工艺风险评估报告模板

1、Risk Assessment Report for XXX Process XXX工艺风险评估报告Report Approval报告批准Company/Title公司/职务Name姓名Signature签名Date日期Written by编写Reviewed by审核Approved by批准Revision History 版本修订索引Rev.版本Date 日期Revision Reasons 修订原因002011/10/30Initial issuance 新制订Index 目录1Overview概述42Purpose 目的43Scope范围44Responsibility 职责45Ab

2、breviations缩略语66Regulation and Guidance 法规和指南77System Description系统描述97.1Plant Description车间概述97.2Product Information产品信息107.3Equipments/System List设备/系统清单158Reference Documents 参考文件169Risk Assessment Method 风险评估方法179.1Conduct a Hazard Analysis进行危害分析179.2Determine the Critical Control points (CCPs)关

3、键控制点的确认209.3Establish Target Levels and Critical Limits建立目标水平和关键限值219.4Establish System(s) to monitoring CCP 建立CCP监测系统219.5Establish an appropriate Corrective Action Plan建立适当的纠正计划229.6Establish Procedures建立规程229.7Establish Documentation and keep records建立文件并保留记录2310Hazard analysis Matrix危害分析矩阵2511CC

4、P Control Matrix关键控制点控制矩阵2612Conclusion结论&建议271Overview 概述This document summarizes the quality risk management report for XXX at the XXX site. The document embraces the principles of ICH Q9 (Quality Risk Management) and uses risk management tools to support manufacturing strategies designed to minim

5、ize risks to product quality.本文件总结了位于XXX 的XXX的质量风险管理报告。 本文件包括ICH Q9（质量风险管理）的原则以及使用合适的风险管理工具来支持设计用于将对产品质量的风险降到最低的生产策略。A formalized risk management approach was applied to the XXX manufacturing facility. This involved a holistic assessment that identified the potential hazards and risks to product qua

6、lity for all products handled in the facility to ensure that appropriate controls were in place to manufacture these products safely. The assessment supported the development of a quality risk management (QRM) that addressed the manufacture of the following products: XXX.对XXXXX生产工厂采用了一种正式化的风险管理方法。 这

7、涉及到能够确定对产品质量的可能危害和风险的全瞻性评估，以保证具有适宜的控制来以安全的方式生产这些产品。 这种评估行为针对XXXX产品生产的质量风险管理（QRM）的制定提供了支持。2Purpose 目的The purpose of this process risk assessment is to evaluate, define, and document all potential hazard and critical control points for XXX Process of Oral Dosage Plant of XXXby applying the principle o

8、f ICH Q9 (Quality Risk Management) and risk management tool of Hazard Analysis and Critical Control Point (HACCP). This assessment activity is to ensure that the products can be manufactured under appropriate control and safety method, and provide support to define process critical control points of

9、 XXX Process.本工艺风险评估的目的是应用ICH Q9（质量风险管理）的原则以及使用危害分析和关键控制点（HACCP）的风险管理工具评估确定出XXX车间XXX生产工艺中所有的潜在危险和关键控制点，并记录在文件中。以保证具有适宜的控制，并以安全的方式生产该产品。这种评估行为针对XXX的生产工艺关键控制点的制定提供了支持。3Scope 范围The risk assessment scope is the XXXX in XXX Plant of XXXX. The Product Code: XXX.本工艺风险评估的范围为XXXX车间XXX，产品代码为XXX。4Responsibilit

10、y 职责XXX responsibility XXX的职责：Risk assessment execution进行风险评估Risk Assessment Report compilation风险评估报告的编写XXX responsibility XXX的职责：To assure that product-specific knowledge and expertise are available for the development of an effective HACCP plan by assembling a multidisciplinary team. Team members

11、should represent all the relevant disciplines, such as research and development, production, quality control, quality assurance, microbiology, engineering and distribution or others as applicable with the ability to:确保具有产品的详细知识和专业技术，用以各专业组开发有效地危害分析和关键工艺控制点的计划。小组成员应代表研发，生产，质量控制，质量保证，微生物学，工程和发货以及其他相关领

12、域能力。Conduct a hazard analysis实施危害分析Identify potential hazards识别潜在的危害Identify hazards which should be controlled识别应该控制的危害Recommend controls and critical limits建议的控制和关键限度Devise procedures for monitoring and verification监测和确认的设计程序Recommend appropriate corrective action where deviations occur对发生的偏差推荐合适的

13、纠正措施Establish Documentation and keep records建立文件并保留记录Verify the HACCP plan确认危害分析和关键控制点计划Other responsibilities:其它职责Information collection信息的收集Supply all procedure, data, manuals, drawing and documentation necessary for the completion of final report提供为报告编写所需要的所有的规程、数据、手册、图纸和文件Taking part in the RA参与

14、风险评估Review and approve the report报告的审核和批准5Abbreviations 缩略语The abbreviations which will be used in this document are listed in the following form.在下面的表格中规定了本文件中使用的缩略语。Abbreviations缩略语Definition定义CCPCritical Control Points关键控制点EUEuropean Union欧洲联盟GMPGood Manufacturing Practice药品生产质量管理规范HACCPHazard An

15、alysis and Critical Control Point危害分析与关键控制点ICHInternational Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use人用药品注册技术要求国际协调会ISPEInternational Society for Productivity Enhancement国际制药工程协会PQPerformance Qualification性能确认PVProcess Validation工艺验证QRMQu

16、ality Risk Management质量风险管理RARisk Assessment风险评估SFDAState Food and Drug Administration国家食品药品管理局SIASystem Impact Assessment系统影响评估SOPStandard Operating Procedure标准操作程序URSUser Requirements Specification用户需求说明6Regulation and Guidance 法规和指南To write this protocol the following reference documents have bee

17、n used:为了编写本报告，参考了以下法规和指南：State Food and Drug Administration (CFDA), China, Good Manufacturing Practice (2010 Revision), March, 2011国家食品药品监督管理局（CFDA），中国，药品生产质量管理规范（2010 年修订），2011 年 03 月ICH Q9: Quality Risk ManagementICH Q9：质量风险管理，2005 年 11 月ISPE Guideline Volume 5, Commissioning and Qualification, 1

18、st Edition, 2001 ISPE 指南 5“调试和确认”， 2001 年第一版ISPE Guideline Volume 7, Risk Based Manufacture of Pharmaceutical Products, 1st Edition,2010ISPE 指南 7“基于风险分析的制药产品生产”，2010 年第一版ISPE Good Practice Guides for Applied Risk Management for Commissioning and Qualification,1st Edition, 2011ISPE 良好实践指南，基于风险分析的调试和确

19、认，2011 年第一版ISPE GAMP 5 (Good Automated Manufacturing Practice 5) ISPE GAMP 5 良好的自动化制造规范,2008 年第五版ISPE Pharmaceutical Engineering Guides for New and Renovated facilities, Volume 4: Water and steam systemsISPE 新建和改造的工厂医药工程指南，第 4 卷-水和蒸汽系统WHO Technical Report series No. 908, 2003, Annex 7 WHO 技术报告系列 No.

20、 908，2003，附录 77System Description 系统描述Plant Description 车间概述7.2 Product Information 产品信息7.2.1Product Name 产品名称：General Name: XXX 通 用 名 称 ：XXX English Name: XXX 英 文 名 称 ：XXX Pinyin: XXX汉语拼音：XXX Dosage: XXX 剂型：XXX7.2.2 Description 描述：Activity ingredients of this product is XXX.本品主要成份为 XXX。Chemical str

21、uctural formula 化学结构式：Molecular Formula: XXX分子式：XXXMolecular Weight 分子量：XXX7.2.3 Character:性状：7.2.4 pH7.2.5 Temperature 温度7.2.6 Method of cleaning 清洗方法7.2.7 Heat treatment 热处理7.2.8 Drying 干燥7.2.9 Screening 筛分7.2.10 Mixing 混合7.2.11 Blending 混合7.2.12 Packaging 包装7.2.13 Storage 储存7.2.14 Distribution an

22、d Transport 发货和运输7.2.15Product Information 产品信息Items项目Product Information产品信息Strength规格Package Materials包装材料Expiry Date有效期36 Month 36个月National Medicine Permit No.国药准字Production Code产品代码Specification执行标准Chinese Pharmacopeia 2010 version 2nd Part中国药典2010年版二部7.2.16 Intended use 计划用途7.2.17 Specificatio

23、n 质量标准Test Items检验项目In-house内控标准CP 20102010版药典7.2.18 Flow Chart工艺流程图7.3 Equipments/System List 设备/系统清单No.序号Equipment Name设备名称Type Mode规格型号Quantity数量1234567891011121314158Reference Documents 参考文件To write this protocol the following reference documents have been used:为了编写本报告，参考了以下文件：Document Name文件名称D

24、ocument No.文件号XXX Process XXX工艺XXX Specification XXX质量标准VMP for Oral Dosage Plant口服制剂车间验证总计划VMP-XXX-00Process Layout for Oral Dosage Plant口服制剂车间工艺布局图Process Equipment Layout for Oral Dosage Plant口服制剂车间工艺设备布局图9Risk Assessment Method 风险评估方法Conduct a Hazard Analysis 进行危害分析Risk evaluation compares the i

25、dentified and analyzed risk against given risk criteria. It determines the quality of the output.风险评估将所识别和分析的风险与给定的风险标准进行对比，确定生产产品的质量。9.1.1Hazard Identification 危害识别Identify all potential hazards that may be reasonably expected to occur at each step from production, testing and distribution to the p

26、oint of use.对各个生产工序中所有可能发生的偏差进行识别。9.1.2 Hazard Analysis 危害分析A two-stage hazard analysis is to be carried out. During the first stage, the team will review the materials, activities, equipment, storage, distribution and intended use of the product. A list of the potential hazards (biological, chemica

27、l and physical) which may be introduced, increased or controlled in each step will be drawn up.开展两个阶段的危害分析，在第一阶段中，评估团队将审核产品的物料，活动，设备，储存，分发和预计用途。每一步骤将写出可能引入、增加或控制的潜在的危害（生物、化学和物理）的清单。In the hazard analysis, the following should be included wherever possible:在危害分析中，可能包括下述问题： The probable occurrence of

28、hazards and the severity of their adverse health effects;可能发生的危害及其危害健康的严重性； The qualitative and/or quantitative evaluation of the presence of hazards;危害存在的定性和/或定量评估； The survival or multiplication of microorganisms of concern;相关微生物的残存或繁殖； The production or present in drugs of toxins, chemicals or ph

29、ysical agents;毒性，物理或化学试剂的生产或在药品中的残留； The conditions leading to the above.上述内容的引导条件。During the second stage, a hazard evaluation will be conducted, i.e. the severity of the potential hazards and the probability of their occurrence will be estimated.第二阶段，危害评估的执行，即，潜在危害的严重性和发生的可能性的评估。The team will then

30、 decide which potential hazards will be addressed in the HACCP plan, and what control measures, if any, exist that can be applied for each hazard. More than one control measure may be required to control a specific hazard(s) and more than one hazard may be controlled by a specified control measure.评

31、估团队将决定在关键工艺控制点计划中说明存在有哪些潜在的危害，采取什么控制措施， 如果存在，可以应用于每个危害。控制一个具体的危害可能要求至少一个控制措施，一个 具体的控制措施可能控制多个危害。Potential hazards in relation to at least the following is to be considered:潜在的危害至少要考虑以下因素： Materials and ingredients;原辅料； Physical characteristics and composition of the product;物理特性和产品的组成； Processing pr

32、ocedures;加工过程； Microbial limits, where applicable;微生物限度，如果适用； Premises;厂房设施； Equipment;设备； Packaging;包装； Sanitation and hygiene;消毒和卫生； Personnel;人员； Risk of explosions;暴露风险； Mix-ups.混淆。9.1.3 Hazard Evaluation危害评估A.Severity 严重性(S)Impact of hazard on product quality.发生危害后对产品质量的影响程度。High: impact to pro

33、duct quality, which must be controlled strictly to ensure the quality. Deviation from parameter range is critical deviation.高：对产品质量有影响，必须严格控制才能保证质量，参数偏离范围为重大偏差。Medium: middle impact to product quality, main deviation may occur unless strictly control is taken.中：对产品质量可能有影响。不严格控制会出现主要偏差。Low: minor imp

34、act to product quality, deviation from parameter range is minor deviation.低：对产品质量影响很小，参数偏离范围为次要偏差。B.Possibility 可能性(P)Possibility of hazard, like deviation or defect.发生偏差或缺陷等危害的可能性。High: operation range is close to setting limit, or parameter range is narrow, and parameter is difficult to control. D

35、eviation from the range may occur even under normal condition.高：操作范围接近于设定范围，或参数范围比较窄，参数本身较难控制。正常情况下也可能会偏离范围。Medium: operation range is close to setting limit, or parameter range is wide, and parameter is easy to control. Deviation from the range may occur only under abnormal condition.中：操作范围接近于设定范围，

36、或参数范围比较宽，参数本身比较容易控制。异常情况下才会偏离范围。Low: operation range is far narrow to setting limit, or parameter range is wide.Deviation from the range may occur only under emergency condition.低：操作范围远比设定范围窄，或参数范围比较宽，紧急情况下才会偏离设计空间。The severity and probability rating will be combined to evaluate criticality. The fol

37、lowing method will be used to define the criticality.将把严重性和可能性合在一起来评价关键性。 将采用如下方法来确定关键性：High Severity严重性高Potential-Critical潜在关键Critical关键Critical关键Medium Severity严重性中等Non-Critical非关键Potential-Critical潜在关键Critical关键Low Severity严重性低Non-Critical非关键Non-Critical非关键Potential-Critical潜在关键Low Possibility可能性

38、低Medium Possibility可能性中等High Possibility可能性高The purposed of evaluation is to define critical, potential-critical and non critical for each critical process and facility. A reasonable proposal should be given for critical and potential-critical control point; appropriate control method must be decide

39、d for critical control point.评估的目的，是对每个关键工序和设施中确定关键、潜在关键和非关键。关键控制点和潜在关键控制点需要给出合理建议，关键控制点需确定适宜的控制方法。9.2 Determine the Critical Control points (CCPs)关键控制点的确认Determination of CCP will depend on the operation concerned, e.g. production, packing, reprocessing, storage, distribution. If a hazard has been

40、identified at a step where controlis necessary for safety, and no control measure exists at that step, or any other, the product or process should be modified at that step, or at an earlier or later stage, to include such a control measure.关键控制点的确认将取决于相关的操作，例如，生产、包装、再加工、储存、发放。如果已经在一个步骤中识别出危害需要安全方面的控

41、制措施，并且在这步骤中并不存在控制措施，或者在其他情况下，产品和工艺在那一步骤中需要修改，或在早期或晚期阶段，也应该包括这样的控制措施。9.3 Establish Target Levels and Critical Limits 建立目标水平和关键限值Critical limits will be specified and verified, if possible, for each critical control point. More than one critical limit may sometimes be elaborated at a particular step.

42、The criteria used often include measurements of temperature, time, moisture level, pH, and sensory parameters, such as visual appearance and texture. Critical limits will be scientifically based.如果可能的话，将对每一个关键控制点的关键限度进行规定和确认。在一个特殊的步骤有时可能超过一个关键限度，通常使用的标准包括温度、时间、水分、pH，和感官参数，例如外观和质感。关键限度必须基于科学的原理。9.4 E

43、stablish System(s) to monitoring CCP 建立 CCP 监测系统The monitoring procedures used must be able to detect loss of control at the CCP, and this information should ideally be available in time to make adjustments to ensure control of the process and prevent violations of the critical limits. Where possibl

44、e, process adjustments should be made when monitoring results indicate a trend towards loss of control at a CCP. These adjustments should be made before a deviation occurs.采用的检测程序必须能检测到关键控制点控制的缺失，并且应能及时了解这些信息进行调整，以确保工艺的控制和避免超出关键限度。然而，当监测到关键控制点缺失的趋势出现时，应该调整工艺，这些调整应该在偏差发生前进行。Data derived from monitori

45、ng must be evaluated by a designated person with the knowledge and authority to carry out corrective actions when indicated.监测的数据必须由指定的具有专业知识和授权的，执行纠正措施的人进行评估。Monitoring measure for critical control point must be defined and performed.对关键控制点制定监控措施并执行。All records and documents associated with monitor

46、ing CCPs must be signed and dated by the person(s) carrying out the monitoring and by a responsible reviewing official(s) of the company.所有的监测关键控制点的相关记录和文件必须由执行监测的人员和审核人员签名和日期。9.5 Establish an appropriate Corrective Action Plan 建立适当的纠正计划Specific corrective actions should be developed for each CCP in

47、 order to deal with deviations when they occur. These actions should ensure that the CCP is brought under control.为了在偏差发生时能够及时进行处理，必须开发每一个关键控制点的具体的纠正措施，这些措施应该确保关键控制点在控制中。Corrective actions should include at least the following:纠正措施应该至少包括以下内容：(a) Determination and correction of the cause of non-compl

48、iance; (a)不符合性原因的确认和纠正；(b) Determination of the disposition of the non-compliant product;(b) 不合格产品处理的确认；(c) Recording of the corrective actions that have been taken. (c)已经采取的纠正措施的记录。Appropriate corrective action for each critical control point should be established toensure deviation occurred in cri

49、tical control point can be corrected in time.应当对建立的每一个关键控制点制定纠正措施，关键控制点出现偏差时能及时的被纠正。9.6 Establish Procedures 建立规程Procedure of monitoring measure shall be drafted to ensure the effective operation of HACCP system. Verification and auditing methods, procedures and tests, including random sampling and

50、analysis, can be used to determine whether the system is working correctly. The frequency of verification should be sufficient to confirm the proper functioning of the system.应该起草危害分析分析和关键控制点系统监测措施程序，以确保其有效的运行。确认和审计方法，程序和测试，包括随机取样和分析，可以用于确认系统是否正常的工作。应该有充分的确认频率以确保系统功能的正确性。Examples of verification act

51、ivities may include, but not limited to:确认活动的例子可能包括，但不局限于： Review of the HACCP system and its records;危害分析和关键控制点系统及其记录的审核； Review of deviations and product dispositions;产品处理和偏差的审核； Confirmation that CCPs are kept under control.关键控制点的确认必须在控制中进行。9.7 Establish Documentation and keep records 建立文件并保留记录Ef

52、ficient and accurate documentation and record should be kept.应该保留有效的和精确的文件和记录。Examples of activities for which documentation is required may include, but not limited to:文件要求的活动的例子可能包括，但不限于： Hazard analysis;危害分析； CCP determination;关键控制点的确认； HACCP plan;危害分析和关键控制点计划； Critical limit determination.关键限度的确

53、认。Examples of activities for which records are required include:要求记录的活动的例子包括： CCP monitoring activities;关键控制点监测活动； Process steps;工艺步骤； Associated hazards;相关的危害； Critical limits;关键的限度； Verification procedures and schedule;程序和时间表的确认； Deviations;偏差； Associated corrective actions;相关的纠正措施； Modifications to the HACCP system.危害分析和关键控制点体系的修改。Relevant procedure shall be followed for quality risk management activities, and relevant documentation and record shall be kept as the evidence of implementation.应当按照规程进行质量风险管理工作并保留文件和记录来证明实施了风险控制措施。10 Ha