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 -or- molecules 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 Pathogenicity Route of Transmission Agent Stability Infectious Dose Concentration Availability of effective prophylaxis Availability of medical surveillance Host susceptibility

Risk Assessment Organism Vector Containment Facility Laboratory specific protocol Training of personnel

Section III: Experiments Covered by the NIH Guidelines III-A transfer of drug resistance III-B cloning of lethal toxins III-C gene therapy III-Dinfectious 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 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 Required to annually submit IBC roster update including curriculum vitae of new members and any significant updates of existing members to OBA rDNA Knowledge Community Interest Research Expertise No fewer than 5 members who exhibit:

UTHSC-H IBC Membership Full Members Serve staggered two year terms (FY 06-08) 3+ faculty members with rDNA experience and/or biological safety and containment 2 community members At least 1 member from each school At least 1 with animal containment At least 1 with infectious disease expertise 1 student member Ex-Officio Members Representative from Risk Management/Legal Affairs Representative from Health Services Director, Environmental Health & Safety AVP, SHERM Executive Vice President for Research Representative from HCPC

IBC Member Expectations 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 acceptedProtocol rejected, tabled or pending

IBC Resources NIH Guidelines for Research Involving Recombinant DNA Molecules Office of Biotechnology Activities CDC/NIH Biosafety in Microbiological and Biomedical Laboratories (BMBL)

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