Does my study need IBC approval

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Does my study need IBC approval?

• Hubert Olipares
• Biosafety Officer
• Biosafety Program
• Environmental Health Safety Office
• 956-3197
• olipares_at_hjawaii.edu, biosafe_at_hawaii.edu,
  uhibc_at_hawaii.edu

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Safety Committees and Compliance Offices at UH
Committee on Human Subjects (CHS)/Institutional
Review Board (IRB) William Dendle
Institutional Animal Care Use Committee
(IACUC) Norman Magno Institutional
Biosafety Committee (IBC) Hubert Olipares/Karen
Quinn Workplace Safety Committee (WSC) Emma
Kennedy Radiation Safety Committee (RSC)
Irene Sakimoto Diving Safety Board (DSB)
Dave Pence
EHSO (Roy Takekawa
Each may require application approvals or
sublicensing prior to use!!
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Who cares?

• National Institutes of Health (NIH)
• Office of Biotechnology Activities (OBA)
• Recombinant DNA Advisory Committee (RAC)
• National Science Advisory Board for Biosecurity
  (NSABB)
• Center for Disease Control (CDC)
• Occupational Safety Health Administration
  (OSHA)
• Environmental Protection Agency (EPA)
• US Department of Agriculture (USDA)
• Department of Justice (DOJ)
• World Health Organization (WHO)
• UN Committee of Experts (UNCOE) International
  Civil Aviation Organization (ICAO), International
  Air Transport Association (IATA)

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Biosafety Concerns

• Biological Material
• Recombinant DNA ANY!!
• Biohazardous waste (with EHSO)
• Shipping biological material, diagnostic
  specimens, dry ice shipments

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You will need IBC approval for research involving

• Any potentially infectious agent
• human blood, other fluids or tissues involved in
  a research project which is treated differently
  (preparation and/or in any location) than any
  sample handled by the clinic or hospital outside
  the scope of the patients normal care
• non-human primate derived material
• viruses, viral vectors
• Any recombinant DNA
• Human gene transfer/therapy
• exempt and non-exempt rDNA protocols
• Shipping of dangerous goods
• Dry ice
• Clinical, diagnostic specimens
• Infectious material
• Cell cultures
• Tissues
• Mammalian tissue culture
• Microbial agents (import - Hawaii Department of
  Agriculture)

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Recombinant DNA (rDNA)

• Section I-B. Definition of Recombinant DNA
  Molecules
•  
• In the context of the NIH Guidelines, recombinant
  DNA molecules are defined as either (i)
  molecules that are constructed outside living
  cells by joining natural or synthetic DNA
  segments to DNA molecules that can replicate in a
  living cell, or (ii) molecules that result from
  the replication of those described in (i) above.
•  
• Synthetic DNA segments which are likely to yield
  a potentially harmful polynucleotide or
  polypeptide (e.g., a toxin or a pharmacologically
  active agent) are considered as equivalent to
  their natural DNA counterpart. If the synthetic
  DNA segment is not expressed in vivo as a
  biologically active polynucleotide or polypeptide
  product, it is exempt from the NIH Guidelines.
•  
• Genomic DNA of plants and bacteria that have
  acquired a transposable element, even if the
  latter was donated from a recombinant vector no
  longer present, are not subject to the NIH
  Guidelines unless the transposon itself contains
  recombinant DNA.

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Recombinant DNANIH/OBAParticularly concerned
about inadvertent transmission of genetic
material into humans and dangerous application of
rDNA technology (dual use)

• A- IBC approval, RAC review, NIH Director
  Approval
• Deliberate transfer of drug-resistance into
  microorganisms
• B - NIH/OBA and IBC Approval
• Cloning toxic molecules, LD50lt100 ng/kg
• C- IBC and IRB Approval, RAC Review
• Human gene transfer (Gene Therapy)
• D- IBC pre-approval
• RG2-4 work or DNA work, restricted agents as
  host/vector,
• viral work in tissue culture, animals, large
  scale (gt10 l)
• E- IBC simultaneous notice
• Work with lt2/3 of eukaryotic viral genome
• Transgenic animals
• F- Exempt
• No significant risk to health or the
  environment

NIH Guidelines (Section IIIA-F Appendix C)
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Recombinant DNA

• UH Policy
• ALL recombinant DNA research must receive IBC
  approval prior to initiation.

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Gene Therapy

• Gene Therapy Gene Transfer with therapeutic
  potential
• Section III-C-1. Experiments Involving the
  Deliberate Transfer of Recombinant DNA, or DNA or
  RNA Derived from Recombinant DNA, into One or
  More Human Research Participants
•  
• For an experiment involving the deliberate
  transfer of recombinant DNA, or DNA or RNA
  derived from recombinant DNA, into human research
  participants (human gene transfer), no research
  participant shall be enrolled (see definition of
  enrollment in Section I-E-7) until the RAC review
  process has been completed (see Appendix M-I-B,
  RAC Review Requirements).

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Gene Therapy Key words

• Key words to look out for
• Gene Therapy
• Recombinant
• DNA
• RNA
• Express (expression)
• Vector
• Plasmid
• Transfect (transfection)
• Transduce (transduction)
• Adenovirus (adenoviral)
• Adeno-associated virus
• Retrovirus (retroviral)
• Lentivirus (lentiviral)
• Transduce
• Transfect
• Promoter (esp. CMV promoter)
• Fusion protein
• Selectable marker

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Handy Biosafety References

• Biosafety in Microbiological and Biomedical
  Laboratories (BMBL)
• http//www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4toc
  .htm
• NIH Guidelines for Research Involving Recombinant
  DNA Molecules (NIH Guidelines)
• http//www4.od.nih.gov/oba/rac/guidelines/guidel
  ines.html

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Biosafety in the Age of Bioterrorism

• Select Agents (HHS/USDA)
• 42 C.F.R. Part 73, 7 C.F.R. Part 331, and 9
  C.F.R. Part 121
• Microorganisms identified by DHHS and USDA as
  having the potential to pose a severe threat to
  human, animal and/or plant health or to animal or
  plant products
• Specific requirements regarding the possession,
  use, and transfer of Select Agents and toxins,
  including requirements for
• registration
• security risk assessments
• safety plans
• security plans
• training
• transfers
• record keeping
• inspections
• notifications
• Appointment of a Responsible Official

http//www.cdc.gov/od/sap/
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http//www.mcg.edu/research/ibc/pdf/salist.pdf
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The IBC and the BSO are here to FACILIATE research

• Evaluate research plans to illuminate any
  potential safety issues in order to circumvent
  the occurrence of adverse events.
• Ensure that research complies with all
  regulations (federal, state, local government and
  UH policies).
• Keeps NIH from potentially withdrawing all funds
  to UH
• Reduces the legal liability risk for UH and the
  individual researchers
• Ensure that all research personnel are properly
  trained to consider biological safety when in the
  laboratory.
• Monitor the safety issues and personnel to
  optimize safety and research needs.

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IBC Biosafety Protocol Approvals

• Are PROTOCOL-specific!
• Must be received prior to the initiation of any
  new research project
• Must be received prior to bringing any new
  biological commodities on to campus
• Must be ammended with changes in
• Experimental design or agents
• Personnel
• Location
• Conditions
• Major Equipment (eg. Biological Safety Cabinets,
  centrifuges)

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The Biosafety Protocol Application Process

• Forms located online
• http//www.hawaii.edu/ehso/bio/forms.htm
• When forms are complete, submit to the Biosafety
  Program (EHSO) or uhibc_at_hawaii.edu
• Deadline Last working day of Feb., May, August,
  Nov.
• IBC meetings Quarterly or as needed

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The Biosafety Application Includes

• Form describing your research
• Nature of biological materials
• Locations
• Safety, transport storage procedures
• Personnel their experience
• Standard Operating Procedures
• Laboratory specific
• Templates accessed via http//www.hawaii.edu/ehso/
  bio/theSOP.htm

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Proof of Biological Safety TrainingRight-To-Know
Training

• Biological Safety Training
• Initial biosafety training
• Required for all research PI and all research
  personnel who will be working with biological
  agents Provided once/month
• Contact biosafe_at_hawaii.edu
• Annual Biosafety Training
• Required annually
• Blood borne pathogen (Required annually for all
  BBP workers)
• http//webct.hawaii.edu/public/manoaBBP/index.ht
  ml
• Biological Commodities Shipping and Recieving
• Required once/2 years

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The Biosafety Protocol Application Process

• Document location and personnel who may come in
  contact with agents
• Cradle to grave
• I pre-evaluate your protocol to determine whether
  any immediate concerns the IBC may have
• May suggest edits (to facilitate IBC approval
  process)
• I audit the facilities on the protocol to
  determine both containment, practices, and
  training of personnel are in compliance
• I submit to IBC. I am your liason to the IBC.

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The Institutional Biosafety Committee

• http//www.hawaii.edu/ehso/bio/IBC_Page.htm
• Chair Dr. James T. Douglas, Microbiology
• ROLE NAME
• Chair James T. Douglas, Ph.D.
•  Plant Sciences Expert  David A. Christopher,
  Ph.D.
•  Animal Principal Expert   Sylvia Y. Kondo, DVM
•  Laboratory Technical Staff   Janet Meeks
•  r-DNA Technology Expert  Elaine Seaver, Ph.D
•  Environmental Consultant   John T. Harrison,
  Ph.D
•  Microbiology Representative   Vivek Nerurkar,
  Ph.D
•  Human Gene Representative   Rebecca Cann, Ph.D.
•  Community Colleges Representative  John
  Berestecky, Ph.D
•  UH Hilo Representative  John Scott, Ph.D
•  Community Member  Rebecca Sciulli
•  Community Member   Lyle Wong, Ph.D
•  Designated Institutional Official Frank Perkins,
  Ph.D. 

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Factors to consider in Risk Assessment

• Virulence (drug resistance? Attenuated?)
• Pathogenicity
• Infective dose
• Environmental stability
• Route of spread
• Communicability
• Operations
• Quantity
• Vaccines or treatment available
• Gene product effects
• toxicity
• physiological activity
• allergenicity

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Blood-Borne Pathogens(OSHA/CDC)

• BSL-2
• Health monitoring
• Vaccinations will be offered or signed waiver
  obtained for all workers
• Health screening for workers necessary to reduce
  liability?
• Tests for HepB, varicella, TB tests, others?
• Post-exposure follow-up availability and plan
  (HIV prophalaxis? )
• Administrative controls
• Record keeping, labeling
• Monitoring for compliance
• Posting SOPs
• Availability of appropriate waste containers
• Eyewash availability
• Work practices to limit exposure (exposure
  control plan SOP)
• Spill clean-up procedures (decontamination and
  reporting to PI and BSO)
• Overt exposure procedures (report to PI and BSO)
• Surface decontamination procedures
• Liquid and solid waste decontamination
  procedures

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Transport, Storage Shipping

• Transport
• Closed, leakproof, primary container
• Closed, leak-proof, (durable) secondary container
• Storage of material
• Well-labeled
• Restricted access
• Personnel have knowledge of hazards
• Shipping
• Saf T Pak certification for shippers of
  diagnostic specimens, infectious waste

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Regulatory Agencies overseeing shipping

• UNCOE United Nations Committee of Experts
• International Civil Aviation Org. (ICAO)
• IATA International Air Transport Assn.
• 49CFR Code of Fed. Regulations, Transportation
  of Dangerous Goods Regulation
• TDGR Transportation of Dangerous Goods
  Regulations, Canada
• RID/ADR European Agreement on International
  carriage of Dangerous Goods by Rail (RID) or by
  road (ADR)

Of these, IATA DGR is the most restrictive
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Liabilities and Training

• Primary responsibility and liability lies with
  the shipper
• Risks with liability potential both criminal and
  civil, with high fines or civil suits with no
  upper limit!
• Proper training and compliant shipping can reduce
  this risk
• General familiarization training
• Function-specific training
• Safety training
• hazards presented by dangerous goods
• safe handling
• emergency response
• Training Performed once every 2 years (keep
  current!)
• Required of both shippers and operators

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Any questions?
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Operational Interactions of the IBC
President
Vice-President for Research
Non-Manoa Systems Functions
Manoa Functions
Vice-Chancellor for Research
DIO
INSTITUTIONAL BIOSAFETY COMMITTEE
Environmental Health and Safety Office
Biosafety Program
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