Transcript NIH Guidelines for Research Involving rDNA Molecules (NIH

NIH Guidelines for Research Involving
rDNA Molecules (NIH Guidelines)
and
Institutional Biosafety Committees
Background
Recombinant DNA work regulated under NIH Office of
Biotechnology Activities (NIH OBA) in:
NIH Guidelines for Research Involving
Recombinant DNA Molecules (May 2011)
rDNA = molecules that are constructed outside of
living cells by joining natural or synthetic DNA
segments to DNA molecules that can replicate in a
living cell
-ormolecules that result from the replication of
those described above
History of the Guidelines
• The NIH Guidelines were implemented in
response to public and scientific concern
over the emerging science of rDNA
technologies in the early 1970’s.
• By 1976, NIH had published the first set
of guidelines which have been amended
over time to allow for greater public
access and a greater emphasis on safety.
Section I: Scope and Applicability
• If your institution receives Federal
funding, then it must comply with the
NIH Guidelines for recombinant DNA
research.
• Even if a project is privately sponsored,
that research experiment must still be
conducted in accordance with the NIH
Guidelines.
Section II: Safety Considerations
Risk Assessment
• Risk Group 1 (RG1) agents are not associated
with disease in healthy adult humans.
• Risk Group 2 (RG2) agents are associated with
human disease which is rarely serious and for
which preventive or therapeutic interventions
are often available.
• Risk Group 3 (RG3) agents are associated with
serious or lethal human disease for which
preventive or therapeutic interventions may be
available.
• Risk Group 4 (RG4) agents are likely to cause
serious or lethal human disease for which
preventive or therapeutic interventions are not
usually available
Section II: Safety Considerations
Containment
Containment should be a combination of
standard microbiology practices,
engineering controls, laboratory facilities
and design.
*Containment is defined in the:
– Laboratory Safety Monograph
– Biosafety in Microbiological and Biomedical
Laboratories (BMBL)
Biosafety Levels
Biosafety levels are a combination of
facilities and practices:
Level 1: basic lab, good lab practices
Level 2: limited lab access, specific training
and practices
Level 3: containment (biosafety cabinet),
specific training and practices
Level 4: full containment, specific facility,
training and practices
Risk Assessment Factors
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Pathogenicity
Route of Transmission
Agent Stability
Infectious Dose
Concentration
Availability of effective prophylaxis
Availability of medical surveillance
Host susceptibility
Risk Assessment
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Organism
Vector
Containment
Facility
Laboratory specific protocol
Training of personnel
Section III: Experiments Covered
by the NIH Guidelines
III-A
III-B
III-C
III-D
transfer of drug resistance
cloning of lethal toxins
gene therapy
infectious agents as vectors & transgenic
animals
III-E transgenic rodents/non-exempt BSL-1
work
III-F exemptions / BSL-1
Experiments Covered by NIH
Guidelines
SECTION III-A
Major Actions
Requires: IBC approval, RAC review, NIH
Director approval prior to the initiation
of work
• Transfer of drug resistance to organisms
-which may compromise human
health/agriculture/medicine
SECTION III-B
Toxin Transfer
Requires: NIH/OBA, IBC Review and
Approval Before Initiation of Work
• Deliberate Cloning of Toxin Molecules
Lethal to Vertebrates at an LD50 of Less
Than 100 Nanograms/Kg of Body Weight
(e.g., Botulinum Toxin)
- Containment determined by
NIH/OBA
SECTION III-C
Deliberate Transfer of Recombinant DNA into Research
Participants (ex. Gene Therapy)
Requires: IBC, IRB, RAC Review and
Approval Before Participant Enrollment
• Human gene therapy protocols
- RAC may require public review prior
to participant enrollment.
SECTION III-D
General Work
• Involves RG 2-4 agents, host/vector
system
• Cloned DNA from RG 2-4 agents into
non-pathogenic prokaryotes
• RG 2-4 agents into whole animals, usually
transgenic
• Recombinant plants
• Large scale experiments greater then 10L
SECTION III-E
Less Restrictive Work
Requires: IBC notification at the initiation of
work (BSL-1 containment)
• rDNA molecules that contains less than
2/3 of any eukaryotic viral genome
• Transgenic rodents with ABSL-1
containment
• Whole plants that require minimal
containment
SECTION III-F
Exemptions
Exempt from the NIH Guidelines and Does Not
Require IBC Review or Approval
Recombinant DNA molecules that are:
• Not in organisms or viruses
• Not a risk to health or the environment
Section IV: Roles & Responsibilities
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Ensure compliance with NIH Guidelines
Establish IBC
Appoint a Biosafety Officer
Ensure IBC has expertise in the research
that is reviewed
• Establish a medical surveillance program
as needed
• Report all incidents to the NIH OBA
IBC Requirements
rDNA Knowledge
Research Expertise
Community Interest
No fewer than 5 members who exhibit:
• Required to annually submit IBC roster
update including curriculum vitae of new
members and any significant updates of
existing members to OBA
UTHSC-H IBC Membership
Full Members
Ex-Officio Members
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Serve staggered two year terms
(FY 06-08)
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Representative from Risk
Management/Legal Affairs
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3+ faculty members with rDNA
experience and/or biological
safety and containment
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Representative from Health
Services
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Director, Environmental Health &
Safety
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AVP, SHERM
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Executive Vice President for
Research
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Representative from HCPC
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2 community members
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At least 1 member from each
school
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At least 1 with animal
containment
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At least 1 with infectious disease
expertise
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1 student member
IBC Member Expectations
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Active participation on the Committee
Sharing expertise and experience
Question and scrutinize protocols
Ensure protocols meet requirements of
rDNA Guidelines, BMBL and other biosafety
guidelines
• Timely response as a member of a
Subcommittee during preliminary reviews
• Participate in member training, at least
annually
UTHSC-H Protocol Review Process
Submitted to Biosafety for assessment
Communication with PI to produce protocol
Submitted to Subcommittee for review
Submit protocol to IBC committee for full review
Protocol accepted
Protocol rejected,
tabled or pending
IBC Resources
NIH Guidelines for Research Involving Recombinant
DNA Molecules
http://oba.od.nih.gov/rdna/nih_guidelines_oba.html
Office of Biotechnology Activities
http://www4.od.nih.gov/oba/
CDC/NIH Biosafety in Microbiological and Biomedical
Laboratories (BMBL)
http://www.cdc.gov/biosafety/publications/bmbl5/
Questions