药品生产企业实施药品GMP过程中存在差距的

1、药品生产企业实施药品 GMP (2010 年修订过程中存在差距的调查问卷Questionnaire for Investigation of the Gaps of Pharmaceutical Enterprises in Relation to the GMP Guidelines (revised in 20101. 在中国药品 GMP (2010年修订的总体实施层面 ,您主要欠缺哪些知识 ,有哪些 培训需 求?What are your major knowledge shortages and need for training in the frame of the impleme

2、ntation of the Chinese GMP Guidelines (revised in 2010?a. 以风险为基础的质量保证体系 , 欠缺的知识Risk based quality assurance systemb. 质量受权人和其他关键人员 , 已经制定本规程Qualified person and other key personsc. 人员培训 , 已经制定本规程Personnel Trainingd. 文件体系 , 已经制定本规程Documentation systeme. 空调净化系统 , 欠缺的知识HVAC systemf. 工艺用水制备 , 欠缺的知识Proces

3、s water preparationg. 设备的校准 ,确认和预防性维护 , 欠缺的知识h. Equipment calibration, qualification, and preventive maintenancei. 工艺验证 , 欠缺的知识Process validationj. 清洁验证 , 欠缺的知识Cleaning validationk. 产品质量回顾 , 欠缺的知识Product quality reviewl. 库房 *, 已经制定本规程Warehousem. 供应商确认 , 已经制定本规程Supplier qualificationn. 委托生产 ,委托检验Cont

4、ract manufacturing / testingo. 质控实验室 , 欠缺的知识QC laboratoryp. 偏差、纠正与预防措施 , 欠缺的知识Deviation / CAPAq. 超标检验数据调查 , 已经制定本规程OOS investigationsr. 变更控制 , 欠缺的知识Change control2. 您所建立的质量保证体系是否以确保产品安全并且符合注册批准要求为目的 , 以科学为准则并且以风险管理为基础 ?Is your quality assurance system established on scientific principles and on risk

5、 management basis to ensure that your products are safe and comply with the requirements of the Marketing Authorization?a. 您的质量保证体系把那些可能影响产品质量的关键参数考虑在内了吗? , 已经考虑b. Does your quality assurance system consider critical parameters that may impact on product quality?c. 那些关键参数及其控制范围是通过风险评估确定的吗 ?它们包含在验证总计

6、 划中了 吗? , 关键参数及其控制范围是通过风险评估确定的 ,包含在验证总计划 中。 Are those critical parameters and their control ranges defined by risk assessment and included in the VMP (Validation Master Plan?d. 您有用于确定那些参数及其范围的系统性方法吗 ,譬如“失效模式影响分析 ”? 没有 Is there a systematic approach such as FMEA (Failure Mode Effect Analysis to defin

7、e those parameters and ranges?e. 您公司有风险评估的书面程序吗 ,尤其是（相关的决策程序 ? ,有Does your company have a written risk assessment procedure, especially for the decision making procedure?3. 对于质量受权人和其他关键人员 (生产、质控、质保、仓储、工程等 ,您是否 系统地制 定了清晰明确的岗位说明 ? , 有岗位职责 ,Have you established a well-defined job description system for

8、 Qualified Persons (QP and other key persons (production, quality control, quality assurance, warehousing, engineering, etc.?a. 质量保证或质量受权人员在质量事务和成品批放行方面,有独立决策权吗 ? ,有 Is there an independence of quality assurance / Qualified Person in making decision of quality matters and batch release of finished p

9、roducts?b. 在法规事务、 检验技术和生产技术方面 , 对质量受权人和其他关键人员有持 续性的培 训吗? ,有Do the Qualified Person and other key persons receive continuous training in regulatory affairs and in analytical and production technology?c. 相关人员在岗位说明书上签字了吗 ? ,岗位说明书在我公司不是这个格式出 现的 Are the job descriptions signed by the people concerned?d.

10、现场是否有 :组织机构图、岗位说明书 (质量受权人、质量保证部经理、质量 控制部 经理和生产部经理 、成品批放行程序。 , 有Documents to be provided: organization diagram, job descriptions for QP, QA, QC and production managers, batch release procedure for finished products.4. 您是否根据药品 GMP (2010年修订的要求适当组织了培训 ?Do you organize training properly according to the

11、GMP Guidelines (revised in 2010?a. 您的培训工作中包括入职培训、药品 GMP 持续性培训、岗位操作培训以及 关于标准 操作规程的培训吗 ? ,有Does your training program include introduction training, continuous GMP training, on-the-job training, and training on SOPs?b. 您对培训需求是怎样定义的 （范围、内容、参加人员、时间安排 ? ,按照指南 操作 How do you define your training needs （sco

12、pe, content, involved persons, time arrangement?c. 培训计划的起草和批准程序是怎样的 ?谁来组织和监督培训 （工作 ?对于那些 偏离（培训日程计划的情形 ,是否有报告制度 ? ,有What is your procedure for preparing and approving the training plan? Who is organizing and supervising the training? Is there a system to report the deviations from the planned schedul

13、e?d. 您的药品 GMP 培训计划中是否包括了您公司不直接参与生产、质控或质保 的高层管 理者,譬如总经理、采购部 （经理等? ,包括Are the top managers of your company , not directly involved in production and quality control/assurance such as general manager, purchasing, etc. included in your GMP training plan?e. 培训师需要具备哪些资质 ?您是如何管理 （公司内部培训师的 ?您定期对他们 进行 适当培训吗

14、? ,培训师主要是公司内部部门的负责人 ,如生产和质量的相关负责 人。 What are the qualifications of trainers? How do you manage the internal trainers? Do they get proper training regularly?f. 您是如何管理培训记录的 ?您如何评估培训效果 ? ,按时记录 ,然后进行评价。 How do you manage your training records and evaluate training effectiveness?5. 您是否建立了清晰明确的药品 GMP 文件体系

15、?Do you establish a well-organized GMP documentation system?a. 您公司把哪些类文件视为药品 GMP 文件?请列表说明。 , GMP 文件系统分 为 :标准、 记录、验证三大类。What types of documents are considered as GMP documentation in your company? Please make a list.b. 您公司一共有多少份标准操作规程 ? , 200 多份 您有关于制定这类文件的标准程序吗 ? ,有How many SOPs do you have in your

16、company? Do you have an SOP for SOPs?c. 谁来起草、签署、发放文件母本 （即原件 ?您是如何保存那些原件的 ?Who is preparing, signing and issuing the master （i.e. original documents? How do you store them?起草文件按照谁使用谁起草的规定,有资质的人员签署,统一有一个 部门 负责管理。d. 您如何准备、发放那些工作 （现场用的文件 ? ,统一有一个部门负责管理。How do you prepare and issue the working documents?

17、e. 文件变更控制体系程序是怎样的 ? , 按照公司的具体情况进行编制。What is the procedure for change control system for the documentation?f. 当（文件发生变更时 ,您是如何确保所有人都得到并且在工作中使用最新版本?When changes occur, how do you ensure that everyone has got and worked with the latest version? , 按照文件的编制程序进行复制、发放、回收、销毁。g. 您的各个文件之间有交叉引用信息吗 ? ,有Do your do

18、cuments have a cross-reference to other documents?h. 您文件的回顾性审查程序是怎样的 ? ,不同的文件设定的周期不同 ,多为 2 年。 回顾 审核的周期是多久 ? , 一般是以年为周期What is your document reviewing procedure and how often do you review them?6. 您按照药品 GMP （2010年修订的要求对空调净化系统进行适当确认了吗 ?Do you perform an HVAC qualification properly according to GMP Gui

19、delines （revised in 2010?a. 您的系统运行时是采用 100%新风方式 ,还是回风参与再循环的方式 ? 采用回 风在循 环的方式 ,目的是在保证净化系统合格的同时进行节能。Is your system operating with 100% fresh air, or is the system operating in recirculation?b. 进风口和出风口使用的分别是哪种规格的过滤器 ? ,通用型号的过滤器What are the types of filters used for air inlet and outlet?c. 您的各个洁净区域 （包括不

20、同级别和同一级别内的不同区域 之间是否有空气 压差 （控 制系统?该系统的设计在防止交叉污染方面是怎样起作用的 ? ,不同区域之 间有压 差装置 ,能有效防止交叉污染。Do you have a differential air pressure system between hygiene zones, and how does the design of your system impact on the prevention of cross-contamination?d. 洁净室（或区域的划分标准是什么 ?尘粒与微生物的监控标准是什么 ,如频 次、取 样点个数、取样工具、警戒限值和行

21、动限值等 ?对 （监控数据进行回顾了吗 ? 怎么 回顾的? ,按照规范的要求进行规定 ,同时用检测的数字来保证。对于相关的指 标, 按照国家规范标准进行控制。What are the criteria for clean room (or area classification and monitoring (frequency, number of sampling points, equipment for sampling, alert and action thresholds, etc. for particles and microorganisms? Are these data

22、 being reviewed and how do you do the review?e. 为了避免交叉污染 ,您在生产中采用 “密闭系统 ”或其他措施了吗 ? ,有Do you have closed system or other measures in the production in order to avoid cross contamination?f. 您的空调净化系统是持续运行 ,还是有“夜间模式 ”的?或者是在完成工作后关 掉系 统 ? ,没有夜间模式Is your HVAC system running continuously, or do you have a n

23、ight mode, or just switch the system off after the working time?g. 现场是否有以下文件 :工厂卫生区域布局图、空调净化系统分布图和压差布 置图。 Documents to be provided: factory layout of hygiene zones, distribution of HVAC systems, and layout showing differential., 有7. 您按照药品 GMP (2010年修订的要求对水系统进行适当确认了吗 ?Do you perform a validation for

24、water system properly according to GMP Guidelines (revised in 2010?a. 您的生产部和实验室使用的水有哪些类 ? ,制药用水 (饮用水、纯化水What type(s of water do you use in production and laboratory?b. 您公司采用了怎样的制水方法 ?(请予提供的文件 :示意图或工艺与仪表图 What is the water preparation method applied in your company (document to be provided: schematic

25、 diagram or process and in strume ntati on diagram 二级反渗透c. 最终纯化步骤之后的储罐和 （送水管路是什么材质的 ? , 304What is the type of material used for the storage tank and piping after the final purification step?d. 系统中使用的阀门有哪些种类 ? , 球阀Which types of valves are used in the system?e. 纯化水的储存温度是多少 ? ,常温What is the temperatu

26、re of storage of purified water?f. 您有在线监测系统吗 ,譬如总有机碳和电导率 ? ,没有Do you have an online monitoring system, such as TOC and conductivity?g. 系统采用什么方法维护 ?储罐和（送水管路采用什么方法消毒 ? ,臭氧What are the methods for maintenance of the system and for sanitation of the storage tanks and the loop?h. 水系统的监控计划 （取样点、取样程序和频次是怎样

27、的 ?监控标准 （警戒限值 和行 动限值 是什么?对那些 （监控 数据, 包括其变化趋势进行回顾了吗 ?如何回顾的 ? What is your monitoring plan （sampling points, sampling procedure, frequency for the water system, and what are the criteria for the monitoring （alert and action thresholds?Are those data bee n reviewed, in elude trending, and how do you do

28、 the review 有i. 发现长菌后怎么办 ?您按规定程序进行有害微生物检查吗 ? , 暂时还没有发现 长菌 What do you do in case you find germs? Are you testing systematically for objectionable microorganisms?8. 您有设备校准、确认和预防性维护程序吗 ?Do you have procedures for equipment calibration, qualification, and preventive maintenance? a您怎样确定购买什么样的设备？用户需求标准”中

29、包括了哪些方面 的考虑 ? How do you define your equipment you are going to buy, and what kinds of considerationare in eluded in URS (User Requireme nt Specificatio n?购买成型设备b. 用户需求标准 ”和“设计确认”的批准程序是怎样的 ? ,按照生产的工艺要求进 行 设计 ,相关部门进行批准。What is your procedure for approval of URS and DQ (Design Qualification?c. 对于供应商能否

30、提供人员培训、校准和维护方面的服务,您与他们进行过沟通吗? Do you communicate with suppliers for availability of services in training, calibrati on, maintenan ce, etc.?有d. 您有安装确认、运行确认和性能确认方面的程序吗 ? ,有Do you have a procedure for IQ (Installation Qualification, OQ (Operation Qualification and PQ (Performance Qualification?e. 您有以风险

31、评估为基础的再确认程序吗 ? ,有Do you have a requalification procedure based on risk assessment?f. 您有校准计划吗 ? , 有Do you have a calibration program?g. 您有预防性维护计划吗 ? , 有Do you have a preventive maintenance program?h. 您保存了设备日志 (或记录吗?您在日志(或记录中记了哪些内容 ? ,有,记录 设 备的开启、运行等内容。Do you keep equipment logbooks? What do you recor

32、d in those logbooks?9. 您按照药品 GMP (2010年修订的要求适当进行工艺验证了吗 ?Do you perform a process validation properly according to GMP Guidelines (revised in 2010? a.对于所有通过风险评估确定的产品关键参数，您都进行了验证吗?,有Do you validate all critical parameters for your products that have been defined by riskassessment?b. 您的工艺验证有哪些种类 ,前瞻性的、

33、同步性的还是回顾性的?,同步性What is the type of the process validation, prospective, concurrent or retrospective?c. 对于回顾性验证 ,实际生产条件与验证批次的生产条件完全一致吗? ,是If the validation is retrospective, do the actual production conditions correspond exactly to those of the validation batches?d. 批记录中包含那些关键参数及其控制范围了吗 ? ,工艺规程要求的参数A

34、re those critical parameters and control ranges included in the batch record?e. 对再验证情况是否进行了定期审核 ? ,有要求Is there a regular review program about revalidation?10. 您按照药品 GMP (2010年修订的要求适当进行清洁验证了吗 ?Do you perform cleaning validation properly according to GMP Guidelines (revised in 2010?a. 在更换产品的清洁验证中 ,前一产

35、品的残留量标准是什么 ? 按照不同产品的特 性进行 指定In the validation for product change, what are the criteria for the residues of the previous product?b. 您是按照ICH Q2分析方法验证：文本及方法学的要求，开发并且验证残留 物检 出和定量的具体分析方法吗 ? ,按照指南要求的Did you develop and validate a specific analytical method for detection and quantification of residues acc

36、ording to ICH Q2Validation of Analytical Procedures： Text and Methodology ?c. 您公司采用的哪种清洁程序 ,原位清洁、原位预洗还是手工清洁 ? ,手工清洁What kind of the cleaning procedure is available in your company, CIP (Cleaning In Place or WIP (Washing In Place or manual cleaning?d. (清洁验证中使用的哪种取样方法 ,冲洗法、擦拭法还是 (无活性成分的空白产 品?如果使用的是擦拭法

37、 ,您是怎样选择取样点的 ?使用的是哪种擦拭棒 ? ,擦拭 法,先 评估最不易清洁的部位 ,最为取样点 ,采用棉签擦拭。What is the sampling method, rinsing, swabbing, or placebo? If swabbing method is used, how do you select the sampling points and what kind of swabs are used?e. 清洁验证中把整个生产线的所有非专用设备都考虑在内了吗 , 包括中间产品 的 (储存 容器? ,不是所有的内容均在里面Is the whole chain of

38、 the non-dedicated equipments considered in the cleaning validation, including containers for intermediates?f. 您的称量间是什么样的 ?更换品种时 ,您对称量区域的清洁情况进行哪些检查 (如天 平、抽风罩等的清洁、无尘 ? 普通乱流称量间 ,更换品种后 ,检查天平 /台秤、 抽 风罩等。What kind of weighing room do you have? What do you check for the cleaning of weighing area in case o

39、f product change (e.g. if balances, extraction hood, etc. are cleaned and free of dust?11. 在年度质量回顾中 , 您对回顾结果进行评估并把必要的内容纳入到相关文件 中了吗?评估 由谁来做 ?以下列表中的各项内容是否都包含在回顾中 ? ,文件规定没 有这样翔实In the annual product review, do you evaluate the results of the review and incorporate them where necessary into the relevant

40、 documents? Who is doing the evaluation? Does your review cover all items in the following list?a. 生产和包装规程Manufacturing and packaging instructions?与上一年度相比的变化 ,并且检查其版本 否Changes compared to the previous year and check the version?作为变更控制的一部分 ,所采取的措施 是Measures as part of change control?变更后的验证状态 是V alida

41、tion status following a changeb. 批生产（到包装工序之前和包装记录Batch production and packaging records?生产和包装过程中工艺参数的实际数值 是Actual values for process parameters during production and packaging?工序过程控制数据 是IPC (In Process Control data?偏差 是Deviations?(每一工序步骤的收率 是Yield (for every step?原料 是Raw materialsc. 检验程序Test procedu

42、res?与上一年度相比质量标准或方法的变化 ,并且检查其版本 否Changes to specifications or methods compared to the previous year and check the version ?作为变更控制的一部分 ,所采取的措施 否Measures as part of change control?检验方法的验证状态 否V alidation status of the test methodsd. 检验报告和检验方法Certificates of analysis and test methods ?均值、单个值和原始数据 是Averag

43、es, individual values and raw data?偏差 是Deviations?超标检验数据 是OOS?故障原因分析 否Failure cause analysise. 原料的检验结果 ,与供应商 （检验数据的对比Analytical results for raw materials and comparison with suppliers' data ?供应商确认 是Supplier qualification?偏差、拒收 （情况 是Deviations, rejectionsf. 关键文件的修订Modification in key documents?建筑

44、物方面的变更 （如房间级别、换气等 否Changes to the building (e.g. classification of rooms, ventilation, etc.?机器或设备装置方面的变更 (软件升级、增加控制点等 否Changes to machines/apparatus (software updates, additional control points, etc.?较高层级文件的变更 (变更控制、超标检验数据、验证总计划等 是Changes in higher level documents (change control, OOS, validation ma

45、ster plan, etc. g. 已提交的、获批准的或遭到拒绝的注册申请Marketing Authorizations submitted, approved or rejected?已提交的注册申请 否Authorizations submitted?已获批准的注册申请 否Authorizations approved?遭到拒绝的注册申请及其原因 否Authorizations rejected and reasonsh. 质量偏差 (内部投诉Deviations in quality (internal complaints?根本原因分析及 (后续措施跟踪 是Root cause a

46、nalysis and follow-upi. 投诉和召回Complaints and recalls?原因分析和 （后续措施跟踪 是Cause analysis and follow-upj. 稳定性数据Stability data?目前的数据支持注册申请资料中对 (产品稳定性的说法吗 ? 是Does the current data support the stability declared in the submission file for marketing authorization?包装材料的变更 是Changes to packaging material?工艺变更 是Pro

47、cess changes?处方变更 是Recipe changesk. 趋势Trends?工艺能力指数 否C pk (process capability indicesl. 退货或挽回的药品 是Returned or salvaged drug products?产品及其批号的清单 是Listing of products and batch numbers?退货原因 是Reasons for returns12. 您是按照药品 GMP (2010年修订要求组织库房 (管理的吗 ?Do you organize your warehouse properly according to the

48、 GMP Guidelines (revised in 2010?a. 货物接收程序是怎样的 ?检查清单中有哪些主要内容 ?What is the procedure for the goods reception? Which elements are included in your checklist?b. 您的库房是怎样划分的 ?您是怎样将不同产品 (原料、包装材料、成品等分开 的? How do you divide your warehouse and separate your products (raw materials, packaging materials, finis

49、hed products, etc.?, 按照产品的不同贮存条件和物料状态进行分区贮存c. 取样间设置的基本原则是什么 ? ,同使用物料的洁净级别一致What is the principle of your sampling room?d. 您的托板有哪些种类 (塑料的、木质的或其他材质的 ? ,塑料的、钢质的What kind of pallets do you have (plastic, wooden or other?e. 您的库房做温度分布测试了吗 ? ,暂没有Have you done temperature mapping within your warehouse?f. 您是

50、怎样记录库房温湿度的 ? ,人工记录How do you record the temperature and humidity in your warehouse?g. 您有3内酰胺类或头抱菌素类物料吗？您是怎样对它们单独储存和取样的？Do you have -lactam or cephalosporin materials, and how do you separate them for stori ng and sampli ng?,没有h. 您是怎样给原料容器贴标签的 ?标签上标示了哪些信息 ?您使用的标签是什么 样 的? , 标签标示物料名称、流水号 /批号、数量等信息 ,一般用

51、纸质的How do you label containers of raw materials? What kind of indications are on the label(s, and what kind of label(s do you use?i. 您是怎样进行虫鼠害控制的 ?您对控制措施的有效性定期进行评估吗 ?How do you perform the pest control, and do you have a regular evaluation on the efficacy of the control measures?采用灭蝇灯、粘鼠板、挡鼠板等措施，暂没有

52、定期评 估。 13. 您有对原料和包装材料供应商的认可程序吗 ?Do you have a supplier qualification procedure for raw materials and packaging materials? a.您的供应商资料中包括哪些文件?,证照、标准等What documents are included in your supplier profile?b. 您对供应商有持续性的评估程序以及相应的评级吗?取样的程序与 (供应商评级有 关联吗 ? , 有,没有。Do you have an ongoing evaluation procedure and

53、 a corresponding ranking for suppliers? Is the sampling procedure linked with the ranking?c. 您多长时间或者在什么情况下对原料供应商进行一次审计 ?是现场审计还是通过文 件来审计 ? , 年度审计 ,方式两者均有How often or under what conditions will you audit the suppliers of starting materials? Do you audit by visiting or by documents?d. 您有审计内容清单吗 ? ,有Do

54、you have a checklist for the audits?e. 您与供应商是否签有合同 ,在合同中明确要求 (物料质量和工艺发生变更时须 提前 通知? ,有Do you have a contract with suppliers specifying changes in quality and process must be notified in advance?14. 您公司是否按照药品 GMP (2010年修订的要求进行委托生产或委托检验 (如有 ? If you have any contract manufacturing / testing arrangement

55、 by your company, do you follow requirements of the GMP Guidelines (revised in 2010?a. 在双方签订合同前 ,委托方是怎样评估受托方的 ? , 委托省药检所。网上评估 ? How does the contract giver evaluate the contractor or tester before making the contract?b. 合同中是否明确规定了质量保证和成品放行的职责 ? ,委托生产中规定有Does the contract specify the responsibilities

56、 for the QA measures, and for the release of the finished products?c. 合同中是否明确规定了偏差、超标检验数据和异常情况的报告职责?哪一方负责跟踪 后续措施 ? , 总体概括说明责任主体Does the contract specify the obligations for reporting deviations, OOS and abnormal situations? And which side is responsible for follow-up actions?d. 委托方是否向受托方提供有关生产或检验方法的

57、完整技术信息和培训 ? ,有Does the contractor or tester get the complete technical information and training from contract giver about manufacture or test method?e. 受托方是否向委托方提供所有的生产或检验记录? ,有Does the contract giver get all manufacture or test records from contractor or tester?f. 委托方是否定期检查或评估受托方 ? , 是Does the contract giver perform regular inspections or evaluations of the contractor or tester?15. 您公司质控实验室工作是按照药品 GMP (2010年修订要求妥善组织的吗 ?Is the QC laboratory of your company well-organized according to the GMP Guidelines (revised in 2010?a. 质控实验室的仪器设备有