【正文】 ontrol articles have been appropriately evaluated for identity, strength, purity, stability and uniformity (as applicable) 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) TESTING FACILITY MANAGEMENT: (cont’d) ? assures appropriate staffing, facilities, equipment and materials are available for scheduled tests ? assures that staff understands the functions they are to perform ? assures deviations reported by QAU are promptly reported to study director 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR Single point of study control has overall responsibility for: ? Protocol preparation ? technical conduct of study ? interpretation of results ? analysis of results ? documentation of results ? reporting of results ? Archiving 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (cont’d) Protocol preparation 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (cont’d) Contributors ? Ophthalmology ? Cardiology ? Immunology ? Analytical – Formulation analysis – Bioanalytical Statistical analysis ? Specialists/Consultants Antibodies Bone marrow differential counts Specialized clinical pathology Sperm Analysis 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (cont’d) Special Procedures Considerations ? Are there SOPs in place? ? Are the staff appropriately trained? Is this training documented? ? Are literature searches necessary? IACUC implications? ? Do you need to use a consultant/PI for the work? 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (cont’d) MultiSite Studies* ? Work (. phase of a GLP study) performed at a geographically distinct site (Not a FDA GLP term) ? Assign a PI to ensure pliance with GLPs – Will sign an Acceptance of Responsibilities form – Will sign a statement to this fact upon pletion of the work ? Study director remains the single point of control and maintains responsibility for overall conduct ? Quality assurance of the test site *OECD requirement 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (cont’d) Study Scheduling Considerations ? Test article availability ? Animal availability/ordering ? Housing ? Trained staff ? Analytical chemistry ? Clinical pathology ? Necropsy ? Reports 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (cont’d) Test Article ? Calculations How much will you need? ? When is it available? ? Final doses? ? Analytical Confirmation ? Storage/handling conditions ? Certificate of Analysis (COA), MSDS, purity, stability ? Is there a dose formulation? 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (cont’d) Protocol – Review amp。 Electronic Signatures US FDA GLP Part 58 要求 ? Describes requirements for conducting and reporting nonclinical laboratory studies – Intent: provides a framework for conducting wellcontrolled studies ? assures quality and integrity of the data ? facilitates study reconstruction ? provides overall accountability ? Nonclinical studies that evaluate safety must be GLP pliant US FDA GLP 檢查 FDA GLP檢查過的美國(guó)國(guó)內(nèi)實(shí)驗(yàn)室 200余家 , CRO, 藥廠 US FDA GLP 檢查 FDA GLP檢查過的美國(guó)境外實(shí)驗(yàn)室 40余家 , CRO, 藥廠 US FDA GLP 檢查： MOU 8 個(gè)國(guó)家 日本 法國(guó) 德國(guó) 加拿大 意大利 瑞典 瑞士 荷蘭 US FDA GLP 檢查：中國(guó) GLP實(shí)驗(yàn)室 2022 年 7月檢查了三家 GLP實(shí)驗(yàn)室 國(guó)家安評(píng)中心 (NCSED) 昭衍（ JOINN) Bridge (康龍化成 ) 昭衍提交的試驗(yàn)報(bào)告獲得美國(guó) FDA 認(rèn)可 , 用于支持美國(guó)的臨床試驗(yàn)。 Drug Administration. 21 CFR Part 58: Good Laboratory Practices for Nonclinical Laboratory Studies 21 CFR Part 11: Electronic Records。 document ? Memoranda ? Notes ? Computer printouts ? All munications (internal/external/sponsors) GLP 規(guī)范要素 Organization and Personnel ?Education ?Training ?Experience ?Job description Personnel Management Study Director QAU ?Follow protocol ?Document deviations ?Archive GLP 規(guī)范要素 Organization and Personnel Review QAU Personnel Study Director ?Master schedule sheet ?Protocols ?Inspection records ?SOPs Management Status report Final study report GLP 規(guī)范要素 Facilities Nonclinical laboratory Receipt and storage Mixing GLP現(xiàn)場(chǎng)核查 Processoriented quality data as a result of proper utilization of and control over facilities, personnel and procedures Allows flexibility in laboratory operation and use of scientific judgment study directors must exert this judgment overall responsibility for technical conduct, interpretation and reporting 現(xiàn)場(chǎng)核查要點(diǎn) Step 1: Inventory Documents 文件清單 ? Make sure necessary documents were included in the study report – Protocol – Protocol amendments 方案修改 – Protocol deviations 方案偏離 (with explanations on possible impact to study interpretation and validity) – Report (with sufficiently detailed summary and individual animal data) 現(xiàn)場(chǎng)核查要點(diǎn) 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(chǎng)核查要點(diǎn) Step 3: The experimental design 試驗(yàn)設(shè)計(jì) ? Studies are fluid。 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。 、設(shè)備和儀器。 、等級(jí)、合格證號(hào)、個(gè)體特征等是否與申報(bào)資料對(duì)應(yīng)一致。 、對(duì)照品的配制、儲(chǔ)存等記錄是否完整，是否和申報(bào)資料中反映的情況相對(duì)應(yīng)。委托證明材料反映的委托單位、時(shí)間、項(xiàng)目及方案等是否與申報(bào)資料記