【正文】 led summary and individual animal data) 現(xiàn)場核查要點 Step 2: Identify test article 供試品 ? test article code or name ? salt form ? formulation ? purity ? Uniformity 均一性 ? Stability 穩(wěn)定性 ? lot or batch 現(xiàn)場核查要點 Step 3: The experimental design 試驗設計 ? Studies are fluid。 Approval ? Management ? SD ? Sponsor (if done by CRO) ? Scientific contributors and laboratory staff ? Report preparation staff ? QAU ? IACUC 現(xiàn)場核查要點：職責 STUDY DIRECTOR: (cont’d) Ovetsight of Study Conduct ? Observe animals and procedures ? Review data ? Communicate with scientific contributors and technical staff ? QA audits – internal and external ? Interactions with contributors/ PIs – Submission of samples – Receipt/review of report ? Respond to unexpected events 現(xiàn)場核查要點：職責 STUDY DIRECTOR: (cont’d) Oversight of Study Conduct ? Protocol amendments a planned change ? Protocol deviations – not planned。 reports for evaluation and inclusion in final reports 案例分析 (2) ? Study director did not receive – TK results for studies X, Y, Z – antibody testing results for studies Q, R, S ? Instead, sponsor rewrote the “final reports” – attached the study director’s report plus separate TK and antibody testing reports – data not acceptable ? study director single point of study control, responsible for evaluating all findings 案例分析 (2) ? Not all changes in, or revisions of, 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。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? ? 數據完整性 ? 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? ? 數據完整性 ? 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。 、設備和儀器。 藥品注冊現(xiàn)場核查要點及判定原則 。 、等級、合格證號、個體特征等是否與申報資料對應一致。 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。 、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。 、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。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。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