Outline

1
Outline

• Introduction to the National Institutes of Health
  Office of Biotechnology Activities
• History and Evolution of IBCs Asilomar to the
  Present
• Overview of the Current NIH Guidelines for
  Research Involving Recombinant DNA Molecules
• Requirements for IBCs in the NIH Guidelines
• Review of the Recombinant DNA Advisory Committee
  and the Protocol Review Process
• Open Forum for Questions

2
Events Leading to AsilomarEarly 1960s

• Viral infection and the transfer of nucleic
  acids
• Moloney mouse leukemia virus
• Unbridled curiosity of scientists
• Viral etiology of human cancer?
• Concerns about lab-acquired cancer

3
Events Leading to AsilomarMid 1960s

• NCI virus cancer programs
• Rapid increase in research funding
• Emphasis on biohazards and environmental
  control
• Guidelines and training

4
Events Leading to AsilomarEarly 1970s

• Experiments of concern
• SV40-lambda hybrid (Berg)
• Nondefective adeno-SV40 hybrids (Lewis)
• First NIH IBC (NIH Biohazards Committee, 1972)
• Asilomar I (January, 1973)
• Gordon Conference on Nucleic Acids (1973)

5
ASILOMAR CONFERENCE January 1973
6
DHEW, NIH, NCIOctober 1974
7
The Asilomar ConferenceFebruary 1975

• Purpose of conference
• Review progress in rDNA research
• Discuss potential biohazards
• Discuss ethical and legal concerns
• Draft a conference summary paper

8
The Asilomar ConferenceAccepted Principles

• In Planning Safe Experiments
• Laboratory safety (containment) is an essential
  consideration in the experimental design
• Effectiveness of safety practices should match,
  as closely as possible, the estimated risk

9
The Asilomar ConferenceAccepted Principles

• Responsibilities of Investigators
• Risk assessment
• Inform laboratory staff of potential hazards
• Assure staff competency in safe practices
• Exercise considerable caution in performing
  experiments

10
The Asilomar ConferenceConsidered Principles

• Thoughts on Institutional Review of Recombinant
  DNA Experiments
• Need for institutional certification of physical
  containment in research laboratories
• A knowledgeable committee should conduct
  certification reviews
• Review process should be efficient and depend on
  local circumstances

11
NIH Guidelines for Research Involving Recombinant
DNA MoleculesJune 1976

• Institutional Responsibilities
• Responsibilities fulfilled by principal
  investigators
• Establishment of an Institutional Biohazards
  Committee (IBC)

12
NIH Guidelines for Research Involving Recombinant
DNA MoleculesJune 1976

• Roles and Responsibilities of the IBC
• Provide advice on institutional policies
• Create and maintain a safety reference resource
• Certify that appropriate physical containment and
  training are in place
• Develop P4 safety and operations manual

13
NIH Guidelines for Research Involving Recombinant
DNA MoleculesJune 1976

• IBC Membership Requirements
• Sufficient experience and expertise in
  disciplines relevant to rDNA technology,
  biological safety, and engineering
• Members may be from the institution or
  consultants

14
NIH Guidelines for Research Involving Recombinant
DNA MoleculesJune 1976

• IBC Membership Requirements (continued)
• Committee should possess or have available to it
  the competence to determine the acceptability of
  its findings in terms of
• applicable laws and regulations
• community attitudes
• health and environmental considerations

15
Revised NIH GuidelinesDecember 1978

• Institutional Responsibilities Principal
  Changes
• Emphasis on ensuring appropriate review and
  implementation procedures
• Delegation of authority to approve certain
  experiments
• IBC focus change from biohazard to biosafety

16
Revised NIH GuidelinesDecember 1978

• Institutional Responsibilities Principal
  Changes (continued)
• Expertise, diversity, and composition of IBC
  membership
• Appointing a Biological Safety Officer
• Training and health surveillance

17
Revised NIH GuidelinesDecember 1978

• IBC Responsibilities Principal Changes
• Independent determination of required safeguards
• Exercise of delegated authority for approving
  certain experiments
• Oversight of facilities, practices, and training

18
Revised NIH GuidelinesDecember 1978

• Laboratory Safety Monograph (July 1978)
• Biosafety reference document
• Provides guidance to IBC
• Tabulation of duties and responsibilities

19
Revised NIH GuidelinesApril 1984

• IBCs become responsible for review of human gene
  transfer research
• New responsibility pursuant to recommendations of
  RAC Working Group for Development of Response to
  Presidents Commission Report on Ethical and
  Social Issues
• Subsequently, RAC Working Group on Human Gene
  Therapy embarks on Points to Consider

20
Revised NIH GuidelinesMay 1986

• Adoption of Points to Consider guidance
  document for gene therapy protocols
• IBC approval prior to submission to NIH
• Points for IBC consideration and review
• Characteristics of the biological system
• Pre-clinical risk assessment studies
• Public health

21
Revised NIH GuidelinesMarch 1990

• Update of Points to Consider guidance document
  (Appendix M)
• Emphasis on gene transfer not therapy

22
Revised NIH GuidelinesJuly 1994

• Adoption of Appendices P (plants) and Q
  (animals)
• Containment guidance for IBCs
• Augments IBC membership

23
Revised NIH GuidelinesOctober 2000

• Amended requirements for submission of gene
  transfer protocols
• Protocols require RAC review prior to
  IBC approval
• Rationale
• Research participants are assured that prior to
  their enrollment in a gene transfer clinical
  trial that is either novel or raises significant
  ethical or safety concerns, their local IRB and
  IBC, and PI are apprised of the results of public
  RAC review and discussion.

24
Revised NIH GuidelinesOctober 2000

• IBC functions specified for review and approval
  of gene transfer protocols
• Ensure PI addresses all aspects of Appendix M
• Ensure new enrollment requirements are met
• Ensure appropriate consideration by PI and IBC of
  results of public RAC review
• Ensure final IBC approval is granted after RAC
  review process
• Ensure compliance with surveillance and reporting
  requirements

25
Summary Comments

• NIH Guidelines is a living document
• Core IBC functions remained consistent over
  time
• Predictors for the future
• Unbridled curiosity of scientists
• Experiments that warrant stringent scrutiny
• Gene transfer protocols that warrant stringent
  scrutiny

26

• Brief questions for clarification?