【正文】 》 、 《 藥品法實施條例 》 ，將 GLP明確為法定要求 2022年 9月 ,SFDA頒布實施 GLP（二號令） 280 條 , 開展 GLP認證檢查 2022年 1月 – 法規(guī)毒理實驗強制要求 GLP 2022年 7月 – 3家在中國的 GLP 實驗室接受美國 FDA檢查 中國 GLP管理規(guī)范 藥物非臨床研究質(zhì)量管理規(guī)范（局令第 2號） 2022年 9自 2022年 9月 1日起施行 共九章 45條 非臨床研究質(zhì)量管理規(guī)范認證標準 280條 藥品注冊現(xiàn)場核查管理規(guī)定 7章、 59條、 5個附件 遵從 GLP 的意義 ? Assures quality data and data integrity ? Protects the wellbeing of subjects in clinical trials many of whom are healthy volunteers (human safety) ? Ensures that a study can be pletely reconstructed from archived records ? 對中國 CRO來說，研究報告可以得到國際認可。藥品研究中 GLP實驗室 實驗原始記錄審核技術要求 龔兆龍博士 資深副總裁兼首席技術官 昭衍新藥研究中心 1 新藥研發(fā)過程 2 新藥研發(fā)過程質(zhì)量規(guī)范 GLP 歷史沿革 遵從 GLP 的意義 GLP 規(guī)范基本要求 原始數(shù)據(jù)核查要點 非臨床實驗室常見錯誤 法規(guī)對 GLP 或非 GLP的要求 案例分析 內(nèi)容提要 4 GLP 歷史 – 美國 What prompted US FDA to issue GLP regulations? In the 1960s and 1970s, in addition to the “Thalidomide” story, FDA found: ? Selectively submitted findings ? Fabricated data ? Falsified data ? Discrepancies in reporting (., between individual and summary data) ? Poor laboratory recordkeeping (resulting in inability to reconstruct study performance) GLP 歷史 – 美國 In the 1960s and 1970s, FDA also found: ? No protocols, protocols written after study performance, study not performed according to protocol ? No one in charge of studies ? Sloppy laboratory practices US FDA GLP 法規(guī) 1976 Congressional hearings ? GLPs proposed 1978 ? GLPs finalized 1979 ? GLPs bee effective US FDA GLP 法規(guī) 21 CFR: Code of Federal Regulations, Food amp。 GLP 規(guī)范要素 What is a nonclinical laboratory? In the SFDA or USFDA regulatory world, a laboratories that conduct nonclinical studies involving test articles to develop data that will be submitted to the agency in support of an application and marketing approval GLP 規(guī)范要素 Test Articles ? the SFDA/USFDAregulated product being tested GLP 規(guī)范要素 Test Systems Mouse/Rat, Guinea Pig, Rabbit, Dog (Beagle), Pig, Monkey, Primate, (Chimpanzee) The ABC of GLP Regulations Definitions Person Individual Partnership Government agency Organizational unit Corporation Scientific or academic establishment GLP 規(guī)范要素 Raw Data ? Laboratory worksheets ? Records amp。 impact on study must be determined ? SOP deviations 現(xiàn)場核查要點：職責 STUDY DIRECTOR: (cont’d) Example of Documentation ? Protocol/protocol amendment ? Protocol/SOP deviations ? Animal order ? Test article receipt/information ? Test article preparation procedure ? Dose accountability (out of range?) ? Study file notes ? Veterinary requests/approval of treatment ? Environmental deviations (. light/dark cycle and humidity) observations of animals/procedures ? Data review ? Correspondence , fax, letter, telephone calls ? Reports 現(xiàn)場核查要點：職責 STUDY DIRECTOR: (cont’d) Report Preparation 現(xiàn)場核查要點：職責 STUDY DIRECTOR: (cont’d) Archiving ? Protocol/amendments ? Raw data ? Documentation ? Specimens ? Final report 現(xiàn)場核查要點：職責 STUDY DIRECTOR: (cont’d) SD Responsibilities for a Final Report ? Data interpretation ? Preliminary draft – audited? unaudited? ? Integration of toxicology, pathology, TK and other supportive data ? Contributing Scientist/PI reports ? Stopped/suspended programs ? GLP pliance ? Deviations and impact on data 現(xiàn)場核查要點：職責 STUDY DIRECTOR: (cont’d) assures that: ? protocol, including any changes, is approved as specified in GLPs, and is followed ? all experimental data, including observations of unanticipated responses of the test system, are accurately recorded and verified ? unforeseen circumstances, that may affect the quality and integrity of the study, are noted when they occur, and that corrective action is taken and documented 現(xiàn)場核查要點：職責 QUALITY ASSURANCE UNIT (QAU): Oversees GLP Compliance in laboratory ? responsible for monitoring each study for GLP pliance ? anizationally, QAU reports to test facility management ? independent of the personnel engaged in the direction and conduct of individual studies ? assures that facilities, equipment, personnel, methods, practices, records, and controls are in conformance with the GLPs 現(xiàn)場核查要點：職責 QUALITY ASSURANCE UNIT (QAU): (cont’d) Oversees GLP pliance in laboratory ? keeps uptodate records of all studies scheduled/performed with master schedule at lab ? maintains copies of all study protocols 現(xiàn)場核查要點：職責 QUALITY ASSURANCE UNIT (QAU): (cont’d) ? Inspects studies – at intervals adequate to assure the integrity of the study – maintains written and properly signed records at each inspection identifying ? date of inspection ? the study inspected ? phase or segment of study inspected ? person performing inspection 現(xiàn)場核查要點：職責 QUALITY ASSURANCE UNIT (QAU): (cont’d) ? maintains written and properly signed records at each inspection identifying ? findings and problems observed during inspection ? scheduled date for reinspection, if applicable ? problems must immediately be brought to attention of study director and management 現(xiàn)場核查要點：職責 QUALITY ASSURANCE UNIT (QAU): (cont’d) ? submits periodic status reports on each study to management and study director – notes problems – notes corrective actions taken ? determines that no deviation from approved protocols or standards operating procedures were made without proper authorization and documentation 現(xiàn)場核查要點：職責 QUALITY ASSURANCE UNIT (QAU): (cont’d) ? Reviews final study report to assure that: – report accurately describes methods and standard operating procedures – reported results accurately reflect the stu