实验室管理之数据完整性3大陷阱！
2019-11-26 10:17
Do Not Delete OrManipulate Laboratory Data
不要删除或操纵实验室数据
A basic tenet ofdata integrity in laboratory operations is expressed in CGMP regulation,namely, that “laboratory records shall include complete data derived from alltests necessary to assure compliance with established specifications andstandards”.2 Recentobservations from FDA warning letters indicate that this basic tenet is stillnot being observed.
CGMP 法规中表达了实验室操作中数据完整性的基本原则，即"实验室记录应包括从所有测试中获得的完整数据，以确保符合既定规范和标准"。近期的FDA警告信缺陷表明，这一基本原则仍未得到遵守。
“Our investigators observed […] deletion of at least six (b)(4) and (b)(4) tests in the audit trails for two instruments used to test sterile (b)(4). Your systems allowed operators to delete files.” And “you identified a total of 25 deleted (b)(4) test results.”
"我们的检查人员 [...]在用于测试无菌（b）（4）的两种仪器的审计追踪中发现至少有六个（b）（4）和（b）（4）检验被。你们的系统允许操作员删除文件。并且"你们总共发现了 25 个被删除的（b）（4）测试结果。
“The audit trail for these tests included the message, ‘deleted result set,’but neither of these two incidents were recorded in the analytical packages for these batches of drug products, nor were they reviewed or investigated by the quality unit.”
这些测试的审计追踪包含"已删除的结果集"字眼，但这两个事件均未记录在药品批检验记录中，也未被质量部门审查或调查。
“Your analyst was unable to retrieve requested data, and explained that he deletes older data to make space for newly acquired data.”
你们的分析人员无法恢复要求的数据，并解释说，他删除了较旧的数据，为新获取的数据腾出空间。
Performingin-person audits of laboratory operations is the most effective method ofensuring compliance in this area. Auditing for basic GDocP is of paramountimportance, as this is a fundamental tenet of CGMP.
对实验室操作进行现场审计是确保该领域合规的最有效方法。对基本 GDocP 的审核是至关重要的，因为这是 CGMP 的基本原则。
“Our investigators found that you had deleted entire chromatographic sequences and individual injections from your stand-alone computers.”
"我们的检查人员发现，你们从单机版计算机中删除了整个色谱序列和个别进针。
“You stored original data in an ‘unofficial’ and uncontrolled electronic spreadsheet on a shared computer network drive. Your analyst stated that original data was first recorded in this ‘unofficial’ spreadsheet and transcribed later to an ‘official’ form. This spreadsheet showed failing results above the limits you established in your procedure, PCH 035 Visible Particle Determination in use prior to September 1, 2014.”
"你们将原始数据存储在共享计算机网络驱动器上的"非正式"和不受控的电子表格中。你们的分析师指出，原始数据首先记录在此"非正式"电子表格中，随后转录为"正式"记录。此电子表格显示的结果超出你们在PCH 035《可见异物检验》中设定的标准。
“Our investigator observed many copies of uncontrolled blank and partially-completed CGMP forms (e.g., environmental monitoring recordings, OOS forms, water testing sheets, and cleanroom entry and exit logs) without any accountability or oversight of your quality unit.”
"我们的检查员发现多个不受控的空白和部分填写的 CGMP 记录复印件（例如，环境监测记录、OOS记录、水检验记录和洁净室进出日志），缺乏质量部门的任何说明或监督
“Our investigators found a large number of trash bags behind a building on your property. The trash bags contained torn original laboratory and production records, such as analytical test reports, (b)(4) water testing reports, and sample notebooks.”
"我们的检查人员在贵司的一栋大楼后面发现了大量垃圾袋。垃圾袋内包含破损的实验室和生产原始记录，如分析检验报告、（b）（4）水检验报告和样品记录。
“Our investigator documented that your employees used paper shredders to destroy critical laboratory and production records without the appropriate controls and procedures. Shredded documents included high performance liquid chromatography (HPLC) chromatograms and a partially-completed OOS form.”10
"我们的检查人员记录到，你们的员工使用碎纸机销毁关键的实验室和生产记录而没有适当的控制和程序。粉碎的文件包括高效液相（HPLC）色谱图和部分填写的 OOS 记录。
“Investigators observed torn, partially complete QA-signed calibration records in the trash and observed QA staff shredding documents without recording the identity or the reason for shredding the documents.”11
检查人员在垃圾箱中发现了撕毁的、部分填写的带QA 签名的校准记录，并观察到 QA 员工在撕碎文件时未记录撕毁文件的原因。
Do Not ConcealUndesirable Test Results
不隐瞒不良测试结果
Manipulation oftests and/or test results to achieve desirable outcomes must be prevented bysufficient quality systems and control strategies, to include (but not limitedto) validation, qualification, and training of personnel. Recent observationsfrom FDA warning letters indicate that this basic tenet is still not beingobserved.
必须通过充分的质量体系和控制策略来防止操纵测试和/或测试结果以达到合格结果，包括（但不限于）验证、确认和人员的培训。FDA警告信最近的缺陷表明，这一基本原则仍未得到遵守。
“Our investigators found a recurring practice of retesting samples until acceptable results were obtained.”
"我们的检查人员发现你们重复测试直至得到合格结果。
“Your original data showed failing results, but data you reported showed passing results.”原始数据显示了失败的结果，但你们报告的数据显示结果是合格的。
“The chromatogram was then manually rescaled, which hid the presence of this peak. Your laboratory set the integration parameters to omit this peak from integration.”
色谱图被人为调整以隐藏某峰的存在。你们的实验室设置积分参数以省略此峰在积分中的值。
“You permanently deleted the first five sample injections. You then renamed the last two injections and reported that they met specifications.”
"你们永久删除了前五针样品。然后，重命名了最后两次进样，并报告它们符合标准。
“Your analyst told our investigator that it is laboratory practice to perform more injections than are required by the procedure, and then delete any undesirable result to ensure passing system suitability results.”
你们的检验人员告诉我们，执行比程序要求更多的进针然后删除任何不合格结果以确保通过系统的适用性，是实验室规范。
“Your firm reported only the passing results from repeat analyses.” "贵公司只报告了重复检验后的合格结果。
“None of the 19 chromatograms generated in the first sequence were maintained and available for review. Only the second set of chromatograms was maintained and relied upon in releasing lots.”18
"第一个序列中生成的 19 个色谱图均未得到保存并可供审查。只保存了第二组色谱图并用于批放行。
“Without providing scientific justification, you repeated analyses until you obtained acceptable results.”And,“You relied on these manipulated test results and incomplete records to support batch release decisions.”
"在没有科学论证的情况下，你们重复检验直到获得合格结果。并且，你们依靠这些操纵的检验结果和不完整的记录来支持批放行决定。
Understand AndReview The Audit Trail
了解并审核审计追踪
While the FDA issaid to be reexamining 21 CFR “Part 11 as it applies to all FDA-regulatedproducts,”20the compliant use of audit trails for computer-connected equipment in thelaboratory remains an area of great importance, as it provides one means ofevidence of compliance with GDocP and CGMP. Surprisingly, the audit trailremains an area of confusion; however, it may be simply understood as “achronology of the‘who, what, when, and why’ of a record.”21 Forcomputer-connected laboratory equipment, it “means a secure,computer-generated, time-stamped electronic record that allows forreconstruction of the course of events relating to the creation, modification,or deletion of an electronic record”.22 Recentobservations from FDA warning letters indicate that this basic tenet is stillnot being observed.
虽然FDA据说正在重新审查21 CFR Part 11，因为它适用于所有FDA监管的产品，"对于计算机连接的实验室设备，审计追踪的合规使用仍然是一个极为重要的领域，因为它提供证明符合GDocP 和 CGMP的方法。令人惊讶的是，审计追踪仍然是一个混乱的领域;然而，它可能被简单地理解为“谁，什么，何时，为什么”的记录。对于计算机连接的实验室设备，它"意味着一种安全的、计算机生成的、带时间戳的电子记录，允许重建与电子记录的创建、修改或删除有关的事件过程"。FDA警告信最近的缺陷表明，这一基本原则仍未得到遵守。
“Analysts manipulated and deleted audit trails.”
"分析人员操纵并删除了审计追踪。
“An analyst deleted audit trails in your gas chromatography equipment #YQ-07-10 from September 15, 2015, through April 24, 2016, and permanently deleted audit trails from November 6 to 13, 2015. In addition, our investigator observed that your quality control manager and quality control deputy manager had full administrative rights on all of your computerized systems, which allows them to manipulate data and turn off audit trails.”
"一名检验员删除了气体色谱设备#YQ-07-10自2015年9月15日至2016 年4月24日的审计追踪，并永久删除了2015年11月6日至13日的审计追踪。此外，我们的检查人员发现，你们的质量控制经理和质量控制副经理对所有计算机化系统拥有完全的管理权限，这使他们能够操纵数据并关闭审计追踪。
“The audit trail showed that you performed this testing in duplicate.”
审计追踪显示你们重复执行测试。
“Our review of audit trail data revealed that your analysts manipulated the date/time settings on your high performance liquid chromatography (HPLC) systems. During the inspection your analysts admitted to setting the clock back and repeating analyses for undocumented reasons.”
"我们对审计追踪数据的审查显示，你们的检验人员操纵了高效液相（HPLC）系统上的日期/时间设置。在检查期间，你们的检验人员承认由于未体现的原因，将时钟倒设并重复测试。
“Our investigator observed that your Empower 3 system audit trail displayed many instances of a ‘Project Integrity Failed’ message, which indicates that injections were missing from the results of analytical testing. For example […] no chromatogram was rendered for the initial run of testing. The data package for this testing clearly shows that the initial run is missing, but your quality unit did not investigate the incident.”
"我们的检查人员观察到，你们的 Empower 3 系统审计追踪显示多个"项目完整性失败"消息，这表明分析测试结果中进针缺失。例如，初始测试的色谱图没有呈现。此测试的数据包清楚地显示初始测试缺失，但质量部门没有调查该事件。
Audit trailfunctionality is common among computer-connected laboratory equipment but mustbe enabled, configured, and managed appropriately. Sufficientqualification/validation must be performed to include procedures and operatortraining to ensure compliance with CGMP and GDocP in laboratory operations.
审计追踪功能在计算机连接的实验室设备中很常见，但必须正确启用、配置和管理。必须进行充分的确认/验证，以包括程序和操作员培训，以确保在实验室操作中符合 CGMP 和 GDocP。
Reinforce BasicCGMP And GDocP In The Laboratory
在实验室中强化基本 CGMP 和 GDocP
Whether in ourown laboratories or those of our suppliers, we must demand a higher standard inestablishing, enforcing, and reinforcing basic CGMP and GDocP. Auditing oflaboratory operations remains a critical success factor.
无论是在我们自己的实验室还是我们的供应商实验室，我们需要一个更高的标准来建立、执行和加强基本 CGMP 和 GDocP 。实验室操作的审计仍然是一个关键的成功因素。
Do not delete or manipulate laboratory data.
不要删除或操纵实验室数据。
Do not conceal undesirable test results.
不要隐瞒不良的测试结果。
Understand and review the audit trail.
了解并查看审计追踪
Only by ensuringthat these basic tenets are a component of our auditing and supplier managementprocesses will we begin to see positive improvement in data integrity inlaboratory operations and stop the cheating in the laboratory.
只有确保这些基本原则成为我们审计和供应商管理流程的组成部分，我们才能开始在实验室操纵中看到数据完整性的积极改善，并阻止实验室中的作弊行为。
通过专业的实验室LIMS产品和整体化解决方案服务帮助实验室用户加速实验室领域的研究，解决在实验室分析领域所遇到的复杂问题与挑战，提高实验室生产力在实验室管理方面尤为重要。
