Biotechnology, Blood, and “Bugs”: An Overview of

the UT Biosafety Program Brian S. Ranger, MS, SM (NRCM), CBSP

UTK/UTIA/GSM Biosafety Officer

The Biosafety Program

• The Biosafety Program for the UT-Knoxville area campuses (UTK, UTIA, GSM) consists of: – The Institutional Biosafety Committee (IBC)

• Consists of 15 voting members; 6 non-voting ex officio members

• Voting representation: – 12 academic departments; – 4 UTK; 4 AgResearch; 3 CVM; 1 GSM; 1 UT System – 2 community representatives (public health)

– The Biosafety Office • Full time Biosafety Officer & Biosafety Specialist • ½ -time Administrative Support Assistant • (Occupational Health Nurse)

Organizational Chart

Biological Safety Office IBC

UTK Associate Vice- Chancellor for Research

Chancellor Institute of Agriculture

Graduate School of Medicine

Principal Investigators

CVM AgResearch

The UTK IBC: A Brief History

• NIH precedent: – Formation of the Recombinant DNA Advisory Committee

(RAC) in 1974; – Release of the first policies governing rDNA in 1976: NIH

Guidelines for Research Involving Recombinant DNA Molecules (“NIH Guidelines”)

• UT Biohazard Safety Committee formed in 1977: – Identify existing biological hazards; – Review all research proposals for use of biohazards in

research; – Review, inspect, monitor all individuals & facilities using

biohazards • Biosafety Office established in 2004:

– Develop comprehensive biosafety program to assist/complement IBC

Current Roles of the IBC:

• Review/approval of recombinant DNA protocols (including transgenics):

– Recombinant DNA procedures involving Risk Group 2 agents must be approved prior to beginning the experiment

• Review/approval of work with agents infectious to humans, animals, and plants

• Review/approval of work with acute biological toxins (ricin, saxitoxin, etc.)

• Review/approval of work with poisonous plants or venomous animals

Roles of the Biosafety Office: • Ensure that regulatory mandates and guidelines

applicable to biological research are followed: – Keep knowledge current

Regulations & Standards

Roles of the Biosafety Office: • Ensure that regulatory mandates and guidelines

applicable to biological research are followed: – Keep knowledge current – Training (safety & compliance) – Lab/facility/site inspections

• Serve as a liaison between the researcher and UT’s Institutional Biosafety Committee (IBC);

• Assist PIs with regulatory permits as necessary (e.g. CDC and USDA/APHIS);

• Assist in the development, review, and implementation of SOPs;

• Assist researchers with biological materials shipping; • Bloodborne Pathogens Standard Compliance and

Exposure Control Officer (Research & all UTIA)

Biological Materials Registration

Biological Safety Office Admin. Review

Principal Investigator

*Approvals: IBC Chair

Department Head Others

IBC

1. rDNA 2. Infectious agents 3. Acute biological toxins

*Average approval time: ~30 days

Recombinant DNA: Then vs. Now

Recombinant DNA: The NIH Guidelines

Scope Specifies practices for constructing and

handling Recombinant DNA molecules Organisms and viruses containing

recombinant DNA molecules

Definition Constructed outside living cells by joining

natural or synthetic DNA segments to DNA molecules that can replicate in a living cell Molecules resulting from the replication of

those described above

The NIH Guidelines Apply to…

Recombinant DNA research that is

Funded by the NIH

Performed at or sponsored by an institution that receives any NIH funding for recombinant DNA research

Rationale: For biosafety/biocontainment to be meaningful, it has to be observed by all investigators at an institution

Are the NIH Guidelines Optional?

“Guidelines” does not mean “optional” They are a term and condition of

NIH funding for recombinant DNA research

NIH Guidelines – Section IV

Roles and Responsibilities

Institution Institutional Biosafety Committee (IBC) Biological Safety Officer (BSO) Principal Investigator (PI) NIH

Office of the Director

Office of Biotechnology Activities (OBA)

Recombinant (DNA) Advisory Committee (RAC)

National Science Advisory Board for Biosecurity (NSABB)

Institutional Responsibilities under the NIH Guidelines

The Institution shall:

Establish an Institutional Biosafety Committee Establish and implement policies for the safe conduct of

recombinant DNA research

Assist and ensure compliance with the NIH Guidelines by investigators

Ensure appropriate training for IBC members and staff, PIs, laboratory staff

Determine necessity for health surveillance of personnel

Report any significant problems or violations to OBA within 30 days

IBCs and NIH OBA

IBCs are the key institutional component of a national system of oversight

IBCs are “sentinels” at the local level, identifying new safety and policy issues for NIH OBA and RAC consideration

IBCs and NIH - Partners in the Oversight of Recombinant DNA Research

RAC National

perspective

NIH OBA NIH

Guidelines

IBC Local

oversight

Institutional Biosafety Committees

Established specifically for the review of recombinant DNA research

Often review other research with biohazardous risks Infectious agents, Select Agents list,

carcinogens, toxins Broader purview is a matter of institutional

discretion

Level of review Example of recombinant DNA research

Relevant section(s) of the NIH Guidelines

IBC, RAC review, and NIH Director review and approval

Experiments that compromise the control of disease agents in medicine through deliberate transfer of a drug resistance trait

III-A

IBC approval and NIH review Experiments involving the cloning of toxin genes with LD50 of less than 100 ng/kg body weight

III-B

IBC and IRB approval and RAC review before research participant enrollment

Deliberate transfer of rDNA into 1 or more human research participants

III-C

IBC approval before initiation Experiments using RG2, RG3, RG4, or restricted agents as host-vector systems

III-D

IBC notice at initiation Experiments not listed in III A-D and F

III-E

Exempt from the NIH Guidelines.

Specific host-vector systems are exempt for Guidelines

III-F

IBC Responsibilities

What do IBCs assess in reviewing recombinant DNA research?

Reagents (organisms, genes, promoters, etc.)

Containment levels per NIH Guidelines

Adequacy of facilities, SOPs, PI and lab personnel training

Institutional and investigator compliance; e.g., adverse event reports

IBC Responsibilities

In a nutshell, what must IBCs review?

Recombinant DNA research for conformity with the NIH Guidelines

Potential risk to environment and public health

The IBC does not critique a PI’s research!

IBC Composition Membership

No fewer than 5 individuals Appropriate recombinant DNA expertise collectively Plant and animal experts, biosafety officer as appropriate Expertise in assessment of risk to environment and public

health At least two members not affiliated with the institution Subject Matter Expertise recruited as necessary

Additional expertise Biological safety and physical containment Knowledge of institutional commitments and policies,

applicable law, professional standards, community attitudes, and environment

Laboratory technical staff (recommended)

Assembling an IBC

The BSO’s duties include:

Periodic inspection of labs Reporting to the IBC and institution of any

problems, violations, research-related accidents or illnesses

Developing emergency plans for handling accidental spills and personnel contamination

Advice on lab security Technical advice to PIs and IBCs on research

safety procedures

Convening an IBC

Frequency

Periodic per protocol review load Once per month

Ongoing surveillance (annual review desirable) Responsibility of BSO Submits report to IBC

IBCs and Other Research Oversight Committees

IBC IRB

IACUC

Institutions should determine best way for these committees to interact and share information

IBCs and IACUCs Animal Research

Joint purview, and ideally collaborative review, over certain types of research

Transgenic or cloned animals

Use of recombinant DNA molecules in animals

Use of genetically modified microbes in animals

Pre-clinical studies and data assessment for human gene transfer protocols

PI Responsibilities under the NIH Guidelines

The Principal Investigator shall (among other things):

Initiate or modify no recombinant DNA research which requires IBC approval until approval is granted

Determine whether experiments are covered under III-E and notify the IBC as appropriate

Be adequately trained in good microbiological techniques

Adhere to IBC emergency plans for spills and personnel contamination

Report any significant problems or violations to OBA within 30 days

NIH Guidelines noncompliance

What are potential consequences of noncompliance with the NIH Guidelines? suspension, limitation, or termination of

NIH funds for recombinant DNA research at the institution, or

a requirement for prior NIH approval of any or all recombinant DNA projects at the institution.

ask Dr. Splitter (UW-Madison)…

Other Biohazards:

Any biological agent or condition that poses a threat to human, animal, or plant health, or to the environment. Examples include: • Infectious agents

Human, animal and plant pathogens • Materials potentially containing infectious

agents or biohazards Blood, tissues, body fluids etc. Waste, carcasses etc.

• Toxins of biological origin • Venomous animals/poisonous plants

Types of Infectious Agents:

How they’ll look....

What they are....

Risk Assessment: Organism-Related Factors

• Host range • Pathogenicity • Availability of prophylaxis • Route of transmission • Viability in the environment • Origin of the source • Additional for recombinant DNA:

– Nature of insert – Environmental impact

Risk Group Matrix

Risk Group Acquisition Source Treatment

Available?

Personal Health Impact

Community Health Impact

1 Rare; contact Primarily indigenous Yes Low Low

2 Contact Primarily indigenous Yes Low to

Moderate Low

3 Contact; inhalation

Indigenous or exotic

Mostly, but not always

Moderate to high

Low to Moderate

4 Contact; inhalation Exotic No High High

Biosafety Level 2

Biosafety Level 3

Use of Infectious Agents at UTK:

• All infectious agents used for research at UTK/UTIA/GSM are RG-1 or RG-2 – No facilities suitable for higher-tiered organisms

• Unless recombinant and subject to the NIH Guidelines, safety and containment procedures are driven by guidance documents (e.g. BMBL) rather than regulations: – Still represent ‘best practices’; – Ultimately determined by a risk assessment of the

of the intrinsic nature of the agent(s) and the procedures to be used.

Infectious Agent Oversight: Why?

• Occupational health concern: – Covered by OSHA “general duty” clause; other

standards may apply – Written risk assessment approved by IBC

• Inventory monitoring: – What/where/how much? – Coordination of emergency response

• Transfer of agents from other institutions or commercial sources (e.g. ATCC): – Assurance of best practices

• Select Agents compliance

The OSHA Bloodborne Pathogens Standard (29 CFR 1910.1030) • The Occupational Safety & Health

Administration’s (OSHA) Occupational Exposure to Bloodborne Pathogens (BBP) Standard [29 CFR 1910.1030] applies to anyone that will handle or may come into contact with human blood or other potentially infectious materials (OPIM) due to the risk of bloodborne pathogens (e.g. HIV, hepatitis B, hepatitis C).

BBPs on the Job... Occupations that bear a risk of exposure to BBPs include:

• Healthcare workers • Emergency responders performing first aid and/or CPR:

– EMTs, paramedics, life guards • Custodial personnel • Researchers/lab personnel

Workers at risk of exposure to BBPs fall under specific OSHA regulations in order to reduce occupational risk!

Shipping Regulations • Shipment by courier • The following items are regulated

for shipment: – cultures of agents infectious to humans

or animals; – patient specimens that are suspected to

contain agents infectious to humans or animals;

– genetically modified organisms or microorganisms

• These items require specific training and packaging for shipment.

Biological Permits

• The following are permit-restricted: – Import of etiological agents affecting humans,

animals, or plants into the U.S.; – Export of etiological agents affecting humans,

animals, or plants from the U.S.; – Interstate movement of plant pathogens,

animal pathogens, or transgenic plants; – Field release trials for plant pathogens or

genetically modified plants and/or plant pathogens;

– Import/export of biological materials obtained from wildlife;

• Warning 1: Biological materials permits may take several weeks to months to obtain. Do not wait until the project is imminent to begin the process of obtaining a permit…the U.S. Government does not make exceptions or give special priority based on your research needs.

• Warning 2: Do not attempt to transport undeclared biological materials in your carry-on or checked luggage while flying! This may result in substantial fines and/or incarceration!

Biological Permits (oh, the biological permits!)

The Challenges:

• The usual suspects?:

•Microbiology •BCMB •Diagnostic Sciences •Biomedical Sciences •Animal Science •SACS/LACS •Entomology/Plant Path. •Anthropology (FAC) •GSM

but what about…. •Chemistry •Materials Sciences •MABE •CBE •Plant Sciences •Hearing and Speech •Electrical Engineering!

Biosafety Progam-Statistics:

• Currently serving >100 P.I.s in ~25 academic departments

• For FY11, the Biosafety Program: – Processed ~30 IBC registrations; – Processed over 70 IBC registrations’ annual reviews; – Conducted over 120 BSL-2 lab inspections; – Trained over 1100 individuals on some aspect of

biosafety (includes online refresher training); – Performed hazard assessments on ~150 IACUC

protocols

The Challenges:

• The assessment games: – Saccharomyces cerevisiae vs.

Schizosacchoromyces pombe; – E. coli vs. E. coli; – Murine CMV – Geomyces destructans and white-nose

syndrome – Let’s have fun with viral vectors:

• Lentivirus vs. MMLV – Should we accept this donation?

The Challenges:

• Most reagents used in biological research are easily procured from collaborators or commercial vendors;

• No centralized method for maintaining an up-to-date biological materials inventory;

• Constant surveillance-value of TERA/PAMS • ‘Lord of the Flies’-a case study in the don’ts of

compliance

Contact me at any time if you have questions/comments:

Brian Ranger, MS, SM (NRCM), CBSP Biosafety Officer UTK/UTIA/GSM 974-1938 branger@utk.edu http://biosafety.utk.edu

Sarah DiFurio, MS, RBP Biosafety Specialist 974-9836 sbottomL@utk.edu

Jessica Woofter Adm. Support Asst. 974-5547 jwoofter@utk.edu

Dr. Amy Knowles, RN, MPH, PhD Occupational Health Nurse 974- aknowles@utk.edu

If you want real answers…

Thank you for your attention!

Questions?