GMP檢查期間發(fā)現(xiàn)的數(shù)據(jù)完整性和驗證問題

1、GMP檢查期間發(fā)現(xiàn)的數(shù)據(jù)完整性和驗證問題Data Integrity issues數(shù)據(jù)完整性問題The FDAinspectors found discrepancies between HMI (human machine interface) data and batch records and practices of operators not following batch instructions. Therefore the agency requires to provideFDA檢驗員發(fā)現(xiàn)HMI (人機界面)數(shù)據(jù)與批記錄數(shù)據(jù)存 在差異，并且操作人員未按批指令操作。因此， FD

2、A要求提供：a comprehensive investigation into the extent of the inaccuracies in data records and reporting;全面調(diào)查數(shù)據(jù)記錄和報告不準確的程度results of the data review for drugs distributed together with a detailed description of the scope and root causes of the data integrity lapses.已放行藥品的數(shù)據(jù)審核結(jié)果，以及數(shù)據(jù)完整性失效的范 圍和根本原因的詳細描述。

3、Validation issues驗證問題The agency observed a lack of process validationand, in addition, a lengthy bulk hold time prior tofilling drug products without assuring that this practice does not impact the chemical and microbiological quality.該機構(gòu)注意到未執(zhí)行工藝驗證，止匕外，漫長的待灌裝產(chǎn) 品保持時間未能確保這種做法不會影響化學和微生物質(zhì)量。The agency th

4、erefore requests因此，該機構(gòu)要求：a detailed summary of the validation program forensuring a state of control throughout the product lifecycle,用以確保在整個產(chǎn)品生命周期中處于受控狀態(tài)的驗證計劃的詳細摘要，associatedproceduresincludingprocessperformance protocol(s), and written procedures (anda program) for qualification of equipment and f

5、acilities;相關(guān)程序，包括工藝性能方案，以及設(shè)備和設(shè)施確認的書面程序（和計劃）a detailed program for designing, validating,maintaining,controllingand monitoringofmanufacturing processes that includes monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control.生產(chǎn)工藝設(shè)計、驗證、維護、控制和監(jiān)測的詳細程序, 包括監(jiān)測批次內(nèi)和批次間變異，以確保持續(xù)受

6、控狀態(tài)。Particles and OOS Results粒子（異物）和OOS吉果According to FDA, the company failed to adequately investigate and document the presence of particles ina product. The manufacturer concluded that the particles were from a broken belt on the filling line, and the corrective action （CA） was to reject a number

7、 of units of this lot. However, this CA did not expandto cover batches that were previously filled at the same line or a preventative maintenance plan to prevent recurrence of similar incidents. In addition, the company failed to conduct an adequate investigation into an OOS test result for content.

8、 The FDA therefore requests to provide據(jù)FDA稱，該公司未能充分調(diào)查和記錄產(chǎn)品中是否存在 顆粒（異物）。制造商得由結(jié)論，顆粒（異物）來自灌裝線 上斷裂的傳送帶，糾正措施（CA）是拒絕此批次產(chǎn)品。但是，此CA未擴展到涵蓋以前在該生產(chǎn)線上灌裝的批次，也 沒有用以防止類似事件再次發(fā)生的預防性維護計劃。止匕外， 該公司沒有對OOSM試結(jié)果進行充分調(diào)查。因此，F(xiàn)DA要求提供a comprehensive, independent assessment of the overall system for investigating deviations, discrepancies, complaints, OOS results, and failures,對偏差、差異、投訴、OOS和不合格結(jié)果調(diào)查的整個系統(tǒng)進行全面、獨立的評估，an independent assessment and remediation plan for the CAPA program,對CAPA序進行獨立評估和補救計劃，a comprehensive assessment and remediation pla