品研究實(shí)驗(yàn)原始記錄審核技術(shù)要求ppt課件

1、1新藥研發(fā)過程新藥研發(fā)過程2新藥研發(fā)過程質(zhì)量規(guī)范新藥研發(fā)過程質(zhì)量規(guī)范GLP 歷史沿革歷史沿革 服從服從 GLP 的意義的意義GLP 規(guī)范根本要求規(guī)范根本要求原始數(shù)據(jù)核對(duì)要點(diǎn)原始數(shù)據(jù)核對(duì)要點(diǎn) 非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤法規(guī)對(duì)法規(guī)對(duì) GLP 或非或非 GLP的要求的要求案例分析案例分析內(nèi)容提要內(nèi)容提要4GLP 歷史歷史 美國(guó)美國(guó)What prompted US FDA to issue GLP regulations?In the 1960s and 1970s, in addition to the “Thalidomide story, FDA found:Selectively

2、 submitted findingsFabricated dataFalsified dataDiscrepancies in reporting (e.g., between individual and summary data)Poor laboratory recordkeeping (resulting in inability to reconstruct study performance)GLP 歷史歷史 美國(guó)美國(guó)In the 1960s and 1970s, FDA also found:No protocols, protocols written after study

3、 performance, study not performed according to protocolNo one in charge of studiesSloppy laboratory practicesUS FDA GLP 法規(guī)法規(guī)1976Congressional hearingsGLPs proposed1978GLPs finalized1979GLPs become effectiveUS FDA GLP 法規(guī)法規(guī) 21 CFR: Code of Federal Regulations, Food & Drug Administration. 21 CFR Pa

4、rt 58: Good Laboratory Practices for Nonclinical Laboratory Studies 21 CFR Part 11: Electronic Records; Electronic SignaturesUS FDA GLP Part 58 要求要求 Describes requirements for conducting and reporting nonclinical laboratory studies Intent: provides a framework for conducting well-controlled studies

5、assures quality and integrity of the data facilitates study reconstruction provides overall accountability Nonclinical studies that evaluate safety must be GLP compliantUS FDA GLP 檢查檢查 FDA GLP檢查過的美國(guó)國(guó)內(nèi)實(shí)驗(yàn)室檢查過的美國(guó)國(guó)內(nèi)實(shí)驗(yàn)室200余家余家, CRO, 藥廠藥廠US FDA GLP 檢查檢查 FDA GLP檢查過的美國(guó)境外實(shí)驗(yàn)室檢查過的美國(guó)境外實(shí)驗(yàn)室40余家余家, CRO, 藥廠藥廠US FDA

6、 GLP 檢查：檢查：MOU 8 個(gè)國(guó)家個(gè)國(guó)家 日本日本 法國(guó)法國(guó) 德國(guó)德國(guó) 加拿大加拿大 意大利意大利 瑞典瑞典 瑞士瑞士 荷蘭荷蘭US FDA GLP 檢查：中國(guó)檢查：中國(guó)GLP實(shí)驗(yàn)室實(shí)驗(yàn)室 2021 年年7月檢查了三家月檢查了三家GLP實(shí)驗(yàn)室實(shí)驗(yàn)室 國(guó)家安評(píng)中心國(guó)家安評(píng)中心 (NCSED) 昭衍昭衍JOINN) Bridge (康龍化成康龍化成) 昭衍提交的實(shí)驗(yàn)報(bào)告獲得美國(guó)昭衍提交的實(shí)驗(yàn)報(bào)告獲得美國(guó)FDA認(rèn)可認(rèn)可, 用于支持美國(guó)的臨床實(shí)驗(yàn)。用于支持美國(guó)的臨床實(shí)驗(yàn)。OECD GLP 規(guī)范規(guī)范 Developed in 1978 USFDA GLP provided the basis fo

7、r OECD Revised OECD principles adopted in 2019 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 d

8、ata (MAD)OECD MAD 數(shù)據(jù)互認(rèn)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 environme

9、nt 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

10、 Kingdom, United States中國(guó)中國(guó)GLP開展歷史開展歷史 1993年年12月，國(guó)家科委發(fā)布了月，國(guó)家科委發(fā)布了GLP試行試行 2019年年10月，月，SDA發(fā)布發(fā)布GLP試行試行 2019年中國(guó)修訂年中國(guó)修訂、 ，將，將GLP明確為法定要求明確為法定要求 2019年年9月月,SFDA公布實(shí)施公布實(shí)施GLP二號(hào)令二號(hào)令280 條條, 開展開展GLP認(rèn)證檢查認(rèn)證檢查 2019年年1月月 法規(guī)毒理實(shí)驗(yàn)強(qiáng)迫要求法規(guī)毒理實(shí)驗(yàn)強(qiáng)迫要求GLP 2021年年7月月 3家在中國(guó)的家在中國(guó)的GLP 實(shí)驗(yàn)室接受美國(guó)實(shí)驗(yàn)室接受美國(guó)FDA檢查檢查中國(guó)中國(guó)GLP管理規(guī)范管理規(guī)范藥物非臨床研討質(zhì)量管理規(guī)

11、范局令第藥物非臨床研討質(zhì)量管理規(guī)范局令第2號(hào)號(hào)2019年年9自自2019年年9月月1日起施行日起施行 共九章共九章45條條 非臨床研討質(zhì)量管理規(guī)范認(rèn)證規(guī)范非臨床研討質(zhì)量管理規(guī)范認(rèn)證規(guī)范280條條 藥品注冊(cè)現(xiàn)場(chǎng)核對(duì)管理規(guī)定藥品注冊(cè)現(xiàn)場(chǎng)核對(duì)管理規(guī)定7章、章、59條、條、5個(gè)附件個(gè)附件服從服從 GLP 的意義的意義 Assures quality data and data integrity Protects the well-being of subjects in clinical trials many of whom are healthy volunteers (human safety

12、) Ensures that a study can be completely reconstructed from archived records 對(duì)中國(guó)對(duì)中國(guó)CRO來說，研討報(bào)告可以得到國(guó)際來說，研討報(bào)告可以得到國(guó)際認(rèn)可。認(rèn)可。GLP 規(guī)范要素規(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

13、 be submitted to the agency in support of an application and marketing approvalGLP 規(guī)范要素規(guī)范要素Test Articlesthe SFDA-/USFDA-regulated product being testedGLP 規(guī)范要素規(guī)范要素 Test Systems Mouse/Rat, Guinea Pig, Rabbit, Dog (Beagle), Pig, Monkey, Primate, (Chimpanzee)The ABC of GLP Regulations DefinitionsPersonI

14、ndividualPartnershipGovernment agencyOrganizational unitCorporationScientific or academic establishmentGLP 規(guī)范要素規(guī)范要素Raw Data Laboratory worksheets Records & document Memoranda Notes Computer print-outs All communications (internal/external/sponsors)GLP 規(guī)范要素規(guī)范要素Organization and PersonnelEducationT

15、rainingExperienceJob descriptionPersonnel RecordPersonnelManagementStudy DirectorQAUFollow protocolDocument deviationsArchiveGLP 規(guī)范要素規(guī)范要素Organization and PersonnelReviewQAUPersonnelStudy DirectorMaster schedule sheetProtocolsInspection recordsSOPsManagementStatus reportFinal study reportGLP 規(guī)范要素規(guī)范要素

16、FacilitiesNonclinical laboratoryReceipt and storageMixingGLP現(xiàn)場(chǎng)核對(duì)現(xiàn)場(chǎng)核對(duì)Process-oriented quality data as a result of proper utilization of and control over facilities, personnel and proceduresAllows flexibility in laboratory operation and use of scientific judgment study directors must exert this judgme

17、nt overall responsibility for technical conduct, interpretation and reporting現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 1: Inventory Documents 文件清單文件清單Make sure necessary documents were included in the study reportProtocolProtocol amendments 方案修正方案修正Protocol deviations 方案偏離方案偏離(with explanations on possible impact to study i

18、nterpretation and validity)Report (with sufficiently detailed summary and individual animal data)現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 2: Identify test article 供試品供試品test article code or namesalt formformulationpurityUniformity 均一性均一性Stability 穩(wěn)定性穩(wěn)定性lot or batch#現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 3: The experimental design 實(shí)驗(yàn)設(shè)計(jì)實(shí)驗(yàn)設(shè)計(jì)Studie

19、s are fluid; what is in a protocol frequently changes during the course of a studyNote important dates (experimental design landmarks)experimental or dosing start date (REPORT)study initiation date (REPORT)protocol amendment date(s) (AMENDMENTS)experimental completion date/necropsy date (REPORT)現(xiàn)場(chǎng)核對(duì)

20、要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 3: The experimental design 實(shí)驗(yàn)設(shè)計(jì)實(shí)驗(yàn)設(shè)計(jì)Note how experimental design/methods changedlook at protocol amendments and deviationsconsider if the changes invalidated the studys objectivesconsider if the changes caused study to be inconsistent with stated guidelines/methods (and evaluate signific

21、ance)Make sure you understand experimental design (as performed) and chronology per amendments and documented deviations現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 4: Compare documents for consistency 一致性一致性Do reports comply with GLP requirements on reporting fortest article characteristicstesting of dosing formulations forpu

22、ritystabilityuniformity現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 4: Compare documents for consistency Make sure that data and their associated documents are consistent with one another. 現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 4: Compare documents for consistency Are protocol-specified evaluations of data applied?statistical testscriteria for acce

23、ptable study, positive finding (e.g., genotoxicity tests)Does selection of highest dose comply with protocol? With referenced guideline?現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 4: Compare documents for consistencyAre findings for all protocol-specified evaluations reportedbody weightclinical chemistryhistopathology for all

24、 protocol-specified dose groupstoxicokinetics現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 5: Do data seem credible?Report Raw data/Reality現(xiàn)場(chǎng)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Step 6: Evaluation of significance of lapses 失誤的評(píng)價(jià)失誤的評(píng)價(jià)The big questions Did problems in study documents result in your inability to draw meaningful conclusions from the study (w

25、ith respect to studys 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)核對(duì)要點(diǎn)現(xiàn)場(chǎng)核對(duì)要點(diǎn)Not all lapses preclude drawing conclu

26、sions from a studymistakes can happen in performing a studyin 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 int

27、erpretation? Do errors speak for a report-specific problem or something that is a systemic problem ?現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé) TESTING FACILITY MANAGEMENT: Overall laboratory management and administrative functionsdesignates study director before study is initiatedreplaces study director (promptly), if nece

28、ssaryassures there is a quality assurance unit (QAU)assures test and control articles have been appropriately evaluated for identity, strength, purity, stability and uniformity (as applicable)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)TESTING FACILITY MANAGEMENT: (contd)assures appropriate staffing, facilities, equipment an

29、d materials are available for scheduled testsassures that staff understands the functions they are to performassures deviations reported by QAU are promptly reported to study director現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR Single point of study controlhas overall responsibility for:Protocol preparationtech

30、nical conduct of studyinterpretation of resultsanalysis of resultsdocumentation of resultsreporting of resultsArchiving現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Protocol preparation現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)Contributors Ophthalmology Cardiology ImmunologyAnalyticalFormulation analysis

31、BioanalyticalStatistical analysisSpecialists/Consultants AntibodiesBone marrow differential countsSpecialized clinical pathologySperm Analysis 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)Special Procedures Considerations Are there SOPs in place? Are the staff appropriately trained? Is this training do

32、cumented? Are literature searches necessary?IACUC implications? Do you need to use a consultant/PI for the work? 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)Multi-Site Studies* Work (i.e. phase of a GLP study) performed at a geographically distinct site (Not a FDA GLP term) Assign a PI to ensure compl

33、iance with GLPsWill sign an Acceptance of Responsibilities formWill sign a statement to this fact upon completion of the work Study director remains the single point of control and maintains responsibility for overall conductQuality assurance of the test site*OECD requirement 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé) STUD

34、Y DIRECTOR: (contd)Study Scheduling Considerations Test article availability Animal availability/orderingHousingTrained staffAnalytical chemistryClinical pathologyNecropsyReports 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)Test Article Calculations - How much will you need?When is it available?Final d

35、oses?Analytical ConfirmationStorage/handling conditionsCertificate of Analysis (COA), MSDS, purity, stabilityIs there a dose formulation? 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)Protocol Review & ApprovalManagement SDSponsor (if done by CRO) Scientific contributors and laboratory staff Report

36、preparation staffQAUIACUC 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Ovetsight of Study Conduct Observe animals and proceduresReview dataCommunicate with scientific contributors and technical staff QA audits internal and externalInteractions with contributors/ PIsSubmission of samplesReceipt/review of

37、 reportRespond to unexpected events現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Oversight of Study Conduct Protocol amendments - a planned changeProtocol deviations not planned; impact on study must be determinedSOP deviations 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Example of DocumentationProtocol/pro

38、tocol amendment Protocol/SOP deviationsAnimal order Test article receipt/information Test article preparation procedureDose accountability (out of range?)Study file notesVeterinary requests/approval of treatmentEnvironmental deviations (e.g. light/dark cycle and humidity) observations of animals/pro

39、cedures Data reviewCorrespondence , fax, letter, telephone callsReports 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Report Preparation現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)ArchivingProtocol/amendmentsRaw data DocumentationSpecimensFinal report 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)SD Responsibili

40、ties for a Final ReportData interpretationPreliminary draft audited? unaudited?Integration of toxicology, pathology, TK and other supportive dataContributing Scientist/PI reportsStopped/suspended programsGLP compliance Deviations and impact on data 現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd) assures t

41、hat: protocol, including any changes, is approved as specified in GLPs, and is followedall experimental data, including observations of unanticipated responses of the test system, are accurately recorded and verifiedunforeseen circumstances, that may affect the quality and integrity of the study, ar

42、e noted when they occur, and that corrective action is taken and documented現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU):Oversees GLP Compliance in laboratoryresponsible for monitoring each study for GLP complianceorganizationally, QAU reports to test facility managementindependent of the personnel

43、 engaged in the direction and conduct of individual studiesassures that facilities, equipment, personnel, methods, practices, records, and controls are in conformance with the GLPs現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU): (contd)Oversees GLP compliance in laboratorykeeps up-to-date records of

44、all studies scheduled/performed with master schedule at labmaintains copies of all study protocols現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU): (contd) Inspects studiesat intervals adequate to assure the integrity of the studymaintains written and properly signed records at each inspection identif

45、yingdate of inspectionthe study inspectedphase or segment of study inspectedperson performing inspection現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU): (contd)maintains written and properly signed records at each inspection identifyingfindings and problems observed during inspectionscheduled date fo

46、r reinspection, if applicableproblems must immediately be brought to attention of study director and management現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU): (contd)submits periodic status reports on each study to management and study directornotes problemsnotes corrective actions takendetermines t

47、hat no deviation from approved protocols or standards operating procedures were made without proper authorization and documentation現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU): (contd)Reviews final study report to assure that:report accurately describes methods and standard operating proceduresrep

48、orted results accurately reflect the studys raw dataPrepares and signs statements to be included with the final report specifying details on inspections現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核對(duì)要點(diǎn)：職責(zé)Facility OperationsStandard operating procedures (SOP)Complete and comprehensiveUp to dateSound science and practicalReagents and

49、solutionsIdentity, titer/concentration, storage requirements, and expiration dateAnimal care and IACUCMajor issues of data auditWhat do we look for while auditing a GLP labStudy DirectorFacility ManagementQuality AssuranceChemistryPathology(Clinical and anatomical)Technical StaffReport writingSponso

50、rAccountingSubcontractors非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤Study directorFailure to follow protocolMost common because everything is driven by protocol. Examples:TA Stability determinationEnvironmental conditionsExposure to test article (dosing)非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤Study director (contd) Final ReportCommonly see f

51、ailures to address issues that occurred during study that could affect outcomes非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤Study director (contd) Failure to record all data and verifyFormulationDosing非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤Study director (contd)Documentation issuesBest way, protocol amendment. Must be done before action (sign

52、ed by SD and also QA, management and sponsor).Second best, deviation report (deviation from protocol or SOP). Completed after-the-fact by person making the observation (signed by SD and also QA and management). Deviation is noted in study report along with description of the impact the deviation has

53、 on study integrity.非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤 Inconsistencies within a protocol or between protocol and SOP Omission of necessary information from protocol Late entries in study books Non GLP corrections Failure to sign and date entries Expired reagents非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤 Failure to issue timely protoco

54、l amendments and deviation reports Paperwork missing from study book Inconsistencies between protocol and report or raw data and report.非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤 QAU fails to authorize deviation Deviations not detected by the QAU, but should have been非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤Transfer of data, specimens, recor

55、ds to archivesAt completion of studyNot all records transferred非臨床實(shí)驗(yàn)室常見錯(cuò)誤非臨床實(shí)驗(yàn)室常見錯(cuò)誤Did not follow SOPs for required auditingInappropriate training record keepingEquipment calibration issuesSanitation cage/room disinfectantsWater system attached to cage rackGLP or not GLP Safety Pharmacology studies,

56、 Core/GLP, follow up studies depending on the design/non GLP Primary Pharmacodynamic/non-GLP, Secondary PD/non GLP unless contribute to the safety evaluation Bridging studies, GLP QT studies, Guidance/GLP, data not required for regulatory submission/ non GLP In Vitro, if pivotal, genotox/GLP, effica

57、cy, MOA, metabolism/non GLPGLP or not GLPStudies that are not within the scope of GLP regulations Include (US domestic only):EfficacyChemical assays for quality controlStability testsConformance pharmacopeia standardsPharmacology and effectivenessNew methodology for toxicology experimentationExplora

58、tory studies on viruses and cell biologyMode of action, synthesis, analysisStudies covered by GMPsGLP or not GLP Disease Model Biologic Systems, Pharmacology, Transgenic animals, efficacy/non GLP, Carc/GLP Animal Rule, Efficacy/GLP Immunotoxicity studies, Guidance does not mention GLP, not pivotal f

59、or safety and most tests routinely not conducted according to GLP Excipients, GLPGLP or not GLPThe Standard is GLPWhen is FDA “more likely to accept non GLP (US domestic only)?Oncology (safety data is from published literature)Biologics (small companies, university, NIH, NCI) tissue cross reactivity

60、 studiesAIDS Drugs (early days, studies done by Academicians)Botanical submissions Known class of drugsOld drugs, change of route of administration to a less hazardous exposure (bridging studies)Drugs marketed overseas, tox studies performed in US but not GLPs (anti malarial, parasitic drugs)GLP or not GLPHowe