Do Not Delete OrManipulate Laboratory Data
不要?jiǎng)h除或操縱實(shí)驗(yàn)室數(shù)據(jù)
A basic tenet ofdata integrity in laboratory operations is expressed in CGMP regulation,namely, that “l(fā)aboratory 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 法規(guī)中表達(dá)了實(shí)驗(yàn)室操作中數(shù)據(jù)完整性的基本原則，即"實(shí)驗(yàn)室記錄應(yīng)包括從所有測(cè)試中獲得的完整數(shù)據(jù)，以確保符合既定規(guī)范和標(biāo)準(zhǔn)"。近期的FDA警告信缺陷表明，這一基本原則仍未得到遵守。
“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.” ??
"我們的檢查人員 [...]在用于測(cè)試無菌（b）（4）的兩種儀器的審計(jì)追蹤中發(fā)現(xiàn)至少有六個(gè)（b）（4）和（b）（4）檢驗(yàn)被。你們的系統(tǒng)允許操作員刪除文件。并且"你們總共發(fā)現(xiàn)了 25 個(gè)被刪除的（b）（4）測(cè)試結(jié)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.”
這些測(cè)試的審計(jì)追蹤包含"已刪除的結(jié)果集"字眼，但這兩個(gè)事件均未記錄在藥品批檢驗(yàn)記錄中，也未被質(zhì)量部門審查或調(diào)查。
????“Your analyst was unable to retrieve requested data, and ????explained that he deletes older data to make space for newly acquired ????data.”
你們的分析人員無法恢復(fù)要求的數(shù)據(jù)，并解釋說，他刪除了較舊的數(shù)據(jù)，為新獲取的數(shù)據(jù)騰出空間。
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.
對(duì)實(shí)驗(yàn)室操作進(jìn)行現(xiàn)場(chǎng)審計(jì)是確保該領(lǐng)域合規(guī)的最有效方法。對(duì)基本 GDocP 的審核是至關(guān)重要的，因?yàn)檫@是 CGMP 的基本原則。
“Our?investigators found that you had deleted entire chromatographic sequences and individual injections from your stand-alone computers.”
????"我們的檢查人員發(fā)現(xiàn)，你們從單機(jī)版計(jì)算機(jī)中刪除了整個(gè)色譜序列和個(gè)別進(jìn)針。
????“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.”
"你們將原始數(shù)據(jù)存儲(chǔ)在共享計(jì)算機(jī)網(wǎng)絡(luò)驅(qū)動(dòng)器上的"非正式"和不受控的電子表格中。你們的分析師指出，原始數(shù)據(jù)首先記錄在此"非正式"電子表格中，隨后轉(zhuǎn)錄為"正式"記錄。此電子表格顯示的結(jié)果超出你們?cè)赑CH 035《可見異物檢驗(yàn)》中設(shè)定的標(biāo)準(zhǔn)。
“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.”
????"我們的檢查員發(fā)現(xiàn)多個(gè)不受控的空白和部分填寫的 CGMP 記錄復(fù)印件（例如，環(huán)境監(jiān)測(cè)記錄、OOS記錄、水檢驗(yàn)記錄和潔凈室進(jìn)出日志），缺乏質(zhì)量部門的任何說明或監(jiān)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.”
"我們的檢查人員在貴司的一棟大樓后面發(fā)現(xiàn)了大量垃圾袋。垃圾袋內(nèi)包含破損的實(shí)驗(yàn)室和生產(chǎn)原始記錄，如分析檢驗(yàn)報(bào)告、（b）（4）水檢驗(yàn)報(bào)告和樣品記錄。
????“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
????"我們的檢查人員記錄到，你們的員工使用碎紙機(jī)銷毀關(guān)鍵的實(shí)驗(yàn)室和生產(chǎn)記錄而沒有適當(dāng)?shù)目刂坪统绦颉７鬯榈奈募ǜ咝б合?#xff08;HPLC）色譜圖和部分填寫的 OOS 記錄。
????“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
????檢查人員在垃圾箱中發(fā)現(xiàn)了撕毀的、部分填寫的帶QA 簽名的校準(zhǔn)記錄，并觀察到 ?QA 員工在撕碎文件時(shí)未記錄撕毀文件的原因。
Do Not ConcealUndesirable Test Results
不隱瞞不良測(cè)試結(jié)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.
必須通過充分的質(zhì)量體系和控制策略來防止操縱測(cè)試和/或測(cè)試結(jié)果以達(dá)到合格結(jié)果，包括（但不限于）驗(yàn)證、確認(rèn)和人員的培訓(xùn)。FDA警告信最近的缺陷表明，這一基本原則仍未得到遵守。
“Our investigators found a recurring practice of retesting samples until acceptable results were obtained.”
"我們的檢查人員發(fā)現(xiàn)你們重復(fù)測(cè)試直至得到合格結(jié)果。
“Your original data showed failing results, but data you reported showed passing ?results.”原始數(shù)據(jù)顯示了失敗的結(jié)果，但你們報(bào)告的數(shù)據(jù)顯示結(jié)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.” ???
色譜圖被人為調(diào)整以隱藏某峰的存在。你們的實(shí)驗(yàn)室設(shè)置積分參數(shù)以省略此峰在積分中的值。
“You permanently deleted the first five sample injections. You then renamed the last two injections and reported that they met specifications.”
"你們永久刪除了前五針樣品。然后，重命名了最后兩次進(jìn)樣，并報(bào)告它們符合標(biāo)準(zhǔn)。
“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.”
你們的檢驗(yàn)人員告訴我們，執(zhí)行比程序要求更多的進(jìn)針然后刪除任何不合格結(jié)果以確保通過系統(tǒng)的適用性，是實(shí)驗(yàn)室規(guī)范。
“Your firm reported only the passing results from repeat analyses.” ???"貴公司只報(bào)告了重復(fù)檢驗(yàn)后的合格結(jié)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
"第一個(gè)序列中生成的 19 個(gè)色譜圖均未得到保存并可供審查。只保存了第二組色譜圖并用于批放行。
“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.”
"在沒有科學(xué)論證的情況下，你們重復(fù)檢驗(yàn)直到獲得合格結(jié)果。并且，你們依靠這些操縱的檢驗(yàn)結(jié)果和不完整的記錄來支持批放行決定。
Understand AndReview The Audit Trail
了解并審核審計(jì)追蹤
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.
雖然FDA據(jù)說正在重新審查21 CFR Part 11，因?yàn)樗m用于所有FDA監(jiān)管的產(chǎn)品，"對(duì)于計(jì)算機(jī)連接的實(shí)驗(yàn)室設(shè)備，審計(jì)追蹤的合規(guī)使用仍然是一個(gè)極為重要的領(lǐng)域，因?yàn)樗峁┳C明符合GDocP 和 CGMP的方法。令人驚訝的是，審計(jì)追蹤仍然是一個(gè)混亂的領(lǐng)域;然而，它可能被簡(jiǎn)單地理解為“誰(shuí)，什么，何時(shí)，為什么”的記錄。對(duì)于計(jì)算機(jī)連接的實(shí)驗(yàn)室設(shè)備，它"意味著一種安全的、計(jì)算機(jī)生成的、帶時(shí)間戳的電子記錄，允許重建與電子記錄的創(chuàng)建、修改或刪除有關(guān)的事件過程"。FDA警告信最近的缺陷表明，這一基本原則仍未得到遵守。
“Analysts manipulated and deleted audit trails.”
"分析人員操縱并刪除了審計(jì)追蹤。
“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.”
????"一名檢驗(yàn)員刪除了氣體色譜設(shè)備#YQ-07-10自2015年9月15日至2016 ????年4月24日的審計(jì)追蹤，并永久刪除了2015年11月6日至13日的審計(jì)追蹤。此外，我們的檢查人員發(fā)現(xiàn)，你們的質(zhì)量控制經(jīng)理和質(zhì)量控制副經(jīng)理對(duì)所有計(jì)算機(jī)化系統(tǒng)擁有完全的管理權(quán)限，這使他們能夠操縱數(shù)據(jù)并關(guān)閉審計(jì)追蹤。
“The audit trail showed that you performed this testing in duplicate.”
審計(jì)追蹤顯示你們重復(fù)執(zhí)行測(cè)試。
“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.”
"我們對(duì)審計(jì)追蹤數(shù)據(jù)的審查顯示，你們的檢驗(yàn)人員操縱了高效液相（HPLC）系統(tǒng)上的日期/時(shí)間設(shè)置。在檢查期間，你們的檢驗(yàn)人員承認(rèn)由于未體現(xiàn)的原因，將時(shí)鐘倒設(shè)并重復(fù)測(cè)試。
“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.”
?"我們的檢查人員觀察到，你們的 Empower 3 系統(tǒng)審計(jì)追蹤顯示多個(gè)"項(xiàng)目完整性失敗"消息，這表明分析測(cè)試結(jié)果中進(jìn)針缺失。例如，初始測(cè)試的色譜圖沒有呈現(xiàn)。此測(cè)試的數(shù)據(jù)包清楚地顯示初始測(cè)試缺失，但質(zhì)量部門沒有調(diào)查該事件。
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.
審計(jì)追蹤功能在計(jì)算機(jī)連接的實(shí)驗(yàn)室設(shè)備中很常見，但必須正確啟用、配置和管理。必須進(jìn)行充分的確認(rèn)/驗(yàn)證，以包括程序和操作員培訓(xùn)，以確保在實(shí)驗(yàn)室操作中符合 CGMP 和 GDocP。
Reinforce BasicCGMP And GDocP In The Laboratory
在實(shí)驗(yàn)室中強(qiáng)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.
無論是在我們自己的實(shí)驗(yàn)室還是我們的供應(yīng)商實(shí)驗(yàn)室，我們需要一個(gè)更高的標(biāo)準(zhǔn)來建立、執(zhí)行和加強(qiáng)基本 CGMP 和 GDocP 。實(shí)驗(yàn)室操作的審計(jì)仍然是一個(gè)關(guān)鍵的成功因素。
Do not delete or manipulate laboratory data.
不要?jiǎng)h除或操縱實(shí)驗(yàn)室數(shù)據(jù)。
Do not conceal undesirable test results.
不要隱瞞不良的測(cè)試結(jié)果。
Understand ?and review the audit trail.
了解并查看審計(jì)追蹤
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.
只有確保這些基本原則成為我們審計(jì)和供應(yīng)商管理流程的組成部分，我們才能開始在實(shí)驗(yàn)室操縱中看到數(shù)據(jù)完整性的積極改善，并阻止實(shí)驗(yàn)室中的作弊行為。
通過專業(yè)的實(shí)驗(yàn)室LIMS產(chǎn)品和整體化解決方案服務(wù)幫助實(shí)驗(yàn)室用戶加速實(shí)驗(yàn)室領(lǐng)域的研究，解決在實(shí)驗(yàn)室分析領(lǐng)域所遇到的復(fù)雜問題與挑戰(zhàn)，提高實(shí)驗(yàn)室生產(chǎn)力在實(shí)驗(yàn)室管理方面尤為重要。
