ROLE OF THE INSTITUTIONAL BIOSAFETY COMMITTEE Bob Hashimoto The University of Kentucky November 22, 2002

INTRODUCTION The Institutional Biosafety Committee must evaluate research experiments with regard to potential environmental risk to the lab workers and the immediate environment. In the case of gene therapy experiments, the IBC must work with the IBC to assess potential environmental risks to the patient as well as the health care worker.

DEFINITIONS Biohazardous material: any material that harbors biohazardous agents including human or animal blood, body fluids, or tissues that may be contaminated with biohazardous agents.

DEFINITIONS Biosafety Level: Laboratory practices, techniques, safety equipment and laboratory facilities appropriate for the operations performed and the hazards posed by the particular biohazard material. The NIH and the Centers for Disease Control and Prevention define four levels of biosafety in the Health and Human Services Publication No. 93-8395, Biosafety in Microbiological and Biomedical Laboratories, 1999.

DEFINITIONS Containment: The confinement of a biohazardous agent that is being cultured, stored, manipulated, transported, or destroyed in order to prevent or limit its contact with people and/or the environment. Methods used to achieve this include: physical and biological barriers and inactivation using physical or chemical means.

DEFINITIONS Director, NIH: Director of the National Institutes of Health, or any other officer or employee of NIH to whom authority has been delegated. Deliberate release: A planned introduction of recombinant DNA-containing microorganisms, plants, or animals into the environment.

DEFINITIONS Minimization: The design and operation of containment systems in order that any incidental release is a minimal release. NIH: National Institutes of Health. OBA: The office within the NIH that is responsible for reviewing and coordinating all activities relating to recombinant DNA and the NIH Guidelines.

DEFINITIONS RAC: Recombinant DNA Advisory Committee, the public advisory committee that advises the Director of the NIH on recombinant DNA matters. Sterilize: The use of a physical or chemical procedure to destroy all microbial life including highly resistant bacterial endospores.

IBC RESPONSIBILITIES Reviewing recombinant DNA research conducted at or sponsored by the institution for compliance with NIH Guidelines as specified in Section lll, Experiments Covered by the NIH Guidelines, and approving those research projects that are found to conform with the NIH guidelines.

RESPONSIBILITIES IBC(SECTION IV-B-2-b-1) PURPOSE OF THE IBC Reviewing recombinant DNA research conducted at or sponsored by the institution for compliance with NIH Guidelines as specified in Section III, Experiments Covered by the NIH Guidelines

This review shall include: RESPONSIBILITIES IBC This review shall include: (i) independent assessment of the containment levels required by the NIH Guidelines (ii) assessment of the facilities, procedures, practices, and training and expertise of personnel involved in recombinant DNA research. (IV-B-2-b-(1))

IBC RESPONSIBILITIES This review shall include: (i) independent assessment if the containment levels required by the NIH Guidelines for the proposed research; (ii) assessment of the facilities, procedures, practices, and training and expertise of personnel involved in recombinant DNA research. lV-B-2-b-(1)

IBC RESPONSIBILITIES All activities involving the use of Class 2 or 3 biohazardous agents must have prior approval by the IBC, who will review the scope of work and assure that the work is being performed at the appropriate biosafety level as described in the Centers for Disease Control and Prevention/National Institutes of Health (CDC/NIH) Guideline, Biosafety in Microbiological and Biomedical Laboratories.

IBC RESPONSIBILITIES The IBC is responsible for advising the institution on all matters related to biosafety, for reviewing and approving proposed uses of biohazardous agents.

IBC RESPONSIBILITIES The IBC publishes and distributes the institution’s Biosafety Manual which contains biosafety standards from the NIH, CDC, and other applicable regulations.

IBC MEMBERSHIP The Institutional Biosafety Committee must be composed of no fewer than five members so selected that they collectively have experience and expertise in recombinant DNA technology and the capability to assess the safety of recombinant DNA research and to identify any potential risk to public health or the environment.

IBC MEMBERSHIP At least two members shall not be affiliated with the institution (apart from their membership on the IBC) and who represent the interest of the surrounding community with respect to health and protection of the environment (e.g. officials of state or local public health or environmental protection agencies, members of other governmental bodies, or persons active in medical, occupational health, or environmental concerns in the community). lV-B-2-a-(1)

IBC CONSTITUENCY In order to ensure the competence necessary to review and approve recombinant DNA activities, it is recommended that the IBC: (i) include persons with expertise in recombinant DNA technology, biological safety, and physical containment;

IBC CONSTITUENCY (ii) include or have available as consultants persons knowledgeable in institutional commitments and policies, applicable laws, standards of professional conduct and practice, community attitudes, and the environment; (iii) include at least one member representing the laboratory technical staff. lV-B-2-a-(3)

IBC MEMBER: THE BIOSAFETY OFFICER When the institution conducts recombinant DNA research at BL3, BL4, or Large Scale (greater than 10 Liters), a Biological Safety Officer is mandatory and shall be a member of the Institutional Biosafety Committee (see section lV-B-3, Biological Safety Officer).

IBC GENE THERAPY EVALUATION It is the responsibility of the IBC: to evaluate the potential of risk of the vector/ biohazard agent to the patient, family members or the environment and determine controls as appropriate. to evaluate the efficacy and the possibility of potential benefits of the therapy versus the concomitant biohazard risk of the vector with regard to the available therapy to the patient.

IBC GENE THERAPY EVALUATION, cont. to evaluate adverse events in previous clinical trials or animal studies to predict the potential for similar events in future trials. to determine the appropriate level of monitoring for potential microbial shedding that may result from recombination, contamination, complementation, mutation or other untoward events.

THE IBC REVIEW PROCESS The IBC must have a formal process to review proposed research. This includes: an application form formally scheduled meetings (with a quorum in attendance) revision or modification mechanism to amend applications as needed.

THE IBC APPLICATION FORM ADMINISTRATIVE INFORMATION The following information should also be included on the form: location of work location of containment equipment who to notify in an emergency the names of all personnel working on the project signature of the investigator

OTHER ESSENTIAL INFORMATION SCOPE OF WORK The Scope of Work narrative should include: technical purpose of the research all procedures involving agent/rRNA manipulation an evaluation of risk as summarized by the PI to include symptoms of exposure and the most likely routes of exposure

OTHER ESSENTIAL INFORMATION SCOPE OF WORK waste disposal procedures medical surveillance requirements, if any, to include available prophylaxis personal protective equipment used availability of containment equipment disinfectants used

PATHOGENICITY OF RECOMBINANT VECTOR ANY information on the virulence, pathogenicity of the strain of the vector should be provided: replication deficient Recombinant (what is inserted) drug resistant concentration used volume of culture used

RAC APPROVAL The Institutional Biosafety Committee may not authorize initiation of experiments which are not explicitly covered by the NIH Guidelines until NIH (with the advice of the RAC when required) establishes the containment requirement. lV-B-2-b-(8)

IBC: CONFLICT OF INTEREST No member of an Institutional Biosafety Committee may be involved (except to provide information requested by the IBC) in the review or approval of a project in which he/she has been or expects to be engaged or has a direct financial interest. lV-B-2-a-(4)

CONCLUSION This presentation was designed to inform the IBC on the duties of the committee as described by the NIH. The IBC must be familiar with the research conducted at the university and should be composed by individuals who are knowledgeable in a broad range of subjects.