The ABCs of the IBC: Navigating the New Institutional Biosafety Committee Application Process

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The ABCs of the IBC Navigating the New
Institutional Biosafety Committee Application
Process

• May 4, 2001
• Sponsored by
• Office of Research Administration, CWRU

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Purpose

• What is the IBC?
• Why does this committee need to review
  investigators research?
• How do I fulfill my responsibilities?
• When do the new procedures go into effect?
• Where do I find educational resources?
• Who do I contact with questions?

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History of the IBC Dr. David Samols, Chair

• Origin of the IBC
• Current committee functions
• Catalyst for updating the procedures
• Expectations for the changes

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Why Is the IBC Necessary?

• Review recombinant DNA (rDNA) research involving
  humans, whole animals or whole plants
• Ensure safety to those involved in rDNA research
  as well as to the community and environment.
• Facilitate research that is in compliance with
  federal guidelines.
• Serve as a resource to clarify the guidelines and
  provide a mechanism for obtaining more
  information.

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Applicable FederalRegulatory Authorities

• Department of Health and Human Services
• National Institutes of Health
• Office of Biotechnology Activities
• Recombinant DNA Advisory Committee
• Food and Drug Administration

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The IBCs Responsibilities An Overview

• Ensures compliance with the NIH Guidelines for
  Research Involving Recombinant DNA Molecules.
• Effect on funding
• As a condition of NIH funding of recombinant DNA
  research, institutions shall ensure that such
  research conducted at or sponsored by the
  institution, irrespective of funding, shall
  comply with NIH Guidelines.

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What is rDNA?

• For the purposes of the Guidelines, rDNA is
  defined as (1) 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 (2) molecules that
  result from the replication of those previously
  described.

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The IBCs Responsibilities Types of
Experiments Reviewed

• Biosafety Level 4 experiments
• Cloning of toxin molecules with LD50 of lt100
  nanograms per kg body weight
• Gene Transfer Research
• Risk Groups 2, 3, 4 or restricted agents as
  host-vector systems
• Formation of rDNA containing no more than
  two-thirds of the genome of any eukaryotic virus

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Exempt Experiments

• Reference Section III-F of the Guidelines
• Examples
• Expression of genes in yeasts unless the source
  of DNA is from a classified pathogen.
• Generation of transgenic flies or fish unless the
  source of DNA is from a classified pathogen.
• Expression of proteins in prokaryotic hosts as
  long as culture volume is less than 10 liters,
  the protein is nontoxic and the source DNA is not
  from a classified pathogen.

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The IBCs Responsibilities The Specifics

• Assessment of the containment levels
• Assessment of the facilities, procedures and
  training and expertise of those involved with the
  research
• Ensure that all aspects of Appendix M Points to
  Consider in the Design and Submission of
  Protocols for the Transfer of Recombinant DNA
  Molecules into One or More Human Research
  Participants are met

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The IBCs Responsibilities The Specifics

• Ensure that no research participant is enrolled
  in a human gene transfer experiment until the
  Recombinant DNA Advisory Committee (RAC) review
  process has been completed
• For publicly reviewed human gene transfer
  experiments, consider RAC issues and
  recommendations

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The IBCs Responsibilities The Specifics

• Ensure that final IBC approval is granted only
  after the RAC review process is completed and
• Ensure compliance with surveillance, data
  reporting, and adverse event reporting
  requirements.

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Containment Levels -Biosafety Levels (BL)

• Definition physical containment for standard
  laboratory experiments which are achieved through
  the use of certain laboratory practices,
  containment equipment, and special laboratory
  design.
• References Appendix G of the NIH Guidelines and
  Biosafety in Microbiological and Biomedical
  Laboratories, 4th Edition.

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Containment Levels -Biosafety Levels (BL)

• BL1 is suitable for work involving agents of
  unknown or minimal potential hazard to laboratory
  personnel and the environment.
• E coli K-12
• Infectious canine hepatitis virus
• BL2 is similar to BL1 and is suitable for work
  involving agents of moderate potential hazard to
  personnel and the environment.
• Hepatitis B virus
• HIV

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Containment Levels -Biosafety Levels (BL)

• BL3 is applicable to clinical, diagnostic,
  teaching, research or production facilities in
  which work is conducted with indigenous or exotic
  agents that may cause serious or potentially
  lethal disease if inhaled.
• Mycobacterum tuberculosis
• St. Louis encephalitis virus

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Containment Levels -Biosafety Levels (BL)

• BL4 is applicable for work with dangerous and
  exotic agents that pose high individual risk of
  life-threatening disease, which may be
  transmitted via the aerosol route and for which
  there is no available vaccine or therapy
• Ebola virus
• Crimean-Congo hemorrhagic fever virus

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Risk Groups (RG)

• Definition classification of risk in assessing
  the prevention of laboratory associated
  infections in individuals
• Consideration of biological agents known to
  infect humans as well as selected animal agents
  that may pose theoretical risks if inoculated
  into humans.
• Helps to assign BLs
• Reference Appendix B for the Guidelines

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Risk Groups (RG)

• RG1 agents not associated with disease in
  healthy adult humans
• RG2 agents are associated with disease which is
  rarely serious and prevention interventions are
  often available.

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Risk Groups (RG)

• RG3 agents are associated with serious or lethal
  human disease and preventive interventions may be
  available.
• RG4 agents are likely to cause serious or lethal
  human disease and preventive interventions are
  not usually available.

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What Are the New Committee Procedures?

• Registration Application for New and Continuing
  Research Projects Involving Recombinant DNA
  Molecules
• Case Western Reserve University Institutional
  Biosafety Committee Procedures for the Use of
  Recombinant DNA

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Where Can the New Application and Procedures Be
Found?

• On the web.
• ora.ra.cwru.edu/main_institutional_biosafety_commi
  ttee_page
• Office of Research Administration, CWRU

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Application/IBC Meeting Dates
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Types of Committee Decisions

• Categories
• Approved
• Unapproved
• Minor Revisions Needed
• Tabled
• Exempt
• Approval is not valid until written notification
  is received by the principal investigator.

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IBC Periodic Summary Requirement

• Experiments conducted at BL 1 and BL 2
• Every three (3) years from date of approval
• Experiments conducted at BL 3 and BL 4
• Annually from date of approval

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Adverse Events

• Reports of adverse events must be made within 14
  working days of discovery.
• Office of Research Administration (ORA)
• Office of Biotechnology Activities (OBA)
• Food and Drug Administration (FDA)
• Required IBC Forms
• Serious Adverse Event Reporting Form for Human
  Gene Transfer Clinical Studies
• Case Western Reserve University Institutional
  Biosafety Committee Adverse Event Agreement for
  Investigators return to ORA with the IBC
  application.

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Modifications or Changes to Protocols

• Changes to the IBC approved protocol regarding
  the use or manipulation of rDNA must not be
  initiated until
• The research has been approved by the IBC and
• Written approval of the change is received by the
  principal investigator.

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The Process A Recap

• Register with the IBC
• Wait for written approval
• Periodically update the committee
• BL 1 or BL 2 must submit review summaries every
  three years from date of approval
• BL 3 and BL 4 must submit review summaries
  annually from date of approval
• Report adverse events and modifications

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New Application and Procedures Go Into Effect

• June 1, 2001

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IBC Contacts

• Shay Gresham Howard, IBC Administrator
• 368.6993 or sxg67.cwru.edu
• Maureen Dore-Arshenovitz, IBC Assistant
• 368.6925 or mxd4_at_po.cwru.edu
• David Samols, IBC Chairman
• 368.3520 or drs10_at_po.cwru.edu