受法规约束的GMP和GDP环境下数据管理和完整性优良规范（中英文）

PIC/S 受法规约束的GMP/GDP环境下数据管理和完整

性优良规范（中英文）

PIC/S GUIDANCE

PIC/S指南

PIC/S：国际药品监查合作计划

GOOD PRACTICES FOR DATA MANAGEMENT AND INTEGRITY IN REGULATED

GMP/GDP ENVIRONMENTS

受法规约束的GMP/GDP环境下数据管理和完整性优良规范

PIC/S August 2016

2016年8月

Reproduction prohibited for commercial purposes.

Reproduction for internal use is authorised, provided that the source is acknowledged.

TABLE OF CONTENTS 目录 1. Document history 2. Introduction 3. Purpose 4. Scope 5. Data governance system 5.1 What is data governance 5.2 Data governance systems 文件历史 引言 目的 范围 数据管理系统 什么是数据管理 数据管理系统 5.3 Risk management approach to data governance 数据管理的风险管理方法 5.4 Data criticality 5.5 Data risk 5.6 Data governance system review 数据关键度 数据风险 数据管理体系审核 6. Organisational influences on successful data 公司对数据完整性管理成功与否integrity management 6.1 General 6.2 Code of ethics and policies 6.3 Quality culture 6.4 Modernising the Pharmaceutical Quality Management System 6.5 Regular management review of quality metrics 质量尺度的定期管理评审 6.6 Resource allocation 6.7 Dealing with data integrity issues found internally 7. General data integrity principles and enablers 一般数据完整性原则和推进者 8. Specific data integrity considerations for paper-based systems 8.1 Structure of QMS and control of blank forms/templates/records 8.2 Why is the control of records important? 8.3 Generation, distribution and control of template records QMS结构和空白表格/模板/记录的控制 为什么记录的控制如此重要？ 模板式记录的产生、分发和控制 纸质系统特定数据完整性考虑 资源配置 内部发现的数据完整性问题处理 的影响 概述 道德和方针准则 质量文化 药物质量管理体系现代化 TABLE OF CONTENTS 目录 8.4 Expectations for the generation, distribution and control of records 8.5 Use and control of records within production 生产区域内记录的使用和控制 areas 8.6 Filling out records 8.7 Making corrections on records 8.8 Verification of records 8.9 Maintaining records 记录填写 记录更正 记录核查 记录维护 产生、分发和控制记录的要求 8.10 Direct print-outs from electronic systems 从电子系统中直接打印出的记录 8.11 True copies 8.12 Limitations of remote review of summary reports 8.13 Document retention 8.14 Disposal of original records 9. Specific data integrity considerations for computerised systems 文件保存 原始记录的废弃 计算机化系统特定数据完整性考虑 真实备份 远程审核报告摘要的局限性 9.1 Structure of QMS and control of computerised QMS结果和计算机化系统的控制 systems 9.2 Qualification and validation of computerised 计算机化系统的确认和验证 systems 9.3 System security for computerised systems 9.4 Audit trails for computerised systems 计算机化系统的系统安全 计算机化系统的审计追踪 9.5 Data capture/entry for computerised systems 计算机化系统的数据捕获/输入 9.6 Review of data within computerised systems 计算机化系统内的数据审核 9.7 Storage, archival and disposal of electronic 电子数据的存贮、归档和废弃 data 10. Data integrity considerations for outsourced 外包活动的数据完整性考虑 activities 10.1 General supply chain considerations 10.2 Routine document verification 一般供应链考虑 日常文件核查 10.3 Strategies for assessing data integrity in 供应链中数据完整性评估策略 the supply chain TABLE OF CONTENTS 目录 11. Regulatory actions in response to data integrity findings 11.1 Deficiency references 11.2 Classification of deficiencies 12. Remediation of data integrity failures 12.1 Responding to significant data integrity issues 12.2 Indicators of improvement 13. Definitions 14. Revision history 改善指标 定义 版本历史 缺陷参考 缺陷分类 数据完整性失败时的弥补方法 对重大数据完整性问题响应 数据完整性缺陷引发的法规行动 1 DOCUMENT HISTORY 文件历史 4-5 July 2016 2016年7月4-5日 18 July – 31 July 2016 2016年7月18日—31日 1 – 9 August 2016 2016年8月1-9日 10 August 2016 2016年8月10日 Draft 1 of PI 041-1 presented to the PIC/S Committee at its meeting in Manchester 曼彻斯特会议期间PI 041-1草案提交给PIC/S委员会 Consultation of PIC/S Participating Authorities on publication of the Good Practices as a draft and implementation on a trial basis 公布PIC/S草案征求参与药监机构意见及试行 Minor edits to Draft 1 第1版本草案轻微修订 Publication of Draft 2 on the PIC/S website 第2版本草案在PIC/S网站上公布 Implementation of the draft on a trial basis and 10 August 2016 – 28 comment period for PIC/S Participating Authorities February 2017 试验实施和征求PIC/S参与药监机构意见阶段 2016年8月10日- 2017年2月28日 Review of comments by PIC/S Participating Authorities ? PIC/S参与药监机构审核所收到的意见 Finalisation of draft 草稿定稿 Adoption by Committee of PI 041-1 PI 041-1被委员会采纳 Entry into force of PI 041-1 PI 041-1生效 ? [Date] [Date]

2 INTRODUCTION 引言

2.1 PIC/S Participating Authorities regularly undertake inspections of manufacturers and

distributors of API and medicinal products in order to determine the level of compliance with GMP/GDP principles. These inspections are commonly performed on-site however may be performed through the remote or off-site evaluation of documentary evidence, in which case the limitations of remote review of data should be considered.

PIC/S参与药监机构定期对原料药和制剂生产商和销售商进行检查，以确定其GMP/GDP符

合性水平。这些检查通常是在现场实施，但也可以通过远程或离厂文件证据评估进行，这时要考虑远程数据审核的局限性。

2.2 The effectiveness of these inspection processes is determined by the veracity of the

evidence provided to the inspector and ultimately the integrity of the underlying data. It is critical to the inspection process that inspectors can determine and fully rely on the accuracy and completeness of evidence and records presented to them.

这些检查流程的有效性是由提供给检查员的证据的真实性所决定的，并最终决定于数据背后

的完整性。检查员可以确定并完全依赖呈交给他们的证据和记录的完整性和准确性对于检查过程来说非常关键。

2.3 Good data management practices influence the integrity of all data generated and

recorded by a manufacturer and these practices should ensure that data is accurate, complete and reliable. While the main focus of this document is in relation to data integrity expectations, the principles herein should also be considered in the wider context of good data management.

优良数据管理规范影响生产商所产生和记录的所有数据，这些做法应能保证数据是准确的、

完整的和可靠的。尽管此文件主要关注的是数据完整性要求，在更广的优良数据管理环境下也应考虑此指南所述原则。

2.4 Data Integrity is defined as “the extent to which all data are complete, consistent and

accurate, throughout the data lifecycle”[1]1 and is fundamental in a pharmaceutical quality system which ensures that medicines are of the required quality. Poor data integrity practices and vulnerabilities undermine the quality of records and evidence, and may ultimately undermine the quality of medicinal products.

数据完整性定义为“所有数据在整个生命周期均完整、一致和准确的程度”，它在药物质量

体系中是基本的要求，它确保药品具备所需的质量。不良的数据完整性做法和弱点会削弱记录和证据的质量，并最终可能破坏药品质量。

2.5 Data integrity applies to all elements of the Quality Management System and the

principles herein apply equally to data generated by electronic and paper-based systems.

数据完整性适用于质量管理体系的所有要素，此中原则等同适用于电子和纸质系统产生的数

据。

2.6 The responsibility for good practices regarding data management and integrity lies with

the manufacturer or distributor undergoing inspection. They have full responsibility and a duty to assess their data management systems for potential vulnerabilities and take steps to design and implement good data governance practices to ensure data integrity is maintained.

数据管理和完整性优良规范的职责由接受检查的生产商或销售商承担。他们负有全部职责和

义务来评估其数据管理体系，发现潜在弱点，设计和实施优良数据管理规范来确保数据完整性得到维护。

3 PURPOSE 目的

3.1 This document was written with the aim of: 本文件编制的目的是：

3.1.1 Providing guidance for inspectorates in the interpretation of GMP/GDP requirements

in relation to data integrity and the conduct of inspections.

为检查员提供与数据完整性相关的GMP/GDP要求诠释及实施检查相关指南。

3.1.2 Providing consolidated, illustrative guidance on risk-based control strategies which

enable the existing requirements for data integrity and reliability as described in PIC/S Guides for GMP[2] and GDP[3] to be implemented in the context of modern industry practices and globalised supply chains.

对基于风险的控制策略提供详细解说的整合指南，促使GMP和GDP的PIC/S指南中所述的

现有数据完整性要求和可靠性在现代化工业做法和全球化供应链的环境下得到实施。 3.1.3 Facilitating the effective implementation of data integrity elements into the routine

planning and conduct of GMP/GDP inspections; to provide a tool to harmonise

GMP/GDP inspections and to ensure the quality of inspections with regards to data integrity expectations.

促进数据完整性要素在日常规划和实施GMP/GDP检查中有效实施，提供一个工具让

GMP/GDP检查保持一致，保证数据完整性要求方面的检查质量。

3.2 This guidance, together with inspectorate resources such as aide memoire (for future

development) should enable the inspector to make an optimal use of the inspection time and an optimal evaluation of data integrity elements during an inspection. 本指南与检查团资源，例如备忘录（用于进一步展开）一起让检查员优化使用检查时间，在

检查中更好地评估数据完整性要素。

3.3 Guidance herein should assist the inspectorate in planning a risk-based inspection

relating to data integrity.

本指南应协助检查组织规划基于风险的数据完整性相关检查。

3.4 This guide is not intended to impose additional regulatory burden upon regulated

entities, rather it is intended to provide guidance on the interpretation of existing PIC/S GMP/GDP requirements relating to current industry practice.

本指南无意对受法规规范的主体形成强制的法规责任，它意在为目前行业规范相关的已有

PIC/S GMP/GDP要求提供诠释。

3.5 The principles of data integrity apply equally to both manual and computerized systems

and should not place any restraint upon the development or adoption of new concepts or technologies. In accordance with ICH Q10 principles, this guide should facilitate the adoption of innovative technologies through continual improvement.

数据完整性原则等同适用于手动和计算机化系统，不应该对发展和采用新概念或技术形成限

制。根据ICH Q10原则，本指南应有助于通过持续改进采纳创新技术。

3.6 This version of the guidance is intended to provide a basic overview of key principles

regarding data management and integrity. The PIC/S Data Integrity Working Group will periodically update, amend and review this guidance in light of inspectorate feedback, experience in using the guide and any other developments.

本版本指南意在为数据管理和完整性核心原则提供基本概貌。PIC/S数据完整性工作组将定

期进行更新，根据检查团的反馈、使用本指南的经验以及任何其它发展修订和审核本指南。

4 SCOPE 范围

4.1 The guidance has been written to apply to both on-site and remote (desktop)

inspections of those sites performing manufacturing (GMP) and distribution (GDP) activities. The guide should be considered as a non-exhaustive list of areas to be considered during inspection.

本指南适用于现场和远程（桌面）检查那些实施生产（GMP）和销售（GDP）活动的场所。

本指南应作为检查期间要考虑领域的未尽清单。

4.2 Whilst this document has been written with the above scope, many principles regarding

good data management practices described herein have applications for other areas of the regulated pharmaceutical and healthcare industry.

尽管此文件写就时覆盖上述范围，但其中许多关于优良数据管理规范的原则亦可应用于受法

规规范的药品和保健行业的其它领域。

4.3 This guide is not intended to provide specific guidance for “for-cause” inspections

following detection of significant data integrity vulnerabilities where forensic expertise may be required.

本指南无意为重大数据完整性漏洞引起的“有因”检查提供特定指南。在有因检查中，可能

需要具有调查技巧的专家。

5 DATA GOVERNANCE SYSTEM 数据管理体系

5.1 What is data governance? 什么是数据管理？

5.1.1 Data governance is the sum total of arrangements which provide assurance of data

integrity. These arrangements ensure that data, irrespective of the process, format or technology in which it is generated, recorded, processed, retained, retrieved and used will ensure a complete, consistent and accurate record throughout the data lifecycle. 数据管理是为数据完整性提供保障的所有安排的总和。这些安排保证数据，不管其产生、记

录、处理、保存、恢复和使用的过程、格式或技术如何，均能在数据的整个生命周期中保证完整、一致和准确的记录。

5.1.2 The data lifecycle refers to how data is generated, processed, reported, checked,

used for decision-making, stored and finally discarded at the end of the retention period.

Data relating to a product or process may cross various boundaries within the lifecycle. This may include data transfer between manual and IT systems, or between different organisational boundaries; both internal (e.g. between production, QC and QA) and external (e.g. between service providers or contract givers and acceptors).

数据生命周期指数据如何产生、处理、报告、检查、用于决策、存贮和在保存期结束后最终

废弃。与一个药品或工艺相关的数据可能在其生命周期内会穿越不同边界。这可能包括手工和IT系统之间的数据转移，不同公司界限之间的数据转移，内部（例如生产、QC和QA之间）和外部（例如，服务提供商或合同发包方和接受方之间）的数据转移。 5.2 Data governance systems 数据管理系统

5.2.1 Data governance systems should be integral to the pharmaceutical quality system

described in PIC/S GMP/GDP. It should address data ownership throughout the lifecycle, and consider the design, operation and monitoring of processes / systems in order to comply with the principles of data integrity, including control over intentional and unintentional changes to, and deletion of information.

数据管理系统应整合于PIC/S GMP/GDP所述的药物质量体系中。它应该说明数据在其生命

周期中的所有者身份，考虑对过程/系统进行设计、运行和监测，以符合数据完整性原则，包括对有意和无意修改和删除信息的控制。

5.2.2 The data governance system should ensure controls over data lifecycle which are

commensurate with the principles of quality risk management. These controls may be: 数据管理系统应保证在数据生命周期进行控制。控制应与质量风险管理原则相称。这些控制

可以是：

? Organisational 从公司角度

? procedures, e.g. instructions for completion of records and retention of completed

paper records;

? 程序，例如，记录完整的指令和完整纸质记录的保存；

? training of staff and documented authorisation for data generation and approval; ? 培训人员和记录数据产生权限并批准；

? data governance system design, considering how data is generated recorded,

processed retained and used, and risks or vulnerabilities are controlled effectively;

? 数据管理系统的设计应考虑数据是如何产生、记录、处理、存贮和使用的，应对风险

和漏洞进行有效控制； ? routine data verification; ? 日常数据核查；

? periodic surveillance, e.g. self-inspection processes seek to verifiy the effectiveness

of the data governance policy.

? 定期监管，例如自检过程中核查数据管理方针的有效性。 ? Technical 技术角度

? computerised system control, ? 计算机化系统控制 ? Automation ? 自动化

5.2.3 An effective data governance system will demonstrate Management?s understanding

and commitment to effective data governance practices including the necessity for a combination of appropriate organisational culture and behaviours (section 6) and an understanding of data criticality, data risk and data lifecycle. There should also be evidence of communication of expectations to personnel at all levels within the organisation in a manner which ensures empowerment to report failures and

opportunities for improvement. This reduces the incentive to falsify, alter or delete data. 一个有效的数据管理系统将证明管理者对有效数据管理规范的了解和承诺，包括适当的公司

文化和行为（第6部分）和对数据关键程度、数据风险和数据生命周期的了解。还应有证据证明在公司内以一定方式将要求沟通传达至各层次人员，保证更大的权力来报告失败和改进机会。如此可以减少伪造、篡改和删除数据的诱因。

5.2.4 The organisation?s arrangements for data governance should be documented within

their Quality Management System and regularly reviewed. 公司对数据管理的安排应记录在其质量管理体系内，并定期审核。

5.3 Risk management approach to data governance 数据管理的风险管理方法 5.3.1 Senior management is responsible for the implementation of systems and procedures

to minimise the potential risk to data integrity, and for identifying the residual risk, using

the principles of ICH Q9. Contract Givers should perform a similar review as part of their vendor assurance programme, (refer section 10)

高级管理层对实施系统和程序以降低数据完整性潜在风险，识别残留风险，使用ICH Q9原

则承担责任。合同发包方应实施类似的审核，作为其供应商保证计划的一部分（参见第10部分）。

5.3.2 The effort and resource assigned to data governance should be commensurate with

the risk to product quality, and should also be balanced with other quality resource demands. Manufacturers and analytical laboratories should design and operate a system which provides an acceptable state of control based on the data integrity risk, and which is fully documented with supporting rationale.

为数据管理所做的工作和所配置的资源应与产品质量风险相称，同时也要与其它质量资源需

求相平衡。生产商和分析化验室应设计和运行一个体系，为数据完整性风险提供可接受的控制状态，并全面记录支持性原理。

5.3.3 Where long term measures are identified in order to achieve the desired state of

control, interim measures should be implemented to mitigate risk, and should be monitored for effectiveness. Where interim measures or risk prioritisation are required, residual data integrity risk should be communicated to senior management, and kept under review. Reverting from automated / computerised to paper-based systems will not remove the need for data governance. Such retrograde approaches are likely to increase administrative burden and data risk, and prevent the continuous improvement initiatives referred to in paragraph 3.5.

如果认为需要采取长期措施，以达到想要的控制状态，则应实施临时措施来将缓解风险，并

监测其有效性。如果需要采取临时措施或者是提高风险优先度，则应与高级管理层沟通所残留的数据完整性风险，保持审核。从自动化/计算机化转化为纸质系统不能解除对数据管理的需求。此种降解方式可能会增加行政负担和数据风险，阻止第3.5段中提提出的持续改进倡议。

5.3.4 Not all data or processing steps have the same importance to product quality and

patient safety. Risk management should be utilised to determine the importance of each data/processing step. An effective risk management approach to data governance will consider:

不是所有数据和处理步骤都对药品质量和患者安全具有等同的重要性。应使用风险管理来确

定每个数据/处理步骤的重要性。对数据管理的有效风险管理方法应考虑：

? Data criticality (impact to decision making and product quality) and ? 数据关键程度（对制订决策和产品质量的影响）以及

? Data risk (opportunity for data alteration and deletion, and likelihood of detection /

visibility of changes by the manufacturer?s routine review processes).

? 数据篡改和删除的数据风险（机会），修改被生产商的日常审核流程所发现/可见的可能性） From this information, risk proportionate control measures can be implemented. 从此信息中可知，可以实施与风险相当的控制措施。 5.4 Data criticality 数据关键程度

5.4.1 The decision that data influences may differ in importance, and the impact of the data

to a decision may also vary. Points to consider regarding data criticality include: 受数据影响的决策可能会在重要程度上有所有不同，数据对决策的影响度可能也不同。关于

数据关键程度要考虑的要素包括：

? ??Which decision does the data influence? 数据影响了什么决策？

For example: when making a batch release decision, data which determines compliance

with critical quality attributes is of greater importance than warehouse cleaning records. 例如，当作出批放行决策时，确定符合关键质量属性的数据比仓库清洁记录要重要。 ? ??What is the impact of the data to product quality or safety? 数据对药品质量或安全有什

么影响？

For example: for an oral tablet, active substance assay data is of generally greater impact

to product quality and safety than tablet friability data.

例如，对于口服特此证明，活性物质含量数据一般要比脆碎度数据对药品质量和安全影响更

大。

5.5 Data risk 数据风险

5.5.1 Data risk assessment should consider the vulnerability of data to involuntary or

deliberate alteration, falsification, deletion, loss or re-creation, and the likelihood of detection of such actions. Consideration should also be given to ensuring complete data recovery in the event of a disaster. Control measures which prevent unauthorised activity, and increase visibility / detectability can be used as risk mitigating actions.

数据完整性应考虑数据在有意和无意修改、伪造、删除、丢失或重新创建，以及被察觉可能

性方面的弱点。还要考虑保证在灾难发生时恢复完整数据。防止未经授权的活动，增加可视性/检出能力的控制措施可以用作风险降低措施。

5.5.2 Examples of factors which can increase risk of data integrity failure include complex,

inconsistent processes with open ended and subjective outcomes. Simple tasks which are consistent, well defined and objective lead to reduced risk.

可能会增加数据完整性失败的风险的因素例子包括复杂的不一致的工艺，有开放型结果和主

观结果。定义明确、客观、一致的简单任务则会降低风险。

5.5.3 Risk assessments should focus on a business process (e.g. production, QC),

evaluate data flows and the methods of generating data, and not just consider IT system functionality or complexity. Factors to consider include:

风险评估应关注一个业务流程（例如，生产、QC），评估数据流和数据产生方法，而不仅是

评估IT系统功能和复杂性。要考虑的因素包括： ? Process complexity; ? 工艺复杂性；

? Methods of generating, storing and retiring data and their ability to ensure data accuracy,

legibility, indelibility;

? 数据生成、存贮和退役的方法以及其保证数据准确性、清晰、不能消除的能力； ? Process consistency and degree of automation / human interaction; ? 工艺一致性和自动/人工互动程度；

? Subjectivity of outcome / result (i.e. is the process open-ended or well defined?); and ? 结果的主观性（即工艺是开放式的还是明确定义的；以及

? The outcome of a comparison between of electronic system data and manually recorded

events could be indicative for malpractices (e.g. apparent discrepancies between analytical reports and raw-data acquisition times).

? 电子系统数据和人工记录事件之间比较的结果可能对于不良规范来说具有指示性（例如，

分析报告和原始数据获得时长之间有明显的差距）。

5.5.4 For computerised systems, manual interfaces with IT systems should be considered

in the risk assessment process. Computerised system validation in isolation may not

result in low data integrity risk, in particular when the user is able to influence the reporting of data from the validated system.

对于计算机化系统，在风险评估过程中应考虑人工与IT系统的界面。计算机化系统验证单独

可能不会导致较低的数据完整性风险，尤其是当用户可以影响来自经过验证的系统中的数据报告时。

5.5.5 Critical thinking skills should be used by inspectors to determine whether control and

review procedures effectively achieve their desired outcomes. An indicator of data governance maturity is an organisational understanding and acceptance of residual risk, which prioritises actions. An organisation which believes that there is ?no risk? of data integrity failure is unlikely to have made an adequate assessment of inherent risks in the data lifecycle. The approach to assessment of data lifecycle, criticality and risk should therefore be examined in detail. This may indicate potential failure modes which can be investigated during an inspection.

检查人员应使用批判性思维技巧来确定控制和审核程序是否能有效地得到其所要的结果。数

据管理成熟度的一个指标就是公司对残留风险的了解和接受，它使得措施按优先顺序排列。一个相信数据“没有风险”的公司不可能对数据生命周期中内在的风险进行充分地评估。因此数据生命周期、关键程度和风险的评估方法应进行详细检查。这样可能会发现潜在的失效模式，在检查期间可以对此进行调查。 5.6 Data governance system review 数据管理系统审核

5.6.1 The effectiveness of data integrity control measures should be assessed periodically

as part of self-inspection (internal audit) or other periodic review processes. This should ensure that controls over the data lifecycle are operating as intended.

数据完整性控制措施的有效性应作为自检（内审）或其它定期审核流程的一部分进行定期评

估。这样才能保证对数据生命周期的控制按既定要求运作。

5.6.2 In addition to routine data verification checks, self-inspection activities should be

extended to a wider review of control measures, including:

除了日常数据核查外，自检活动还应延伸到更宽的控制措施审核，包括：

? A check of continued personnel understanding of data integrity in the context of

protecting of the patient, and ensuring the maintenance of a working environment which is focussed on quality and open reporting of issues, e.g. by review of continued training in data integrity principles and expectations.

? 检查人员对保护患者环境下数据完整性意义的持续理解，确保维护工作环境是关注质量的，

敞开接受问题报告，例如，通过审核员工在数据完整性原则和要求方面的持续培训。 ? A review for consistency of reported data/outcomes against raw data entries. ? 对所报告数据/结果对比原始数据输入进行一致性审核。

? In situations where routine computerised system data is reviewed by a validated

?exception report?[4], a risk-based sample of computerized system logs / audit trails to ensure that information of relevance to GMP activity is reported as expected

? 如果计算机化系统数据已通过经验证的“异常报告”方式进行日常审核，则对计算机化系

统日志/审计追踪基于风险抽样，以确保GMP活动相关的信息按预定要求进行报告 5.6.3 An effective review process will demonstrate understanding regarding importance of

interaction of company behaviours with organisational and technical controls. The outcome of data governance system review should be communicated to senior management, and be used in the assessment of residual data integrity risk.

有效的审核流程将证明对公司行为与公司和技术两方面的控制互动重要性的了解。数据管理

系统审核的结果应与高级管理层进行沟通，可以用于残留数据完整性风险的评估。 6

ORGANISATIONAL

MANAGEMENT

INFLUENCES

ON

SUCCESSFUL

DATA

INTEGRITY

公司对成功的数据完整性管理的影响

6.1 General 通则

6.1.1 It may not be appropriate or possible to report an inspection citation relating to organisational behaviour. An understanding of how behaviour influences (i) the incentive to amend, delete or falsify data and (ii) the effectiveness of procedural controls designed to ensure data integrity, can provide the inspector with useful indicators of risk which can be investigated further.

检查报告中表扬公司行为可能不现实或者并不恰当。了解公司行为如何影响（1）什么诱使员工修订、删除或伪造数据（2）设计来确保数据完整性的程序控制的有效性，可以让检查人员获得可以进一步调查的有用风险指标。

6.1.2 Inspectors should be sensitive to the influence of culture on organizational behaviour, and apply the principles described in this section of the guidance in an appropriate way. An effective ?quality culture? and data governance may be different in its implementation from one location to another. Depending on culture, an organisation?s control measures may be:

检查人员应对于文化对公司行为的影响很敏感，并适当应用本指南本部分所述的原则。一个有效的“质量文化”和数据管理可能在其实施时会因公司有差异。根据文化的不同，一个公司的控制措施可能会是：

l ?open? (where hierarchy can be challenged by subordinates, and full reporting of a systemic or individual failure is a business expectation)

l “开放的”（这种情况下下级可以挑战等级，全面报告系统或个人失败是业务要求） l ?closed? (where reporting failure or challenging a hierarchy is culturally more difficult) l “封闭的”（这种情况下报告失败或挑战等级从文化角度来讲更困难） 6.1.3 Good data governance in ?open? cultures may be facilitated by employee empowerment to identify and report issues through the quality system. In ?closed? cultures, a greater emphasis on oversight and secondary review may be required to achieve an equivalent level of control due to the social barrier of communicating undesirable

information. The availability of anonymous escalation to senior management may also be of greater importance in this situation.

在“开放的”文化中，优良数据管理可能会由于员工受到鼓励而有助于识别并报告整个质量体系中的问题。而在“封闭的”文化中，更强调监管，因为社交障碍而无法沟通非期望信息，则需要有第二层闪的审核来达到同等水平的控制。在这种情况下，匿名向高级管理层越级报告的方法也可能会更重要。

6.1.4 The extent of Management?s knowledge and understanding of data integrity can influence the organisation?s success of data integrity management. Management must know their legal and moral obligation (i.e., duty and power) to prevent data integrity lapses from occurring and to detect them, if they should occur.

管理层在数据完整性方面的知识和了解程度可能会影响公司成功地进行数据完整性管理。管理层必须知道其防止数据完整性失误发生，并在发生时发现这些失误的法定和道德义务（即责任和权力）。

6.1.5 Lapses in data integrity are not limited to fraud or falsification, they can be unintentional and still pose risk. Any potential for compromising the reliability of data is a risk that should be identified and understood in order for appropriate controls to be put in place, (refer sections 5.3 - 5.5). Direct controls usually take the form of written policies and procedures, but indirect influences on employee behaviour (such as incentives for productivity in excess of process capability) should be understood and addressed as well.

数据完整性失误不仅局限于欺诈或伪造，他们可能是无意的，但仍具有风险。任何让数据可靠性受到损害的可能均是风险，应该识别并了解，以进行适当控制（参见第5.3-5.5部分）。直接控制通常是书面方针和程序，但对员工行为的非直接影响（例如，超出产能的生产率诱因）也需要了解和说明。

6.1.6 Data integrity breaches can occur at any time, by any employee, so management needs to be vigilant in detecting issues and understand reasons behind lapses, when found, to enable investigation of the issue and implementation of corrective and preventative actions.

数据完整性被破坏可能会发生在任何时间，来自于任何员工，因此管理层需要保持警警惕，发现问题并在发现后了解问题后面的原因，以促进问题的调查和CAPA的实施。

6.1.7 There are consequences of data integrity lapses that affect the various stakeholders (patients, regulators, customers) including directly impacting patient safety and undermining confidence in the organisation and its products. Employee awareness and understanding of these consequences can be helpful in fostering an environment in which quality is a priority.

数据完整性发生问题会产生不良后果，影响大量的利益相关方（患者、法规管理方、客户），包括直接影响患者安全，动摇公司及其产品的可信度。员工明白和理解这些不良后果有助于培育质量优先的环境。

6.1.8 Management should establish controls to prevent, detect and correct data integrity breaches, as well as verify those controls are performing as intended to assure data integrity. To achieve success with data integrity, Management should address the following:

管理层应建立控制来防止、发现和纠正数据完整性偏离情况，以及核查那些意在保证数据完整性实施的控制。为了成功达到数据完整性要求，管理层应强调以下要求：

6.2 Code of ethics and policies 道德准则和方针

6.2.1 A Code of Values & Ethics should reflect Management?s philosophy on quality, achieved through policies (ie. a Code of Conduct) that are aligned to the quality culture and develop an environment of trust, where all individuals are responsible and accountable for ensuring patient safety and product quality.

价值观和道德准则应反映管理层的质量理念，通过方针来达成（即行为准则）。方针应与质量文化一致，建立一种信任的环境，在其中所有员工均承担保证患者安全和药品质量的职责。

6.2.2 The company?s general ethics and integrity standards need to be established and known to each employee and these expectations should be communicated frequently and consistently.

公司应建立基本道德和完整性标准，让每位员工知晓，并且持续频繁地就这些要求进行沟通。

6.2.3 Management should make personnel aware of the importance of their role in ensuring data integrity and the implication of their activities to assuring product quality and protecting patient safety.

管理层应让员工明白其职责在保证数据完整性上的重要性，暗示其活动将确保药品质量和保护患者安全。

6.2.4 Code of Conduct policies should clearly define the expectation of ethical behaviour, such as honesty. This should be communicated to and be well understood by all personnel. The communication should not be limited only to knowing the requirements, but also why they were established and the consequences of failing to fulfill the requirements.

行为准则方针应清楚定义道德行为的要求，例如诚实。所有员工均应该沟通并理解。沟通不应仅仅局限于知道该要求，还要知道为什么要建立方针，如果不能满足要求后果会是什么。

6.2.5 Unwanted behaviours, such as deliberate data falsification, unauthorised changes, destruction of data, or other conduct that compromises data integrity should be addressed promptly. Disciplinary action may be taken, when warranted. Similarly, conforming behaviours should be recognised appropriately.

有害的行为，如蓄意篡改、未经授权更改、毁坏数据，或其它损害数据完整性的行为均应及时说明。必要时应采取处分措施。类似地，应恰当认可符合性行为。

6.2.6 There should be a confidential escalation program supported by company policy and procedures whereby it encourages personnel to bring instances of possible breaches to the Code of Conduct to the attention of management without consequence.

公司方针应支持机密升级计划和程序，它能鼓励员工将可能会打破行为准则的事件报告给管理层知道而不会受到处罚。

6.3 Quality culture 质量文化

6.3.1 Management should aim to create a work environment (ie. quality culture) that is transparent and open, one in which personnel are encouraged to freely communicate failures and mistakes, including potential data reliability issues, so that corrective and preventative actions can be taken. Organisational reporting structure should permit the information flow between personnel at all levels.

管理层应致力于创建一个透明公开的工作环境（即质量文化）。在这样的环境下，员工被鼓励自由沟通失败情况和所犯错误，包括潜在的数据可靠性问题，这样能够采取纠正和预防措施。公司报告结构应允许所有层级之间的信息流。

6.3.2 It is the collection of values, beliefs, thinking, and behaviours demonstrated consistently by management, team leaders, quality personnel and all personnel that contribute to creating a quality culture to assure data integrity.

它是价值观、信仰、思维和行为的集合，由管理层、团队领导、质量人员和所有涉及创造质量文化确保数据完整性的人员一致遵守。

6.3.3 Management can foster quality culture: 管理层可以培养以下质量文化：

l Ensure awareness and understanding of expectations (eg. Code of Ethics and Code of Conduct);

l 确保员工明白和理解要求（例如，道德准则和行为准则）；

l Lead by example, management should demonstrate the behaviours they expect to see ;

l 以身作则，管理层应自身实践他们所期望看到的行为； l Ensure accountability for actions and decisions; l 保证行为和决策职责；

l Stay continuously and actively involved; l 保持持续主动参与；

l Set realistic expectations, consider the limitations that place pressures on employees;

数据完整性属性 Attributable 要求 It should be possible to identify the individual who performed the recorded task. The need to document who performed the task / function, is in part to demonstrate that the function was performed by trained and qualified personnel. This applies to changes made to records as well: corrections, deletions, changes, etc. 可追溯性 应该可以识别出实施了记录的任务的个人。记录下谁实施了任务/职责的需求是证明该职责是由经过培训有资质的人员实施的一部分。这也适用于对记录进行修正时：修正、删除、变更等。 Legible All records must be legible – the information must be readable in order for it to be of any use. This applies to all information that would be required to be considered Complete, including all Original records or entries. Where the ?dynamic? nature of electronic data (the ability to search, query, trend, etc) is important to the content and meaning of the record, the ability to interact with the data using a suitable application is important to the ?availability? of the record. 清晰 所有记录均应清晰---信息必须可以读出以便任何用途。这适用于要求完整的所有信息，包括所有原始记录或输入。如果电子数据的“动态”属性（能够搜索、查询、做趋势分析等）对于记录的内容和含义很重要，则使用适当的软件与数据互动的能力对于记录的“可获得性”就很重要。 Contemporaneous The evidence of actions, events or decisions should be recorded as they take place. This documentation should serve as an accurate attestation of what was done, or what was decided and why, i.e. what influenced the decision at that time. 同步 动作、事件或决策的证据应在其发生时记录。此记录应作为做了什么、决定了什么以及为什么的准确证明，即在当时是什么影响了决策。 Original The original record can be described as the first-capture of information, whether recorded on paper (static) or electronically (usually dynamic, depending on the complexity of the system). Information that is originally captured in a dynamic state should remain available in that state. 原始 原始记录可以在信息首次被捕获时描述，可以是记录在纸上（静态），也可以是电子的（通常是动态的，取决于系统的复杂性）。原始以动态状态捕获的信息应保持在该状态可获得。 Accurate Ensuring results and records are accurate is achieved through many elements of a robust Pharmaceutical Quality Management System. This can be comprised of: - equipment-related factors such as qualification, calibration, maintenance and computer validation. - policies and procedures to control actions and behaviours, including data review procedures to verify adherence to procedural requirements - deviation management including root cause analysis, impact assessments and CAPA - trained and qualified personnel who understand the importance of following established procedures and documenting their actions and decisions. Together, these elements aim to ensure the accuracy of information, including scientific data, that is used to make critical decisions about the quality of products. 准确 括： 通过稳健的药物质量管理体系许多元素来保证结果和记录是准确的。这可以包- 与设备相关的因素，如确认、校正维护和计算机验证 - 控制措施和行为的方针和程序，包括数据审核程序用以核查是否符合程序要求 - 偏差管理，包括根本原因分析，影响分析和CAPA - 受过培训的有资质的人员了解遵守既定程序和记录其活动和决策的重要性 这些要素一起保证信息的准确性，包括用于做出关于产品质量关键决策的科学数据。 Complete All information that would be critical to recreating an event is important when trying to understand the event. The level of detail required for an information set to be considered complete would depend on the criticality of the information. (see section 5.4 Data criticality). A complete record of data generated electronically includes relevant metadata. 完整 当试图了解一件事情时，所有在还原该事件时关键的信息都是重要的。一个信息需要考虑成为完成时所需的详细程度取决于信息的关键程度（参见第5.4部分数据关键程度）。一个由电子方式产生的数据的完整记录包括相关的元数据。 Consistent Good Documentation Practices should be applied throughout any process, without exception, including deviations that may occur during the process. This includes capturing all changes made to data. 一致 优良文件记录规范应适用于所有过程，没有例外，包括在过程中发生的偏差。这包括了捕获对数据所做的所有变更。 Enduring Part of ensuring records are available is making sure they exist for the entire period during which they might be needed. This means they need to remain intact and accessible as an indelible/durable record. 持久 保证记录可以获得的一部分内容是确保其在可能需要的整个时间段都存在。这表示他们需要用为一份清晰/持久的记录保持完好无损并且可以获取。 Available Records must be available for review at any time during the required retention period, accessible in a readable format to all applicable personnel who are responsible for their review whether for routine release decisions, investigations, trending, annual reports, audits or inspections. 可获得 记录必须在其所要求的保存期间随时可以获得用于审核，负责其日常放行决策、调查、趋势分析、年报、审核或检查中审核的所有适合的人员都能可读格式获得。 7.6 If these elements are appropriately applied to all applicable areas of GMP and GDP-related activities, along with other supporting elements of a Pharmaceutical Quality Management System, the reliability of the information used to make critical decisions regarding drug products should be adequately ensured. 如果这些要素恰当应用于所有GMP和GDP相关活动领域，与其它PQMS的支持要素一起，用于做出药品关键决策的信息的可靠信就能得到充分保证。 8 SPECIFIC DI CONSIDERATIONS FOR PAPER-BASED SYSTEMS

纸质系统特定DI考虑

8.1 Structure of quality management system (QMS) and control of blank forms/templates/records QMS结构和空白格式/模板/记录控制

8.1.1 The effective management of paper based documents is a key element of GMP/GDP. Accordingly the documentation system should be designed to meet GMP/GDP

requirements and ensure that documents and records are effectively controlled to maintain their integrity.

纸质文件的有效管理是GMP/GDP的关键要素。因而，文件记录系统的设计应符合GMP/GDP要求，确保文件和记录有效受控，以保持其完整性。

8.1.2 Paper records must be controlled and must remain attributable, legible, indelible/durable, contemporaneous, original and accurate (ALCOA) throughout the data lifecycle.

纸质记录必须受控，必须在数据生命周期中保留其ALCOA属性。

8.1.3 Procedures outlining good documentation practices and arrangements for document control should be available within the QMS. These procedures should specify:

QMS内应该有文件控制程序列出优良文件记录规范和安排。这些程序应指定： l How master documents and procedures are created, reviewed and approved for use;

l 主记录和程序如何创建、审核和批准使用；

l Generation, distribution and control of templates used to record data (master , logs, etc.);

l 用于记录数据的模板的生成、发放和控制（主文件、日志等）； l Retrieval and disaster recovery processes regarding records. l 记录恢复和灾难恢复过程；

l The process for generation of working copies of documents for routine use, with specific emphasis on ensuring copies of documents, e.g. SOPs and blank forms are issued and reconciled for use in a controlled and traceable manner.

l 生成日常使用的工作记录的流程，具体强调保证文件的副本，例如，SOP和空白表格应使用受控和可追溯方式发放和平衡数量；

l Guidance for the completion of paper based documents, specifying how individual operators are identified, data entry formats and amendments to documents are recorded.

l 纸质文件填写指南，说明各操作人员如何识别记录，说明数据输入格式以及如何增补更正文件；

l How completed documents are routinely reviewed for accuracy, authenticity and completeness;

l 填写完成的记录日常如何审核其准确性、可信性和完整性；

l Processes for the filing, retrieval, retention, archival and disposal of records. l 记录的填写、恢复、保存、归档和废弃流程；

l How data integrity is maintained throughout the lifecycle of the data. l 在整个数据的生命周期维护数据完整性。

8.2 Why is the control of records important? 记录控制为什么很重要？

l Evidence of activities performed; l 活动实施的证据；

l Evidence of compliance with GMP requirements and company policies, procedures and work instructions;

l 符合GMP要求和公司方针、程序和工作指令的证据； l Effectiveness of Pharmaceutical QMS; l 药物QMS有效性； l Traceability; l 可追溯性；

l Process authenticity and consistency ; l 工艺真实性和一致性；

l Evidence of the good quality attributes of the medicinal products manufactured; and l 所生产的药品具有优良质量属性的证据；以及

l In case of complaints, records could be used for investigational purposes. l 如果有客户投诉，记录可以用于调查。

8.3 Generation, distribution and control of template records 模板记录的生成、发放和控制

8.3.1 Why is managing and controlling master records necessary? 为什么要管理和控制母版记录？

Managing and controlling master records is necessary to ensure that the risk of someone inappropriately using and/or falsifying a record ?by ordinary means? (i.e. not requiring the use of specialist fraud skills) is reduced to an acceptable level.

管理和控制母版记录对于保证将人们“通过常规方法”（即不需要使用专家级造假技巧）不恰当使用和/或伪造记录的风险降至可接受水平是必须的。

The following expectations should be implemented using a quality risk management approach, considering the risk and criticality of data recorded (see section 5.4, 5.5).

以下要求应使用质量风险管理方式实施，同时考虑数据记录的风险和关键程度（参见第5.4，5.5部分）。

8.4 Expectations for the generation, distribution and control of records 记录生成、发放和控制要求 Expectations 要求 Potential risk of not meeting expectations/items to be checked 不符合要求时需要检查的潜在风险 Item: 1 All documents should have a the version number) and should be Uncontrolled documents increase the as these documents may not be designed to Generation 产生 unique identification number (including potential for omission or loss of critical data checked, approved, signed and dated. correctly record critical data. The use of uncontrolled documents should be prohibited by local procedures. The use of temporary recording practices, e.g. scraps of paper should be prohibited. 所有文件均应有唯一的识别号（包括署日期。 It may be easier to falsify uncontrolled records. Risk of using superseded forms if there is no version control or controls for issuance. 非受控文件记录增加了关键数据丢失或利于正确记录关键数据。 版本号），应进行检查、批准、签名并签忽略的可能性，因为这些文件记录的设计不应通过程序禁止使用非受控文件。应禁止使用临时记录的做法，例如刮擦纸张。 2 The document design should entries. 伪造非受控的记录可能会更容易一点。 如果没有版本控制和发放控制，则会产生使用失效的格式的风险。 Handwriting data may not be clear and are not sufficiently sized. If additional pages of the documents are added to allow complete documentation, the number of, and reference to any pages added should be clearly documented on the main record page and signed. provide sufficient space for manual data legible if the spaces provided for data entry 记录设计应留出足够的空白让员工书写数据。 如果没有留出足够的空白，手书记录可能会不清楚，无法阅读。 如果给记录附加了页，使得员工可以写完记录内容，则每页应该加编号和索引号，并记录在主记录页中，并在加页上签字。 3 The document design should make it clear what data is to be provided in entries. Ambiguous instructions may lead to inconsistent/incorrect recording of data. Ensures clear, contemporaneous and indelible/durable completion of entries. 文件设计时应写清楚在输入中要提供什么数据。 指令不清可能会导致数据记录不一致/不正确。 保证书写内容清楚、同步、可读/持久及完整。 4 Documents should be stored in a manner which ensures appropriate version control. Master copy (in soft copy) should be prevented from unauthorised or Inappropriate storage conditions can allow unauthorised modification, use of expired and/or draft documents or cause the loss of master documents. The processes of implementation and inadvertent changes. E.g.: For the the following precautions should be in place: - Access to master templates should be controlled; - process controls for creating and updating versions should be clear and practically applied/verified; - master documents should be stored in a manner which prevents unauthorised changes; 文件记录存贮方式应保证受到恰当的版本控制。 主文件（软复本）应保护不会被未经授权或不经意地修改。例如，对于以电子方式存贮的模板式记录，应有以下注意事项： - 应控制接触模板母本的权限 - 版本创建和更新过程控制应清楚，并实际可操作/核查 - 主文件存贮方式应能防止未经授权的修改 Item: 制 1 Updated versions should be distributed in a timely manner. Obsolete master documents and files should be archived and their access restricted. Distribution and Control 分发和控the effective communication are just as template records stored electronically, important as the document. Master copies should contain distinctive marking so to distinguish the master from a copy, e.g. use of colored papers or inks so as to prevent inadvertent use. 不恰当的存贮条件可能会发生未经授权的修改、使用过期的和/或草稿文件或导致主文件丢失。 实施流程和有效沟通与文件一样重要。 主件应有清楚标识，与副本相区别，例如，使用有颜色的纸张或墨水，这样防止不经意误用。 There may be a risk that obsolete versions can be used by mistake if available for use. Any issued and unused physical documents retrieved and destroyed accordingly. 更新后的版本应及时分发。 过期母版文件记录应归档，接受它们的权限应进行限制。 所有已发放但未使用的纸质文件应相应收回和销毁。 2 Issue should be controlled by written procedures that include the following controls: - using of a secure stamp, or paper color code not available in the working areas or another appropriate system. - ensuring that only the current Without the use of security measures, there is a risk that rewriting or falsification of data may be made after photocopying or scanning the template record (which gives the user another template copy to use). Obsolete version can be used intentionally or by error. A filled record with an anomalous data template. All unused forms should be accounted returned for secure filing. 如果过期版本能够被拿到，则有被误用的风险。 approved version is available for use. entry could be replaced by a new rewritten - allocating a unique identifier to each blank document issued and a register. - numbering every distributed copy (e.g.: copy 2 of 2) and sequential numbering of issued pages in bound books. - Where the re-issue of additional copies of the blank template is necessary, a controlled process regarding re-issue should be followed. All distributed copies should be maintained and a justification and recording the issue of each document in for, and either defaced and destroyed, or approval for the need of an extra copy should be recorded, e.g.: “the original template record was damaged”. - All issued records should be reconciled following use to ensure the accuracy and completeness of records. 应有书面程序控制记录分发，包括以下控制： - 使用工作区域无法获得的安全保存的印章或有色纸，或者使用其它合适的系统 - 保证只能获得批准的现行版本供使用 - 为发放的每份空白记录给定一个唯一识别标志，并在登记册上记录每份文件的发放 - 为每个分发的副本编号（例如，副本2，共有2），对装订成册的记录每页均给定连续编号 - 如果需要多次发放空白模板副本，则应遵守多次发放的受控程序。所有发放的副本均应维护，需要额外副本的时应说明和批准并记录，例如“原模板记录受损”。 - 所有发放的记录在使用后应计数平衡，以保证记录的准确性和完整性。 8.4.1 An index of all the template records should be maintained by QA organisation. This index should mention for each type of template record at least the following information: title, reference number including version number, location (e.g., documentation data base, effective date, next review date, etc. 如果不使用安全措施，则会存在影印或扫描模板记录（当发给用户一个模板使用时）后重新书写或伪造数据的见险。 过期版本可能会被有意或无意使用。 填写好的记录如果有反常数据输入，可能会被使用新的重写过的模板替换。 所有未使用的表格均应计数，要么划掉并销毁，要么退回安全归档。

QA部门应维护一份所有模板记录的清单。此索引清单应至少提到各类模板记录中的以下信息：标题、索引号包括版本号、位置（例如，文件记录数据库）、有效日期、下次审核日期等。

8.5 Use and control of records within production areas 生产区域记录使用和控制

8.5.1 Records should be appropriately controlled in the production areas by

designated persons or processes. These controls should be carried out to minimize the risk of damage or loss of the records and ensure data integrity. Where necessary, measures must be taken to protect records from being soiled (e.g. getting wet or stained by materials, etc).

在生产区域的记录应由指定人员或流程进行恰当控制。应实施这些控制来减少记录受损或丢失的风险，保证数据完整性。必要时，必须采取措施保护记录不被污损（例如，弄湿或被物料弄脏等）。

8.6 Filling out records 记录填写

8.6.1 The items listed in the table below should be controlled to assure that a record is properly filled out.

下表中列出的项目应进行控制，以保证记录填写符合要求。 Expectations 要求 Specific elements that should be checked / Potential risk of not meeting expectations 应检查的具体要素/不符合要求的潜在风险 Item项目 成 1 Handwritten entries must be made by the person who executed the task. Unused, blank fields within Check that handwriting is consistent for entries made by the same person. Check the entry is legible and clear (i.e. unambiguous; and does not include Completion of records 记录完 Expectations 要求 Specific elements that should be checked / Potential risk of not meeting expectations 应检查的具体要素/不符合要求的潜在风险 Item项目 成 Completion of records 记录完 documents should be crossed-out, dated and signed. Handwritten entries should be made in clear and legible writing. The completion of date fields for the site. E.g. dd/mm/yyyy or mm/dd/yyyy. 手书记录必须是执行任务的人书写。 文件中未经使用的空白格应划掉、签名并书写日期。 手书记录应清晰可读。 日期格式应按工厂要求填写完者是2位月+2位日+4位年 2 Filling out operations should be contemporaneous[1]. the use of unknown symbols / abbreviation, e.g. use of ditto (“) marks. Check for completeness of data recorded. Check correct pagination of the should be done in the format defined records and are all pages present. 检查同一员工填写的记录笔迹一致。 检查书写内容清晰可读（即，没有不清楚，不包括使用未知符合/缩写，例如使用表示重复内容的两点。 检查所记录数据是否完整。 检查记录页编号是否正确，是否无缺失整，例如：2位日+2位月+4位年，或页。 Verify that records are available within the immediate areas in which they are used, i.e Inspectors should expect that sequential recording can be performed at the site of operations. If the form is not available at the point of use, this will not allow operators to fill in records at the time Expectations 要求 Specific elements that should be checked / Potential risk of not meeting expectations 应检查的具体要素/不符合要求的潜在风险 Item项目 成 Completion of records 记录完 of occurrence. 操作内容的填写必须同步。 核查记录是否在其使用区域可以获得，即，检查员应要求在操作现场就地完成记录。如果在使用点找不到记录，则操作员不可能在操作同时填写记录。 3 Records should be indelible. Check that written entries are in ink, which is not erasable and/or will not smudge or fade (during the retention period). Check that the records were not filled out using pencil prior to use of pen (overwriting). Note that some paper printouts from systems may fade over time, e.g. thermal paper. 记录应可读。 检查书写内容是否用墨水写就，应不可擦除和/或模糊褪色（在保存期间）。 检查记录是否在用铅笔书写之前用铅笔写过（套写）。 注意一些从系统里打印的纸质打印件可能会在一定时长后褪色，例如热敏纸。 4 Records should be signed and Check that there are signature and dated using a unique identifier that is initials logs, that are controlled and current Expectations 要求 Specific elements that should be checked / Potential risk of not meeting expectations 应检查的具体要素/不符合要求的潜在风险 Item项目 成 Completion of records 记录完 attributable to the author. and that demonstrate the use of unique examples, not just standardized printed letters. Ensure that all key entries are signed & dated, particularly if steps occur over time, i.e. not just signed at the end of the page and/or process. The use of personal seals is generally not encouraged; however, where used, seals must be controlled for access. There should be a log which clearly shows traceability between an individual and their personal seal. Use of personal seals must be dated (by the owner), to be deemed acceptable. 记录的签名和日期应有唯一的识别标志，可以追溯到书写人。 检查是否有签名和首字母名清单。清单应该受控并且是现行的，它证明使用了唯一的样子，而不只是标准化印刷的字母。 保证所有关键的书写内容都有签字和日期，尤其是如果步骤发生在一定时长内，即不止是在页尾和/或工艺结束时签字。 应该有一份清单，在其中显示个人及其名鉴之间的可追溯性。使用个人名鉴必须要Expectations 要求 Specific elements that should be checked / Potential risk of not meeting expectations 应检查的具体要素/不符合要求的潜在风险 Item项目 成 Completion of records 记录完 有日期（持有人书写），这样是可以接受的。 8.7 Making corrections on records 记录更正

Corrections to the records must be made in such way that full traceability is maintained.

对记录进行更正必须保持全面可追溯性。 Item 项目 1 Cross out what is to be changed with a single line. Check that the original data is readable not obscured (e.g.: not obscured How should records be corrected? 记录要如何更正？ Specific elements that should be checked when reviewing records: 在审核记录时要检查的具体要素： by use of liquid paper; overwriting is not Where appropriate, the reason for permitted) the correction must be clearly recorded and verified if critical. Initial and date the change made. If changes have been made to critical data entries, verify that a valid reason for the change has been recorded and that supporting evidence for the change is available. Check for unexplained symbols or entries in records

用单删除线划掉要更正的部分。 适当时必须清楚记下更正的理由，关键的话还要核查。 更正人签名首字母和日期。 检查原始记录是否被遮盖，是否仍可读（例如，没有使用修正液遮盖，不允许重叠书写）。 如果是对关键数据进行更正，则要核查是否记录了有效的更正理由，以及是否有支持变更的证据。 检查记录中没有解释的符合或内容。 Corrections must be made in indelible ink. Check that written entries are in ink, which is not erasable and/or will not smudge or fade (during the retention period). Check that the records were not filled out using pencil prior to use of pen (overwriting). 更正必须采用不可擦除的墨水。 检查书写是否使用的墨水，是否不能擦除和/或模糊或褪色（在存贮期间）。 检查记录填写是否在用铅笔之前用铅笔打底（套写）。 8.8 Verification of records (secondary checks) 记录核查（第二人检查） Item 项目 1 A- Batch production records of critical process steps should be: - reviewed/witnessed by designated personnel (e.g.: production supervisor) at the time of operations occurring; and When and who should verify the records? 什么人什么时间要对记录进行核查？ Specific elements that should be checked when reviewing records: 在审核记录时要检查哪些具体要素： Verify the process for the handling of production records within processing areas to ensure they are readily available to the correct personnel at the time of performing the activity to which the record relates. Verify that any secondary checks - reviewed by an authorised them to the QC department; and - reviewed and approved by the Quality Qualified Person) before release or distribution of the batch produced. B- Batch production records of non-critical process steps is generally reviewed by production personnel according to an approved procedure. This verification must be conducted after performing production-related tasks and activities. This verification must be signed or initialed and dated by the appropriate persons. Local SOPs must be in place to performed during processing were and independent personnel, e.g. production supervisor or QA. Check that documents were person within production before sending performed by appropriately qualified Assurance Unit (e.g. Authorised Person / reviewed by production and then quality personnel following completion of operational activities. describe the process for review of written documents. A-关键工艺步骤的批生产记录应： - 由指定人员（例如生产主管）在操作发生时进行审核/现场查看；并且 - 由生产部门内经过授权的人员在将记录送交QC部门前进行审核，并且由QA部门（例如授权人/QP）进行审核和批准，然后放行或销售所生产的批次 B-非关键工艺步骤的批生产记录通常由生产部人员根据批准的程序进行审核。 此核查必须在生产相关任务和活动实施之后再执行。此核查必须由适当的人员签字或签首写字母并签署日期。 核查生产区域内处理生产记录的程序以保证正确的人员在实施记录相关操作时可以很容易获取该记录。 核查是否在工艺期间由适当资质和独立的人员，例如生产主管或QA进行第二人检查。 检查文件记录是否在操作活动完成之后由生产部审核，然后由质量人员审核。 必须有SOP描述书面文件记录的审核流程。 How should records be double checked? 如何对记录进行双重检查？ Specific elements that should be checked when reviewing records: 在审核记录时要检查哪些具体要素： 2 Check that all the fields have been completed correctly using the current was critically compared to the acceptance criteria. Inspectors should review company procedures for the review of manual processes. Check that the secondary reviews calculations used. View original data (where possible) to confirm that the correct data was transcribed for the calculation. 检查是否所有空格都使用现行（批准准此数据是否关键。 检查员应审核公司审核人工数据的(approved) templates, and that the data data to determine the adequacy of Check items 1, 2, 3, and 4 of section of data include a verification of any 8.5 and Items 1 and 2 of section 8.6. 的）模板填写完整正确，相比于可接受标程序以确定程序的充分性。 检查对数据是否有第二人审核，包检查第8.5部分的项目1、2、3和第括对所用计算方法的核查。 8.6部分的项目1和2. 查看原始数据（如可能）以确认转抄用于计算的数据是正确的。 8.9 Maintaining Records 记录维护 Item How should records be maintained? 项目 1 Companies should implement a Check if the records are stored in an orderly manner and are easily identifiable. 记录应如何维护？ Specific elements that should be checked when reviewing records: 审核记录时应检查的特定要素： defined system(s) for storage and recovery of records. All records must be stored in the specified location in a traceable and accessible manner. Systems should ensure that all GMP/GDP relevant records are stored for periods that meet GMP/GDP requirements[2]. 公司应定义并实施记录存贮和恢复系统。 所有记录必须存贮在指定的位置，可以追踪并可以获得。 系统应确保所有GMP/GDP相关记录存贮时长符合GMP/GDP要求的时长。 2 All records should be protected Check if there are systems in place to protect records (e.g. pest control and sprinklers). 检查记录存贮方式是否有序，易于识别。 from damage or destruction by: - fire; Note: Sprinkler systems can be - liquids (e.g. water, solvents and implemented provided that they are buffer solution); designed to prevent damage documents, - rodents; e.g. documents are protected from water - hygrometry etc. - unauthorised personnel access, who may attempt to amend, destroy or replace records 所有记录应受到保证，不会受到以下操作或毁坏： - 火 检查是否存在有系统保护记录（例如，虫鼠控制和自动喷淋灭火装置）。 注：如果自动喷淋系统是设计来保护文(e.g. by covering them with plastic film). 件的，例如，文件是防水的（例如，文件已- 液体（例如，水、溶剂和缓冲液） 用塑料膜覆盖），则可以实施自动喷淋系统 - 啮齿动物 - 湿度测定等 - 未经授权的人员进入，该人可能试图修改、损毁或替换记录 3 Strategy for disaster recovery Check for system is in place for the recovery of records in a disaster situation 灾难恢复策略 检查是否具备灾难情形下恢复记录的系统。 8.10 Direct print-outs from electronic systems 从电子系统直接打印出的打印件

8.10.1 Paper records generated by very simple electronic systems, e.g. balances, pH meters or simple processing equipment which do not store data provide limited opportunity to influence the presentation of data by (re-)processing, changing of electronic date/time stamps. In these circumstances, the original record should be signed and dated by the person generating the record and the original should be attached to batch processing records.

从不存贮数据的非常简单的电子系统，如天平、pH计或简单工艺设备中产生的纸质记录，其通过对数据进行再处理、改变电子日期/时间戳的方式影响数据呈现的机会受到限制，则可以由生成记录的人对原始记录签名日期，并将原始记录附入批处理记录。

8.11 True copies 真实备份

8.11.1 Copies of original paper records (e.g. analytical summary reports, validation reports etc.) are generally very useful for communication purposes, e.g. between companies operating at different locations. These records must be controlled during their life cycle to ensure that the data received from another site (sister company, contractor etc.) are maintained as “true copies” where appropriate, or used as a “summary report” where the requirements of a “true copy” are not met (e.g. summary of complex analytical data).

原始纸质记录（例如，分析汇总报告，验证报告等）的副本一般在交流时非常有用，例如，当公司在不同地方操作时。这些记录必须在其生命周期中受控，以确保从另一场所（兄弟公司，合同商等）收集来的数据在适当时作为“真实备份”得到维护，或者是在不符合“真实备份”要求（例如，复杂的分析数据的汇总）时用作“总结报告”。

8.11.2 It is conceivable for raw data generated by electronic means to be retained in an acceptable paper or pdf format, where it can be justified that a static record maintains the integrity of the original data. However, the data retention process must be shown to include verified copies of all raw data, metadata, relevant audit trail and result files, software / system configuration settings specific to each analytical run, and all data processing runs (including methods and audit trails) necessary for reconstruction of a given raw data set. It would also require a documented means to verify that the printed records were an accurate representation. This approach is likely to be onerous in its administration to enable a GMP compliant record.

可以想象，对于电子方式产生的原始数据会以可接受的纸质方式或PDF格式保存，这时可以论证静态的记录维持了原始数据的完整性。但是，数据保存流程必须包括对经过核对的所有原始数据、元数据、相关审核追踪和结果文件、每次分析运行时的软件/系统参数设置、以及所有过程运行数据（包括方法和审核追踪），这是重新构建指定的原始数据系列时所需要的内容。这也要求有书面方法来核查所打印的记录是一份准确的表达。这种方法可能会太麻烦，难以管理让其符合GMP记录要求。

8.11.3 Many electronic records are important to retain in their dynamic (electronic) format, to enable interaction with the data. Data must be retained in a dynamic form where this is critical to its integrity or later verification. This should be justified based on risk.

许多电子记录要保存在其动态（电子）格式，使得可以与数据互动。数据必须以对其完整性至为关键的形式保存，并要在保存后进行核查。应基于风险来论证此方式。

8.11.4 At the receiving site, these records (true copies) may either be managed in a paper or electronic format (e.g., PDF) and should be controlled according to an approved QA procedure.

在接收场所，这些记录（真实副本）可以以纸质方式或电子格式（例如PDF）保存，应根据批准的QA程序受控。

8.11.5 Care should be taken to ensure that documents are appropriately authenticated as “true copies” either through the use of handwritten or digital signatures.

应小心确保文件经过适当的“真实副本”认证，可以是通过手书或数字签名达到此目的。 Item How should the “true copy” be issued and controlled? Specific elements that should be checked when reviewing records: 项目 1 “真实备份”应如何签发和受控？ 在审核记录时要检查的具体要素： Creating a “true copy” of a paper document. At the company who issues the true copy: - Obtain the original of the document to be copied Verify the procedure for the generation of true copies. Check that true copies issued are identical (complete and accurate) to original records. Copied records should be checked against the original document records to make sure there - Photocopy the original document is no tampering of the scanned image. ensuring that no information from the Check that scanned or saved original copy is lost; records are protected to ensure data - Verify the authenticity of the integrity. copied document and sign and date the new hardcopy as a “true copy”; After scanning paper records and verifying creation of a ?true copy?, it The “True Copy” may now be sent to may be possible to permit destruction the intended recipient. of the original documents from which Creating a “true copy” of a electronic the scanned images have been document. A ?true copy? of an electronic record should be created by electronic means metadata. Creating pdf versions of electronic data should be discouraged, as this is equivalent to a printout from the electronic system, which risks loss of metadata. The “True Copy” may now be sent to the intended recipient. A distribution list of all issued “true copies” (soft/hard) should be maintained. (electronic file copy), including all required created. There should be a documented approval process for this destruction. 创建一份纸质文件的“真实备份”。 在签发真实备份的公司： - 获得要备份的文件原件 核查真实备份的生成流程。 检查所签发的真实备份是否与原始记录相同（完整准确）。备份记录应和原始文件记录对比检查，确认没有篡- 对原始文件进行影印，确保没有遗改扫描影像。 漏原件上任何信息 检查扫描或保存的记录受到保护，- 核对复印件的真实性，在复印件上能保证数据完整性。 签名/日期，将新的复印件作为“真实备份” 在扫描了纸质记录和核对“真实备“真实备份”现在可以发送给接收方。 创建一份电子文件的“真实备份”。 电子记录的“真实备份”应采用电子方式创建（电子文件备份），包括所有所需的元数据。不鼓励创建电子数据的PDF版本，因为这等于从电子系统打印出一份打印件，这时有丢失元数据的风险。 “真实备份”现在可以发送给接受方。 要维护所有签发的“真实备份”（软备份/硬备份）的发放清单。 2 At the company who receives the true copy: - The paper version, scanned copy filed according to good document management processes. The document should clearly indicate that it is a true copy and not an original record. 收到真实备份的公司： - 纸质版本、扫描备份或电子文件应根据优良文件记录管理流程进行审核和存检查所收到的记录是否经过适当的检查和保存。 应该有一个系统核对“真实备份”的Check that received records are 份”的创建后，可以允许销毁已经扫描创建过“真实备份”的原始文件。 此销毁过程应有书面批准的程序。 checked and retained appropriately. A system should be in place to e.g. through verification of the correct signatories. or electronic file should be reviewed and verify the authenticity of “true copies” 档。 文件记录应清楚显示其是真实备份，而不是原始记录。

正被性，例如，通过验证其正确签名。 8.11.6 A quality agreement should be in place to address the responsibilities for the generation and transfer of “true copies” and data integrity controls. The system for the issuance and control of “true copies” should be audited by the contract giver and receiver to ensure the process is robust and meets data integrity principles.

应有质量协议说明“真实备份”产生和转移的职责以及数据完整性控制。签发和控制“真实备份”的系统应由合同发包方和合同接受方进行审计，以确保流程稳健，符合数据完整性原则。

8.12 Limitations of remote review of summary reports 对汇总报告进行远程审核的局限性

8.12.1 The remote review of data within summary reports is a common necessity; however, the limitations of remote data review must be fully understood to enable adequate control of data integrity.

对汇总报告中的数据进行远程审核通常是必须的。但是，必须全面了解远程数据审核的局限性，以对数据完整性进行充分控制。

8.12.2 Summary reports of data are often supplied between physically remote manufacturing sites, Market Authorisation Holders and other interested parties. However, it must be acknowledged that summary reports are essentially limited in their nature, in that critical supporting data and metadata is often not included and therefore original data cannot be reviewed.

数据汇总报告通常会在物理距离上比较远的生产场所、上市许可持有人和其它利益相关方之间传递。但是，必须知道汇总报告从根本上来说受限于其特性，其中通常并不包括关键支持性数据和元数据，因此无法对原始数据进行审核。

8.12.3 It is therefore essential that summary reports are viewed as but one element of the process for the transfer of data and that interested parties and inspectorates do not place sole reliance on summary report data.

因此有必要仅是将审核汇总报告作为数据转移过程中的一个环节，利益相关方和检查组织并不仅仅依赖于汇总报告的数据。

8.12.4 Prior to acceptance of summary data, an evaluation of the supplier?s quality system and compliance with data integrity principles should be established through on-site inspection when considered important in the context of quality risk management.

在接受汇总数据之前，考虑到质量风险管理环境下其重要性，应通过现场检查对供应商的质量体系和数据完整性原则符合性进行评估。

The inspection should ensure the veracity of data generated by the company, and include a review of the mechanisms used to generate and distribute summary data and reports.

检查应确保公司所产生的数据的真实性，包括对用来产生和分发汇总数据和报告体制的审核。

8.13 Document retention (Identifying record retention requirements and archiving records) 文件记录保存（识别记录保存要求和归档记录）

8.13.1 The retention period of each type of records should (at a minimum) meet those periods specified by GMP/GDP requirements. Consideration should be given to other local or national legislation that may stipulate longer storage periods.

每类记录的保存时长应（至少）符合GMP/GDP要求中指定的时长。应考虑其它可能规定了更长保存期限的当地或国家法规。

8.13.2 The records can be retained internally or by using an outside storage service subject to quality agreements. A risk assessment should be available to demonstrate retention systems/facilities/services are suitable and that the residual risks are understood.

记录可以内部保存，也可以使用外部保存服务，但要签订质量协议。应进行风险评估证明保存系统/设施/服务是适当的，并了解残留风险。 Item Where and how should records be archived? 项目 1 A system should be in place Check that the system 在哪儿如何归档记录？ Specific elements that should be checked when reviewing records: 审核记录时要检查的具体要素 describing the different steps for archiving implemented for retrieving archived records (identification of archive boxes, list

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