Upload
javier
View
44
Download
0
Tags:
Embed Size (px)
DESCRIPTION
International guidelines and laws. Timo Nevalainen University of Eastern Finland Finland. The EU Directive 6106/10/EEC. Member States shall ensure that - PowerPoint PPT Presentation
Citation preview
11
International guidelines and International guidelines and lawslaws
Timo NevalainenTimo Nevalainen
University of Eastern FinlandUniversity of Eastern Finland
Finland Finland
22
European regulations
Council of EuropeCoE, Strasbourg
European UnionEU, Brussels
EU DirectiveCoE Convention
Appendix Ahousing and care
EU statistical tables
Articles Articles
The EU Directive 6106/10/EECThe EU Directive 6106/10/EECMember States shall ensure thatMember States shall ensure that wherever possible, a scientifically satisfactory method wherever possible, a scientifically satisfactory method
or testing strategy, not entailing the use of live or testing strategy, not entailing the use of live animals, shall be used instead of a procedure.animals, shall be used instead of a procedure.
the number of animals used in projects is reduced to the number of animals used in projects is reduced to a minimum without compromising the objectives of a minimum without compromising the objectives of the project.the project.
refinement of breeding, accommodation and care, refinement of breeding, accommodation and care, and of methods used in procedures, eliminating or and of methods used in procedures, eliminating or reducing to the minimum any possible pain, suffering, reducing to the minimum any possible pain, suffering, distress or lasting harm to the animals.distress or lasting harm to the animals.
33
44
The EU Directive 6106/10/EECThe EU Directive 6106/10/EEC
The Commission and the Member States shall contribute The Commission and the Member States shall contribute to the development and validation of alternative to the development and validation of alternative approaches which could provide the same or higher approaches which could provide the same or higher levels of information as those obtained in procedures levels of information as those obtained in procedures using animals, but which do not involve the use of using animals, but which do not involve the use of animals or use fewer animals or which entail less painful animals or use fewer animals or which entail less painful procedures, and they shall take such other steps as they procedures, and they shall take such other steps as they consider appropriate to encourage research in this field.consider appropriate to encourage research in this field.
Member States shall assist the Commission in identifying Member States shall assist the Commission in identifying and nominating suitable specialised and qualified and nominating suitable specialised and qualified laboratories to carry out such validation studies.laboratories to carry out such validation studies.
55
The 3 R’sThe 3 R’s
Reduction: Reduction: any decrease in the numbers of any decrease in the numbers of animals used to obtain information animals used to obtain information of a given amount and precisionof a given amount and precision
Refinement:Refinement: any decrease in the incidence or any decrease in the incidence or severity of procedures applied to severity of procedures applied to animals necessarily usedanimals necessarily used
Replacement: Replacement: the substitution of conscious living the substitution of conscious living vertebrates by non-sentient vertebrates by non-sentient materialmaterial
Revised directive / ScopeRevised directive / Scope
This Directive shall apply to the following This Directive shall apply to the following animals:animals: (a) live non-human vertebrate animals, (a) live non-human vertebrate animals,
including:including: i) independently feeding larval forms, andi) independently feeding larval forms, and ii) foetal forms of mammals as from the last ii) foetal forms of mammals as from the last
third of their normal development;third of their normal development; (b) live cephalopods.(b) live cephalopods.
66
Stricter national measuresStricter national measures
Member States may, while observing the Member States may, while observing the general rules laid down in the Treaty, general rules laid down in the Treaty, maintain provisions in force on …*, aimed maintain provisions in force on …*, aimed at ensuring more extensive protection of at ensuring more extensive protection of animals falling within the scope of this animals falling within the scope of this Directive than those contained in this Directive than those contained in this Directive.Directive.
77
Purposes of proceduresPurposes of procedures
(a) basic research;(a) basic research; (b) translational or applied research with any of (b) translational or applied research with any of
the following aims:the following aims:(i) the avoidance, prevention, diagnosis or treatment of (i) the avoidance, prevention, diagnosis or treatment of disease, ill-health or other abnormality or their effects in disease, ill-health or other abnormality or their effects in human beings, animals or plants;human beings, animals or plants;
(ii) the assessment, detection, regulation or (ii) the assessment, detection, regulation or modification of physiological conditions in human modification of physiological conditions in human beings, animals or plants; orbeings, animals or plants; or
(iii) the welfare of animals and the improvement of the (iii) the welfare of animals and the improvement of the production conditions for animals production conditions for animals reared for agricultural reared for agricultural purposes.purposes.
88
Continues…Continues… (c) for any of the aims in point (b) in the development, (c) for any of the aims in point (b) in the development,
manufacture or testing of the quality, effectiveness and manufacture or testing of the quality, effectiveness and safety of drugs, foodstuffs and feed-stuffs and other safety of drugs, foodstuffs and feed-stuffs and other substances or substances or products;products;
(d) protection of the natural environment in the interests (d) protection of the natural environment in the interests of the health or welfare of human of the health or welfare of human beings or animals;beings or animals;
(e) research aimed at preservation of the species;(e) research aimed at preservation of the species; (f) higher education, or training for the acquisition, (f) higher education, or training for the acquisition,
maintenance or improvement of maintenance or improvement of vocational skills;vocational skills; (g) forensic inquiries.(g) forensic inquiries.
99
PrimatesPrimates
Great apes bannedGreat apes banned
F2 requirementF2 requirement
1010
Classification of severity of Classification of severity of proceduresprocedures
Member States shall ensure that all Member States shall ensure that all procedures are classified as "non-procedures are classified as "non-recovery", "mild", "moderate", or "severe“ recovery", "mild", "moderate", or "severe“
Member States shall ensure that a Member States shall ensure that a procedure is not performed if it involves procedure is not performed if it involves severe pain, suffering or distress that is severe pain, suffering or distress that is likely to be long-lasting and cannot be likely to be long-lasting and cannot be ameliorated.ameliorated.
1111
TrainingTraining
The staff shall be adequately educated The staff shall be adequately educated and trained before they perform any of theand trained before they perform any of the
following functions:following functions: (a) carrying out procedures on animals;(a) carrying out procedures on animals; (b) designing procedures and projects;(b) designing procedures and projects; (c) taking care of animals; or(c) taking care of animals; or (d) killing animals.(d) killing animals.
1212
Animal-welfare bodyAnimal-welfare body
..shall ensure that each breeder, supplier ..shall ensure that each breeder, supplier and user sets up an animal-welfare and user sets up an animal-welfare body.body.
The animal-welfare body shall include at The animal-welfare body shall include at least the person or persons responsible for least the person or persons responsible for the welfare and care of the animals and, in the welfare and care of the animals and, in the case of a user, a scientific member. the case of a user, a scientific member. The animal-welfare body shall also receive The animal-welfare body shall also receive input from the designated veterinarian or input from the designated veterinarian or the expert referred to in Article 25.the expert referred to in Article 25.
1313
Retrospective assessmentRetrospective assessment
……shall ensure that .. the retrospective assessment shall ensure that .. the retrospective assessment shall be carried out by the competent authority which shall be carried out by the competent authority which shall, on the basis of the necessary documentation shall, on the basis of the necessary documentation submitted by the user, evaluate the following:submitted by the user, evaluate the following:
(a) whether the objectives of the project were achieved;(a) whether the objectives of the project were achieved;
(b) the harm inflicted on animals, including the numbers (b) the harm inflicted on animals, including the numbers and species of animals used, and the severity of the and species of animals used, and the severity of the procedures; andprocedures; and
(c) any elements that may contribute to the further (c) any elements that may contribute to the further implementation of the requirement of implementation of the requirement of replacement, replacement, reduction and refinement.reduction and refinement.
1414
Non-technical project summariesNon-technical project summaries
The non-technical project summary shall The non-technical project summary shall provide the following:provide the following: (a) information on the objectives of the (a) information on the objectives of the
project, including the predicted harm andproject, including the predicted harm and benefits and the number and types of animals benefits and the number and types of animals
to be used;to be used; (b) a demonstration of compliance with the (b) a demonstration of compliance with the
requirement of replacement, reduction and requirement of replacement, reduction and refinement.refinement.
1515
Infrastructure for the 3RsInfrastructure for the 3Rs
Union Reference LaboratoryUnion Reference Laboratory Revised name and tasks for ECVAMRevised name and tasks for ECVAM
National committees for the protection of National committees for the protection of animals used for scientific purposesanimals used for scientific purposes
Member States shall nominate a single Member States shall nominate a single point of contact to provide advice on the point of contact to provide advice on the regulatory relevance and suitability of regulatory relevance and suitability of alternative approaches proposed for alternative approaches proposed for validation.validation.
1616
1717
European housing and care guidelines of European housing and care guidelines of laboratory animals laboratory animals Council of Europe (app A)Council of Europe (app A)
in effect from July 2007 onin effect from July 2007 on European UnionEuropean Union
adopted the same text in June 2007adopted the same text in June 2007
available in all EU languagesavailable in all EU languages
1818
Old Appendix AOld Appendix A
Quite similar to old – 1996 - US Quite similar to old – 1996 - US requirements (PHS policy)requirements (PHS policy) revised 2010revised 2010 http://download.nap.edu/cart/http://download.nap.edu/cart/
download.cgi?download.cgi?&record_id=12910&free=1 &record_id=12910&free=1
UK requirement considerably higherUK requirement considerably higher
1919
Space: Rational of App ASpace: Rational of App A
minimum requirements - limits set arbitrarilyminimum requirements - limits set arbitrarily
justified by science-based arguments-> exact justified by science-based arguments-> exact values cannot be scientifically provenvalues cannot be scientifically proven
a compromise between standard cage sizes, a compromise between standard cage sizes, practical experience and economic practical experience and economic reasoningreasoning
depend on minimum enrichment depend on minimum enrichment requirementsrequirements
2020
Space:Space:Standard European CagesStandard European Cages
Floor area Floor area cmcm22
Height cmHeight cm Acceptable Acceptable
Type IType I 180180 12-1412-14 NoNo
Type IIType II 330330 12-1412-14 Mice onlyMice only
Type IIIType III 815815 14-1814-18 Yes Yes
Type IVType IV 18001800 19-2019-20 YesYes
2121
Minimum floor areaMinimum floor area
Mouse Rat Hamster Gerbil Guinea pig
0
500
1000
1500
2000
2500
Appendix A ProposalEarlier Now
2222
Minimum cage heightMinimum cage height
Mouse Rat Hamster Gerbil Guinea pig
0
5
10
15
20
25
Appendix A ProposalEarlier Now
2323
Stocking densities for miceStocking densities for mice
Weight in grammes<20 <25 <30 <40
0
20
40
60
80
100
Appendix A Proposal, exp
Proposal, breeding
Earlier
Now for breeding
Now for experiments
2424
Stocking densities for ratsStocking densities for rats
Weight in grammes<50 <100 <150 <200 <300 <400 <600 >600
0
100
200
300
400
500
600
Appendix A Proposal, exp
Proposal, breeding
Earlier
Now for breeding
Now for experiments
2525
2626
2727
2828
Terms used in App ATerms used in App A
Environmental complexityEnvironmental complexity
Structured environmentStructured environment
Environmental enrichmentEnvironmental enrichment
Exposure
Environmental complexity
Structured environment
Outcome
Environmental enrichment
2929
Any refinement shouldAny refinement should
be scientifically validatedbe scientifically validated
be truly beneficial to the animalsbe truly beneficial to the animals
not detract from the scientific integrity not detract from the scientific integrity
Efficacy
Safety
Method
3030
App A - part B - minimum App A - part B - minimum enrichment - rodentsenrichment - rodents
Mouse -> nesting materialMouse -> nesting material
Rat -> refuges, such as nesting boxes, Rat -> refuges, such as nesting boxes, pipes, nesting material pipes, nesting material
Hamster -> nesting material, climbing rack, Hamster -> nesting material, climbing rack, refuge area (refuge area (e.g.e.g. tube, hut), roughage and tube, hut), roughage and gnawing objectsgnawing objects
Guinea-Pig-> refuges (tubes, shelters) Guinea-Pig-> refuges (tubes, shelters) should be provided. Sterilized wood sticks should be provided. Sterilized wood sticks may be consideredmay be considered
3131
App A text - rodentsApp A text - rodents
Nesting materials should allow the rodents to manipulate Nesting materials should allow the rodents to manipulate the material and construct a nestthe material and construct a nest
Nest boxes should be provided if insufficient nesting Nest boxes should be provided if insufficient nesting material is provided to build a complete, covered nestmaterial is provided to build a complete, covered nest
Guinea-pigs should always be provided with manipulable Guinea-pigs should always be provided with manipulable materials such as hay for chewing and concealmentmaterials such as hay for chewing and concealment
To increase environmental complexity the addition of To increase environmental complexity the addition of some form of enclosure enrichment is strongly some form of enclosure enrichment is strongly recommendedrecommended
3232
Statistical tables / EU
3333
3434
Other guidelines ? Other guidelines ?
Grant application may require compliance Grant application may require compliance with other guidelineswith other guidelines US GrantsUS Grants
Quality systemsQuality systems GLP GLP
OECD, FDA, JapaniOECD, FDA, Japani
http://www.cfsan.fda.gov/~dms/opa-pt58.html http://www.cfsan.fda.gov/~dms/opa-pt58.html ISOISO AAALAC (www.aaalac.org )AAALAC (www.aaalac.org )
3535
GLP – why and where?GLP – why and where?GLP – why and where?GLP – why and where?
GLP is applied in safety evaluation GLP is applied in safety evaluation studiesstudies
GLP is part of quality thinkingGLP is part of quality thinking Originally established to prevent Originally established to prevent
falsifications in safety evaluationfalsifications in safety evaluation New chemicals directive in EuropeNew chemicals directive in Europe
3636
What Do GLPs Do?What Do GLPs Do?
GLPs define a process.GLPs define a process.
GLPs will NOT assure good science.GLPs will NOT assure good science.
3737
GLP inspectionsGLP inspectionsGLP inspectionsGLP inspections
GLP guidelinesGLP guidelines FDAFDA OECDOECD JapanJapan
Each country has national inspection bodyEach country has national inspection body
Unit announces that GLP is appliedUnit announces that GLP is applied National body carries out inspectionsNational body carries out inspections
Inspector can come from FDA or OECDInspector can come from FDA or OECD
3838
GLP in laboratory animal unitsGLP in laboratory animal unitsGLP in laboratory animal unitsGLP in laboratory animal units
Pharmaceutical companiesPharmaceutical companies
Contract laboratoriesContract laboratories
Very few universities and government Very few universities and government research institutesresearch institutes Other studies do not requireOther studies do not require Other quality systems may be betterOther quality systems may be better
3939
FDA - OECDFDA - OECDFDA - OECDFDA - OECD
FDAFDA Laboratory animalLaboratory animal U.S. Federal Register, U.S. Federal Register,
Nonclinical Laboratory Nonclinical Laboratory Studies, GLP Regulations, Studies, GLP Regulations, U.S. FDA, Department of U.S. FDA, Department of Health, Education and Health, Education and Welfare. Fed Reg 43:59986-Welfare. Fed Reg 43:59986-60025. 1978.60025. 1978.
OECDOECD Test systemTest system OECD Guidelines for testing of OECD Guidelines for testing of
Chemicals, Appendix, Decision Chemicals, Appendix, Decision of the Council, OECD. OECD of the Council, OECD. OECD Test Guidelines, OECD Test Guidelines, OECD Principles of GLP, C(81) 30 Principles of GLP, C(81) 30 Final, pp 1-29Final, pp 1-29
http://www.oecd.org/document/http://www.oecd.org/document/63/0,2340,en_2649_34381_23463/0,2340,en_2649_34381_2346175_1_1_1_1,00.html 6175_1_1_1_1,00.html
4040
AAALACAAALAC
Association for Assessment and Association for Assessment and Accreditation of Laboratory Animal Care Accreditation of Laboratory Animal Care International, Inc. International, Inc.
Private nonprofit organization that Private nonprofit organization that accredits organizations using animals in accredits organizations using animals in research, teaching or testing.research, teaching or testing.
Available worldwide.Available worldwide.
4141
Why Accreditation?Why Accreditation?
Accreditation….Accreditation…. Represents quality of a laboratory animal Represents quality of a laboratory animal facility.facility.
Promotes scientific validity of research results.Promotes scientific validity of research results.
Provides a confidential peer-review process.Provides a confidential peer-review process.
Impresses funding sources and research Impresses funding sources and research partners.partners.
4242
ISOISO
International Organization for Standardization (ISO)International Organization for Standardization (ISO)
ISO is a network of the national standards institutes of ISO is a network of the national standards institutes of 148 countries, on the basis of one member per country, 148 countries, on the basis of one member per country, with a Central Secretariat in Geneva, Switzerland, that with a Central Secretariat in Geneva, Switzerland, that coordinates the system. coordinates the system.
Non-governmentalNon-governmental Members are government agencies, institutes, and private Members are government agencies, institutes, and private
entities (e.g., associations, trade partnerships)entities (e.g., associations, trade partnerships)
4343
ISO Practice StandardsISO Practice Standards
ISO 9000 – ISO 9000 – Systematized Quality ManagementSystematized Quality Management
Management systemManagement system refers managing business refers managing business processes or activities in order that the products or processes or activities in order that the products or services produced meet the objectives desired, such as:services produced meet the objectives desired, such as:
satisfying the customer's quality requirementssatisfying the customer's quality requirementscomplying with regulationscomplying with regulations
meeting environmental objectivesmeeting environmental objectives
Management system standards refers to all those Management system standards refers to all those features of a product (or service) which are required by features of a product (or service) which are required by the customer. the customer.
4444
ISO 9000 for Animal ResearchISO 9000 for Animal Research
Laboratory animal diet manufacturers and dealersLaboratory animal diet manufacturers and dealers Microbiology of animal feedstuffsMicrobiology of animal feedstuffs Composition of animal feedstuffsComposition of animal feedstuffs (numerous ISO 9000 standards on feedstuffs)(numerous ISO 9000 standards on feedstuffs)
Animal ExperimentationAnimal Experimentation ISO 10993-2:1992 Biological evaluation of medical devices - Part 2: ISO 10993-2:1992 Biological evaluation of medical devices - Part 2:
Animal welfare requirementAnimal welfare requirement
Specifies minimum requirements for the use of animals in biological Specifies minimum requirements for the use of animals in biological testing.testing.
Establishes guidelines which allow the scientist to respect life in general, Establishes guidelines which allow the scientist to respect life in general, to reduce the number of animal experiments and the number of animals to reduce the number of animal experiments and the number of animals used in experiments, to minimize suffering and maintain the quality of life used in experiments, to minimize suffering and maintain the quality of life of the animals used in the experiments.of the animals used in the experiments.
Applies to the experimentation performed on vertebrates.Applies to the experimentation performed on vertebrates.
4545
4646
Future Chemicals Policy of the EU -Future Chemicals Policy of the EU -A challenge and an opportunity for A challenge and an opportunity for
alternative methodsalternative methods
Up to 30100 existing chemicals that are Up to 30100 existing chemicals that are currently marketed, but have not been tested currently marketed, but have not been tested so farso far
Appropriate alternative methods will be used Appropriate alternative methods will be used as much as possible for the safety as much as possible for the safety evaluation of these chemicalsevaluation of these chemicals