【正文】 ial/skeletal data fairly represented the specimens. ? External findings were reasonable, parable to literature. No satisfactory explanation for the low rates IN SOFT TISSUES 案例分析 (1) 案例分析 (1) Q: ? what is the deficiency of this GLP repro tox study audited vs regulations? ? Is data acceptable for supporting safety evaluation? 案例分析 (1) A: ? what is the deficiency of this GLP repro tox study audited vs regulations? ? 人員資質(zhì) ? 培訓(xùn) ? Is data acceptable for supporting safety evaluation? ? NO?。? 案例分析 (2) Inspection at ABC Company Findings: ? The final study report did not include the signed and dated reports of the individual scientists or other professionals involved in the study: – study director did not receive contributing scientists39。 ，并與申報(bào)資料的記載一致。 一致。 、人員、日期、數(shù)據(jù)、以及實(shí)驗(yàn)結(jié)果等是否與申報(bào)資料一致。 藥品注冊(cè)現(xiàn)場(chǎng)核查要點(diǎn)及判定原則 其他部門(mén)或單位進(jìn)行的研究、試制、檢測(cè)等工作，是否有委托證明材料。 國(guó)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(guó)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? Visit us at or contact me at Question? Contact John Gong at 13581646905 (China) or (301) 5405988 (US) Email: 謝謝！ 。被委托機(jī)構(gòu)出具的報(bào)告書(shū)或圖譜是否為加蓋其公章的原件。 （包括電子圖表）和照片是否保存完整，與申報(bào)資料一致。 ，實(shí)驗(yàn)動(dòng)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(dòng)物的資質(zhì)證明及動(dòng)物飼養(yǎng)繁殖的記錄。 ，是否具有使用記錄，記錄時(shí)間與研究時(shí)間是否對(duì)應(yīng)一致，記錄內(nèi)容是否與申報(bào)資料一致。 months after the fact ? possibly immunesensitized males transferred from 107 to 113, replaced with na239。 what is in a protocol frequently changes during the course of a study ? Note important dates (experimental design landmarks) – experimental or dosing start date (REPORT) – study initiation date (REPORT) – protocol amendment date(s) (AMENDMENTS) – experimental pletion date/necropsy date (REPORT) 現(xiàn)場(chǎng)核查要點(diǎn) Step 3: The experimental design 試驗(yàn)設(shè)計(jì) ? Note how experimental design/methods changed – look at protocol amendments and deviations – consider if the changes invalidated the study’s objectives – consider if the changes caused study to be inconsistent with stated guidelines/methods (and evaluate significance) – Make sure you understand experimental design (as performed) and chronology per amendments and documented deviations 現(xiàn)場(chǎng)核查要點(diǎn) Step 4: Compare documents for consistency 一致性 ? Do reports ply with GLP requirements on reporting for – test article characteristics – testing of dosing formulations for ? purity ? stability ? uniformity 現(xiàn)場(chǎng)核查要點(diǎn) Step 4: Compare documents for consistency Make sure that data and their associated documents are consistent with one another. Compa re th is…. …to thi s prot ocol GLPs prot ocol st at ed gu i delin e/meth od prot ocol re po rt’s metho ds sec tio n prot ocol amendmen ts re po rt’s metho ds sec tio n prot ocol devia tio ns re po rt’s metho ds sec tio n re po rt tex t re po rt su mmary ta bles prot ocol , proto col a mendme nt s an d devi at io ns re po rt ov er al l re po rt su mmary ta bles re po rt ind iv idu al tables re po rt GLPs re po rt re st of s ub miss io n 現(xiàn)場(chǎng)核查要點(diǎn) Step 4: Compare documents for consistency ? Are protocolspecified evaluations of data applied? – statistical tests – criteria for acceptable study, positive finding (., genotoxicity tests) – Does selection of highest dose ply with protocol? With referenced guideline? 現(xiàn)場(chǎng)核查要點(diǎn) Step 4: Compare documents for consistency ? Are findings for all protocolspecified evaluations reported – body weight – clinical chemistry – histopathology for all protocolspecified dose groups – toxicokiics 現(xiàn)場(chǎng)核查要點(diǎn) Step 5: Do data seem credible? Report Raw data/Reality 現(xiàn)場(chǎng)核查要點(diǎn) Step 6: Evaluation of significance of lapses 失誤的評(píng)估 The big questions – – Did problems in study documents result in your inability to draw meaningful conclusions from the study (with respect to study’s stated objective)? – Did inconsistencies in this part of the submission, relative to other parts of the submission, make you have less faith in the integrity of other portions of the submission? In the conclusions of other studies? 現(xiàn)場(chǎng)核查要點(diǎn) Not all lapses preclude drawing conclusions from a study ? mistakes can happen – in performing a study – in describing fact ? sometimes fact is not convenient ? The evaluation of mistakes requires an evalution of their magnitude and nature. ? Are errors widespread? Limited? ? Do errors occur in reporting of endpoints that are critical to scientific interpretation? ? Do errors speak for a reportspecific problem or something that is a systemic problem ? 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) TESTING FACILITY MANAGEMENT: Overall laboratory management and administrative functions ? designates study director before study is initiated ? replaces study director (promptly), if necessary ? assures there is a quality assurance unit (QAU) ? assures test and c