1、1新藥研發(fā)過(guò)程新藥研發(fā)過(guò)程2新藥研發(fā)過(guò)程質(zhì)量規(guī)范新藥研發(fā)過(guò)程質(zhì)量規(guī)范GLP 歷史沿革歷史沿革 遵從遵從 GLP 的意義的意義GLP 規(guī)范基本要求規(guī)范基本要求原始數(shù)據(jù)核查要點(diǎn)原始數(shù)據(jù)核查要點(diǎn) 非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)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: Selective

2、ly submitted findings Fabricated data Falsified data Discrepancies 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 afte

3、r study performance, study not performed according to protocol No one in charge of studies Sloppy laboratory practicesUS FDA GLP 法規(guī)法規(guī)1976Congressional hearings GLPs proposed1978 GLPs finalized1979 GLPs become effectiveUS FDA GLP 法規(guī)法規(guī) 21 CFR: Code of Federal Regulations, Food & Drug Administratio

4、n. 21 CFR Part 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-control

5、led studies 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(guò)的美國(guó)國(guó)內(nèi)實(shí)驗(yàn)室檢查過(guò)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(guò)的美國(guó)境外實(shí)驗(yàn)室檢查過(guò)的美國(guó)境外實(shí)驗(yàn)室40余家余家, CRO,

6、藥廠藥廠US FDA GLP 檢查：檢查：MOU8 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 2009 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) 昭衍提交的試驗(yàn)報(bào)告獲得美國(guó)昭衍提交的試驗(yàn)報(bào)告獲得美國(guó)FDA認(rèn)可認(rèn)可, 用于支持美國(guó)的臨床試驗(yàn)。用于支持美國(guó)的臨床試驗(yàn)。OECD GLP 規(guī)范規(guī)范 Developed in 1978 USFDA GLP provided the basis

7、 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 o

8、f data (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 en

9、vironment 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,

10、 United Kingdom, United States中國(guó)中國(guó)GLP發(fā)展歷史發(fā)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） 1999年年10月，月，SDA發(fā)布發(fā)布GLP（試行）（試行） 2001年中國(guó)修訂年中國(guó)修訂中華人民共和國(guó)藥品管理法中華人民共和國(guó)藥品管理法、 藥品法實(shí)施條例藥品法實(shí)施條例，將，將GLP明確為法定要求明確為法定要求 2003年年9月月,SFDA頒布實(shí)施頒布實(shí)施GLP（二號(hào)令）（二號(hào)令）280 條條, 開(kāi)展開(kāi)展GLP認(rèn)證檢查認(rèn)證檢查 2007年年1月月 法規(guī)毒理實(shí)驗(yàn)強(qiáng)制要求法規(guī)毒理實(shí)驗(yàn)強(qiáng)制要求GLP 2009年年7月月 3家在中國(guó)的

11、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)范藥物非臨床研究質(zhì)量管理規(guī)范（局令第藥物非臨床研究質(zhì)量管理規(guī)范（局令第2號(hào)）號(hào)）2003年年9自自2003年年9月月1日起施行日起施行 共九章共九章45條條 非臨床研究質(zhì)量管理規(guī)范認(rèn)證標(biāo)準(zhǔn)非臨床研究質(zhì)量管理規(guī)范認(rèn)證標(biāo)準(zhǔn)280條條 藥品注冊(cè)現(xiàn)場(chǎng)核查管理規(guī)定藥品注冊(cè)現(xiàn)場(chǎng)核查管理規(guī)定7章、章、59條、條、5個(gè)附件個(gè)附件遵從遵從 GLP 的意義的意義 Assures quality data and data integrity Protects the well-being of subjects in clin

12、ical trials many of whom are healthy volunteers (human safety) Ensures that a study can be completely reconstructed from archived records 對(duì)中國(guó)對(duì)中國(guó)CRO來(lái)說(shuō)，研究報(bào)告可以得到國(guó)際來(lái)說(shuō)，研究報(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 nonclini

13、cal studies involving test articles to develop data that will be submitted to the agency in support of an application and marketing approvalGLP 規(guī)范要素規(guī)范要素Test Articles the 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, Prim

14、ate, (Chimpanzee)The ABC of GLP Regulations DefinitionsPersonIndividualPartnershipGovernment 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/exte

15、rnal/sponsors)GLP 規(guī)范要素規(guī)范要素Organization and PersonnelEducationTrainingExperienceJob descriptionPersonnel RecordPersonnelManagementStudy DirectorQAUFollow protocolDocument deviationsArchiveGLP 規(guī)范要素規(guī)范要素Organization and PersonnelReviewQAUPersonnelStudy DirectorMaster schedule sheetProtocolsInspection re

16、cordsSOPsManagementStatus reportFinal study reportGLP 規(guī)范要素規(guī)范要素FacilitiesNonclinical laboratoryReceipt and storageMixingGLP現(xiàn)場(chǎng)核查現(xiàn)場(chǎng)核查Process-oriented quality data as a result of proper utilization of and control over facilities, personnel and proceduresAllows flexibility in laboratory operation and use

17、 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)現(xiàn)場(chǎng)核查要點(diǎn)Step 1: Inventory Documents 文件清單文件清單 Make sure necessary documents were included in the study report Protocol Protocol amendments 方案修改方案修改 Protocol d

18、eviations 方案偏離方案偏離(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)現(xiàn)場(chǎng)核查要點(diǎn)Step 2: Identify test article 供試品供試品 test article code or name salt form formulation purity Uniformity 均一性均一性 Stability 穩(wěn)定性穩(wěn)

19、定性 lot or batch#現(xiàn)場(chǎng)核查要點(diǎn)現(xiàn)場(chǎng)核查要點(diǎn)Step 3: The experimental design 試驗(yàn)設(shè)計(jì)試驗(yàn)設(shè)計(jì) Studies are fluid; 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 amendm

20、ent date(s) (AMENDMENTS) experimental completion date/necropsy date (REPORT)現(xiàn)場(chǎng)核查要點(diǎn)現(xiàn)場(chǎng)核查要點(diǎn)Step 3: The experimental design 試驗(yàn)設(shè)計(jì)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 studys objectives consider if the changes c

21、aused 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)現(xiàn)場(chǎng)核查要點(diǎn)Step 4: Compare documents for consistency 一致性一致性 Do reports comply with GLP require

22、ments on reporting for test article characteristics testing of dosing formulations for purity stability uniformity現(xiàn)場(chǎng)核查要點(diǎn)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. 現(xiàn)場(chǎng)核查要點(diǎn)現(xiàn)場(chǎng)核查要點(diǎn)Step 4: Compare documents for consis

23、tency Are protocol-specified evaluations of data applied? statistical tests criteria for acceptable study, positive finding (e.g., genotoxicity tests) Does selection of highest dose comply with protocol? With referenced guideline?現(xiàn)場(chǎng)核查要點(diǎn)現(xiàn)場(chǎng)核查要點(diǎn)Step 4: Compare documents for consistency Are findings for

24、 all protocol-specified evaluations reported body weight clinical chemistry histopathology for all protocol-specified dose groups toxicokinetics現(xiàn)場(chǎng)核查要點(diǎn)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)現(xiàn)場(chǎng)核查要點(diǎn)Step 6: Evaluation of significance of lapses 失誤的評(píng)估失誤的評(píng)估The big questions Did pr

25、oblems in study documents result in your inability to draw meaningful conclusions from the study (with 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 th

26、e submission? In the conclusions of other studies?現(xiàn)場(chǎng)核查要點(diǎn)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 err

27、ors widespread? Limited? Do errors occur in reporting of endpoints that are critical to scientific interpretation? Do errors speak for a report-specific problem or something that is a systemic problem ?現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) TESTING FACILITY MANAGEMENT: Overall laboratory management and administrative f

28、unctions designates study director before study is initiated replaces study director (promptly), if necessary assures 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)

29、核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)TESTING FACILITY MANAGEMENT: (contd) 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

30、責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)STUDY DIRECTOR Single point of study controlhas 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)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Protocol preparation現(xiàn)場(chǎng)核查

31、要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)Contributors Ophthalmology Cardiology Immunology Analytical Formulation analysis BioanalyticalStatistical analysis Specialists/Consultants AntibodiesBone marrow differential countsSpecialized clinical pathologySperm Analysis 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (c

32、ontd)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)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)Multi-Site Studies* Work

33、(i.e. phase of a GLP study) performed at a geographically distinct site (Not a FDA GLP term) Assign a PI to ensure compliance with GLPs Will sign an Acceptance of Responsibilities form Will sign a statement to this fact upon completion of the work Study director remains the single point of control a

34、nd 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)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)Study Scheduling Considerations Test article availability Animal availability/ordering Housing Trained staff Analytical chemistry Clinical pathology Necropsy

35、Reports 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DIRECTOR: (contd)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)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé) STUDY DI

36、RECTOR: (contd)Protocol Review & 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)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Ovetsight of Study Conduct Observe animals and procedures Review data Communicate with scienti

37、fic 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)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Oversight of Study Conduct Protocol amendments - a planned change Protocol devi

38、ations not planned; impact on study must be determined SOP deviations 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Example of DocumentationProtocol/protocol amendment Protocol/SOP deviationsAnimal order Test article receipt/information Test article preparation procedureDose accountability (out of range?

39、)Study file notesVeterinary requests/approval of treatmentEnvironmental deviations (e.g. light/dark cycle and humidity) observations of animals/procedures Data reviewCorrespondence email, fax, letter, telephone callsReports 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)Report Preparation現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職

40、責(zé)STUDY DIRECTOR: (contd)Archiving Protocol/amendments Raw data Documentation Specimens Final report 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd)SD Responsibilities for a Final Report Data interpretation Preliminary draft audited? unaudited? Integration of toxicology, pathology, TK and other supportive

41、data Contributing Scientist/PI reports Stopped/suspended programs GLP compliance Deviations and impact on data 現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)STUDY DIRECTOR: (contd) assures that: protocol, including any changes, is approved as specified in GLPs, and is followed all experimental data, including observations of u

42、nanticipated 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(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU):Oversees GLP C

43、ompliance in laboratory responsible for monitoring each study for GLP compliance organizationally, 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, record

44、s, and controls are in conformance with the GLPs現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU): (contd)Oversees GLP compliance in laboratory keeps up-to-date records of all studies scheduled/performed with master schedule at lab maintains copies of all study protocols現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)QUALITY ASSURA

45、NCE UNIT (QAU): (contd) 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(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)QU

46、ALITY ASSURANCE UNIT (QAU): (contd) 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(chǎng)核查要點(diǎn)：職責(zé)

47、現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU): (contd) 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 an

48、d documentation現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)QUALITY ASSURANCE UNIT (QAU): (contd) Reviews final study report to assure that: report accurately describes methods and standard operating procedures reported results accurately reflect the studys raw data Prepares and signs statements to be included with the final

49、report specifying details on inspections現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)現(xiàn)場(chǎng)核查要點(diǎn)：職責(zé)Facility Operations Standard operating procedures (SOP) Complete and comprehensive Up to date Sound science and practical Reagents and solutions Identity, titer/concentration, storage requirements, and expiration date Animal care and IACUCMaj

50、or issues of data auditWhat do we look for while auditing a GLP labStudy DirectorFacility ManagementQuality AssuranceChemistryPathology(Clinical and anatomical)Technical StaffReport writingSponsorAccountingSubcontractors非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤Study director Failure to follow protocolMost common because

51、 everything is driven by protocol. Examples: TA Stability determination Environmental conditions Exposure to test article (dosing)非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤Study director (contd) Final ReportCommonly see failures to address issues that occurred during study that could affect outcomes非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤St

52、udy director (contd) Failure to record all data and verifyFormulationDosing非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤Study director (contd) Documentation issues Best way, protocol amendment. Must be done before action (signed by SD and also QA, management and sponsor). Second best, deviation report (deviation from protoc

53、ol 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 on study integrity.非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤 Inconsistencies within a protocol or between protocol and

54、 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(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤 Failure to issue timely protocol amendments and deviation reports Paperwork missing from study book Inconsistencies between proto

55、col and report or raw data and report.非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)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(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤Transfer of data, specimens, records to archives At completion of study Not all records transferred非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤非臨床實(shí)驗(yàn)室常見(jiàn)錯(cuò)誤 Did not foll

56、ow SOPs for required auditing Inappropriate training record keeping Equipment calibration issues Sanitation cage/room disinfectants Water system attached to cage rackGLP or not GLP Safety Pharmacology studies, Core/GLP, follow up studies depending on the design/non GLP Primary Pharmacodynamic/non-GL

57、P, 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, efficacy, MOA, metabolism/non GLPGLP or not GLPStudies that are not within the scope of GLP regul

58、ations Include (US domestic only): Efficacy Chemical assays for quality control Stability tests Conformance pharmacopeia standards Pharmacology and effectiveness New methodology for toxicology experimentation Exploratory studies on viruses and cell biology Mode of action, synthesis, analysis Studies

59、 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 for safety and most tests routinely not conducted according to GLP Excipients, GLPG

60、LP 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 studies AIDS Drugs (early days, studies done by Academicians) Botanical submissions Know