FDA關(guān)于碎紙機(jī)的檢查缺陷

質(zhì)量部門對碎紙機(jī)銷毀 GMP 及非 GMP 文件缺乏有效監(jiān)督管理

lYour Quality Unit lacked oversight on destruction of documents using shredder. For example, on November12 and 13, 2024, we observed white shredded pieces of documents inside the shredder located in QC documentation room of your west direction QC building. Your firm identified type of documents destroyed using shredder were GMP and non-GMP documents. Your firm maintains similar shredding machine inside production, technical, and process engineering departments among other non-GMP areas (administrative and finance department) of your facility. There is no oversight from your Quality Assurance department on controlling and management of GMP documents that are potentially shredded using the shredders located inside these departments.

質(zhì)量部門對碎紙機(jī)銷毀文件缺乏監(jiān)督。例如，2024年11月12日及13日，我們觀察到位于西側(cè)QC樓文件室的碎紙機(jī)內(nèi)有白色碎紙片。貴公司確認(rèn)被銷毀文件包括GMP和非GMP文件，且生產(chǎn)、技術(shù)、工藝工程等非GMP區(qū)域（如行政及財(cái)務(wù)部）也配備同類碎紙機(jī)。質(zhì)量保證部門未對上述部門內(nèi)碎紙機(jī)可能銷毀的GMP文件進(jìn)行控制與管理監(jiān)督。

公司碎紙垃圾桶中現(xiàn)不合規(guī) GMP 文件，文件打印數(shù)量無限制

lA)Partially completed original GMP documents including but not limited to laboratory sheets and stability study sheets were found in the firm’s shred bins. The firm’s procedure, SOP QA0001 – Good Documentation Practices, prohibits this practice.

在公司的碎紙機(jī)里發(fā)現(xiàn)了部分完成的GMP原始文件，包括但不限于實(shí)驗(yàn)室單和穩(wěn)定性研究表單。公司的程序，SOP QA0001良好文件規(guī)范，禁止這種做法。

B)Multiple copies of blank fillable original GMP documents including but not limited to sterility worksheets and additional laboratory worksheets were found in the firm’s shred bins. The firm maintains GMP documents in MasterControl QMIS which allows authorized personnel to download documents to individual computer terminals with a 24- hour restriction; however, there are no restrictions on the number of copies that can be printed.

在該公司的碎紙垃圾桶中發(fā)現(xiàn)了多份可填寫的原始藥品生產(chǎn)質(zhì)量管理規(guī)范（GMP）空白文件副本，包括但不限于無菌檢查工作表以及其他實(shí)驗(yàn)室工作表。該公司通過 MasterControl 質(zhì)量管理信息系統(tǒng)（QMIS）來管理 GMP 文件，該系統(tǒng)允許經(jīng)授權(quán)的人員將文件下載到個(gè)人計(jì)算機(jī)終端，且下載后有 24 小時(shí)的使用限制；然而，對于可打印的文件副本數(shù)量卻未作任何限制。

工廠內(nèi)未受控調(diào)查文件待粉碎，文件追溯及碎紙機(jī)日志存缺失問題

lA. During the walk-through inspection of your facility, we observed the presence of at least three uncontrolled investigation documents in a locked bin that were placed for shredding. Your SOP QA103, Rev R04, 'Investigation' section 6.3.3 requires, 'Responsible person shall perform the investigation and prepare the investigation report as per format F-QA-0314 m EDMS electronically as per SOP QA 116 "Management of Electronic Document Management System (EDMS)" for further review and approval'. However, the investigation documents found in the bin were prepared outside of EDMS and Track Wise with no document control number and traceability. For example, the signed copy of document identified in the destruction bin titled, "Experimental analysis protocol" which was signed on 26DEC2023 could neither be located in the corresponding Track Wise deviation record or EDMS system. No reference was found in the Track Wise for the existence of such document. Also, your log for the shredder does not identify what type of documents are destroyed.

在對您的工廠進(jìn)行巡視檢查期間，我們觀察到至少有三份未受控制的調(diào)查文件放在一個(gè)上鎖的箱子中，準(zhǔn)備粉碎。您的標(biāo)準(zhǔn)操作程序QA103，版本R04，“調(diào)查”第6.3.3節(jié)要求，“負(fù)責(zé)人應(yīng)根據(jù)標(biāo)準(zhǔn)操作程序QA 116“電子文件管理系統(tǒng)（EDMS）的管理”進(jìn)行調(diào)查，并按照格式F-QA-0314 m EDMS以電子方式編制調(diào)查報(bào)告，以供進(jìn)一步審查和批準(zhǔn)”。然而，在垃圾箱中發(fā)現(xiàn)的調(diào)查文件未使用EDMS分發(fā)的，沒有文件控制編號和可追溯性。例如，2023年12月26日簽署的標(biāo)題為“實(shí)驗(yàn)分析方案”的銷毀箱中確定的文件的簽名副本既不能在相應(yīng)的Track wise偏差記錄中找到，也不能在EDMS系統(tǒng)中找到。在Trackwise中沒有找到關(guān)于此類文檔存在的參考資料。此外，你的碎紙機(jī)日志并沒有確定哪些類型的文件被銷毀。

FDA的破解建議

背景：GMP并沒有要求禁止在工廠內(nèi)放置使用碎紙機(jī)，不過，鑒于最近與碎紙機(jī)和碎紙相關(guān)的發(fā)現(xiàn)項(xiàng)，最好還是有關(guān)于碎紙機(jī)和銷毀文件的指南。

問題：對放置使用碎紙機(jī)有限制嗎？

澄清：沒有限制在工廠內(nèi)放置使用碎紙機(jī)。不過，由于存在未經(jīng)許可將GMP記錄碎紙的風(fēng)險(xiǎn)，在執(zhí)行GMP功能的區(qū)域，特別是建立原始數(shù)據(jù)的區(qū)域，包括生產(chǎn)、倉庫、實(shí)驗(yàn)室這些風(fēng)險(xiǎn)區(qū)域，建議企業(yè)禁止碎紙機(jī)或其它潛在的未經(jīng)許可的文件記錄銷毀方式。在不產(chǎn)生GMP文件記錄的區(qū)域，包括HR、財(cái)務(wù)及其它管理區(qū)域，有碎紙機(jī)是認(rèn)可的，不過還是建議有控制程序。

非GMP記錄可以用企業(yè)決定的任何方式來銷毀，包括碎紙機(jī)（只要不違背相關(guān)的文件保留政策）。GMP記錄只有在達(dá)到其保存期，或者已經(jīng)建立了真實(shí)副本來代替原始記錄后，才可以銷毀。

出于保密的目的，企業(yè)可以選擇將要銷毀的還未碎紙的文件放在安全柜中。如果這些安全柜在GMP區(qū)域或鄰近GMP區(qū)域，建議企業(yè)建立程序，規(guī)定如何銷毀。有些情況下，例如審計(jì)或懷疑文件或數(shù)據(jù)管理不當(dāng)，經(jīng)質(zhì)量部門審核后再處理可能比較適當(dāng)。

研發(fā)部門可能有GMP和非GMP研究。建議建立控制程序，防止研發(fā)部門的GMP記錄的未經(jīng)許可的銷毀。

同樣，對涂改液和便利貼也沒有限制，但還是建議在GMP區(qū)域禁止使用。