Academic Research in the New Millennium: an EH&S Perspective Institutional Biological and Chemical Safety Committee/ Environmental Health and Safety Joe Kanabrocki Biological Safety Officer

Biological & Chemical Safety at WUSM

Evolving Issues Biomedical technology. Gene “therapy”; gene transfer. Xenotransplantation. Emerging infectious diseases. Bioterrorism/biowarfare threat. Agricultural biotechnology.  Hilltop

Gene Transfer Technologies  First research subject admitted to NIH Clinic for gene therapy approx. ten years ago.  Initial assumption: gene transfer to focus on study & treatment of genetic deficiency diseases: true gene therapy.  Gene transfer clinical trials to date: Cancer (62%), monogenetic deficiency diseases (13%), AIDS (9%)  Patient dies at U. Penn.; gene trials/human studies scrutiny greatly increases.

Gene Transfer Technologies  Three types of delivery vectors employed:  Viral vectors: retroviruses adenoviruses adeno-associated viruses vaccinia/fowlpox viruses Herpes virus Lentiviruses (HIV based vectors)  Cationic liposomes  Plasmids

Infection Control for Gene Transfer Technologies  Traditional Infection Control  Prevent infection.  Diagnosis and therapy known.  Isolation to prevent transmission.  Gene transfer  Produce infection.  Contain infection.  Usually not treatable by conventional therapy.  Isolation to prevent transmission.

Xenotransplantation  Animal organs used to “bridge” human transplant patients.  Transgenic animals produced to produce organs recognized as human (MHC genes).  Presents infection control issues:  zoonoses (animal pathogens infecting humans)  novel pathogens able to cross species barriers.

Emerging Diseases Examples of new and reemerging diseases.

Emerging Diseases Response to H5N1 avian influenza outbreak in Hong Kong.

Emerging Diseases Benefits of emerging diseases research.

Emerging Diseases Emerging diseases funding (National Institute of Allergy and Infectious Diseases).

Threat of Biological Terrorism and Warfare

Federal response to terror attacks Federal agencies have requested that research institutions develop an inventory describing the nature & use of research materials associated with research activities. Centers for Disease Control and Prevention (CDC) Federal Bureau of Investigation (FBI) Department of Justice-Office of Inspector General (DOJ-OIG) Mandate is forthcoming (December 2002?).

Regulatory Compliance: Response to terror threats & attacks Select Agent Transfer (SAT) Rule Rule pertains to select bacteria, viruses, fungi and toxins with potential for use as WMD. Purpose of SAT Rule is to ensure that: select infectious agents & toxins shipped only to institutions/individuals equipped to handle appropriately. transfer of these agents is to those who have legitimate reasons to use them. system is implemented whereby scientists and researchers involved with legitimate research may continue transferring these agents without undue burden.

Regulatory Compliance: Response to terror threats & attacks U.S. PATRIOT Act ( Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism-2001) Extends limitations of the SAT Rule to use and possession of Select Agents. Prohibits certain personnel from access to select agents. Criminal records. Foreign nationals from certain countries. Drug abusers.

Research Protocol Registration at WUStL Why this request? What does “research protocol registration” mean? What types of research protocols must be registered? Who should register their research? With whom is the research registered? How does a PI register his/her protocol? When and how often are protocols registered?

Why this request? Federal response to terror attacks. FBI, CDC, DOJ, USDA Regulatory compliance. NIH (recombinant DNA) OSHA (BBP and Lab Standard) DOT/FAA The “right” thing to do. Facilitate research activities

Regulatory Compliance: Long-established requirements National Institutes of Health: Guidelines for Research Involving Recombinant DNA Molecules (1976). Guide for the Care and Use of Research Animals (Occupational Health and Safety requirements for workers and investigators) OSHA: Laboratory Standard (1990) Bloodborne Pathogens Standard (1991) Other funding agency requirements: e.g. American Heart Association, DOD, etc.

The “Right” Thing To Do Provides basis for assessment of research associated risks: Primary function of Institutional Biological and Chemical Safety Committee (IBC). Allows for determination of appropriateness of facilities and lab work practices. Provides basis for staff training needs. Provides EH&S with info on hazardous waste disposal needs.

The “Right” Thing To Do Provides mechanism for institutional and PI accountability. Public outcry for accountability. St. Louis Fire Department requirements include the establishment of inventories of research materials. Security

Inventory of Biohazardous Materials Inventory to be maintained in Biohazardous Materials Database. Access database. Tracks research reagents, research locations, personnel, training, grants supporting research, lab audit data, fume hood test data Component of Environmental Management System (EPA initiative)

Biohazardous Materials Database Occupational & public health info for exposure prophylaxis. Info for support personnel (e.g. maintenance, custodial, etc.) Info for lab decommissioning. Regulatory compliance records. Provides registry of WUStL research resources for campus investigators.

What does “research protocol registration” mean? Completion of a registration form describing research program elements and protocols. Program-based research protocol description, not grant-based. Graded approach-emphasis on risk The greater the risk, the greater the required detail.

Who should register their research? Investigators should register their research if: they have Principal Investigator status; their research involves regulated or hazardous biological agents and/or materials or select chemical agents.

With whom is the research registered? Registration Program administered through the Office of Biological and Chemical Safety on behalf of the Institutional Biological and Chemical Safety Committee (IBC). Program of the Environmental Health and Safety Department, FMD, School of Medicine.

Institutional Biological & Chemical Safety Committee (IBC)  Med School & Hilltop representation (CHAIR: Sam Stanley, M.D.).  Membership to reflect required expertise.  Charge:  Review and assess risks associated with research involving etiologic agents, biological or chemical.  Review and assess risks associated with research involving recombinant DNA.

Draft IBC Policy: Research Registration The Institutional Biological and Chemical Safety Committee (IBC) endorses registration with the IBC of all research activities (in vitro and in vivo) involving regulated and/or potentially hazardous biological or select chemical research materials. The bases for this endorsement include regulatory compliance documentation, inventory assessment, security and establishment of a registry of research resources for the WUStL research community (24 April 2002).

What types of research protocols must be registered? Recombinant DNA molecules and recombinant DNA-containing organisms or cell cultures which are subject to the NIH Guidelines for Research Involving Recombinant DNA Molecules, including human gene therapy trials. Pathogenic microorganisms or agents potentially infectious to humans and/or animals. Human blood, tissues, and cell lines as well as potentially infectious animal blood, tissues and cell lines.

What types of research protocols must be registered? Carcinogens, mutagens, teratogens, drugs, and toxins when administered in vivo to animals or in vitro to cell or tissue cultures to induce a biological outcome. Animals for which a reasonable potential for transmission of zoonotic agents exists, e.g., wild- trapped animals, sheep, & rhesus macaques. Exotic plants, animals or microbes (e.g., non- indigenous plant or insect pathogen, or biological control agent).

How does a PI register his/her protocol? Complete Recombinant DNA and Hazardous Research Materials Protocol form. Available at: Can be filed as attachment. Requires printing of cover page only for signatory purposes.

When and how often are protocols registered? Protocols are considered active for five years. Amendments can be made in the interim when novel (relative to the protocol) risks or regulated materials are added to the protocol.

EH&S Initiatives  IBC administrative support.  Research materials and compliance database.  Web-based on-line research registration.  Coordinated compliance effort.