【正文】 , an approved protocol and the reasons therefore were documented, signed by the study director, dated, and maintained with the protocol – protocol amendment not contemporaneous with study event ? signed by the study director 1189。 months after the fact ? possibly immunesensitized males transferred from 107 to 113, replaced with na239。ve males – protocol violated during this time period 案例分析 (2) ? The final study report did not include a description of all circumstances that may have affected the quality or integrity of the data – final reports for studies X and Y did not discuss potential immune sensitization of male and female guinea pigs in the respective studies as circumstances that may have affected data quality and integrity 案例分析 (2) Q: ? what is the deficiency of this GLP study audited vs regulations? ? Is data acceptable for supporting safety evaluation? 案例分析 (2) ? what is the deficiency of this GLP study audited vs regulations? ? SD ? 試驗記錄 ? 試驗報告 ? QA ? Is data acceptable for supporting safety evaluation? ? NO??！ 案例分析 (3) Inspection at DEF Labs Findings: ? protocol called for weekly weights, but study reported biweekly weights. ? for many of the weights, the biweekly weights looked very peculiar. ? body wt data discrepancies 案例分析 (3) ? the founder/president/study director claimed he personally recorded the body wt and denied falsification by duplication or adding digits ? the Sponsor attempted to pursuade the study director and the histopathologist to change the study results (unrelated to body wt). 案例分析 (3) Q: ? what is the deficiency of this GLP study audited vs regulations? ? Is data acceptable for supporting safety evaluation? 案例分析 (3) ? what is the deficiency of this GLP tox study audited vs regulations? ? 方案 ? SD ? 試驗記錄 ? 試驗報告 ? Is data acceptable for supporting safety evaluation? ? NO！！ 案例分析 (4) Audit findings at GHI labs: ? Study director didn’t always know if the intended dose was the actual dose administered – test article characteristics and results of dosing formulation testing not provided to study director 案例分析 (4) ? Contributing scientist reports submitted separately – study director not given the opportunity to evaluate the data/conclusions ? Absence of intact contributing scientist reports – unclear if study director’s text is attributed to or reflective of contributing scientist conclusions 案例分析 (4) Q: ? what is the deficiency of this GLP study audited vs regulations? ? Is data acceptable for supporting safety evaluation? 案例分析 (4) ? what is the deficiency of this GLP tox study audited vs regulations? ? SD ? 試驗報告 ? Is data acceptable for supporting safety evaluation? ? NO??！ 案例分析 (5) Findings of inspection at JKL labs ? Study inplete when safety summary written – recovery group not yet sacrificed – histopathologic findings not available – memo used to prepare the integrated safety summary not maintained 案例分析 (5) Q: ? what is the deficiency of this GLP study audited vs regulations? ? Is data acceptable for supporting safety evaluation? 案例分析 (5) ? what is the deficiency of this GLP tox study audited vs regulations? ? 數(shù)據(jù)完整性 ? Is data acceptable for supporting safety evaluation? ? NO?。? 案例分析 (6) Findings at MNO labs ? Actual dose administered unknown – no concentration results for the dosing formulation – final report did not discuss impact on study integrity ? Reason for change in automated data entries not documented ? Studyspecific activities conducted prior to study initiation – animal randomization ? Protocol lacked methods of study conduct 案例分析 (6) Q: ? what is the deficiency of this GLP study audited vs regulations? ? Is data acceptable for supporting safety evaluation? 案例分析 (6) ? what is the deficiency of this GLP study audited vs regulations? ? 數(shù)據(jù)完整性 ? Is data acceptable for supporting safety evaluation? ? NO??！ 藥品注冊現(xiàn)場核查要點及判定原則 （二）藥理毒理方面 ，并在研究中予以執(zhí)行。 ，并與申報資料的記載一致。 、設備和儀器。 ，是否具有使用記錄，記錄時間與研究時間是否對應一致，記錄內(nèi)容是否與申報資料一致。 藥品注冊現(xiàn)場核查要點及判定原則 。 一致。 、等級、合格證號、個體特征等是否與申報資料對應一致。 ，實驗動物為本單位飼養(yǎng)繁殖的，是否能提供本單位具有飼養(yǎng)動物的資質(zhì)證明及動物飼養(yǎng)繁殖的記錄。 藥品注冊現(xiàn)場核查要點及判定原則 、準確、完整，是否與申報資料一致。 、人員、日期、數(shù)據(jù)、以及實驗結果等是否與申報資料一致。 、對照品的配制、儲存等記錄是否完整，是否和申報資料中反映的情況相對應。 （包括電子圖表）和照片是否保存完整，與申報資料一致。 、病理報告及病理試驗記錄是否保存完整并與申報資料一致；若病理照片為電子版，是否保存完好。 藥品注冊現(xiàn)場核查要點及判定原則 其他部門或單位進行的研究、試制、檢測等工作，是否有委托證明材料。委托證明材料反映的委托單位、時間、項目及方案等是否與申報資料記載一致。被委托機構出具的報告書或圖譜是否為加蓋其公章的原件。必要時，可對被委托機構進行現(xiàn)場核查，以確證其研究條件和研究情況。 國外 GLP檢查發(fā)現(xiàn) The German inspectorate conducted 33 GLP inspections in 21 foreign test facilities. 221 inspection reports from the years 2022 to 2022 were analyzed for GLP observations which were categorized into the ten GLP principles 國外 GLP檢查發(fā)現(xiàn) Observations Number % 1 Studies: Study Plan / Report 353 2 Insufficient Documentation / Document Handling 259 3 SOP: Administration – Use 170 4 Organization/Personnel: Personnel Records 169 5 Apparatus/Materials/Reagents/Samples: Apparatus 152 7 6 Study: Raw Data 127 7 Test and Reference Items 119 5 8 Study: Conduct 112 5 9 Electronic data acquisition/processing / IT Systems 110 5 10 Archiving: Procedures and Access / Retrieval Options 101 11 Quality Assurance: Inspection Procedures 89 4 12 Facility 85 4 13 Insufficient separation GLP / nonGLP 61 14 Insufficient Procedures Related to MultiSite Studies 56 Questions? 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