International guidelines and laws

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International guidelines and laws

• Timo Nevalainen
• Universities of Kuopio
• Finland

www.uku.fi/tnevalai/int20glines20and20laws.ppt

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Legislation

• The EU Directive 86/609/EEC
• An experiment shall not be performed on an
  animal, if another scientifically satisfactory
  method of obtaining the result sought, is
  reasonably and practicably available.
• The European Commission and the EU Member States
  must actively encourage and support the
  development, validation and acceptance of methods
  which could reduce, refine or replace the use of
  laboratory animals.

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The 3 Rs

• Reduction any decrease in the numbers of
  animals used to obtain information of a
  given amount and precision
• Refinement any decrease in the incidence or
  severity of procedures applied to animals
  necessarily used
• Replacement the substitution of conscious
  living vertebrates by non-sentient material

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Council of Europe (CoE) Convention

• Appendix A EU Recommendation
• CoE working groups
• species specific documents
• general, rodents, rabbit, dogs, cats, primates,
  fish and farm animals
• enrichment and group housing
• mandatory unless there is a veterinary or
  scientific reason not to

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• European housing and care guidelines of
  laboratory animals
• Council of Europe (app A)
• in effect from July 2007 on
• European Union
• adopted the same text in June 2007
• available in all EU languages

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Old Appendix A

• Quite similar to the US requirements (PHS policy)
• www.nap.edu/books/0309053773/html/index.html
• single copies can be ordered free
  OLAW_at_od.nih.gov
• UK requirement considerably higher

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Space Rational of App A

• minimum requirements - limits set arbitrarily
• justified by science-based arguments-gt exact
  values cannot be scientifically proven
• a compromise between standard cage sizes,
  practical experience and economic reasoning
• depend on minimum enrichment requirements

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SpaceStandard European Cages
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Minimum floor area
Earlier
Now
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Minimum cage height
Earlier
Now
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Stocking densities for mice
Earlier
Now for experiments
Now for breeding
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Stocking densities for rats
Earlier
Now for experiments
Now for breeding
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Enrichment?

• Hebb (1947)
• any modification of animals environment by
  providing physical or social stimuli
• Baumans (1999)
• any modification in the environment of the
  animals that seeks to enhance its physical and
  psychological well-being by providing stimuli
  meeting the animals species-specific needs
• housing (Refinement Definition)

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Terms used in App A

• Environmental complexity
• Structured environment
• Environmental enrichment

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Any refinement should

• be scientifically validated
• be truly beneficial to the animals
• not detract from the scientific integrity

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App A - part B - minimum enrichment - rodents

• Mouse -gt nesting material
• Rat -gt refuges, such as nesting boxes, pipes,
  nesting material
• Hamster -gt nesting material, climbing rack,
  refuge area (e.g. tube, hut), roughage and
  gnawing objects
• Guinea-Pig-gt refuges (tubes, shelters) should be
  provided. Sterilized wood sticks may be
  considered

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App A text - rodents

• Nesting materials should allow the rodents to
  manipulate the material and construct a nest
• Nest boxes should be provided if insufficient
  nesting material is provided to build a complete,
  covered nest
• Guinea-pigs should always be provided with
  manipulable materials such as hay for chewing and
  concealment
• To increase environmental complexity the addition
  of some form of enclosure enrichment is strongly
  recommended

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Statistical tables / EU
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Report on Directive 86/609 s (2001/2259(INI))

• by
• Committee on the Environment, Public Health and
  Consumer Policy
• EU-wide training course for those undertaking
  research using animals as well as for those
  responsible for the care of animals used for
  experiments should be introduced as a mandatory
  requirement
• Although voluntary guidelines exist on the
  education and training of persons working with
  laboratory animals (FELASA), there is currently
  no EU-wide standard course that can be followed

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Draft for new Directive

• Nonhuman primates / F2
• 3 step (ethics) approval
• Education and training
• Reference laboratories
• May go to Europarlament in April 2009

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Other guidelines ?

• Grant application may require compliance with
  other guidelines
• US Grants
• Quality systems
• GLP
• OECD, FDA, Japani
• http//www.cfsan.fda.gov/dms/opa-pt58.html
• ISO
• AAALAC (www.aaalac.org )

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Terms

• GLP Good Laboratory Practice
• GMP Good Manufacturing Practice
• SOP Standard Operating Procedures
• FDA Food Drug Administration
• OECD Organization for Economic Co-operation and
  Development

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GLP why and where?

• GLP is applied in safety evaluation studies
• GLP is part of quality thinking
• Originally established to prevent falsifications
  in safety evaluation
• New chemicals directive in Europe

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What Do GLPs Do?

• GLPs define a process.
• GLPs will NOT assure good science.

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GLP inspections

• GLP guidelines
• FDA
• OECD
• Japan
• Each country has national inspection body
• Unit announces that GLP is applied
• National body carries out inspections
• Inspector can come from FDA or OECD

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GLP in laboratory animal units

• Pharmaceutical companies
• Contract laboratories
• Very few universities and government research
  institutes
• Other studies do not require
• Other quality systems may be better

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FDA - OECD

• FDA
• Laboratory animal
• U.S. Federal Register, Nonclinical Laboratory
  Studies, GLP Regulations, U.S. FDA, Department of
  Health, Education and Welfare. Fed Reg
  4359986-60025. 1978.

• OECD
• Test system
• OECD Guidelines for testing of Chemicals,
  Appendix, Decision of the Council, OECD. OECD
  Test Guidelines, OECD Principles of GLP, C(81) 30
  Final, pp 1-29
• http//www.oecd.org/document/63/0,2340,en_2649_343
  81_2346175_1_1_1_1,00.html

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Animal health

• Arriving animals should be isolated and their
  health status evaluated with acceptable
  veterinary procedures
• At the beginning of a study animals should of
  free of diseases, which may interfere with the
  results or their interpretation
• If animals contract a disease, which may cause
  interference, they should be isolated

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What is interference?

• Principle investigator decides which are
  conditions that cause interference
• Animals may carry diseases which do NOT cause
  interference
• Interference is the decisive factor

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Animal care

• Standard Operating Procedures (SOP)
• Housing equipment
• Feeding
• Handling
• Animal Care

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AAALAC

• Association for Assessment and Accreditation of
  Laboratory Animal Care International, Inc.
• Private nonprofit organization that accredits
  organizations using animals in research, teaching
  or testing.
• Available worldwide.

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Why Accreditation?

• Accreditation.
• Represents quality of a laboratory animal
  facility.
• Promotes scientific validity of research results.
• Provides a confidential peer-review process.
• Impresses funding sources and research partners.

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ISO

• International Organization for Standardization
  (ISO)
• ISO is a network of the national standards
  institutes of 148 countries, on the basis of one
  member per country, with a Central Secretariat in
  Geneva, Switzerland, that coordinates the system.
  
• Non-governmental
• Members are government agencies, institutes, and
  private entities (e.g., associations, trade
  partnerships)

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ISO Practice Standards

• ISO 9000 Systematized Quality Management
• Management system refers managing business
  processes or activities in order that the
  products or services produced meet the objectives
  desired, such as
• satisfying the customer's quality requirements
• complying with regulations
• meeting environmental objectives
• Management system standards refers to all those
  features of a product (or service) which are
  required by the customer.

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ISO 9000 for Animal Research

• Laboratory animal diet manufacturers and dealers
• Microbiology of animal feedstuffs
• Composition of animal feedstuffs
• (numerous ISO 9000 standards on feedstuffs)
• Animal Experimentation
• ISO 10993-21992 Biological evaluation of medical
  devices - Part 2 Animal welfare requirement
• Specifies minimum requirements for the use of
  animals in biological testing.
• Establishes guidelines which allow the scientist
  to respect life in general, to reduce the number
  of animal experiments and the number of animals
  used in experiments, to minimize suffering and
  maintain the quality of life of the animals used
  in the experiments.
• Applies to the experimentation performed on
  vertebrates.

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Future Chemicals Policy of the EU -A challenge
and an opportunity for alternative methods

• Up to 30100 existing chemicals that are currently
  marketed, but have not been tested so far
• Appropriate alternative methods will be used as
  much as possible for the safety evaluation of
  these chemicals

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COST
The main objective of the Action is to increase
knowledge necessary for both ethically
sustainable and scientifically valid use of
laboratory animals in research.
COST Action B24 Laboratory Animal Science and
Welfare
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B24 Working Groups

• WG1 Housing of animals and scientific integrity
  (2004-2006)
• WG2 Refinement of procedures (2004-2006)
• WG3 Genetically modified (GM) animals and other
  new models (2005-2007)
• WG4. Ethical evaluation and cost-benefit analysis
  (2005-2007)
• WG5 Quality operation (2007-2008)