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嘉峪檢測網(wǎng) 2025-02-05 19:35
近日，F(xiàn)DA發(fā)布了對中國藥科大學(xué)儀器分析中心的警告信，警告信中披露該單位作為一個(gè)合同檢測實(shí)驗(yàn)室，業(yè)務(wù)中包含對藥物API和中間體的USP樣品進(jìn)行檢測，F(xiàn)DA對其進(jìn)行延伸檢查并發(fā)現(xiàn)以下缺陷：
未能建立實(shí)驗(yàn)室控制記錄
樣品測試記錄僅包含兩行數(shù)字，沒有標(biāo)題或抬頭。在檢查期間，該單位解釋說，這些數(shù)字代表樣品的檢測日期、批號和處理數(shù)據(jù)。
檢測記錄未記錄樣品制備、檢測程序和系統(tǒng)適用性
在檢測結(jié)果發(fā)送給與客戶之前，未對所有測試記錄進(jìn)行第二人審核
未能確保在檢查期間隨時(shí)提供實(shí)驗(yàn)室記錄。
該單位告知檢查人員，2023 年 11 月之前的測試數(shù)據(jù)都存儲在外部硬盤驅(qū)動器上。但是，當(dāng)檢查人員要求查看此數(shù)據(jù)時(shí)，他們表示可能很難找到數(shù)據(jù)，因?yàn)橛性S多歸檔的硬盤驅(qū)動器，并且只有歸檔人員才能檢索數(shù)據(jù)。
計(jì)算機(jī)化系統(tǒng)沒有足夠的控制措施來防止未經(jīng)授權(quán)的訪問或更改數(shù)據(jù)。其中，檢驗(yàn)儀器還用于學(xué)術(shù)教學(xué)和研究，不同用戶共享同一個(gè)具有完全管理訪問權(quán)限的登錄 ID。
在檢查期間被問及是否跟蹤任何偏差和實(shí)驗(yàn)室錯(cuò)誤時(shí)，該單位回答說他們只提供測試結(jié)果。
該單位的實(shí)驗(yàn)室主管表示，該單位不參與CGMP 活動，但是，F(xiàn)DA表示：他們的客戶將數(shù)據(jù)用于 CGMP 目的。
FDA在警告信中表示：該單位作為合同檢測實(shí)驗(yàn)室，必須了解自己有責(zé)任完全按照 CGMP 進(jìn)行作，并將這些藥物測試過程中遇到的任何不合格結(jié)果或重大問題告知所有客戶。
警告信翻譯如下：
Dear Mr. Shen:
The U.S. Food and Drug Administration (FDA) inspected your contract testing laboratory, Center for Instrumental Analysis of China Pharmaceutical University, FEI 3005037448, at Zhongyang Road, No. 24 Tongjiaxing Road, Nanjing, Jiangsu, from September 18 to 20, 2024.
This warning letter summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (APIs).
FDA 于2024 年 9 月 18 日至20 日檢查了位于江蘇省南京市通嘉興路 24 號中陽路的中國藥科大學(xué)儀器分析中心（FEI 3005037448）。 本警告信總結(jié)了活性藥物成分 （API） 與CGMP的重大違規(guī)。
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, the APIs you tested are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).
由于你們的制造、加工、包裝或保存方法、設(shè)施或控制不符合CGMP，你們所測試的 API 按照FD&C 法案501（a）（2）（B）、21 U.S.C. 351（a）（2）（B）被認(rèn)定為摻假。
We reviewed your September 23, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.
我們詳細(xì)審閱了你們于 2024 年 9 月 23 日對FDA 483的回復(fù)，并確認(rèn)收到你們的后續(xù)信件。
During our inspection, our investigators observed specific deviations including, but not limited to, the following.
在我們的檢查過程中，我們的檢查人員觀察到了具體的缺陷，包括但不限于以下：
1. Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure your API and intermediates complies with established specifications and standards.
未能建立實(shí)驗(yàn)室控制記錄，其中包括從所有實(shí)驗(yàn)室測試中獲得的完整數(shù)據(jù)，以確保API 和中間體符合既定規(guī)范和標(biāo)準(zhǔn)。
Your firm is a contract testing laboratory that analyzes APIs and intermediates, including samples of crude(b)(4), (b)(4), and (b)(4) USP, for the presence of (b)(4) using 1H Nuclear Magnetic Resonance spectroscopy (NMR).
貴單位是一家合同檢測實(shí)驗(yàn)室，使用 1H 核磁共振波譜 （NMR） 分析 API和中間體，包括粗品 （b）（4）、（b）（4） 和 （b）（4） USP 樣品中是否存在（b）（4）。
Your firm failed to ensure that laboratory testing records were complete. For example, your test record of samples, “(b)(4)(USP) Experiment Records” for Lot (b)(4) contained only two lines of numbers with no explanation headers or titles. During the inspection, you explained that these numbers represented the testing date, lot number, and processing data for (b)(4) samples you analyzed for your customers. Further, the testing records did not document sample preparation, the test procedure(s), and system suitability. Additionally, not all the testing records were reviewed by a second person prior to the results being shared with your customers.
貴單位未能確保實(shí)驗(yàn)室檢測記錄完整。例如，你們的樣品測試記錄，XX批次的“XX（USP）實(shí)驗(yàn)記錄”僅包含兩行數(shù)字，沒有說明標(biāo)題或抬頭。在檢查期間，你們解釋說，這些數(shù)字代表你們?yōu)榭蛻舴治龅?（b）（4） 樣品的檢測日期、批號和處理數(shù)據(jù)。此外，檢測記錄未記錄樣品制備、檢測程序和系統(tǒng)適用性。此外，在與客戶共享結(jié)果之前，并非所有測試記錄都由第二人審核。
Your firm also failed to ensure that laboratory records were readily available during the inspection. You informed our investigators that your(b)(4) 1H NMR testing data before November 2023 were stored on external hard drives. However, when our investigators requested to review this data, you stated that it might be difficult to locate the data because there were many archived hard drives and only the archiving personnel could retrieve the data. As a result, you did not provide any CGMP data stored on the external hard drives for review during the inspection. We acknowledge that you provided limited data after the inspection.
貴單位也未能確保在檢查期間隨時(shí)提供實(shí)驗(yàn)室記錄。你們告知我們的檢查人員，你們在2023 年 11 月之前的 （b）（4） 1H NMR 測試數(shù)據(jù)都存儲在外部硬盤驅(qū)動器上。但是，當(dāng)我們的檢查人員要求查看此數(shù)據(jù)時(shí)，你們表示可能很難找到數(shù)據(jù)，因?yàn)橛性S多歸檔的硬盤驅(qū)動器，并且只有歸檔人員才能檢索數(shù)據(jù)。因此，在檢查期間，你們沒有提供存儲在外部硬盤驅(qū)動器上的任何CGMP 數(shù)據(jù)以供審計(jì)。我們也知道你們在檢查之后提供了有限的數(shù)據(jù)。
Additionally, your firm failed to ensure that your computerized systems, such as the computers used to control to the NMR equipment, and to store raw data files or process data, have adequate controls in place to prevent unauthorized access or changes to data. The NMR equipment was also used for academic teaching and research, and it appears that various users shared one login ID with full administrative access.
此外，貴單位未能確保你們的計(jì)算機(jī)化系統(tǒng)（例如用于控制NMR 設(shè)備以及存儲原始數(shù)據(jù)文件或過程數(shù)據(jù)的計(jì)算機(jī)）具有足夠的控制措施來防止未經(jīng)授權(quán)的訪問或更改數(shù)據(jù)。NMR 設(shè)備還用于學(xué)術(shù)教學(xué)和研究，似乎不同的用戶共享同一個(gè)具有完全管理訪問權(quán)限的登錄 ID。
In your response, you acknowledge your failure to keep adequate records and have now established procedures outlining requirements for laboratory documentation and sample tracking. You also state that you implemented user management settings on your computerized system and completed the system validation.
在你們的回復(fù)中，你們承認(rèn)未能保存足夠的記錄，并且現(xiàn)在已經(jīng)建立了概述實(shí)驗(yàn)室文件和樣品追溯要求的程序。你們還聲明在計(jì)算機(jī)化系統(tǒng)上實(shí)施了用戶管理設(shè)置并完成了系統(tǒng)驗(yàn)證。
Your response is inadequate because the procedures appear to lack sufficient detail to be effective. Moreover, you did not consider a retrospective review and risk assessment to evaluate the potential impact of the inadequate documentation and lack of access controls, along with their associated risks, on the validity of your test results.
你們是回復(fù)是不充分的，因?yàn)檫@些程序似乎缺乏足夠的細(xì)節(jié)來確保有效。此外，你們沒有考慮進(jìn)行回顧性審查和風(fēng)險(xiǎn)評估，以評估文件不充分和缺乏訪問控制及其相關(guān)風(fēng)險(xiǎn)對測試結(jié)果有效性的潛在影響。
In response to this letter, provide:
回復(fù)此函，請?zhí)峁?/span>
A complete assessment of documentation systems used throughout your laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.
對整個(gè)實(shí)驗(yàn)室操作中使用的文件系統(tǒng)進(jìn)行全面評估，以確定文件記錄實(shí)踐不足的地方。包括詳細(xì)的糾正措施和預(yù)防措施計(jì)劃，全面糾正你們的文件記錄實(shí)踐，以確保在整個(gè)操作過程中保留可追溯、清晰、完整、原始、準(zhǔn)確、同步的記錄。
A risk assessment summarizing the potential impact of inadequate documentation on product quality, and a commitment to notify customers of any deficiencies.
一份風(fēng)險(xiǎn)評估總結(jié)文件不充分對產(chǎn)品質(zhì)量的潛在影響，并承諾將任何缺陷通知客戶。
A risk assessment summarizing the potential impact of lack of access controls of the computers and NMR equipment on product quality, and a commitment to notify customers of any deficiencies.
一份風(fēng)險(xiǎn)評估總結(jié)計(jì)算機(jī)和 NMR 設(shè)備缺乏訪問控制對產(chǎn)品質(zhì)量的潛在影響，并承諾將任何缺陷通知客戶。
See FDA’s guidance documentData Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download.
請參閱 FDA指南《藥物 CGMP 的數(shù)據(jù)完整性和合規(guī)性》，了解有關(guān)在建立和遵循 CGMP 合規(guī)數(shù)據(jù)可靠性實(shí)踐的指南。
2. Failure of your quality unit to ensure that drugs are appropriately tested and the results are reported.
質(zhì)量部門未能確保藥物得到適當(dāng)?shù)臏y試并報(bào)告結(jié)果。
You failed to establish a quality unit (QU), including defining responsibilities and procedures applicable to a QU. Additionally, when asked during the inspection whether you track any deviations and laboratory errors, you responded that you only provide testing results. Your laboratory director stated that the firm is not involved in CGMP activities, however, your customers used your data for CGMP purposes.
你們未能建立質(zhì)量部門（QU），包括制定適用于 QU 的責(zé)任和程序。此外，在檢查期間被問及你們是否跟蹤任何偏差和實(shí)驗(yàn)室錯(cuò)誤時(shí)，你們回答說你們只提供測試結(jié)果。你們的實(shí)驗(yàn)室主管表示，貴單位不參與CGMP 活動，但是，你們的客戶將你們的數(shù)據(jù)用于 CGMP 目的。
Without an adequate QU and quality system in place, there is inadequate assurance that controls are implemented to ensure that your CGMP testing operations are performing in a state of control.
如果沒有足夠的 QU 和質(zhì)量體系，就無法充分保證實(shí)施控制措施來確保你們的 CGMP 測試操作在受控狀態(tài)下執(zhí)行。
In your response, you state that you established a quality department and provided supporting documentation, including standard operating procedures. Your response is inadequate as your procedures appear to lack sufficient detail and comprehensive coverage of all the systems supporting your CGMP testing operations.
在回復(fù)中，你們聲明建立了質(zhì)量部門并提供了支持文件，包括標(biāo)準(zhǔn)操作程序。你們的回復(fù)是不充分的，因?yàn)槟銈兊某绦蛩坪跞狈ψ銐虻募?xì)節(jié)并全面覆蓋支持 CGMP 測試操作的所有系統(tǒng)。
In response to this letter, provide:
回復(fù)此函，請?zhí)峁?/span>
A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:
全面的評估和補(bǔ)救計(jì)劃，以確保你們的 QU 獲得有效運(yùn)行的權(quán)限和資源。評估還應(yīng)包括但不限于：
A determination of whether procedures used by your firm are robust and appropriate.
確定貴單位所使用的程序是否穩(wěn)健和適當(dāng)。
Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.
在整個(gè)操作過程中進(jìn)行QU 監(jiān)督的規(guī)定，以評估對適當(dāng)做法的遵守情況。
A complete and final review of the laboratory record for each sample and its related information before the QU disposition decision.
在 QU 處置決定之前，對每個(gè)樣本的實(shí)驗(yàn)室記錄及其相關(guān)信息進(jìn)行完整和最終的審查。
Oversight and approval of investigations and discharging of all other QU duties to ensure validity of the laboratory test results without having negative impact on identity, strength, quality, and purity of your customers’ drug products.
監(jiān)督和批準(zhǔn)調(diào)查并履行所有其他 QU 職責(zé)，以確保實(shí)驗(yàn)室檢測結(jié)果的有效性，而不會對客戶藥品的特性、強(qiáng)度、質(zhì)量和純度產(chǎn)生負(fù)面影響。
A comprehensive, independent assessment of your change management system. This assessment should include, but not be limited to, your procedures to ensure changes, such as changes to or deviations from a validated test method, are justified, reviewed, investigated, and approved by your QU. Your change management program should also include provisions for determining change effectiveness.
對變更管理系統(tǒng)進(jìn)行全面、獨(dú)立的評估。此評估應(yīng)包括，但不限于，你們的程序，以確保變更，例如對已驗(yàn)證的分析方法的變更或偏差，由你們的QU論證、審查、調(diào)查和批準(zhǔn)。你們的變更管理程序還應(yīng)包括確定變更有效性的規(guī)定。
An adequate QU overseeing all elements of CGMP is necessary to consistently ensure drug product quality. Your firm’s quality systems are inadequate. See FDA’s current thinking on quality systems in the FDA guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/media/71023/download for help in implementing quality systems and risk management approaches.
一個(gè)適當(dāng)?shù)?QU監(jiān)督 CGMP 的所有要素對于始終如一地確保藥品質(zhì)量是必要的。貴單位的質(zhì)量體系不足。請參閱 FDA 指南《藥品 CGMP 法規(guī)的質(zhì)量體系方法》中 FDA 對質(zhì)量體系的當(dāng)前考量，以幫助實(shí)施質(zhì)量體系和風(fēng)險(xiǎn)管理方法。
Responsibilities of a Contract Testing Lab
合同測試實(shí)驗(yàn)室的職責(zé)
FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your customers. It is essential that you understand your responsibility to operate in full compliance with CGMP, and that you inform all your customers of any out-of-specification results or significant problems encountered during the testing of these drugs.
FDA 將承包商視為制造商自身設(shè)施的延伸。你們不符合CGMP 可能會影響你們?yōu)榭蛻魴z測的藥物的質(zhì)量、安全性和有效性。你們必須了解自己有責(zé)任完全按照 CGMP 進(jìn)行操作，并將這些藥物測試過程中遇到的任何不合格結(jié)果或重大問題告知所有客戶。
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