試驗動物使用

1、實驗動物的使用及動物實驗管理小組介紹國家實驗動物中心張維正1Why do we need animal experiments?23Animal Rights is a philosophical view that animals have rights similar or the same as humans. There is no rational basis for saying that a human being has special rights. A rat is a pig is a dog is a boy. Theyre all mammals.Animal rig

2、hts supporters reject all animal use, no matter how humane .Ingrid Newkirk, founder of People for the Ethical Treatment of Animals Animal rights 4Animal welfare . a human responsibility that encompasses all aspects of animal well-being, including proper housing, management, nutrition, disease preven

3、tion and treatment, responsible care, humane handling, and, when necessary, humane euthanasia.The American Veterinary Medical Association5What is laboratory animal?6What is laboratory animal?AWA: The term animal means live dogs, cats, monkeys (nonhuman primate mammals), guinea pigs, hamsters, and ra

4、bbits.Guide: Laboratory animals include any vertebrate animal (e.g., traditional laboratory animals, farm animals, wildlife, and aquatic animals) used in research, teaching, or testing.7動 物 保 護(hù) 法第一章總則第三條 本法用詞定義如下： 一、動物：指犬、貓及其他人為飼養(yǎng)或管領(lǐng)之脊椎動物，包括經(jīng)濟(jì)動物、實驗動物、寵物及其他動物。二、經(jīng)濟(jì)動物：指為皮毛、肉用、乳用、役用或其他經(jīng)濟(jì)目的而飼養(yǎng)或管領(lǐng)之動物。三、實驗

5、動物：指為科學(xué)應(yīng)用目的而飼養(yǎng)或管領(lǐng)之動物。四、科學(xué)應(yīng)用：指為教學(xué)訓(xùn)練、科學(xué)試驗、製造生物製劑、試驗商品、藥物、毒物及移植器官等目的所進(jìn)行之應(yīng)用行為。 8Animal Protection Law第三章動物科學(xué)之應(yīng)用 第十五條 使用動物進(jìn)行科學(xué)應(yīng)用，應(yīng)儘量減少數(shù)目，並以使動 物產(chǎn)生最少痛苦及傷害之方式為之。 中央主管機(jī)關(guān)得依動物之種類訂定實驗動物之來源、 適用範(fàn)圍及管理方法。 第十六條 進(jìn)行動物科學(xué)應(yīng)用之機(jī)構(gòu)應(yīng)組成動物實驗管理小組， 以督導(dǎo)該機(jī)構(gòu)進(jìn)行實驗動物之科學(xué)應(yīng)用。 中央主管機(jī)關(guān)應(yīng)設(shè)置實驗動物倫理委員會，以監(jiān)督並 管理動物之科學(xué)應(yīng)用。 前項委員會至少應(yīng)含獸醫(yī)師及民間動物保護(hù)團(tuán)體代表 各一名。

6、 動物實驗管理小組之組成、任務(wù)暨管理辦法與實驗動 物倫理委員會之設(shè)置辦法，由中央主管機(jī)關(guān)定之。9Animal Protection Law第十七條 科學(xué)應(yīng)用後，應(yīng)立即檢視實驗動物之狀況，如其已失 去部分肢體器官或仍持續(xù)承受痛苦，而足以影響其生 存品質(zhì)者，應(yīng)立即以產(chǎn)生最少痛苦之方式宰殺之。 實驗動物經(jīng)科學(xué)應(yīng)用後，除有科學(xué)應(yīng)用上之需要，應(yīng) 待其完全恢復(fù)生理功能後，始得再進(jìn)行科學(xué)應(yīng)用。 第十八條 國民中學(xué)以下學(xué)校不得進(jìn)行主管教育行政機(jī)關(guān)所定課 程標(biāo)準(zhǔn)以外，足以使動物受傷害或死亡之教學(xué)訓(xùn)練。10Animal Protection Law第五章行政監(jiān)督第二十三條 直轄市、縣(市)主管機(jī)關(guān)應(yīng)置動物保護(hù)檢查

7、人員，並得甄選義務(wù)動物保護(hù)員，協(xié)助動物保護(hù)檢查工作。 動物保護(hù)檢查人員得出入動物比賽、宰殺、繁殖、買賣、寄養(yǎng)、訓(xùn)練、動物科學(xué)應(yīng)用等場所，稽查、取締違反本法規(guī)定之有關(guān)事項。 對於前項稽查、取締，不得規(guī)避、拒絕或妨礙。動物保護(hù)檢查人員於執(zhí)行職務(wù)時，應(yīng)出示身分證明文件，必要時得請警察人員協(xié)助。 11動物實驗動物實驗管理小組設(shè)置辦法 (92.01.30修正) 第一條 本辦法依動物保護(hù)法（以下簡稱本法）第十六條第四項規(guī)定訂定之。 第二條 進(jìn)行動物科學(xué)應(yīng)用之機(jī)構(gòu)，應(yīng)組成動物實驗管理小組(以下簡稱管理小組)；由相關(guān)人員三至十五人組成，其中應(yīng)包括獸醫(yī)師或經(jīng)中央主管機(jī)關(guān)指定動物實驗管理訓(xùn)練合格專業(yè)人員。進(jìn)行動物

8、科學(xué)應(yīng)用之機(jī)構(gòu)應(yīng)於管理小組組成後三十日內(nèi)，將成員名冊報中央主管機(jī)關(guān)備查，異動時亦同。12動物實驗管理小組設(shè)置辦法 第三條 管理小組之任務(wù)如下：一、 審核該機(jī)構(gòu)進(jìn)行實驗動物之科學(xué)應(yīng)用。 二、 提供該機(jī)構(gòu)有關(guān)動物實驗設(shè)計之科學(xué)應(yīng)用諮詢意見。 三、 提供該機(jī)構(gòu)有關(guān)實驗動物飼養(yǎng)設(shè)施改善之建議。 四、 監(jiān)督該機(jī)構(gòu)實驗動物之取得、飼養(yǎng)、管理及應(yīng)用等行為。 五、 提供該機(jī)構(gòu)年度執(zhí)行實驗動物科學(xué)應(yīng)用之監(jiān)督報告。 前項年度執(zhí)行報告應(yīng)於年度結(jié)束後三個月內(nèi)報中央主管機(jī)關(guān)備查。 13動物實驗管理小組設(shè)置辦法 第四條 利用動物進(jìn)行科學(xué)實驗者，其需採用之實驗動物種類、 品種、數(shù)量及實驗設(shè)計應(yīng)先申請，經(jīng)管理小組審議核可，

9、始得進(jìn)行。 第五條 本管理小組發(fā)現(xiàn)該機(jī)構(gòu)進(jìn)行實驗動物之科學(xué)應(yīng)用，違反 本辦法相關(guān)規(guī)定時，經(jīng)限期改善，逾期仍未改善者，得 終止其實驗動物之使用。 第六條 本辦法相關(guān)書表格式由中央主管機(jī)關(guān)定之。 第七條 本辦法發(fā)布後利用動物進(jìn)行科學(xué)應(yīng)用之機(jī)構(gòu)，應(yīng)於本辦 法施行後一年內(nèi)，依本辦法之規(guī)定組成管理小組，逾期 未辦理者，依本法第二十九條處罰。 第八條 本辦法自發(fā)布日施行。14動物實驗管理小組設(shè)置辦法依據(jù)：動物實驗管理小組設(shè)置辦法第六條，訂定動物實驗申請表、年度動物實驗管理小組監(jiān)督報告格式，如附件 ( )。 15動物科學(xué)應(yīng)用機(jī)構(gòu)查核輔導(dǎo)要點一、行政院農(nóng)業(yè)委員會(以下簡稱本會)為監(jiān)督及管理動物之科學(xué)應(yīng)用，並俾

10、利動物科學(xué)應(yīng)用機(jī)構(gòu)之查核輔導(dǎo)，特訂定本要點。二、本要點之查核方式分內(nèi)部查核及外部查核二種，內(nèi)部查核由動物科學(xué)應(yīng)用機(jī)構(gòu)之動物實驗管理小組（以下簡稱管理小組）依據(jù)動物科學(xué)應(yīng)用機(jī)構(gòu)內(nèi)部查核表（如附表一）所定項目每半年查核一次，查核結(jié)果如有缺失自行改進(jìn)，並保存紀(jì)錄三年以上，該查核表應(yīng)列為管理小組年度監(jiān)督報告之附件。 外部查核由本會實驗動物倫理委員會委員以任務(wù)編組方式組成，並會同該轄區(qū)之直轄市或縣(市)政府動物保護(hù)檢查員、實驗動物相關(guān)專家及該機(jī)構(gòu)目的事業(yè)主管機(jī)關(guān)代表，依據(jù)動物科學(xué)應(yīng)用機(jī)構(gòu)外部查核表（如附表二）實地查核輔導(dǎo)，以每年二十至四十場為辦理原則。16動物科學(xué)應(yīng)用機(jī)構(gòu)查核輔導(dǎo)要點三、外部查核時，該科

11、學(xué)應(yīng)用機(jī)構(gòu)之管理小組應(yīng)備妥之相關(guān)文件如下：（一）管理小組成立、異動、作業(yè)流程與標(biāo)準(zhǔn)及會議等相關(guān)文件與規(guī)章。（二）歷年動物實驗申請表。（三）動物飼養(yǎng)管理標(biāo)準(zhǔn)作業(yè)程序相關(guān)文件。（四）歷年管理小組年度監(jiān)督報告。（五）歷年本要點所附內(nèi)部及外部查核表。171819202122How to treat animal well?Goal of the Guide To promote the humane care of animals used in biomedical and behavioral research, teaching, and testing.Objective of the Gui

12、de enhance animal well-being, the quality of biomedical research, and the advancement of biologic knowledge that is relevant to humans or animals.2324Institutional Animal Care and Use Committee GuidebookA. The IACUC A.1. Timeline, Background and HistoryA.2. Authority, Composition and FunctionsA.3. O

13、peration and AdministrationA.4. Training for MembersA.5. Legal Concerns25Institutional Animal Care and Use Committee GuidebookA.1. Timeline1950 Formal establishment of Animal Care Panel.1963 First edition of the Guide for the Care and Use of Laboratory Animals (Guide) developed by the Animal Care Pa

14、nel.1965 Incorporation of the American Association for the Accreditation of Laboratory Animal Care (AAALAC).1966 Congress passed the Laboratory Animal Welfare Act (PL 89-544) and the USDA was named the responsible agency.1967 Animal Care Panel changed its name to the American Association for Laborat

15、ory Animal Science (AALAS).1971 NIH Policy on Humane Care and Use of Laboratory Animals for PHS Supported Institutions.1973 First Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals.1979 PHS Policy required each animal-using grantee institution to have a PHS Assurance and

16、 a committee to maintain oversight of its animal care program.1985 Health Research Extension Act (P.L.99-158) passed by Congress.26Institutional Animal Care and Use Committee GuidebookA.1. Timeline (conti.)1985 Animal Welfare Act Amendments passed by Congress.1990 The structure of the Office for Pro

17、tection from Research Risks (OPRR) was changed to establish a Division of Animal Welfare.1992 First Institutional Animal Care and Use Committee Guidebook was developed ARENA and OPRR.1996 7th Edition of the Guide for the Care and Use of Laboratory Animals revised by an ILAR committee and published b

18、y the NRC.1996 AAALAC became the Association for the Assessment and Accreditation of Laboratory Animal Care International.2000 OPRR Division of Animal Welfare was separated from OPRR and became the Office of Laboratory Animal Welfare (OLAW), NIH.2002 ARENA/OLAW Institutional Animal Care and Use Comm

19、ittee Guidebook. Second edition.2728Program of Education and Training for New IACUC MembersObjectives1. To introduce members to the role of the IACUC and its evolution2. To provide the basic information necessary for IACUC members to discharge their responsibilities3. To provide a forum for response

20、 to, and discussion of, members concerns and questions29Program of Education and Training for New IACUC MembersSyllabusThe IACUC Genesis and chronologyU.S. Government PrinciplesCriteria for membershipAuthority of the IACUCProposal (protocol) submission and reviewIACUC review criteriaMonitoring of ap

21、proved protocols30Program of Education and Training for New IACUC MembersProtocol changes (amendments)RecordsSemiannual reviewsHandling animal welfare concernsInstitutional Official (IO)Community31Program of Education and Training for IACUC MembersObjectives1. To increase members knowledge, understa

22、nding and awareness2. To keep members current on:Laws (federal, state, local)Regulations (proposed, promulgated/issued)GuidelinesDevelopments and trendsInstitutional policies3. To address issues, concerns and questions raised by IACUC members,institutional staff, and the community.32Program of Educa

23、tion and Training for IACUC MembersSyllabusQuestions and concerns brought to the attention of the IACUCOfficial directivesPublicationsNotices of, and reports from, conferences, seminars, etc.Animal facility staff and/or veterinarians observations and recommendationsFacility inspections and program e

24、valuationsProblem situations33Institutional Animal Care and Use Committee GuidebookB. Oversight of the Animal Care and Use ProgramB.1. Program and Facility ReviewB.2. Animal Environment, Housing and ManagementB.2.a. GeneralB.2.b. Animal EnvironmentB.2.c. HusbandryB.2.d. Facility MaintenanceB.2.e. Em

25、ergency, Weekend and Holiday Care34Facility ReviewAll animal housing facilities must be inspected in the semiannual review.35Facility ReviewCategories to be Inspected sanitation, food and water provisions, animal identification, waste disposal, animal health records, controlled and/or expired drugs,

26、 environmental control, occupational health and safety concerns, staff training, knowledge of applicable rules and regulations, and security.36B.2. Animal Environment, Housing and ManagementThe Guide states: Proper housing and management of animal facilities are essential to animal well-being, to th

27、e quality of research data and teaching or testing programs in which animals are used, and to the health and safety of personnel. A good management program provides the environment, housing, and care that permit animals to grow, mature, reproduce, and maintain good health; provides for their well-be

28、ing; and minimizes variations that can affect research results. Specific operating practices depend on many factors that are peculiar to individual institutions and situations. Welltrained and motivated personnel can often ensure high quality animal care, even in institutions with less than optimal

29、physical plants or equipment.37Institutional Animal Care and Use Committee GuidebookB.2.f. Behavioral Management for Laboratory AnimalsB.3. Role of the VeterinarianB.4. Occupational Health and SafetyB.5. Personnel Training and EducationB.6. Emergency PreparednessB.6.a. Security and Crisis Management

30、B.6.b. Disaster Planning38B.3. Role of the Veterinarianimmunization against infectious pathogens;surveillance of colonies for specific infectious microbial agents;disease prophylaxis utilizing pharmaceutical agents;isolation and quarantine of incoming animals; andseparate housing of animals accordin

31、g to species, source or different background microbial floras.39B.3. Role of the VeterinarianSpecific areas requiring the veterinarians attention and guidance are:the selection and utilization of suitable anesthetic and analgesic agents and methods of euthanasia;appropriate selection of species for

32、research projects; andproper performance of surgical procedures and adequate preoperative, surgical, and post-operative care.40Occupational Health and Safety ProgramTraining should include information about:zoonoses,chemical safety,microbiologic and physical hazards (e.g., allergens, radiation),haza

33、rds associated with experimental procedures,handling of waste materials, andpersonal hygiene.41424344Institutional Animal Care and Use Committee GuidebookC. Review of Proposals C.1. Fundamental IssuesC.2. Protocol Review CriteriaC.2.a. Alternatives Replacement, Reduction and RefinementC.2.b. Euthana

34、siaC.2.c. Humane EndpointsC.2.d. Minimization of Pain and DistressC.2.e. Personnel QualificationsC.2.f. Veterinary Review and Consultation45The “3 Rs”Alternatives are framed within the context of the “3 Rs” articulated originallyby Russell and Burch in 1959; they include:1. Replacement, or utilizing

35、 non-animal models;2. Reduction of numbers of animals used; and3. Refinement, or elimination or reduction of unnecessary pain and distress in animals.46The following topics should be considered in the preparation and review of animal care and use protocols:Rationale and purpose of the proposed use o

36、f animals. Justification of the species and number of animals requested. Whenever possible, the number of animals requested should be justified statistically. Availability or appropriateness of the use of less-invasive procedures, other species, isolated organ preparation, cell or tissue culture, or

37、 computer simulation (see Appendix A, Alternatives). Adequacy of training and experience of personnel in the procedures used. Unusual housing and husbandry requirements. Appropriate sedation, analgesia, and anesthesia. (Scales of pain or invasiveness might aid in the preparation and review of protoc

38、ols; see Appendix A, Anesthesia, Pain and Surgery.) Unnecessary duplication of experiments. Conduct of multiple major operative procedures. Criteria and process for timely intervention, removal of animals from a study, or euthanasia if painful or stressful outcomes are anticipated. Postprocedure car

39、e. Method of euthanasia or disposition of animal. Safety of working environment for personnel. 47Review of ProposalsProposal Review Procedures Full committee review Designated member reviewCategories of IACUC Actions Approval Modifications required to secure approval Withhold approval Defer or table

40、 review4849Pain management50Do animals experience pain?No direct evidenceSubtle behavioural responsesComplex learning to avoid noxious stimuliSelf-administration of analgesics in chronic pain conditionsResponse to analgesicsAssessment central51Why treat pain?Legal and ethical reasonBeneficial for th

41、e animalBeneficial for reserachRapid return to normal functionA higher survival rateCounteract physiological changes Thoracic and abdominal pain affect ventilationReduction in food and water consumption52Pain managementPrevention: preemptive approachRecognition of painChoice of substanceDrug dose an

42、d duration53Recognition of painSigns to look forGeneral appearance and conditionAttitude, posture and movementsInteractions with cage matesReactions to manipulationFood and water consumptionProduction of faeces and urine Species-typical signs of pain and distressProcedure-specific signs5455Postopera

43、tive painPeripheral sensitizationCentral sensitizationAmplification of pain sensationSurgeryInflammatory painNeuropathic painPrevention by preemptive analgesia56Management of postoperative painPreemptive analgesiaGood surgical technique Sterile techniqueSupportive therapy Soft foodLong drinking nipp

44、lesSoft beddingWarm environmentAvoid social isolation57Minor proceduressingle dose of an opioid or NSAID sufficient (preoperatively when possible)More invasive surgeryContinue treatment for up to 24-36h After major surgeryContinue analgesic administration for 36-72 hoursCombination therapyOpioidNSAI

45、DLocal analgesia Management of postoperative pain cont. 58USDA classifications for pain-associated project59USDA classifications for pain-associated projectClassification A: This category is no longer in use. Classification B:Classification C:Classification D:Classification E:60USDA classifications

46、for pain-associated projectClassification B:Animals being bred, conditioned, or held for use in teaching, testing, experiments, research, or surgery, but not yet used for such purposes.61USDA classifications for pain-associated projectExamples:Breeding colonies of any animal species that are held in

47、 legal sized caging and handled in accordance with the Guide and other applicable regulations. Breeding colony includes parents and offspring. Newly acquired animals that are held in proper caging and handled in accordance with applicable regulations. Animals held under proper conditions or wild ani

48、mals that are being observed.62USDA classifications for pain-associated projectClassification C:Animal upon which testing, research, experiments, or tests will be conducted involving no pain, distress, or use of pain-relieving drugs.63USDA classifications for pain-associated projectExamples:Procedur

49、es performed correctly by trained personal such as administration of electrolytes/fluids, administration of oral medication, blood collection from a common peripheral vein per standard veterinary practice or catherization of same, standard radiography, parenteral injections of non-irritating substan

50、ces. Euthanasia performed in accordance with the recommendations of the most recent AVMA Panel on Euthanasia, utilizing procedures that produce rapid unconsciousness and subsequent humane death. 64USDA classifications for pain-associated projectClassification D:Animals upon which experiments, teachi

51、ng, research, surgery, or tests will be conducted involving accompanying pain or distress to the animals and for which the use of appropriate anesthetic, analgesic, or tranquilizing drug will be used.65USDA classifications for pain-associated projectExamples:Surgical procedures conducted by trained personnel in accordance with standard veterinary practice such as biopsies, gonadectomy, exposure of blood vessels, chronic catheter implantation, laparotomy or laparoscopy. Blood collection by more invasive r