工艺验证的GMP要求.docx

1、工艺验证的GMP要求工艺验证的GMP要求Inspection of Process Validation工艺验证的检查 GMP Requirements for Process Validation工艺验证的GMP要求The expectations placed upon the manufacturer regarding GMP compliant execution of process validations can be categorized into three levels:对生产商提出的符合GMP标准的工艺验证执行期望可分为三个级别:The quality assuranc

2、e system must include GMP compliant requirements for process validation.质量保证体系必须包括符合GMP标准的工艺验证要求。Process validations must be executed according to the general requirements of the QS system.工艺验证必须根据质量体系的一般要求执行。The product and process-specific validation design must be appropriate for the specific ris

3、ks to the patient health and be scientifically justified.对患者健康的特定风险具有适当的产品和工艺相应的验证设计, 并科学合理。 The expectations which GMP inspectors should place on process validations are presented in the following.GMP检验员对工艺验证的期望如下所述：If not noted otherwise, the expectations apply regardless of the validation approac

4、h used (e.g. traditional or continuous process verification).如果没有其他说明, 无论使用何种验证方法 (例如传统或持续工艺确认), 都适用这些期望。 Quality Handbook and Process Validation质量手册和工艺验证The Quality Handbook should include a voluntary commitment declaration by the general management to perform process validations in accordance with

5、 the EU GMP Guidelines requirements, to provide the necessary organisational framework and the necessary personnel and material resources permanently.质量手册应包括总经理的自愿承诺声明, 以便按照欧盟GMP准则的要求进行工艺验证, 并提供必要的组织架构、人员和物质资源。The commitment to process validation applies also for manufacturers which produce medicina

6、l products on behalf of third parties. Responsibility for the validity of manufacturing processes in production cannot be delegated.工艺验证的承诺也适用于委托第三方生产药品的生产商。生产过程中工艺有效性的责任不能下放。Should only a portion of the medicinal product manufacturing steps be performed at a manufacturing site, then the limitation

7、of responsibility for process validations should be regulated in a quality agreement between contract giver and contract acceptor.如果在生产现场只执行一部分药品生产步骤, 则应在委托方和受托方之间的质量协议中规定工艺验证责任的范围。Contract giver must be obligated to provide all the necessary information which a manufacturer requires to fulfil his r

8、esponsibility.委托方应有义务提供生产商履行其职责所需的所有必要信息。Standard Operating Procedures for Process Validation工艺验证的标准操作规程The fundamental approach to process validations used at a manufacturing site and the general work procedures should be described in a standard operating procedure (SOP). It is at the discretion of

9、 the company whether this SOP be an individual document or be integrated in the validation master plan.生产现场使用的工艺验证的基本方法和一般工作程序应在标准操作规程 (sop) 中描述。公司自行决定此 SOP是单独成一个文件还是整合到验证总计划中。The following aspects should be addressed in the SOP at a minimum:该SOP应至少包括以下方面:Definition of the scope:定义范围Areas for which

10、this SOP applies该SOP适用的领域Types of products for which the manufacturing processes are to be validated需要进行生产工艺验证的产品类型Responsibilities of personnel for process validation工艺验证的人员职责Listing of manufacturing processes subject to validation and their validation status in the validation master plan (VMP)在验证主

11、计划 (vmp) 中列出需要验证的生产工艺及其验证状态Initiation procedure for initial process validations (events, role of the VMP)初始工艺验证的启动程序 (事件、VMP 的角色)Organisation of and procedures involved in process validation, approved validation approaches工艺验证、经批准的验证方法的组织和涉及的程序Required documents for the planning, execution and repor

12、ting of process validations (approval process, minimum content)规划、执行和报告工艺验证所要求的文档 (审批流程、内容要求)Assurance that the prerequisites for the execution of process validations (qualification of the equipment to be used, validation of test methods, ) are fulfilled确保工艺验证的先决条件 (对要使用的设备进行确认, 分析方法验证,.)已完成Performa

13、nce of risk assessments to determine the validation scope进行风险评估以确定验证范围Accepted validation approaches for the initial process validation (traditional, continuous process verification, or potentially hybrid approach) as required, including information regarding prerequisites to allow implementation of

14、 concurrent validation instead of prospective validation对于首次工艺验证(传统工艺验证、持续工艺确认或混合方法)，接受的验证方法, 包括对执行前先决条件允许同步验证而不是前验证的信息。Planning of initial validations; generation of validation protocols初始验证的计划；形成验证方案Assurance of marketing authorisation conformity of the validation design确保验证设计与上市许可一致Execution, eva

15、luation and documentation of the validation runs验证的执行、评价和文件记录Handling of unexpected deviations from the manufacturing instructions, test instructions or validation requirements对偏离生产指令、测试指令或验证要求的非预期偏差的处理Management of the generated validation data (ensuring data integrity, traceability of reports back

16、 to the raw data)生成的验证数据的管理 (确保数据完整性、从报告到原始数据的的可追溯性)Reporting for process validations工艺验证的报告Release of a validated process验证工艺的放行Conditions for the release of validation batches for market use prior to completion of the initial validation在完成验证之前，验证批次放行上市的条件Establishment and execution of ongoing proc

17、ess verification持续工艺确认的建立和执行Execution of re-validations in instances of process changes or transfer of a validated process from another production site在工艺变更或已验证工艺转移至另一生产地点时，执行再验证 Process Validations as Part of the Validation Master Plan工艺验证作为验证主计划的一部分In the validation master plan all the manufacturi

18、ng processes subject to validation should be listed (e.g. also including the processes for the production of the media used in manufacturing).在验证主计划中, 应列出所有需要验证的生产工艺 (例如, 还包括生产中使用的介质的生产工艺)。The procedure for identifying the processes must be quality assurance controlled to ensure that all relevant pr

19、ocesses are actually listed in the VMP.确定这些工艺的过程应受质量保证的控制, 以确保所有相关工艺都如实列在VMP中。For every manufacturing process the following information should be listed in the VMP:对于每个生产工艺，VMP中应列出以下信息:Unique name of the manufactured product, or manufacturing stage, as applicable所生产产品或生产阶段的唯一名称 (如适用)Document no. of

20、the master batch record used所使用主生产记录的文件编号Validation status of the process (released for commercial production yes/no)工艺的验证状态 (是否放行用于商业生产)incl. date of release or declaration of the phase which the validation is currently in, scheduled date for completion of the validation包括放行的日期或声明验证当前所处的阶段，完成验证的预定日

21、期Validation approach (traditional or continuous process verification)验证方法 (传统或持续工艺确认)Type of validation (prospective or concurrent)验证的类型（前验证或同步验证）Whether the process has previously been validated using the bracketing approach该工艺以前是否已使用括号法进行验证If this specific process has not been validated: indication of the reference process used to deduce the validity of the process如果这一具体工艺没有得到验证: 说明用于证实工艺有效性的参考程序