Research with Biohazards and Select Agents

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Research with Biohazardsand Select Agents

• SCAW IACUC-Advanced
• University of Notre Dame

Jim Swearengen, DVM, DACLAM, DACVPM Director of
Comparative Medicine National Biodefense Analysis
and Countermeasures Center Frederick, MD
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Roadmap

• Responsibility and the IACUC
• Institutional Policies
• Animal Environment and Management
• Veterinary Medical Care
• Physical Plant and potential impacts of changes
  in the 5th Edition of the BMBL
• Additional Issues for Select Agent Research

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The IACUC

• The IACUC is appointed to oversee and evaluate
  the institutions animal program, procedures, and
  facilities to ensure they are in compliance with
  applicable regulations and guidance.

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Other Responsibilities

• Represent institution and community
• Serve as local oversight arm for other agencies
• Foster a culture within the institute of good
  animal care and use practices
• Clearly articulate policies and procedures
• Ensure guidance is implemented using
  scientifically sound, performance-based standards
• Ensure effective training programs are
  established
• Stimulate improvements in the program

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Expectations

• IACUC evaluates all animal care and use programs
  and animal-activity areas
• Key components of a program review
• IACUC membership and function
• Personnel qualifications and training
• Occupational health and safety
• Animal environment, housing and management
• Veterinary Medical Care

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Compliance-Meeting the Intent While Facilitating
Research

• Select agent work does not release an
  organization from compliance with regulations
• Consequences can be very serious to the
  individual and institution
• Creative solutions are essential to balance
  competing requirements

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ABSL versus BSL

• Adding animals presents new hazards and
  challenges
• May generate aerosols
• Animals bite and scratch
• Greater variability in job tasks is likely

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Key Issues of IACUC Oversight

• Study endpoints
• Post-challenge monitoring
• Well defined intervention criteria for diseases
  of a known pathogenesis
• Treatment
• Nursing care
• Analgesic administration
• Euthanasia
• Clear hierarchy for reporting observations and
  decision making

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Key Issues of IACUC Oversight

• Study endpoints (Cont.)
• Provisions for unexpectedly severe signs
• Checklist of observations on which the endpoint
  will be based
• Frequency of monitoring
• Increased with development of clinical signs
• Sufficient trained staff to perform inside
  containment

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Key Issues of IACUC Oversight

• Consideration of analgesics
• Appropriate justification for not using
• Sufficient personnel resources to administer
• Selection of appropriate drug
• Efficacious
• Does not interfere with data

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Key Issues of IACUC Oversight

• Semiannual program review and facility inspection
• IACUC member entrance into ABSL suites or other
  methods of viewing
• Have method for reviewing records located in
  containment areas
• IACUC membership
• Biosafety member highly useful,
• Or need highly integrated safety office

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Veterinary Care

• . Veterinary Care must be provided
• . Must include access to all animals

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Personnel Qualifications and Training

• The level of qualifications required and the
  intensity of the training program depend heavily
  on several issues, including
• Species used
• Nature of the research being performed
• Research in biocontainment greater scrutiny of
  qualifications and an intense, well documented
  training program

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Personnel Qualifications and Training

• Examples of high-risk procedures
• Handling infected animals
• Administering injections
• Obtaining biosamples
• Using sharps
• Performing necropsies
• Personnel performing these types of procedures
  should be limited to a select few highly trained,
  highly experienced individuals

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Occupational Health and Safety

• Pre-placement medical evaluations
• Level of detail should be risk related, examples
  
• High risk detailed medical questionnaire and
  comprehensive exam by physician
• Moderate risk detailed medical questionnaire
  reviewed by a health professional
• Low risk screening evaluation reviewed by health
  professional

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Occupational Health and Safety

• Periodic health evaluations
• Components and frequency depend on nature of
  potential hazards
• Can identify health alterations, leading to, but
  not yet causing serious health problems (e.g.,
  allergies)
• Physical exams typically not a routine component,
  but depends on level of risk

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Occupational Health and Safety

• Immunizations
• Based on risk of infection or exposure
• Examples
• Tetanus
• Rabies
• Working with hazardous biological agents
• Thorough risk assessment

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Occupational Health and Safety

• Zoonoses, experimental, job related risks
• Personnel should be trained on specific risks
• Knowledge of procedures for notifying supervisor
• Potential or known exposures to hazards
• Suspected zoonotic hazards in the workplace
• Bites, scratches, allergic reactions
• Illnesses
• Notification and follow-up procedures clearly
  delineated

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Compliance Using a Performance Standard Approach

• Caregivers handling rabbits challenged with
  Bacillus anthracis understand potential hazards
• Personnel with exposure to rodents can describe
  symptoms of rodent allergies
• Cagewash personnel can describe safety mechanisms
  and procedures for rack washer
• PPE requirements consistently followed throughout
  facility

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Occupational Health and Safety

• Must have a well thought-out plan for handling
  of potential exposures to infectious agents and
  toxins!

Rusnak, et al, 2004. Management Guidelines for
Laboratory Exposures to Agents of Bioterrorism.
J Occup Environ Med. 46791-800 Rusnak, et al,
2004. Experience in the Medical Management of
Potential Laboratory Exposures to Agents of
Bioterrorism on the Basis of Risk Assessment at
the USAMRIID. J Occup Environ. Med. 46801-811
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Animal Environment and Management

• Primary enclosures should meet Guide
  recommendations
• Space
• Temperature and Humidity
• Ventilation
• Illumination
• All exceptions should be justified, with IACUC
  approval
• Structural and social environments still need to
  be considered in biocontainment

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Animal Environment and Management (Cont.)

• Husbandry
• Feed, water, bedding, and cage sanitation should
  be checked daily
• Exceptions to Guide recommended sanitation
  schedules need justification and IACUC approval
• Well documented waste streams and decontamination
  procedures
• Equipment should be designed for containing
  infectious agents/toxins (ventilated cage units,
  cage changing hoods, etc.)

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Veterinary Medical Care

• Preventive medicine
• Facilities for quarantine, stabilization, and
  separation of species
• Minimum of daily observation of all animals by
  trained personnel
• Methods in place for disease surveillance and
  diagnosis
• Prompt notification and timely delivery of
  veterinary medical care, and associated
  documentation

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Veterinary Medical Care

• Clinical observations
• Due to complex and arduous entry requirements,
  many biocontainment facilities utilize husbandry
  staff to conduct daily health assessments
• This approach requires intensive training and
  close interaction with veterinarian and
  veterinary staff

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Veterinary Medical Care

• Euthanasia
• Clear criteria for initiating euthanasia
• Conducted by trained personnel
• Confirmation of death
• Consider vocalization and pheromone release
• Method of euthanasia
• Species
• Safety considerations in biocontainment
• IACUC approval for any deviations from the AVMA
  Panel on Euthanasia

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Potential SOPs Physical Plant

• HVAC
• Regular monitoring of HVAC performance
• Air changes per hour
• Pressure differentials
• Visual indicator at room level
• Fail safe to prevent sustained positive
  pressurization
• Temperature and humidity
• Emergency power
• Cage/equipment washing facilities
• If outside containment effective methods for
  decontaminating prior to washing
• If inside containment protection of cage wash
  staff
• Quality assurance program

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Changes in the BMBLSpecial Practices

• Handling animal waste
• Transported in durable, leak proof, covered
  containers
• Container must have biohazard symbol
• ABSL-2 decontamination is recommended before
  movement outside areas where infectious animals
  are housed/manipulated
• ABSL-3 method for decontamination must be
  available within facility, preferably where
  infectious animals are housed/manipulated
• Decontamination before removal from where animals
  are housed

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Changes in the BMBLSpecial Practices

• Other new for ABSL-3
• Handling of infected animals must be conducted in
  a BSC or other containment device
• When it cant, then a combination of PPE and
  other containment devices must be used
• Use of restraint devices/practices to reduce risk
  of exposure during animal manipulations
• Adds HEPA-filtered isolators and caging systems
  as possible mechanisms to reduce risk of aerosol
  infection from animals

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Changes in the BMBLSpecial Practices

• Other new for ABSL-3 (cont.)
• Criteria for actively ventilated caging systems
• Designed to contain microorganisms
• Sealed exhaust plenums
• HEPA filtered exhaust
• Safety interlock to prevent cages and exhaust
  plenums from becoming positive to room
• System alarmed to indicate malfunction

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Changes in the BMBLSafety Equipment

• New for ABSL-2/3
• Primary biosafety containment for animals
• When indicated by risk assessment
• Filter top cages for rodents
• Primary containment systems for larger animals

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Changes in the BMBLLaboratory Facilities

• New for ABSL-3
• Entry into containment area is via a double door
  entry which constitutes an anteroom/airlock and a
  change room
• Showers based on risk assessment
• Decontamination of entire animal room
• Gross contamination
• Significant change in usage
• Major renovations/maintenance

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Changes in the BMBLLaboratory Facilities

• New for ABSL-3 (Cont.)
• Cages should be autoclaved or otherwise
  decontaminated prior to removal from ABSL-3 space
• 4th Edition cages are autoclaved or
  decontaminated before bedding is removed and
  before they are cleaned and washed
• Cages are washed in a mechanical cage washer

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Changes in the BMBLLaboratory Facilities

• New for ABSL-3 (Cont.)
• Autoclave available which is convenient to animal
  rooms. If not convenient, special practices
  should be developed for transport of infectious
  materials.
• Equipment that may produce infectious aerosols
• must be contained in devices that have HEPA
  filtered exhaust or equivalent technology
• Should be tested or replaced annually

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Additional Issues for Select Agents

• Safety
• Emergency Response
• Training

Photo by Dr. Tom Geisbert, USAMRIID, 2005
Implementing regulation 42 CFR Part 73
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Safety Requirements Select Agent Rule

• Safety considerations
• Must have a written safety plan
• Complies with applicable regulations/guidelines
• Responsible Official (RO), or designee, conducts
  routine inspections (not less than annually) for
  compliance with the safety plan
• Inspection must be documented, any deficiencies
  must be corrected.

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Safety Requirements BMBL, 5th Edition

• Safety manuals
• Specific to animal facility
• Consultation with animal facility director and
  appropriate safety personnel
• Must be available and accessible
• Personnel advised of hazards
• Personnel required to read and follow
  instructions
• ABSL-2/3 Should include specific biohazards
  unique to animal and protocol

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Emergency ResponseSelect Agent Rule

• Do you have an emergency response plan that
  addresses
• Hazards associated with BSATs
• Decontamination
• Emergency medical treatment and first aid
• Safety distances and places of refuge
• Planning and coordination with outside parties
• Emergency alert and response procedures
• PPE and emergency equipment
• Special procedures for each agent
• Animals exposed to select agents

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Emergency ResponseBMBL, 5th Edition

• Need for advanced consideration for emergency and
  disaster recovery plans added to all ABSLs

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Training

• Documentation should be available for required
  safety training
• Initial training (prior to assignment/entry)
• Refresher training (not less than annually)
• RO can waive initial training
• Training documentation must include
• Name of individual
• Date of training
• Means used to verify employee understood training

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TrainingBMBL, 5th Edition

• Animal care, laboratory and support personnel
  must have specific training
• Duties
• Animal husbandry procedures
• Potential hazards
• Manipulation of infectious agents
• Precautions to prevent exposures
• Hazard exposure evaluation procedures
• Must receive annual updates OR when procedures
  change

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References

• Delong, D., Gerrity, L.W., and Bayne, K. 2001.
  Elements of an occupational health and safety
  program Deficiencies identified by AAALAC
  International. Lab Animal, 30(4)23-26.
• National Research Council. Occupational Health
  and Safety in the Care and Use of Research
  Animals. National Academy Press, Washington
  D.C., 1997.
• National Research Council. Guide for the Care
  and Use of Laboratory Animals. National Academy
  Press, Washington D.C., 1996.
• Copps, J. 2005. Issues related to the use of
  animals in biocontainment research facilities.
  ILAR Journal. 46(1)34-43.
• CDC/NIH. Biosafety in Microbiological and
  Biomedical Laboratories. 5th Edition, U.S.
  Government Printing Office, Washington D.C.,
  2007.
• 42CFR, Part 73. Possession, Use, and Transfer of
  Select Agents and Toxins. DHHS, 2002

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Questions?