MHRA GMP数据完整性老话新谈：第二部分

MHRA GMP数据完整性老话新谈：第二部分  
Good Manufacturing Practice (GMP) data integrity: a new look at an old topic, part 2
MHRA GMP数据完整性老话新谈：第二部分
David Churchward, 14 July 2015 — Compliance matters, Good manufacturing practice
2015年7月14日---符合性问题，GMP，作者DAVID CHRUCHWARD
Data integrity is fundamental in a pharmaceutical quality system which ensures that medicines are of the required quality. A robust data governance approach will ensure that data is complete, consistent and accurate, irrespective of the format in which data is generated, used or retained.
数据完整性在药品质量体系中是一个基本的问题，它确保药品具备所需的品质。坚实的数据管理方法可以确保数据完整、一致和准确，而不论数据产生形式如何，如何使用或保存。
This is the second in a series of 3 blogs exploring the impact of organisational behaviour and procedures on reliable, consistent and accurate data in medicines manufacture. The first blog in this series looked at the impact of organisational behaviour.
本博客是探索有组织的行为和程序对药品生产中数据可靠性、一致性和准确性影响的三篇系列博文中的第二篇。第一篇博文探讨了有组织行为的影响。

Designing systems to assure data quality and integrity 设计体系以确保数据质量和完整性
A mature data governance system adopts a ‘quality risk management’ approach across all areas of the quality system. It requires continuous review, proportionate risk-reduction measures, and an understanding of residual risk across the organisation. Despite recent high-profile regulatory cases regarding falsification of analytical data, the collective experience of the MHRA Inspectorate is that data governance is not limited to laboratories or computerised systems. There are opportunities to strengthen both paper and computerised elements of the data lifecycle.
一个成熟的数据管理体系是在质量体系所有领域中采用“质量风险管理”的方法。它要求持续的审核，适当的风险降低措施，以及对整个组织中残留风险的了解。尽管最近有少法规案例是关于分析数据造假的，MHRA检查的总体心得是数据管理并不仅限于实验室或计算机化系统。有许多机会来提升数据生命周期中纸质和计算机化要素。
A useful acronym when considering data integrity is ALCOA; data must be attributable, legible (permanent), contemporaneous, original and accurate. The expectations for designing systems which reduce opportunities for data integrity failure are described in more detail in guidance published by MHRA. Simple (and often low cost) system design can have significant impact on the success of data governance. Some are included below as indicators of the ALCOA principles.
在考虑数据完整性时，有一个很有用的词：ALCOA，即数据的可追踪性、清晰性（永久性）、同步、原始性和准确性。在MHRA公布的指南中，描述了设计系统来降低数据完整性失败可能性需要达到的要求。简单（通常也是低成本）的系统设计可能会对数据管理的成功实施具有重大影响。以下包括了ALCOA原则的一些指标：
Attributable: 可追踪
The identity of the person completing a record should be unambiguous. The use of aliases or abridged names should only be permitted where this is consistently used, and attributable to an individual. The same alias or IT system log-in which cannot differentiate between different individuals should not be used.
完成一份记录的人员身份应该清楚。如果使用别名或姓名缩写，应该是公司允许并且持续一致地使用，还要求能追溯到个人。如果有相同的别名，或IT系统登录名，不能区分个人，则不可使用。
Legible (permanent): 清晰（永久性）
It should not be possible to modify or recreate data without an audit trail which preserves the original record. It is important not to forget paper records in this context. Blank forms for manual recording of data should also be controlled in a manner which prevents unauthorised re-creation.
应该不可能不被审计追踪记录下来就修改或创建数据，审计追踪要保存原始的记录。在此不要忘记了纸质记录也是很重要的。手工记录数据的空白表格也应受控，防止未经授权就重新写就。
MHRA GMP数据完整性老话新谈：第二部分 - Julia - 成功是永远的追逐，追逐是永远的成功

It is important not to forget paper records
不要忘记纸质记录也很重要
Exceptionally, there may be a valid reason to re-create a record, eg where it has been damaged beyond use, or where an error does not enable a GMP compliant correction of the original. This must be managed through the quality system, either by making a ‘true copy’ (verified as being a true replicate of the original), or by re-writing a new copy and retaining the original as evidence. In all cases, this must be approved through the quality system, with QA oversight and justification for the action.
当然也有例外，可能会有一些理由来重新写就一份记录，例如，被损坏不能再使用，或有一个错误，但没法在符合GMP前提下对原件进行更正。这时必须通过质量体系来进行管理，可以是作一份“真实备份”（通过查验作为原始记录的真实复制品），或重新写一份新的记录，保留原始记录作为证据。在所有情形下，都必须通过质量体系进行批准，需要QA监督和判定这样的操作。
It is generally accepted that correction fluid is not acceptable in GMP areas. However, companies may be unaware that their computerised systems often have ‘data annotation tools’ enabled. These permit changes to data which can alter the appearance of reports, and may not have a visible audit trail. From a practical perspective, this is ‘electronic correction fluid’, and should not be permitted.
一般来说，在GMP领域中不能使用修正液的观念已被大家所接受。但是，公司可能并不明白其计算机化系统通常会有“数据注释工具”。这就允许对数据进行修改，它能改变报告的外观，可能就没有可见的审计追踪了。从实际操作角度来看，这就是“电子修正液”，不应被允许。
Contemporaneous: 同步
System design has significant impact upon contemporaneous record keeping. The availability of records in the right place at the right time removes the need for staff to use loose scraps of paper, or their memory, to retain information for retrospective completion in the official record.
系统设计对同步保存记录具有重大影响。在正确的时间和正确的位置能找到记录，员工就不需要使用散装的便签本，或记忆力来保存信息，然后过段时间再通过回忆和抄写来填写完成正式的记录。
When inspecting packaging operations, I still find it a common approach for manufacturers to use a single batch packaging record (BPR) for blistering and cartoning of a solid dosage form. However, if the BPR is located in the secondary packing area, it is impossible for staff in the primary packing area to make contemporaneous records, and vice versa. The BPR may also require periodic checks, such as equipment performance. Specifying exact time intervals (eg ‘every 60 minutes’) may result in an incentive for staff to ‘back date’ the time of the check if they were occupied at the exact time the activity was required. The system is encouraging staff to falsify the record, particularly if there is concern that missing an exact time point might lead to disciplinary measures.
在检查包装操作时，我还发现生产商常会使用一份单独的批包装记录（BPR），用于固体制剂的泡罩加工和装盒操作。但是，如果BPR放在外包区域，则内包区域的员工是无法进行同步记录的，相反亦然。BPR也可需要进行定期检查，例如，设备性能。指定的时间间隔（例如，每60分钟），如果他们在这个准点的时间正好在做别的事情，员工可能就会为达到此间隔而“倒签”检查时间。这样的体系鼓励了员工假造记录，特别是如果错过了检查时间点会导致公司对员工采取违规措施时。
MHRA GMP数据完整性老话新谈：第二部分 - Julia - 成功是永远的追逐，追逐是永远的成功

Splitting the BPR into 2 parts (primary and secondary) encourages the correct behavior
将BRP拆成2部分（内包和外包）鼓励正确操作
This can be addressed by 2 simple changes. Specifying an acceptable window for completion of the activity (eg.‘every 60 ±5 minutes’), and splitting the BPR into 2 parts (primary and secondary) encourages the correct behaviour, and removes both opportunity and incentive to falsify the record.
这个问题可以通过2个简单变更来解决。指定一个完成任务的窗口时间（例如，每60 ±5分钟），同时将BPR分拆成2部分（内包和外包），鼓励正确的行为，这样就消除了假造记录的诱因和机会。
Original: 原始性
Original records must preserve data accuracy, completeness, content and meaning. Metadata (data about data) is vital in this aim by enabling reconstruction of an activity – who did what, where and when. There are certain limitations in relation to file formats which may not maintain the full metadata record; so-called ‘flat files’ such as .pdf, .doc etc. We may know who created the file, and when, but there may be no information on how, when or by whom the data presented in that document was created, processed or amended. There is therefore an inherently greater data integrity risk with flat files, as they are easier to manipulate and delete as a single record with limited opportunity for detection.
原始记录必须保有数据准确性、完整性、内容和意义。元数据（数据的数据）在重建一个活动中是必不可少的----谁做的，在哪儿及何时。有些文件格式无法保存全部的元数据记录，即所谓的“平面文件”例如PDF和DOC等文件。我们可能知道是谁创建了文件，何时，但可能没有这些平面文件是如何创建、在何时或由谁创建、处理或修正的信息。因此，平面文件先天具有更大的数据完整性风险，因为它们更容易被伪造，可以作为一份单独的文件被删除，而被发现的机会则很有限。
Accurate: 准确性
Automated data capture, with the required IT controls, provides greater control over the accuracy of a record. Where automation is not possible or feasible, real-time second operator verification of quality-critical observed values may be necessary.
自动数据捕捉，具有所需的IT控制，能为一份记录的准确性提供更大的控制。如果自动化不可能或不现实，则可能需要有第二人实时核查质量关键性的观察值。
Data review must include a review of raw data in its original form. If access to electronic raw data is not possible remotely, this is a good opportunity for the reviewer to escape the confines of their office. Reviewing paper copies or flat file reports of electronic data, even from a validated secure system, is unlikely to enable detection of anomalies. This is because the preparation of reports still requires operator intervention, which can influence what data is reported, and how it is presented.
数据审核必须包括对其原始形态原始数据的审核。如果不能远程进入原始的电子数据，那么这对于审核人员来说是个逃离办公室空间的好机会。审核纸质文件或电子数据的平面文件报告，甚至是从一个经过验证的安全的系统中产生的报告，也不可能发现异常现象。这是因为报告的制作还需要操作人员的干涉，这可能会对所报告的数据以及展现的方式产生影响。
The final blog in this series will look at the recurring problem of ‘trial analysis’, and ways in which organisations within the supply chain can take steps to build confidence and reliance on each other’s data.
本系列的最后一篇博文将探讨一再发生的“试针”问题，以及供应链中组织间采取措施来建立彼此数据的可信度和可靠性的方法。

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