【正文】 必要時(shí)，可對(duì)被委托機(jī)構(gòu)進(jìn)行現(xiàn)場(chǎng)核查，以確證其研究條件和研究情況。 、病理報(bào)告及病理試驗(yàn)記錄是否保存完整并與申報(bào)資料一致；若病理照片為電子版，是否保存完好。 藥品注冊(cè)現(xiàn)場(chǎng)核查要點(diǎn)及判定原則 、準(zhǔn)確、完整，是否與申報(bào)資料一致。 藥品注冊(cè)現(xiàn)場(chǎng)核查要點(diǎn)及判定原則 。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(yàn)記錄 ? 試驗(yàn)報(bào)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(yàn)記錄 ? 試驗(yàn)報(bào)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(yàn)報(bào)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(cè)現(xiàn)場(chǎng)核查要點(diǎn)及判定原則 （二）藥理毒理方面 ，并在研究中予以執(zhí)行。 Approval ? Management ? SD ? Sponsor (if done by CRO) ? Scientific contributors and laboratory staff ? Report preparation staff ? QAU ? IACUC 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) 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(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (cont’d) Oversight of Study Conduct ? Protocol amendments a planned change ? Protocol deviations – not planned。 OECD GLP 規(guī)范 ? Developed in 1978 – USFDA GLP provided the basis for OECD – Revised OECD principles adopted in 1997 ? Primary objective similar to USFDA – To ensure the generation of high quality and reliable test data related to the safety of industrial chemical substances and preparations in the framework of harmonising testing procedures for the mutual acceptance of data (MAD) OECD MAD （數(shù)據(jù)互認(rèn)） ? Data generated in the testing of chemicals in an OECD member country in accordance with OECD Test Guidelines and OECD Principles of GLP shall be accepted in other Member countries for purposes of assessment and other uses relating to the protection of man and the environment ? OECD Member Countries – Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Japan, Korea, Luxembourg, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Slovak Republic, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States 中國(guó) GLP發(fā)展歷史 1993年 12月，國(guó)家科委發(fā)布了 GLP（試行） 1999年 10月， SDA發(fā)布 GLP（試行） 2022年中國(guó)修訂 《 中華人民共和國(guó)藥品管理法