GMP偏差处理中英文

1、1.PURPOSE 目的Whenever a product, material or system fails to meet the specifications or in the event of a failure to comply with relevant documentation or regulatory requirements, an appropriate investigation must be undertaken, the cause(s) identified and the necessary corrective actions taken 当产品、物

2、料或系统不符合质量标准要求或某事件不符合相关文件或法规要求时,必须进行适当的调查,查明原因并采取必要的改正举措.2. SCOPE 范围This SOP covers all failures and unplanned incidents related to Chemical components, Packaging materials, Drug Products, Processes, Systems, Equipments, Utilities and Facilities used to produce and control them.本SOP适用于处理所有失误及非方案性故障事件

3、,含概用于产品并限制产品的化学成分、 包装材料、药品、工艺、系统、设备、公共设施和厂房等.3. DEFINITIONS/ABBREVIATIONS 定义/缩写Deviation (also known as anomaly ): Any unplanned change from a written procedure/document, during manufacturing or testing or a non-conformance to approved specifications or any failure on GMP-related systems. Deviations

4、 are assessed according to compliance and /or the risk they present to patient health and/or with regulatory requirements. Deviations are to be classified as critical or major or minor 偏差(通常也称为异常)：在药品生产过程中,任何与既定的程序、文件不符的非方案的变更或 与批准的质量标准不符,或与GMP相关的系统失败.偏差根据对患者造成的风险何国家法规的符合性进行评估.偏差可分为三类“严重偏差、主要偏差、微小偏差

5、Critical Deviations:严重偏差：Critical deviations require immediate investigation, root cause analysis and corrective-preventive action.严重偏差需要立即进行调查,查找问题的根本原因并制定纠正预防举措.A deficiency in material, drug product, medical device, system or service that can affect significantly the quality, purity, safety or ef

6、ficacy of a product/medical device or can lead to health threatening conditions in drug product, or medical device. Alternatively, any deficiency that can lead to a non-compliant drug product/medical device or to a situation that may be cited by regulatory authorities as critical.存在物料、产品、医疗器械或任何系统、

7、维护方面能严重影响产品质量、纯度、平安、成效,能对产品或身体健康产生危害的缺陷；或者会导致产品质量不符合,或可能被法规部门视为严重缺陷项的缺陷；Major Deviation:主要偏差：Major deviations require investigations, root cause analysis and corrective-preventiveaction.主要偏差需要进行调查,查找问题的根本原因并制定纠正预防举措.A non-critical deviation which potentially affects the quality, purity, safety or ef

8、ficacy of a product/medical device or ability to meet GMP requirements.非严重偏差可能潜在影响产品的质量、纯度、平安、成效或GMP法规的依从性.Minor Deviation微小偏差:Minor deviation require investigation, root cause analysis and corrective-preventive action.微小偏差需要调查,查找问题的根本原因并制定纠正预防举措.A deviation not classified as critical or major, whic

9、h potentially impacts a GMP system, utility, equipment, material, component, environment or documentation, but does not affect product/medial device quality, purity, safety, or efficacy.潜在影响GMP系统,公用设施,设备、物料、成分、环境或文件,但不影响产品的质 量、纯度、平安、成效,不属于严重及主要偏差的缺陷.Deviations will typically, but not exclusively, fa

10、ll into one of the following categories:Confirmed Out of Specification (OOS) test resultsControlled Zone Environmental results outside of limitsFailure to comply with instructions in standard documents (Deviation from StandardOperating Procedures, Deviation from Batch processing parameters duringMan

11、ufacture, Packaging, labelling orTesting)Process or equipment failure which affects product qualityReconciliation or yield outside SpecificationFailure to comply with established program (calibration, preventive maintenance and stability test, etc)Material damage or contamination in storage or handl

12、ing偏差通常,但不绝对,发生在以下几个类别中：确认的超出标准的测试结果受控区域环境超标不符合标准文件规定的操作不符合标准操作规程的操作,生产、包装、贴标签或测试过程中操作参数的错误等影响产品质量的操作失误或设备故障物料平衡或产率超过限度物料在储存或处理过程中出现的损坏和污染情况.活动未能根据方案进行校准,预防性维护及稳定性试验等4. SAFETY 平安N.A.无5.PROCEDURE 程序1.1 RESPONSIBILITIES 责任1.1.1 Manufacturing, Logistic, Engineering,QC,HR Managers 生产、物流、工程部、QC、HR经理It is

13、 their responsibility to immediately notify to QA of the occurrence of any event thatcould lead to a potential failure event and to actively participate in investigation process其责任为当那些可能导致潜在失误事件发生时,立即通知QA,并积极参与调查活动.Initiate the Quality Deviation Report.起草质量偏差报告Implementing corrective action resultin

14、g from deviation reports when approved by the Head of Quality .执行质量部经理批准的偏差改正举措.Ensuring all personnel in their Department are trained in the content of this SOP and know that all quality deviations are to be reported.保证本部门人员接受本SOP的培训并清楚所有需要报告的偏差.1.1.2 Site IQC manager is responsible for 质量部经理负责Ensu

15、ring that this SOP is maintained and complies with corporate and local GMP standards. 保证本SOP始终符合集团及中国 GMP的要求.Approval of corrective action resulting from deviation reports.批准偏差的改正举措.Approval the disposition of the batch in case of Batch deviations.当发生批生产偏差时决定批次的处理.Site IQC Manager is responsible for

16、 further communication to the impacted unit and to the respective Operational Industrial Quality and Compliance (IQC) management If the failure or deviation is critical or if other sites/sub-contractors are potentially impacted.如异常事件或偏差程度严重或其他工厂或下级合同商可能受到影响,工厂质量部经理负 责与受影响的单位以及相关区域质量运营部进一步沟通.For crit

17、ical deviations affecting product on the market, please follow the SOP Quanlity Alert Management ,site IQC Management is responsible to involve Industrial Quality and Compliance/Risk Management to ensure the consistent handling of such critical deviations. 对于影响到市场产品的严重偏差,根据“质量警戒的治理,由质量部经理负责利用风 险评估系统

18、向IQC通报以保证类似严重偏差处理的一致性.1.1.3 QA is responsible for QA 负责Assure that the appropriate investigation is conducted into any failure and that an investigative report is issued to document the situation according to the requirements of this SOP保证每个偏差都进行了适当的调查,并按本 SOP要求发放偏差报告.Maintaining a log of all deviat

19、ion reports.保管登记所有偏差报告的日志.Filing a copy of all deviation reports.将偏差报告存档Following up reports ensuring that they are closed out in a timely manner.跟踪偏差报告保证它们及时结束.Reviewing all deviations of this year at least annually etc.至少每年进行一次当年所有偏差的审阅等.1.1.4 QC manager is responsible for QC经理负责Ensuring all test

20、result deviations are reported according to SOP S-QC035, Out of Specification Results " OOS .保证根据SOP S-QC035报告实验结果发生的偏差.Perform all the tests requested by the investigation report to investigate the cause of the deviation and/or the quality of the product.进行调查所需的测试以配合查明原因或确定产品质量.Reviewing all O

21、OS of the year at least annually and producing a report showing trends etc. 至少每年进行一次当年所有OOS的审阅并作趋势分析等.1.1.5 All Department Personnel are responsible for所有人员负有如下责任Reporting all quality deviations to their Department Supervisor or Department Head.向部门主管或部门经理报告所有质量偏差.Ensure communication to Health, Safe

22、ty and Environment (HSE) if the deviation may have an impact on HSE matters.如果偏差可能影响到HSE保证通知健康、平安、环境部门.1.2 Reporting of Quality Deviations质量偏差的报告1.2.1 Planned Deviations 方案性偏差Planed Deviation must not be done on an ongoing basis but exceptional use only.方案性的偏差只能作为非常规的特例使用.Planed Deviation must be pr

23、e-authorized by QO Manager.方案性的偏差一定要被质量部经理预先授权认可.Documentation of the purpose of the deviation and approval by QO Manager is required.要求书面记录偏差的目的以及经质量部经理批准.1.2.2 Unplanned Deviations 非方案性偏差All instances of quality deviations must be reported immediately to the relevant area Department Manager or Sup

24、ervisor.所有质量偏差必须立即向相关的部门主管或经理报告.The area Department is to initiate the Quality Deviation Report using the form shown in the Attachments section of this SOP.偏差发生部门负责起草质量偏差报告见本SOP附件1.2.3 Principles and methods 偏差处理的原那么及方法 Deviation initial 偏差发起The following guidelines are given to assist comple

25、tion of the report.以下方针用以协助报告的完成1. The Manager/Supervisor or the operator of the Department where the deviation occurred is to complete the following details in the sections 1,2,3:发生偏差的部门的经理/主管或发现偏差的操彳人员应填写第1、2、3、局部：In the section 1:第 1 局部- Department name 部门名称- Date raised发现日期- Raised by name发现者姓名I

26、n the section 2:第 2 局部- Product name and batch number if it is a Product failure, Equipment name if one equipment failure or Utility name if the failure affected one utility.假设是产品偏差,记录发生的产品名称和批号；如果是设备误差,记录设备名称；如 果是影响到公共设施的偏差,记录受影响的公共设施的名称.In the section 3:第 3 局部- Detailed explanation of the incident

27、 and the other products/batches can be affected in their quality.误差事故的详细描述及可能影响到质量的其他产品/批次.- Report every immediate action which is approved by department manager or supervisor after deviation found.报告偏差发现后采取的每一个部门经理或主管批准的紧急举措. Deviation Evaluation 偏差的评估After completion of these steps the Qua

28、lity Deviation Form has to be given to QA to: 在这些质量偏差报告步骤完成后交给QA以进行：- QA should make a decision whether it is necessary to quarantine product or materials if the deviation is product or material related. The decision shall be filled in section 3 as an immediate action.如果偏差与产品或物料有关,发生后QA应立即决定是否需要立即将产

29、品或物料“待检起来.决定应被记录在第3局部作为一项紧急举措.- Fill the section 4 and record in the Deviations logbook. 填写第4局部并在日志中登记.- Call and organize a meeting with the involved Department Manager / Supervisor and all other functions that can help in discussing and set the investigation to find the cause(s) of the failure/dev

30、iation召集所有相关部门的经理/主管以及其他对于讨论并找出偏差的原因有帮助的职能部门人员开会.- During the investigation the extent of the problem, for example, implications for previous or subsequent batches of the same/other product(s) should be taken into consideration, as well as, depending on the nature of the deviation, it may be necessa

31、ry to execute additional stability studies and so on. Report the investigation observation in the section 5 of the form Quality Deviation Report. Attach to the form all the memos, e-mails and so on related to the problem.在调查过程中,要考虑问题的扩展程度,比方是否牵涉相同/不同产品的前几批或后几批；还有,依据偏差的性质,可能需要进行额外的稳定性试验等.在质量偏差报 告的第5局

32、部报告调查的发现.将所有与调查有关的备忘、电子邮件等等附在报告 上.The deviation evaluation is based on the comparison to the safty risk evaluation and capability to detect the defect偏差评估应基于对质量平安风险的评估及缺陷被发现的可能性的综合评价.The severity of the impact is defined as per below descriptions:严重性等级分类描述如下：RatingClassificationDescription等级分类描述Comp

33、liance with dossier/cGMP but increase risk for complaints 符合注册文件及现行GMP的要求,但增加投诉的风险1MinorOr/and defect leading to products that do not cause any微小adverse health reaction. They may pose a constraint for theuser or may impair the market imagine of the products.和/或缺陷导致产品不会对健康产生任何不良影响,但可能 致产品使用受到限制或影响产品形

34、象.Non compliance with dossier /cGMP ; no or minor influence2Moderateon product quality(safety , efficiency) ；一般不符合注册文件或现行 GMP要求,对产品质量无影响或微 小影响；Or and defects ,which may not pose a significant hazard to health but where a recall could be initiated (perhaps not required by the competent authority) for

35、 other reasons, but are not class 1 or 2;和/或缺陷,不会对健康产生严重影响但可能会因其他原因发起召回(可能不会被法规部门要求),但不属于1、2类缺陷；A situation in which use of or exposure to a compromised product is not likely to cause adverse health consequences ； 使用或让步使用的情形不会对公众健康产生不良影响；Non compliance with dossier /cGMP ; major influence on product

36、 quality(safety , efficiency)；不符合注册文件或现行GMP要求,对产品质量(平安、功效)产生重大影响；Or and defects ,which could cause illness or mistreatment, but4Majorare not class 1;关键和/或缺陷,可能导致疾病或错误治疗,但不属干-类缺陷；A situation in which use of or exposure to a compromised product may cause temporary or medically reversible adverse healt

37、h consequences is remote ；使用或让步使用的情形对患者健康产生临时或可逆的治疗不利影响的可能极小；Non compliance with dossier /cGMP ; critical influence on product quality(safety , efficiency) ；不符合注册文件或现行GMP要求,对产品质量(平安、功效)产生严重影响；Or/ and defects ,which are potentially life threading or could5Severe严重cause serious risk to health;和/或缺陷,对生

38、命存在潜在威胁或可能导致对健康产生严重风险；A situation in which there is a reasonable probability that the use of or exposure to a compromised product will cause serious adverse health consequences or death.有依据可证实使用或让步使用的情形对健康产生严重不良 影响或致死；The occurrence definitions are proposed:可能性分类如下:RatingOccurrenceDescription等级可能性描述

39、1Extremely rare/very unlikely 极少/几乎不可能Very unlikely几乎不口能First time that the event is observed第一次发现此事件Rare2Remote/rare很少微乎其微/很少Isolated in the concerned batch在相关的批次中独立Possible, do not expect reoccurrence可能,不希望再次发生3Occasional偶尔Event observed 0 to 1 time a month/a campaign or/and isolated cluster in th

40、e concerned batch 在一个月内或一个批组内内发生0-1次的事件,或在不连续的批次内发生.Probable, possible reoccurrence很可能,可能再次发生4Likely可能Event observed 2 to 3 times a month/a campaign or/and Unpredictable number of units impacted in the concerned batch 在一个月内或一个批组内内发生2-3次的事件,或在相关的批次内不可预知发生的次数.Frequent to permanent, or unknown occurren

41、ce 频繁固定的发生,或不可知发生性Almost certain or unknownEvent observed 4 to 5 times a month/a5几乎肯定会发生/不能确campaign or/and previous and/or following定batches also impacted.在一个月内或一个批组内内发生4-5次的事件,或在后续的批次也深受影响的.The safety risk level is given by multiplying the severity of impact and the likelihood of occurrence.The re

42、sult is compared to the following chart:质量风险严重等级来自于缺陷的严重性及发生的可能性的乘积,结论见下表：Severity of impactLikelihood ofAlmost certainOccurrenceorevenunknown 5LikelyMinor 1Moderate 2Major 4Sever 551020254816204Occasional3Remote2Extremely rare 1321612154810245Based on the results given in the above chart, the safet

43、y risk level is evaluated:Low if the number is <4( green area)Moderate if the number is >3 and < 10 (orange area)High if the number is >8 (red area)根据上表,质量风险严重等级为：如果乘积小于4 (绿色区域)为低；如果乘积大于3而小于10 (黄色区域)为中；如果乘积大于8 (红色区域)为高；The Detection definitions are proposed:可发现性分类如下：RatingDetectionDescri

44、ption等级可发现性描述High高100% control with a performance close to 100%;1100%限制性能指标,检查接近100%High probability to detect and reject the defect 发现并剔除缺陷产品的可能性很高；100%c control with a performance significantly different to 100% or partial control (e.g. IPC, statistical);100%限制性能指标,大量检查但不能100%检查或采用局部木查(如：IPC,数理统计2

45、moderate等)；Would most probably be detected during distribution or by the handler (health care professional ) or by the patient (odour, color, appearance)在销售或处理(医务人员)或患者(品种, 颜色,外观)等极启可能被发现的；Low probability to detect, most likely by random chance.3low发现的可能性很低,可能会被很偶然的时机 发现Would most probably not be de

46、tected before the use在使用前几乎不可能被发现Severity risk level质量风险的严重等级Probability ofLowdetection1可发现性Moderate2High3Low 1Moderate 2High 3369246123Based on the results given in the above chart, the deviation is evaluated:Minor if the number is <3 (green area)Major if the number is >2and < 6 (orange ar

47、ea)Critical if the number is >4 (red area)根据上表的结果,偏差等级评估为：如果两者乘积小于3 (绿色区域)为微小偏差；如果两者乘积大于2,小于6 (黄色区域)为主要偏差；如果两者乘积大于4 (红色区域)为严重偏差；When investigation has been finished, department manager shall f川 evaluation of investigation and immediate actions, and QA make batch determination, if the deviation is

48、 product related, in section 5.当调查结束后部门经理应在第5局部填写对调查和紧急举措的评价,如果偏差与产品有关,QA同时做出批次处理决定.According to the classification of deviation and the evaluation, QA tick the type of the deviation in section 5 as " critical/major and minor :根据偏差的分类及对本偏差的评价结果,由 QA在偏差报告表的第五局部偏差类型“严重/主要/微小打勾做好标记. Correct

49、ive action and preventive action纠正预防举措After the investigation has been completed, the department manager/supervisor has to report in the section 6 of the form the recommended corrective actions identified, clarify who is responsible for each action and the due date. The corrective action must be app

50、roved and signed by Quality manager.在调查结束后,部门经理/主管必须在第6局部中记录建议的改正举措,明确各项活动的负责人和预期完成时间.质量部经理将批准改正举措并签字.The investigation and the corrective action(s) plan (from step 1 to 6) must be completed within 30 business days. If this time is exceeded, it must be justified by the involved Departments manager a

51、nd QA, and an action plan with time commitments must be issued. All deviations investigations exceeding 30 business days must be notified to the Quality and Site Manager and justification filled in section 6.所有调查和改正举措确实定(自第 1到6步)必须在30个工作日之内完成.如果超时,必须由 相关部门经理及 QA判断是否事出有因,同时必须给出行动方案的时间承诺.所有超过30天的偏差调查必

52、须通报质量部经理和厂长并且将合理解释填写于第6局部.As soon as the corrective actions have been implemented the responsible person for each action has to fill the section 7 of the Deviation form and his manager review the actual work.在改正举措完成后责任人填写偏差报告第7局部同时部门经理复核实际的情况.All the documents and reports should be attached to the D

53、eviation form.所有文件和报告应附在偏差报告后.After all the corrective actions have been completed the Department(s) Manager(s) and the QO Manager have to sign the section 8 for approval and forward the form to QA for filing.在所有改正举措完成后,部门经理应对所有举措进行评价并和质量部经理在第8局部签字并送交QA存档.For Unplanned Bach Deviation, the corrective

54、 actions may include reprocessing. Please follow SOP QA007( Reprocessing Procedure ) to perform such actions. All the further reprocessing mustpre-authorized by QO Manager and documents should be filled together with their Batch Record Sheet or Packing Record Sheet.对于非方案性批生产偏差,改正举措可能包括再处理.操作时请遵守SOP

55、QA007(再处理程序)进行.所有进一步的返工或再处理必须由质量部经理预先授权,文件应和批生产纪录或批包装记录一起存档.If change involved in the correction action of a deviation, a change control should be implement according to SOP QA003.如果偏差制定的纠正、预防举措为永久性举措的,涉及到变更,要遵守QA003 (变更限制).1.3 Filing of Deviation Reports 偏差报告的存档The original deviation report and additional relevant documentation link with batch product is to be filed by the QA. A copy of this report is to be filed with the respective batch documents. Where batch records do not exist (for a non-batch related deviation) the original deviation report is