continued) Validation protocol Performance Qualification Pageof TitleName of facility: | Performance Qualification Report Results: Conclusions: | Written byate Verified byate |
* This format is used for training purposes and reflects some of the possible contents for a performance qualification protocol.
8. Requalification 再验证 Note: see also “Supplementary guidelines on good manufacturing practices (GMP): validation”. 注：也请参见“GMP补充指南：验证” 8.1 Requalification of systems and equipment should be done in accordance with a defined schedule. The frequency of requalification may be determined on the basis of factors such as the analysis of results relating to calibration, verification and maintenance. 系统和设备再验证应根据设定的计划进行。再验证频次可能基于一些因素来确定，例如与校正、确认和维护相关的结果的分析。 8.2 There should be periodic requalification. 应进行周期性再验证。 8.3 There should be requalification after changes. The extent of requalification after the change should be justified based on a risk-assessment of the change. Requalification after change should be considered as part of the change control procedure. 在变更后应进行再验证。变更后再验证的程度应基于变更的风险评估进行论述。变更后的再验证应作为变更控制程序的一部分。 9. Qualification of “in-use” systems and equipment “在用”系统和设备的确认 9.1 There should be data to support and verify the suitable operation and performance of systems and equipment that have been “in use” for a period of time, and which had not been subjected to installation and or operational qualification. 应有数据支持和确认已“在用”一段时间，未经过安装和运行确认的系统和设备的运行和性能是适当的。 9.2 These should include operating parameters and limits for critical variables, calibration, maintenance and preventive maintenance, standard operating procedures (SOPs) and records. 这些确认应包括运行参数和关键变量的限度、校正、维护和预防性维护、标准操作规程和记录。 10. Reference 参考文献 A WHO guide to good manufacturing practice (GMP) requirements. Part 2: Validation. Geneva, Global Programme for Vaccines and Immunization, Vaccine Supply and Quality, Global Training Network, World Health Organization, 1997 (WHO/VSQ/97.02). WHO的GMP指南要求，第二部分，验证
Appendix 7 附件7 Non-sterile process validation 非无菌工艺验证 1. Principle 原则 2. Scope 范围 3. General 通则 4. Prospective validation 前验证 5. Concurrent validation 同步验证 6. Retrospective validation 回顾性验证 7. Revalidation 再验证 8. Change control 变更控制 1. Principle 原则 1.1 Process validation provides documented evidence that a process is capable of reliably and repeatedly rendering a product of the required quality. 工艺验证提供文件证据证明工艺可以可靠地重复生产出所要求质量的产品。 1.2 The principles of planning, organizing and performing process validation are similar to those for qualification. It should be done in accordance with process validation protocols, data should be collected and reviewed against predetermined acceptance criteria, and reflected in process validation reports. 计划、组织和实施工艺验证的原则与确认的原则相似，应该根据工艺验证方案实施，应该收集数据并进行审核，与预定的可接受标准比较，并反映在工艺验证报告中。 2. Scope 范围 2.1 These guidelines describe the general aspects of process validation for the manufacture of non-sterile finished products. 这些指南描述了非无菌制剂生产工艺验证中的一般问题。 2.2 Normally process validation should cover at least the critical steps and parameters (e.g. those that may have an impact on the quality of the product) in the process of manufacturing a pharmaceutical product. 通常工艺应至少包括药品生产工艺中的关键步骤和参数（例如，那些可能对产品质量有影响的参数）。 3. General 通则 3.1 The policy and approach to process validation should be documented, e.g. in a validation master plan, and should include the critical process steps and parameters. 工艺验证的方法和方针应该有文件记录，例如，在验证主计划中，应包括关键艺步骤和参数。 3.2 Process validation should normally begin only once qualification of support systems and equipment is completed. In some cases process validation may be conducted concurrently with performance qualification. 工艺验证一般要等支持性系统和设备确认完成后才可以开始。在某些情况下，工艺验证可能与性能确认同步开展。 3.3 Process validation should normally be completed prior to the manufacture of finished product that is intended for sale (prospective validation). 工艺验证一般在销售用成品生产前进行（前验证）。 Process validation during routine production may also be acceptable (concurrent validation). 在常规生产进行中实施工艺验证也可以接受（同步验证）。 4. Prospective validation 前验证 4.1 Critical factors or parameters that may affect the quality of the finished product should be identified during product development. To achieve this, the production process should be broken down into individual steps, and each step should be evaluated (e.g. on the basis of experience or theoretical considerations). 在产品研发过程中，应识别对成品质量会产生影响的关键因素和参数。为此，生产工艺应分为单个步骤，对每个步骤均应进行评估（例如，基于经验或理论考虑）。 4.2 The criticality of these factors should be determined through a “worst-case” challenge where possible. 如可能，这些因素的关键程度应通过一个“最差情形”挑战来决定。 4.3 Prospective validation should be done in accordance with a validation protocol. The protocol should include: 前验证应根据验证方案实施。方案应包括 — a description of the process; — 工艺描述 — a description of the experiment; — 实验的描述 — details of the equipment and/or facilities to be used (including measuring or recording equipment) together with its calibration status; — 要使用的设备和/或设施的详细情况（包括测量或记录设备）及其校正状态 — the variables to be monitored; — 要监控的变量 — the samples to be taken — where, when, how, how many and how much (sample size); — 取样，取样点，时间，取样方法，样品数量 — the product performance characteristics/attributes to be monitored, together with the test methods; — 需要监控的产品性能特性/属性，及其检测方法 — the acceptable limits; — 可接受限度 — time schedules; — 时间计划 — personnel responsibilities; and — 人员职责 — details of methods for recording and evaluating results, including statistical analysis. — 记录和评估结果的方法细节，包括统计分析 4.4 All equipment, the production environment and analytical testing methods to be used should have been fully validated (e.g. during installation qualification and operational qualification). 所有使用的设备，生产环境和检验方法均应经过完整验证（例如，在安装确认和运行确认中）。 4.5 Personnel participating in the validation work should have been appropriately trained. 参与验证工作的人员均应经过适当培训。 4.6 Batch manufacturing documentation to be used should be prepared after these critical parameters of the process have been identified, and machine settings, component specifications and environmental conditions have been determined and specified. 所使用的批生产文件均应在对工艺的关键参数被识别，设备设置、组分质量标准和环境条件被确认和指定后进行准备， 4.7 A number of batches of the final product should then be produced. 要生产一些批次的成品。 The number of batches produced in this validation exercise should be sufficient to allow the normal extent of variation and trends to be established and to provide sufficient data for evaluation. 在验证实施中所生产的这些批次应足够常规的验证程度，可以建立趋势，可以提供充分的数据供评估。 4.8 Data within the finally agreed parameters, from at least three consecutive batches, giving product of the desired quality may be considered to constitute a proper validation of the process. 从生产的连续三批符合预定质量要求的产品中，所获得的数据符合最终同意的参数范围，可以考虑构成工艺验证内容。 4.9 The batches should be of the same size, and should be the same as the batch size intended in full-scale production. Where this is not possible, the reduced batch size should be considered in the design of the protocol and when full-scale production starts, the validity of any assumptions made should be demonstrated. 所有批次批量应该相同，应该是想要生产的全批量。如果无法做到，则可以考虑在方案中设计将批量降低，如果全批量生产开始，则需要证明所有假设的有效性。 4.10 Extensive testing should be performed on the product at various stages during the manufacturing process of the batches, including on the final product and its package. 在批次生产过程中，对各步骤的产品应进行大量测试，包括最终成品及其包装。 4.11 The results should be documented in the validation report. As a minimum, the report should include: 结果应记录在验证报告中。报告最少应包括 l a description of the process: batch/packaging document, including details of critical steps; l 工艺描述：批/包装记录，包括关键步骤的详细内容 l a detailed summary of the results obtained from in-process and final testing, including data from failed tests. When raw data are not included, reference should be made to the sources used and where it can be found; l 中控和最终测试结果的详细汇总，包括失败测试的数据。如果未包括原料数据，则需要在记录中说明哪些原料被使用，在什么地方可以找到这些数据 l any work done in addition to that specified in the protocol, or any deviations from the protocol should be formally noted along with an explanation; l 方案以外的所有额外工作，或任何偏离方案的偏差均应正式记录，并进行解释 l a review and comparison of the results with those expected; and l 对结果进行审核并与预期要求进行比较 l formal acceptance or rejection of the work by the team or persons designated as being responsible for the validation, after completion of any corrective action or repeated work. l 在所有纠正措施或重复工作完成后，由小组或负责验证的人员正式接受或拒绝所做工作 4.12 A conclusion and recommendation should be made on the extent of monitoring and the in-process controls necessary for routine production, on the basis of the results obtained. 基于所获得的数据，应给出结论和建议，说明验证时的监控和中控是否都需要在日常生产中常规执行。 4.13 The conclusion and recommendation should be incorporated into the batch manufacturing and batch packaging documents and/or standard operating procedures (SOPs) for routine use. Limits and frequencies of testing and monitoring should be specified. Actions to be taken in the event of the limits being exceeded should be specified. 所做出的结论和建议应结合到日常使用的批生产记录和批包装文件和/或标准操作规程SOP中，要说明测试和监控所进行的频次，如果超出限度需要采取的措施。 4.14 Batches manufactured as part of the validation exercise, and intended to be sold or supplied, should have been manufactured under conditions that comply fully with the requirements of good manufacturing practice and the marketing authorization (where applicable). 生产的批次作为验证实践，如果想要销售或供给后续生产，则生产必须完全符合GMP要求和上市许可的要求（适用时）。 5. Concurrent validation 同步验证 5.1 In certain cases, it may be appropriate to validate a process during routine production, e.g. where the product is a different strength of a previously validated product, a different tablet shape or where the process is well understood. 在特定情况下，也可以在常规生产中进行工艺验证，例如，所生产的产品是一个已经过验证的产品的不同剂量，不同片剂形状，或已对工艺有很好的了解。 5.2 The decision to carry out concurrent validation should be made by appropriately authorized personnel. 应由适当的被授权人作出同步验证的决定。 5.3 It is essential that the premises and equipment to be used during concurrent validation have been previously qualified. 同步验证所用的设施设备均应在之前已确认。 5.4 Prospective validation should be done in accordance with a validation protocol. 前验证应根据验证方案实施。 5.5 The results should be documented in the validation report. 结果应记录在验证报告中。 6. Retrospective validation 回顾性验证 6.1 Retrospective validation is based on a comprehensive review of historical data to provide the necessary documentary evidence that the process is doing what it is believed to do. This type of validation also requires the preparation of a protocol, the reporting of the results of the data review, a conclusion and a recommendation. 回顾性验证是基于对历史数据的综合审核，提供必要的文件证据证明工艺可以达到预期目的。这类验证也要求准备方案，报告数据审核的结果，结论和推荐。 6.2 Retrospective validation is not the preferred method of validation and should be used in exceptional cases only. It is acceptable only for well-established processes and will be inappropriate where there have been changes in the composition of the product, operating procedures or equipment. 回顾性验证不是优先的验证方法，只应该用于例外情况下。只有用于已运行良好的工艺才可以接受，如果产品组分、操作程序或设备有变更。则不适用。 6.3 Sufficient data should be reviewed to provide a statistically significant conclusion. 应审核足够的数据，以进行统计学分析，作出显著结论 6.4 When the results of retrospective validation are considered satisfactory, this should serve only as an indication that the process does not need to be subjected to validation in the immediate future. 如果回顾性验证可以令人满意，则仅能作出结论认为工艺不需要在中期计划中要求验证。 7. Revalidation 再验证 Note: see main text on “Validation”. The need for periodic revalidation of non-sterile processes is considered to be a lower priority than for sterile processes. 注：参见“验证”正文。非无菌工艺被认为比无菌工艺在周期性再验证方面的要求更低。 7.1 In the case of standard processes using conventional equipment, a data review similar to that which would be required for retrospective validation may provide an adequate assurance that the process continues to be under control. The following points should also be considered: 如果标准工艺使用传统设备，数据审核与回顾性验证要求相似，充分证明工艺持续受控。还应考虑以下问题点 — the occurrence of any changes in the master formula, methods, starting material manufacturer, equipment and/or instruments; — 在主配方、方法、起始物料生产商、设备和/或仪器变更发生后 — equipment calibrations and preventive maintenance carried out; — 所实施的设备校正和预防性维护 — standard operating procedures (SOPs); and — 标准操作规程 — cleaning and hygiene programme. — 清洁和卫生程序 8. Change control 变更控制 Note: see main text on “Validation”. 注：同时参见“验证”正文 8.1 Products manufactured by processes that have been subjected to changes should not be released for sale without full awareness and consideration of the change and its impact on the process validation. 工艺变更后所生产的产品，只有在对变更有全面了解和考虑，以及评估了变更对工艺验证的影响后才可以放行。 8.2 Changes that are likely to require revalidation may include: 可能会需要进行再验证的变更包括 — changes in the manufacturing process (e.g. mixing times, drying temperatures); — 生产工艺变更（例如，混合时间，干燥温度） — changes in the equipment (e.g. addition of automatic detection systems); — 设备变更（例如，增加自动检测系统） — production area and support system changes (e.g. rearrangement of areas or a new water treatment method); — 生产区域和支持性系统变更（例如，区域重排或新的水处理方法） — transfer of processes to another site; and — 工艺转移至另一个场地 — unexpected changes (e.g. those observed during self-inspection or during routine analysis of process trend data). — 预期外的变更（例如，在自检中或工艺趋势数据常规分析发现的问题）
WHO第961号技术报告 附件10 药品的预认证程序 2011（中英文） 2014-01-28 18:35:27| 分类： WHO | 标签：
World Health Organization WHO Technical Report Series, No. 961, 2011 Annex 10 附件10 Procedure for prequalification of pharmaceutical products 药品的预认证程序 1. Introduction 介绍 2. Glossary 术语 3. Purpose and principles 目的和原则 4. Steps of the procedure 程序步骤 5. Invitation for expressions of interest 表达兴趣的 6. Data and information to be submitted 要提交的数据和信息 7. Screening of dossiers submitted 提交文件的筛选 8. Dossier assessment 文件评估 9. Site inspection 现场检查 10. Reporting and communication of the results of the evaluation 评估结果的报告和沟通 11. Outcome of the prequalification procedure 预认证程序的结果 12. Maintenance of prequalification status 预认证状态的维护 13. Cost recovery 成本回收 14. Confidentiality undertaking 保密义务 15. Conflict of interest 利益冲突 Appendix 1 附件1 Flowchart of WHO prequalification of pharmaceutical products 药品WHO预认证流程图 Appendix 2 附件2 Characteristics of the prequalified pharmaceutical product to be made available for public access on the WHO web site WHO官网上向公共开放的预认证药品信息
1. Introduction 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WHO向联合国机构提供根据该机构所采购药品是否可接受的建议。 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的本活动的目的使获得符合WHO推荐质量标准的优先基本药品的通道更方便。WHO负责基于产品生产商或其它申请人提交的信息，基于对相关生产场所和临床试验场所进行的检查，对药品的质量进行综合评估。这些活动都是根据WHO推荐质量标准的标准程序来运作的。药品质量显然对于这类药品的安全性和有效性非常关键。 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 Children’s 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. 所有被发现符合WHO推荐质量标准的药品均包括在药品清单中，包括其指定的生产场所，这些生产场所均被认为是可以接受的。这些清单中的药品供联合国机构采购选用。通过预认证的产品的清单原则上来说是供联合国机构使用的---包括联合国爱滋病规划署（UNAIDS）、联合国儿童基金（UNICEF）和联合国人口基金（UNFPA）--指导其采购决策。逐渐增加的符合WHO推荐标准的药品清单可能也会对其它组织和国家有益，这些国家可能会希望参与批量采购药品。 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. 药品和生产场所包括在清单中并不意味着被WHO批准（那是国家药监机构专有的权利）。并且，包括在清单中并不表示WHO保证其所有产品对特殊目的的适用性，包括其在治疗特定疾病时的安全性和/或有效性。 2. Glossary 术语 The definitions given below apply to the terms used in this procedure. They may have different meanings in other contexts. 以下给出的定义适用于本程序中所用的术语。在其它上下文中可能有不同含义。 active pharmaceutical ingredient (API) 活性药物成分 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. 活性药物成分：用于制剂成品的一种物质，具有药物活性，或对诊断、治愈、缓解或预防疾病有直接影响，或对恢复、纠正或修复人类生理功能产生直接作用。 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 the required documentation on such product(s). 在期限前，提交EOI表达想要参与产品预认证程序，并提交本程序所需的文件的人或实体。 contract research organization (CRO) 合同研发组织（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. 合同研发组织：接受申请人可能将要提交WHO作预认证的产品中，有些与临床研究有关的任务或义务外包的组织（商业、学术或其它）。 finished pharmaceutical product (FPP) 制剂产品 A finished dosage form of a pharmaceutical product, which has undergone all stages of manufacture, including packaging in its final container and labelling. 制剂产品：已完成所有生产步骤，包括最终包装和标签的制剂成品。 invitation for expressions of interest (EOIs) or invitation 表达兴趣的邀请 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. 表达兴趣的邀请：召集有兴趣组织（例如，生产商或其它申请人），根据WHO列在邀请中的产品，在指定的期限前向WHO提交表示其兴趣，以参与WHO预认证程序。该EOI应与涉及产品所需的资料一起提交。 Manufacturer 生产商 A company that produces, packages, repackages, labels and/or relabels pharmaceutical products. 生产商：一个生产、包装、再包装、标签和/或再标签药品的公司。 pharmaceutical product 药品 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. 药品：所有销售或生产准备销售的物质或物质混合物，用于治疗或防止人类疾病，或诊断人类疾病，或恢复、纠正或修复人类的生理功能。 Prequalification 预认证 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. 预认证：WHO的标准质量评估程序，用于评价联合国机构所采购的药品的可接受性。机构在使用这些通过预认证收集的信息前，要另外采取一些确认措施，例如确认经济稳定性、供应商的立场、供应所需数量的能力、供应链的安全性、发货前质量控制和其它相关方面。 stringent regulatory authority (SRA) For the purpose of this procedure, a stringent regulatory authority (SRA) is: 严格法规机构：本程序下，严格法规机构指 — 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 — 国家药品法规机构是：（a）是ICH成员之一（欧盟、日期和美国），或（b）ICH观察员，是欧洲自由贸易联盟EFTA由瑞士药监和加拿大药监代表（可能会随时更新），或（c）通过合法联系、共认协议 与ICH成员协作的药监局，包括澳大利亚、冰岛、里兹本、挪威（可能会随时更新），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 http://www.picscheme.org.— 仅与GMP检查相关：药品法规当局是PIC/S组织的成员之一 3. Purpose and principles 目的和原则 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WHO程序的目的是评估特定的药品（WHO认为治疗艾滋病、肺结核、疟疾和其它疾病，或生殖健康必须的药物）是否符合由WHO推荐的要求，是否在符合GMP的条件下生产。 This procedure established by WHO is based on the following principles: 本程序由WHO建立，基于以下原则 — 适合预认证的药品在WHO官网上公布的EOI邀请中列出 — a general understanding of the production and quality control activities of the manufacturer; — 对生产商的生产和质量控制活动的共同了解 — 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; — 对生产商提交的药品安全、有效性和质量的数据和信息进行评估，包括产品配方、生产和检测数据和结果 — inspection of finished pharmaceutical product (FPP) and active pharmaceutical ingredient (API) manufacturing site(s) for compliance with GMP; — 对原料药和制剂生产场所GMP符合性的检查 — 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); — 对实施临床研究的临床试验单位或合同研究机构（CROs）进行GCP和GLP符合性检查 — reliance on the information supplied by stringent national medicines regulatory authorities; — 依赖由严格国家药监机构提供的信息 — random sampling and testing of pharmaceutical products supplied; — 对供货的药品进行随机抽样和检测 — handling of complaints and recalls reported to WHO; and — 处理报告至WHO的客诉和召回，以及 — monitoring of complaints from agencies and countries. — 药监机构和国家对客诉的监控 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可能与国家药监局（NMRA）一起进行对产品资料的评审和现场检查。根据以下第4部分的情况，产品预认证也可以基于严格法规机构的批准。 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推荐申请人将表达要参与预认证程序的情况通知其生产所在国的NMRA，要求他们与WHO合作进行质量评审过程。建议申请人向NFRA提供必要的授权，在资料评审过程中与WHO代表讨论相关产品资料，并参与现场检查（必要时，服从适当的保密条款）。 4. Steps of the procedure 程序步骤 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.) 基于申请人提交的资料，WHO对药品的质量进行综合评估，对相关的生产和临床试验场所进行现场检查。（预认证流程图见附件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，同时考虑其所收到的来自相关联合国机构的信息，向有兴趣的组织公布邀请，请求他们自愿参与本程序，进入邀请中提到产品的预认证程序。 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. 申请人提交EOI，表示愿意与WHO共享所有与指定药品相关的生产和控制的信息，以及做出的变更和/或计划的变更。有兴趣的申请人通过按指定的格式提交产品资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 (http://apps.who.int/prequal/); — 对产品资料的评估，资料中必须包括在申报指南中列出的产品数据和信息，在WHO官网上可以找到 — inspection of manufacturing sites of FPPs and active pharmaceutical ingredients (APIs), to assess compliance with GMP; — 对制剂和原料药的生产场所进行检查，以对其GMP符合性进行评估 — inspection of clinical sites (if applicable), to assess compliance with GCP and GLP as appropriate. — 对临床试验场所（如适用）进行检查，评估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. 如果上述评估证明产品和其相应的生产（和临床试验）场所符合WHO推荐的标准，则该产品会被放入可以接受的药品清单中，原则上，供联合国机构采购。 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. 如果申请人不能提供所要求的信息，和/或不能实施所有的WHO可能会要求在一定时间完成的纠正措施，或者提供的信息不充分，使得程序无法完成，WHO保留权利中止对该产品的评估。 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对相关产品进行的评估所适用的质量标准与WHO推荐的其实是等同的，如果NMRA愿意与WHO分享所讨论产品的特定信息，WHO会考虑将这些产品直接列入WHO预认证产品清单。如果WHO可以获得这些信息，这类产品的法规批准持有人表达其想要WHO对这些产品进行预认证的兴趣，则WHO就可以进行上述操作。在所在国家药监当局对该药品进行科学性评审，实施现场检查，并且该国家药监当局与WHO交换相关信息的基础上，这些药品会被加入WHO预认证的产品清单中。 An inspection of a manufacturer or CRO may not be required if: 如果满足以下条件，可能不需要对生产商或CRO进行检查 1. There has been an inspection by an SRA; and 由SRA检查过，以及 2. The inspection was conducted within the last three years; and 检查是在最近三年内进行的，以及 3. Information on the inspection (including inspection report and responses to any deficiencies) is available for review by WHO; and WHO可以审核检查信息（包括检查报告和对所有缺陷的回复），以及 4. Based on this and other available information, it is determined[1] that the site(s) in question meet(s) the applicable WHO-recommended standards. 基于此和其它可以获得的信息，决定所讨论的工厂符合WHO推荐的适用标准。 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. 在协调检查活动时，根据本程序的相关规定，为避免重复检查，无偏见地共享信息，保护申请人和生产商的知识产权，WHO会将检查相关的信息共享给WHO成员国药监机构、是PIC/S成员的药监机构。 5. Invitation for expressions of interest 表达兴趣的邀请 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邀请中列出的药品是WHO认为对某些特定疾病（包括艾滋病、疟疾和肺结核）或生殖健康进行治疗和预防所必须的药品。这些药品一般包括在WHO基本药物清单中，或者包括在WHO相关的治疗指南和建议中（或两者中均包括）。 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基本药物清单里的产品是满足人口基本健康的药品。它们是在疾病流行程度、有效性和安全性证据、性价比分析基础上，从其它标准中选出来的。包括在WHO治疗指南中的产品是在对利益、风险、成本和不同情况下使用的适当性的证据评估基础上选择的，同时考虑了特殊人群的需要，价值和使用它们的专业人士和病人组的优先情况。 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. 每个邀请都是公开透明的，邀请所有相关方提交列出产品的EOI。这种邀请一般在WHO官网上公布，也可以通过其它媒体，例如国际出版物找到。 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认为情况为公众健康相关性特别高，则组织也可能直接邀请相关方提交指定产品文件，由根据本程序WHO进行评估，而不公开EOI邀请。 6. Data and information to be submitted 要提交的数据和信息 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 invitation. Guidance and instructions developed for the submission of the dossiers are made available on the WHO web site. 感兴趣的组织应提交一份符合EOI邀请中的要求的药品资料。申请人应在邀请所指定的截止期前，将其产品资料与所要求的信息一起提交至WHO。关于资料提交的指南和操作指导可以在WHO官网上找到。 Normally the applicants who participate in the WHO prequalification scheme for pharmaceutical products are the manufacturers of the FPPs, as specified in the invitations for EOIs. In the case that an applicant is not the manufacturer of the FPP, all relevant documentation, including (but not limited to) contract manufacturing documentation, should be submitted, demonstrating that the applicant is in full control of the manufacturing process for, and quality assurance of, the products submitted for prequalification. 一般，就象EOI邀请里所说的，参与WHO药品预认证计划的申请人应该是制剂生产商。如果申请人不是制剂生产商，则所有相关文件，包括（但不仅限于）合同生产文件，均应提交给WHO，证明申请人对所提交预认证的产品的生产工艺和质量保证可以全面控制。 In submitting an EOI for product evaluation, the applicant should send the following to the WHO focal point: 在提交供产品评估的EOI时，申请人应提交以下内容给WHO： — a covering letter, expressing interest in participating in the WHO prequalification procedure and confirming that the information submitted in the product dossier is complete and correct; — 一封封面函，表达要参与WHO预认证程序的兴趣，确认在产品资料中提交的信息是完整和正确的 — a product dossier, in the format specified in the WHO guidance documents on submitting product data and information; — 一个产品 申报资料，按 WHO关于提交产品数据和信息的指南要求格式准备 — product samples, to enable visual examination and chemical and pharmaceutical analysis; — 产品样品，以便目视检查和化学、药学分析 — a site master fi le (SMF) for each manufacturing site listed in the product dossier, in the format specified in the WHO guidance documents for submitting an SMF; and — 在产品申报资料中涉及的每个生产场所均需一份工厂主文件（SMF），格式采用WHO提交SMF文件指南中要求的格式，以及 — a contract research organization master file (CROMF) for each clinical site listed in the dossier, in the format specified in the WHO guidance documents for submitting a CROMF. — 在申报资料中所列出的每个临床试验场所的合同组织主文件（CROMF），格式采用WHO关于提交CROMF文件指南中要求的格式 All documentation should be submitted in English. 所有文件均应用英文提交。 For the purposes of this procedure, different requirements for documentation to be submitted apply to the following categories of products: 为此目的，对以下产品类别要提交的文件适用不同要求 — multisource (generic) FPPs to be assessed by WHO; — 要由WHO评估的多来源（仿制）制剂 — innovator FPPs approved by SRAs; and — 由SRA批准的原创制剂，以及 — multisource (generic) FPPs approved by SRAs. — 由SRA批准的多来源（仿制）制剂 上述类别的文件要求在WHO网站上可以找到。这些要求可能会被不时修订。 Multisource generic products must be shown, either directly or indirectly, to be therapeutically equivalent to the comparator product if they are to be considered interchangeable. WHO will maintain and make public the list of comparator products for this purpose. The WHO web site provides guidance on the evidence needed for a product to be considered equivalent without the need for in vivo equivalence studies (i.e. application of biowaiver). 多来源仿制产品必须显示直接或间接与被比较的产品的相等的治疗效果，考虑查是否具有可互换性。为为此，WHO会维护并公开比较产品的清单。WHO官网会提供所需体内生物等效性证据指南（即申请免除生物等效性）。 If considered necessary or desirable by either party, and before the actual evaluation process starts, a discussion may be held between the manufacturer and WHO. This meeting should be scheduled as early as possible with a predefined agenda to address questions sent in advance to WHO by the manufacturer. 如果有任何一方认为必要或希望，在实际的评估过程开始前，可以在生产商和WHO之间召开讨论会。该会议应尽可能早地计划，最好有预订的议程，由供应商将需要讨论的问题提交发送给WHO。 7. Screening of dossiers submitted 提交文件的筛选 Each product dossier submitted by an applicant will be screened for completeness before being evaluated. Dossiers submitted for products which are not listed in an invitation for EOIs or have not otherwise been invited by WHO will not be accepted for assessment. 申请人提交的每个产品文件均会在开始评估前进行完整性筛选。如果提交的产品不在EOI清单里，或其它原因未被WHO邀请，则不会进入评审程序。 Similarly WHO will not consider dossiers that are incomplete. The applicant will be informed that an incomplete dossier has been received and will be requested to complete the dossier within a specified time period. 同样，WHO不会考虑不完整的文件，WHO会通知申请人收到了不完整的文件，要求其在指定的时间内补充完整。 In the event of non-compliance, the dossier may be rejected on grounds of incompleteness and returned to the applicant. Dossiers that are considered complete as the result of the screening will be retained by WHO for assessment. 如果不符合要求，则文件可能会因为不完整被退回给申请人。被认为完整的文件则由WHO留下进行进一步评审。 After screening, if the dossier is accepted for assessment the applicant will be informed of this, including the dossier reference number, by letter. This letter will serve as an agreement between WHO and the applicant for the participation in prequalification and a commitment to comply with the provisions of the prequalification procedure. 在筛选完成后，如果文件被接受进行评审，WHO会用信件通知申请人，通知中包括文件索引编号。该信函会作为WHO和申请人之间的参与预认证协议，并承诺符合预认证程序条款。 8. Dossier assessment 文件评估 The product information submitted in the dossiers will be assessed by teams of experts (assessors) appointed by WHO. The assessors involved in dossier assessment must have the relevant qualifications and experience in the fields of pharmaceutical development, quality assessment of pharmaceutical products, quality assurance, biopharmaceutics and other relevant fields. The assessors will be appointed in accordance with a standard operating procedure (SOP) established by WHO. The assessors should preferably be from NMRAs and they will act as temporary advisers to WHO. The assessors must comply with the confidentiality and conflict of interest rules of WHO, as laid down in the relevant sections of this procedure. 在文件中提交的生产信息将由WHO聘请的专家（评审员）进行评审。参与评审的评审员必须具有相关药品研发、药品质量评估、质量保证、生物制药和其它相关领域的资质和经验。WHO会根据WHO的SOP要求聘用评审员，评审员优先来自于NMRA，他们将临时作为WHO的顾问。评审员必须满足保密要求，满足在本程序中相关部分规定的WHO的利益冲突规则。 The assessment of product dossiers will be done in accordance with SOPs established by WHO for that purpose so as to ensure uniformity in evaluation and timeliness of assessment activities. If needed, WHO may provide training to these experts. 对产品资料的评审会根据WHO的SOP进行，以保证评审的一致性，和评审活动的时间限制。必要时，WHO可以给这些专家提供培训。 Following the assessment of each part of the dossier, a report will be provided to the applicant. Applicants are expected to submit responses to comments and any additional information that may be requested as soon as possible. Within one month, the applicant should inform WHO of the estimated time frame required to address and respond to all queries. The procedure is usually suspended (i.e. WHO will not undertake any further action) until all required responses and any additional information is received by WHO. 在对文件的各部分评审完成后，申请人会收到一份报告。申请人需要尽快提交回复，对问题进行答复，或提交所要求的补充资料。申请人在一个月内要告知WHO估计需要回复所有问题的时间期限。这时程序会停摆（即WHO不会采取进一步措施），直到WHO收到所要求的回复和所有补充资料。 Each applicant may request a hearing or meeting with the WHO experts involved in the assessment of this applicant’s dossier to clarify issues identified by the WHO experts. WHO may provide technical assistance to applicants regarding appropriate product information to be submitted as well as production and control requirements. 每个申请人都可以申请听证或与评估该申请人资料的WHO专家召开会议，以澄清由WHO喜剧之王提出的一些问题。WHO可以给申请人提供技术协助，在要提交的产品信息和生产、控制要求方面对其进行帮助。 9. Site inspection 工厂检查 WHO will plan and coordinate, in accordance with SOPs established by WHO and based on quality risk management (QRM) principles, the performance of inspections of the site(s) of manufacture of the API(s) and the FPP, and of the clinical testing units or CROs. WHO会根据WHO的SOP，基于质量风险管理原则，计划、协调对原料药和制剂的生产场所和临床试验单位或CRO场所进行检查。 The following factors will be taken into account when planning inspections: 在计划检查时，会考虑以下因素 — the results of previous inspection(s) by WHO or an SRA, and history of compliance of the company or facility with GMP, GCP and or GLP as appropriate; — 由WHO或一个SRA上次所进行的检查结果，公司/工厂GMP/GCP/GLP符合性 — the outcome of the assessment of data submitted to WHO; — WHO对所提交的数据的评估结果 — complexity of the site, processes and product; — 工厂、工艺和产品的复杂性 — number and significance of known quality defects (e.g. complaints, recalls); — 已知质量缺陷的数量和重大性（例如，客诉，召回） — major changes to, e.g. buildings, equipment, processes, key personnel; — 建筑、设备、工艺、关键人员的重大变更 — site experience with manufacturing and testing of a product; and — 工厂所具有的生产和检测一种产品的经验，以及 — test results of official control laboratories. — 官方控制化验室的检验结果 The inspections of the manufacturing site(s) are conducted to assess compliance with GMP as recommended by WHO and include data verification. SMFs submitted by the applicant will be reviewed before an inspection is performed. 对生产场所实施检查是为了评估与WHO推荐的GMP的符合性，包括数据确认。由申请人提交的工厂主文件在检查前进行审核。 The inspections of clinical testing units or CROs are carried out to assess compliance with GCP and GLP, and to perform data verification. 对临床试验单位或CRO实施的检查是用于评估GCP和GLP符合性，并进行数据确认。 适用于原料药、制剂、临床试验单位或CRO的标准可以在WHO官网上找到。这些要求可能会不时修订。 The inspections will be performed by a team of inspectors usually including experts appointed by WHO, preferably from NMRA inspectorates, who will act as temporary advisers to WHO. The inspectors must have the relevant qualifications and experience to perform such inspections, be competent in areas such as production and quality control of pharmaceuticals, and have appropriate experience in GMP and GCP or GLP. The inspectors must comply with the confidentiality and conflict of interest rules of WHO, as laid down in the relevant sections of this procedure. If needed, WHO may provide training to these experts. 检查由一个检查组执行，检查组通常包括WHO聘请的专家，优先来自于NMRA检查团，这些专家会作为WHO的临时顾问来工作。检查官必须具有实施这类检查相关的资质和经验，在生产、药品质量控制领域具有资质，在GMP、GCP或GLP方面具有适当的经验。检查员必须遵守WHO在本程序相关部分列举的保密守则和利益冲突守则。必要时，WHO可以给这些专家提供培训。 A WHO staff member will coordinate the team and will normally lead the inspection team. Each team will perform the inspections and report its findings to WHO in accordance with SOPs established by WHO for that purpose so as to ensure a standard harmonized approach. A representative of the NMRA of the country of manufacture would normally be expected to accompany the team to the manufacturing and testing facilities to assess the compliance with GMP and GCP or GLP. 有一个WHO工作人员会协调检查组，并且一般会领导检查组。每个小组会根据WHO的SOP要求执行检查，向WHO报告所发现的缺陷，以保证行为的一致性。一般希望生产商所在国的NMRA派出一位代表在生产和检测场所陪同检查小组，以评估GMP、GCP或GLP的符合性。 In accordance with SOPs established by WHO and based on QRM principles, an on-site inspection by a WHO inspection team may be waived provided that the site in question is found to meet the applicable WHO recommended standards following a desk review of requested inspection reports, the manufacturers response(s) to the relevant inspectorate describing corrective actions to any deficiencies identified in the inspection reports and an acceptable product quality review report for the identified product(s). 根据WHO建立的SOP，基于QRM原则，如果要接受检查的场所被发现其实符合WHO推荐的标准，在对所要求的检查报告、生产商所检查所发现缺陷的纠正措施所做的回复、对相关产品的质量回顾报告进行审核后，可能不需要由WHO检查组实施现场检查。 10. Reporting and communication of the results of the evaluation 评估结果的报告和通知 Each assessment and inspection team will finalize its reports according to the established WHO SOP and format, describing the findings and including recommendations to the applicant, manufacturer(s) and/or CROs where relevant. 每个评审和检查组会根据已有的WHO的SOP要求和格式形成一份最终报告，说明发现的缺陷，包括对申请人、生产商和/或CRO（相关时）的建议。 The findings from the dossier assessment including, but not limited to, deficiencies of the documentation and data submitted, shall be communicated in writing to the applicant requesting submission of the missing data and information, as appropriate. 在文件评审中发现的缺陷包括，但不限于，文件记录缺陷、所提交数据的缺陷，应通过书面方式与申请人进行沟通，必要时，要求提交缺失的数据和资料。 The inspection report will be communicated to the manufacturer or CRO as applicable. With the written agreement of the manufacturer or CRO, a copy of the inspection report may also be provided to the applicant (if other than the manufacturer or CRO). If any additional information is required, or corrective action has to be taken by the manufacturer or CRO, WHO will postpone its decision on the acceptability of the site(s) concerned until such information has been evaluated or the corrective action has been taken and found satisfactory in light of the specified standards. 必要时，WHO会与生产商或CRO就检查报告进行沟通。根据生产商或CRO签署的书面协议，检查报告副本也会提供给申请人（如果申请人不是生产商或CRO）。如果需要任何补充信息，或需要由生产商或CRO采取纠正措施，WHO会推荐其对涉及场所可接受性的决定，直到对这些信息完成评估，或纠正措施圆满完成，符合指定的标准。 WHO reserves the right to terminate this procedure for a specific product if the applicant is not able to provide the required information or implement the corrective actions within a specified time period, or if the information supplied is inadequate to complete this procedure. 如果申请人未能在指定的期限内提供所要求的信息，或实施所纠正措施，或者如果所提供的信息根据本程序判定为不充分时，WHO保留终止本程序的权利。 In the event of any disagreement between an applicant and WHO, an SOP established by WHO for the handling of such disagreements will be followed to discuss and resolve the issue. 如果申请人和WHO之间不能达成一致，则WHO按照已有的处理这类有争议情况的SOP来进行评论和解决问题。 As WHO is responsible for the prequalification procedure, the ownership of the reports lies with WHO. Thus, WHO shall be entitled to use and publish such reports subject always, however, to the protection of any commercially sensitive confidential information of the applicant, manufacturer(s) and/or testing organization(s). “Confidential information” in this context means: 由于WHO对预认证程序承担责任，因此报告的所有权归属WHO。因此，在保护申请人、生产商和/或检测组织的所有商业敏感的保密保息的基础上，WHO有权使用和出版这些报告。在此处“保密信息”指： — confidential intellectual property, know-how and trade secrets (including, e.g. formulas, processes or information contained or embodied in a product, unpublished aspects of trade marks, patents, etc.); and — 机密的知识产权，工艺诀窍和商标秘密（包括，例如，配方、工艺或产品中包括或结合的、商标中未公开的部分、专利等），以及 — commercial confidences (e.g. structures and development plans of a company). — 商业机密（例如，一个公司的组织机构和研发计划） Provisions of confidentiality will be contained in the exchange of letters, to be concluded before the assessment of the product dossier or inspection of the manufacturing and clinical sites, between WHO and each applicant, manufacturer or CRO. 在对产品资料开始评审前，或对生产场所和临床研究场所进行检查前，保密条款会在WHO与各申请人、生产商或CRO交换的信函中载明。 Notwithstanding the foregoing, WHO reserves the right to share the full assessment and inspection reports with the relevant authorities of any interested Member State of the Organization and interested United Nations agencies. 尽管有前述规定，WHO保留与任何利益相关的组织成员的相关药监机构，和利益相关联合国机构共享全部评估和检查报告的权利。 11. Outcome of the prequalification procedure 预认证程序的结果 Once WHO is satisfied that this procedure is complete for the relevant product, and that the WHO-recommended standards are met, the product, as manufactured at the specified manufacturing site(s), will be included in the list of prequalified pharmaceutical products. The list of prequalified pharmaceutical products will be compiled in accordance with an SOP established by WHO for final decision-making on inclusion in the list. 一旦WHO认为相关产品圆满完成本程序，在指定的生产场所生产的药品符合WHO推荐的标准，则会将其列入预认证药品清单。预认证药品清单会根据WHO的WOP进行汇整，最终决定是否包括在清单内。 The list will be published on the WHO web site and will specify the characteristics of the prequalified pharmaceutical products, as described in Appendix 2 to this procedure. 清单会公布在WHO官网上，说明预认证药品的相关信息，内容参见本程序附件2. Each applicant will receive a letter of prequalification from WHO informing it of the outcome of the quality assessment process in regard of the submitted product(s). Once the product(s) are included in the list of prequalified pharmaceutical products, the applicant shall be responsible for keeping WHO continuously updated on all relevant aspects of the manufacture and control of such product(s) and to meet any requirements, as agreed with WHO. 各申请人均会收到一封来自WHO的预认证信函，告知所提交的产品的质量评审过程过程的结果。一旦产品被包括在预认证药品清单，申请人应象与WHO共识的那样，保持向WHO更新所有与该产品生产和控制相关的方面，并符合所有要求。 In accordance with World Health Assembly Resolution WHA57.14 of 22 May 2004, WHO will — subject to the protection of any commercially sensitive confidential information — publish WHO Public Assessment Reports (WHOPAR(s)) on the product dossier assessments and WHO Public Inspection Reports (WHOPIR(s)) on the manufacturers and CROs, that were found to be in compliance with WHO-recommended guidelines and standards. These reports will be published on the WHO web site. 根据2004年5月22日的世界卫生大会决议WHA57.14,WHO会---在对商业敏感的机密信息进行保护的前提下---公布对产品文件评审的WHO公共评估报告（WHOPAR），和对生产商和CRO的WHO公共检查报告（WHOPIR），在其中说明符合WHO推荐指南和标准。这些报告会在WHO官网上公布。 Subject always to the protection of commercially sensitive confidential information, WHO shall also be entitled to publish negative evaluation outcomes in accordance with SOPs established by WHO. These include notices of concern as well as notices of suspension. 除受到商业敏感保密信息的保护的信息外，WHO有权根据WHO建立的SOP公布不好的评估结果。这些包括关注通知和搁置通知。 The decision to list a pharmaceutical product is made based upon information available to WHO at that time, i.e. information in the submitted dossier and on the status of GMP, GLP and GCP at the facilities used in the manufacture and testing of the product at the time of the site inspection(s) conducted by WHO or at the time of the site inspection(s) conducted by an SRA, the outcome of which has been determined by WHO to meet the applicable WHO-recommended standards, in accordance with the terms of this procedure. This decision is subject to change on the basis of new information that may become available to WHO. If serious safety and/or quality concerns arise in relation to a prequalified product, WHO may delist the product after evaluation of the new evidence and a risk–benefit assessment, or may suspend the product until results of further investigations become available and are evaluated by WHO. 根据本程序的规定，基于WHO在当时可以获得的信息，即，提交的资料和其在WHO或SRA现场检查期间，用于产品生产和检测的场所的GMP、GLP和GCP状态，WHO作出的是否符合适用的WHO推荐标准的结论，WHO会作出是否将一种药品列入清单的决定。该决定可能根据WHO所获得的新的信息进行更改。如果预认证的药品有严重的安全和/或质量问题，WHO可能会在对新的证据进行评估，进行风险-利益评估后，将该产品从清单上删除，或搁置直到WHO有进一步调查结果，并且WHO对此进行评估为止。 12. Maintenance of prequalification status 预认证状态的维护 Applicants are required to communicate details to WHO of any changes (variations) in manufacture and control that may have an impact on the safety, efficacy and quality of the product. 申请人应与WHO沟通所有关于产品的，可能会对产品安全性、有效性和质量产生影响的生产、控制方面的变更。 关于预认证资料的变更指南可以在WHO官网上找到。这些要求可能会修订。 It is the applicant’s responsibility to provide WHO with the appropriate documentation (referring to relevant parts of the dossier) to prove that any intended or implemented variation will not have a negative impact on the quality of the product that has been prequalified. WHO will undertake an evaluation of variations according to the established WHO guidelines and SOPs and communicate the outcome to the applicant within the prescribed time lines. Adherence to the reporting requirements will be verified during the inspections carried out by WHO. 申请人有责任向WHO提供适当的文件（参照所提交资料的相关部分）证明所有将要实施或已实施的变更不会对已通过预认证的产品质量产生负面影响。WHO会根据WHO指南和SOP对变更进行评估，在指定的期限内与申请人沟通评估结果。WHO会实施检查以确认符合报告的要求。 Random samples of prequalified products supplied by listed manufacturers or applicants will be taken for independent testing of final product characteristics. 列入清单的生产商或申请人要提供通过预认证的随机样品，供WHO进行最终产品特性的独立测试。 Certificates of analysis of final products released by the manufacturer and specifications for test methods should be provided by the manufacturer or applicant to WHO for review upon request. In the event of failure to meet the established criteria for testing, WHO will investigate the problem and communicate the outcome of this investigation to the manufacturer and applicant, if other than the manufacturer. 最终产品的检验报告由生产商放行，在WHO要求时，生产商或申请人应向WHO提供检验方法与质量标准，以进行审核。如果未能满足检测的标准，WHO会对问题进行调查，与生产商和申请人（如果申请人不是生产商）就调查结果进行沟通。 Complaints concerning prequalified pharmaceutical products communicated to WHO will be investigated in accordance with an SOP established by WHO for that purpose. After investigation, WHO will provide a written report of the problem and include recommendations for action where relevant. WHO will make the report available to the applicant/manufacturer, and to the NMRA of the country where the manufacturing site is located. WHO会根据WHO建立的相关SOP，对收到的关于预认证药品的投诉进行调查。在调查后，WHO会提供一份书面报告，包括相关行动的建议。WHO会向申请人/生产商、生产场所所在国的NMRA提供报告。 Subject always to the protection of commercially sensitive information as referred to above, WHO shall be entitled to make such reports public. In addition, WHO reserves the right to share the full report with the relevant authorities of interested Member States of the Organization and interested United Nations agencies. 除受上述商业敏感信息的保护要求的信息外，WHO有权公开这些报告。另外，WHO保留与利益相关的组织成员国的药监机构和利益相关的联合国机构共享完整报告的权利。 Manufacturers of prequalified pharmaceutical products and associated API manufacturers will be re-inspected at regular intervals as determined by WHO, but normally at least once every three years. Re-inspections are conducted to verify compliance with GMP as recommended by WHO and include data verification. 预认证药品的生产商和相关联的原料药生产商会受到定期再检查，间隔时间由WHO决定，但一般至少每三年才会检查一次。进行再检查是为了确认与WHO推荐的GMP的符合性，以及对数据的确认。 Furthermore, in order to maintain their prequalification status, WHO will arrange for prequalified pharmaceutical products to be requalified at regular intervals. 另外，为了维护其预认证状态，WHO将安排经过预认证的药品接受定期的复认证。 Every five years from the date of prequalification, or when requested to do so by the WHO Prequalification of Medicines Programme, the holder of a prequalified product is required to submit data and information in relation to the product to WHO for assessment. The purpose of this assessment is to verify that the product conforms to information and data submitted in relation to prequalification, conforms to current norms and standards, and to verify the consistency of the quality of the product and its manufacturing process(es) over the identified period. 自预认证开始每隔5年，或在WHO药品预认证程序要求时，预认证产品的持有人应提交与产品有关的数据和资料给WHO，供WHO进行评估。该评估的目的是确认该产品仍符合预认证时提交的资料和数据，符合现行标准，验证产品质量和生产工艺在一定时间内仍保持一致。 已经预认证的产品的再认证程序和指南可以在WHO官网上找到。这些要求可能会进行修订。在下列情况下，可能会实施现场再检查和/或再认证。 — if any fraud or omissions by the applicant, manufacturer(s) of an FPP or API, or CROs in the initial assessment procedure or during the followup activities, become evident; and — 如果有证据证明申请人、制剂或原料药、或CRO在初始评审程序中，或在跟踪活动中，有伪造或删除数据行为 — if WHO or any United Nations agency considers that a batch or batches of supplied prequalified pharmaceutical products are not in compliance with the specifications which were found to be applicable upon prequalification — 如果WHO或任何联合国机构认为供应的预认证的一批或多批产品不符合预认证时所用的质量标准 — If, as a result of re-inspection or requalification, it is found that a product and/or specified manufacturing site no longer complies with the WHO recommended standards, such products and manufacturing sites may be suspended or removed from the list of prequalified pharmaceutical products. — 如果，作为再次检查或复认证的结果，发现一个产品和/或指定的生产场所不再符合WHO推荐的标准，该产品和生产场所可能会被搁置或从预认证药品清单上删除 Failure of a manufacturer or applicant to participate in re-inspection or requalification (as applicable) may also lead to suspension or removal from this list. 生产商或申请人不参与再检查或复认证（适用时），也可能会被搁置或删除。 13. Cost recovery 成本回收 WHO reserves the right to charge for this procedure on a cost-recovery basis. WHO保留为本程序收取成本费用的权利。 14. Confidentiality undertaking 保密义务 The assessors and inspectors will treat all information to which they will gain access during the assessments and inspections, or otherwise in connection with the discharge of their responsibilities in regard to the above-mentioned project, as confidential and proprietary to WHO or parties collaborating with WHO in accordance with the terms set forth below. 所有评审员和检查官会将评审和检查过程中获得的信息，上述项目履行职责相关的信息，作为保密信息和知识产权信息对待，根据以下条款对WHO及相关方以外保守机密。 Assessors and inspectors will take all reasonable measures to ensure that confidential information: 评审员和检查官会采取所有合理的措施以保证这些机密信息 — is not used for any purpose other than the assessment/inspection activities described in this document; and — 不被用于除本文件描述的评审/检查活动以外的任何目的，以及 — is not disclosed or provided to any person who is not bound by similar obligations of confidentiality and non-use as contained herein. — 不被公开，不被提供给任何不受类似保密条款约束的人 Assessors and inspectors will not, however, be bound by any obligations of confidentiality and non-use to the extent they are clearly able to demonstrate that any part of the confidential information: 评审员和检查官的以下信息不受保密条款责任约束 — was known to them prior to any disclosure by or on behalf of WHO (including by manufacturers); or — 他们在WHO或代表WHO（包括生产商）之前已知的信息，或 — was in the public domain at the time of disclosure by or on behalf of WHO (including by manufacturers); or — 由WHO或代表WHO（包括生产商）获得该信息时，已为公众所知的信息，或 — has become part of the public domain through no fault of theirs; or — 已因为评审员和检查官的原因成为公众所知的一部分信息，或 — has become available to them from a third party not in breach of any legal obligations of confidentiality. — 评审员和检查官可以从不负有法定保密责任的第三方获得的信息 15. Conflict of interest 利益冲突 Before undertaking the work, each assessor and inspector will also (in addition to the above-mentioned confidentiality undertaking) be required to sign a declaration of interest. If, based on this declaration of interest, it is felt that there is no risk of a real or perceived conflict of interest (or it is felt that there is only an insignificant and/or irrelevant conflict of interest), and it is thus deemed appropriate for the assessor or inspector in question to undertake this work, he/she will discharge his/her functions exclusively as adviser to WHO. In this connection, each assessor and inspector is required to confirm that the information disclosed by him/her in the declaration of interest is correct and complete, and that he/she will immediately notify WHO of any change in this information. 在接受该工作前，每个评审员和检查官还（除上述保密要求外）被要求签署一份无利益冲突申明。如果，基于利益冲突申明，没有已存或可预期的利益冲突（或仅有不重要的和/或不相关的利益冲突），因此该评审员和检查官适于担任此工作，他/她会排外地承担该WHO的顾问工作。在此情况下，每个评审员和检查官均被要求确认其在申明中提供的信息正确完整，他/她会立即通知该类信息的变更。 All inspectors furthermore agree that, at the manufacturer’s or CRO’s request, WHO will advise the manufacturer or CRO, in advance, of the identity of each inspector and the composition of the team performing the site inspection, and provide curricula vitae of the inspectors. The manufacturer or CRO then has the opportunity to express possible concerns regarding any of the inspectors to WHO before the visit. If such concerns cannot be resolved in consultation with WHO, the manufacturer or CRO may object to a team member’s participation in the site visit. Such an objection must be made known to WHO by the manufacturer or CRO within 10 days of receipt of the proposed team composition. In the event of such an objection, WHO reserves the right to cancel all or part of its agreement with, and the activities to be undertaken by, that inspector. 所有的评审员和检查员还要同意，在生产商或CRO的要求下，WHO会提前告知生产商或CRO各参与现场检查的检查官和检查组成员身份，提供检查官简历。这样，生产商和CRO有机会在检查开始前向WHO表达其对检查官的意见。如果该意见无法通过WHO解决，生产商和CRO可以反对该外部检查参加现场检查。如果是这样，生产商或CRO必须在收到WHO的检查组成员名单后10天内告知WHO其反对意见。这种情况下，WHO有权取消该检查官的协议，或取消其部分或全部活动。
Appendix 1 附件1 Flowchart of WHO prequalification of pharmaceutical products WHO药品预认证流程图
EOI, expression of interest; FPP, finished pharmaceutical product; API, active pharmaceutical ingredient; CRO, contract research organization; WHOPIR, public inspection report; WHOPAR, public assessment report.
Appendix 2 附件2 Characteristics of the prequalified pharmaceutical product to be made available for public access on the WHO web site WHO官网上向公共开放的预认证药品信息 — WHO product reference number — WHO产品索引号 — International Nonproprietary Name (INN) of active pharmaceutical ingredient(s) (API(s)) — 活性药物成份（API）国际非专用名（INN） — dosage form and strength — 剂型和剂量 — trade name(s) of the product (if applicable) — 产品商品名（适用时） — name of applicant and official address — 申请人名称和正式地址 — name of manufacturer of finished pharmaceutical product (FPP) — 制剂生产商名称 — physical address of manufacturing site(s) (and unit, if applicable) — 生产商（和单位，适用时）的物理地址 — name of API manufacturer, physical address of manufacturing site(s) (and unit, if applicable) — 原料药生产商的名称、生产场所的物理地址（和单位，适用时） — product description (as in FPP specifications, i.e. coated, scored, etc.) — 产品描述（按制剂质量标准，即包衣后等） — pack size(s), primary and secondary packaging material(s) — 包装规格，内包和外包材料 — storage conditions — 存贮条件 — shelf-life (provisional, if applicable) — 货架期（有条件的，适用时） — summary of product characteristics — 产品特性总结 — package leaflet — 产品说明书 — Labeling — 标签
[1] Taking into account any known specific risk(s) associated with the product(s), the results of previous inspections conducted by WHO or an SRA, any complaints (if known), the scope and detail of the inspection report, the number and type of any GMP deficiencies reported, the comprehensiveness of the manufacturer?s response and the timelines for implementation of corrective action(s). 考虑所有已知的伴随产品的特定风险、WHO或SRA在此前的检查结果、所有投诉（如果已知）、检查报告的范围和详细信息、报告的所有GMP缺陷的数量和类型、生产商回复的综合内容以及纠正措施实施的时间限。
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