Concepts of Biocontainment & Biosafety Training

UNIVERSITY OF NORTH CAROLINA - CHARLOTTE/ APRIL 30, 2014

CLIENT NAME / DATE Regulatory Guidance

. OSHA Bloodborne Pathogen Standard . NIH Recombinant Guidelines – Apply to all institutions receiving NIH funding – Covers rDNA work, but also includes risk group listing . Biosafety in Microbiological and Biomedical Laboratories (BMBL) . Select Agent and Toxin regulations . Dangerous goods shipping regulations . North Carolina Dept. of Environment and Natural Resources

CLIENT NAME / DATE US Guidance for Laboratories

. BMBL Outlines: – Standard Microbiological Practices – Special Microbiological Practices – Safety Equipment – Facilities . Includes – Agent summary statements – BSC design and use – Toxin handling http://www.cdc.gov/biosafety/publications/bmbl5/index.htm CLIENT NAME / DATE Layers of Protection

CLIENT NAME / DATE Definitions

. Biohazard

– A biological agent capable of self- replication that can cause disease in humans, animals, or plants – Generally, a microorganism, or toxins and allergens derived from those organisms

. Biocontainment Class III cabinets at the U.S. Biological Warfare Laboratories, Camp Detrick, Maryland (Photo, 1940s) – the physical containment of pathogenic organisms or agents to prevent accidental infection of workers or release into the surrounding community .

CLIENT NAME / DATE Biosafety . Fundamental objective: – Containment of potentially harmful biological agents

. Risk assessment: – Helps to assign the biosafety level that reduces to an absolute minimum the worker’s exposure to agents, their risk of an LAI (lab associated infection), and potential impact on the community and the environment

CLIENT NAME / DATE Biosafety Levels (BSLs)

. Combinations of lab practices and techniques, safety equipment, and laboratory facilities . Appropriate level determined by risk assessment . Specifically appropriate for: – Organism in use – Operations performed in the laboratory – Known or suspected routes of infection

CLIENT NAME / DATE Determining BSLs

. Conditions under which the agent ordinarily can be handled in the laboratory . Final determination by responsible scientists on the Institutional Biosafety Committee (IBC) . Based on a risk assessment – Resources include: . Published data, including animal data . Epidemiological data . Guidelines and regulations . Biological safety officer (BSO)

CLIENT NAME / DATE RISK ASSESSMENT PROCESS

CLIENT NAME / DATE Basic Sources of Information . The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules . Risk Group listing . Public Health Agency of Canada . Pathogen Safety Data Sheets and Risk Assessment . CDC Agent Summary Statements – In BMBL . CDC website . CDC/MMWR recommendations . Others

CLIENT NAME / DATE Risk Assessment . Consideration of: – Manipulations to be done – Volumes handled – Virulence – Pathogenicity – Antibiotic resistance patterns – Vaccine and treatment availability – Other factors

CLIENT NAME / DATE Risk Management— Remember the “Chain of Infection”

Presence of a pathogen

Susceptible Pathogen is host virulent

Sufficient Portal of numbers of entry organisms

CLIENT NAME / DATE Infectious Dose . Agent . Dose

• Ebola virus • 1 Salmonella, NIH • TB • 1 - 10 • Tularemia • 10 • Anthrax (inhalational) • 8,000-50,000 est. • Cholera • 108 • Salmonella typhi • 105 • E. coli (enteropathogenic) • 108 – 1010 • Shigella • 10 – 200 • Norovirus • 18 CLIENT NAME / DATE Routes of Exposure . Parenteral (needlestick, scratch) . Exposure to non-intact skin . Inhalation . Droplet . Ingestion . Mucous membranes . Absorption (e.g., toxins) . Animal bites and scratches

CLIENT NAME / DATE Laboratory Associated Infections (LAIs) . Where no known exposure event – usually attributed to aerosols . Aerosols can be produced by equipment: – Centrifuges – Blenders – Sonicators – Vortex mixer – Homogenizers, etc. . Aerosols also produced by: – Any liquid manipulation – Pipetting practices – Opening lyophilized cultures – Flaming loops and needles – Changing bedding of infected animals CLIENT NAME / DATE

Aerosols

. Lab equipment – Produces aerosols more efficiently than natural methods (coughing, sneezing, etc.) . Materials encountered – Higher titered than in natural setting . Modest aerosol-producing activity could be infectious – Larger quantities being manipulated – Agent that is not normally aerosol-transmissible may be transmitted under these circumstances . Use the BSC to contain aerosols – Class I or II BSC for containment of small equipment (blenders, homogenizers, etc.) Banthrax Versa Dome

CLIENT NAME / DATE Particle Size and Routes of Transmission . Large droplets (>50-100 µm in diameter) – Subject to gravity – Travel only a few feet – Do not remain suspended for very long . Intermediate droplets (10-50 µm) – Affected by temp, humidity, air velocity and air currents – With water loss, may become “droplet nuclei” quickly . Small particles (<10 µm) – Remain airborne for extended periods of time – Dispersion affected by air currents – Infective if organism can survive desiccation – Can reach the pulmonary region of the lung with variable efficiency

CLIENT NAME / DATE

Particle Size and Routes of Transmission

CLIENT NAME / DATE Susceptibility to Infection . Genetics . Inherited immune problems . “Healthy Adult” . Factors affecting immune status: . Chemotherapy, smoking, immune suppressive drugs, . Lupus, HIV, etc. CDC/James Gathany . Immune function usually decreases with age . Vaccination Status . Reduces chance of infection . Reduces severity of infection (chickenpox) . Never reduce risk 100% . Reproductive Risks . Risks to fetus: Toxoplasma, Listeria, CMV, Rubella, HIV . Mother may be asymptomatic, but fetal effects are severe

CLIENT NAME / DATE HIERARCHY OF CONTROLS

CLIENT NAME / DATE Hierarchy of Controls

CLIENT NAME / DATE CONCEPTS OF BIOCONTAINMENT LABS (ENGINEERING CONTROLS)

CLIENT NAME / DATE Biocontainment Concepts

. Containment Barriers – Primary - BSC’s, personnel protective gear, containment equipment – Secondary - Room, systems – Tertiary - Containment around systems

. Access Control and Separation

. Redundancy and Reliability

. Decontamination

CLIENT NAME / DATE Biosafety Levels 1 & 2

BSL-1 BSL-2

CLIENT NAME / DATE Directional Airflow

Provides “Zone Control” of hazards and odors

Air flow from lowest to highest hazard

CLIENT NAME / DATE BSL-3

CLIENT NAME / DATE BSL-3 facility design

. Isolated from other lab areas . Access through two self-closing doors . Single pass, unidirectional air in-flow . HEPA filters not required on exhaust air . Interior surfaces sealed to allow decon . Air space around penetrations sealed . Autoclave available in facility

CLIENT NAME / DATE BSL-4 Labs . Suitable for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections and life-threatening disease.

.Exposure potential to pathogens – That may be spread by aerosol or – With unknown risk of transmission

. Infection possibly lethal

. Examples: . Ebola Zaire . Sin Nombre virus . Rift Valley Fever

CLIENT NAME / DATE Biosafety Level 1, 2, 3 . Provide access to autoclaves to treat potentially contaminated waste materials (e.g., gloves, lab coats, etc.) from laboratories before disposal or reuse

CLIENT NAME / DATE All Biosafety Levels

. Sinks are required to wash hands after: – Handling infectious materials – Removing gloves before leaving the lab – Spills and/or exposures . Ideally, the hand washing sink is located at the exit to each laboratory . Non-hand operated is recommended

CLIENT NAME / DATE Biological Safety Cabinets (BSCs)

. Class 2, Type A cabinets . 2 HEPA (high efficiency particulate air) filters . Filtered air discharged to room (no volatile toxic compounds) . Use to contain aerosols and maintain sterility of specimens . Protect you, your work and the environment . Dependent on scrupulous work practices . Read BSC Operating Procedure

CLIENT NAME / DATE Vacuum Set-Up

CDC drawing

Flasks should be plastic, plastic-coated glass or covered with netting A – disinfectant containing flask B – overflow flask C – in-line HEPA filter D – vacuum system

CLIENT NAME / DATE ADMINISTRATIVE AND WORK PRACTICE CONTROLS

CLIENT NAME / DATE Purpose of Administrative and Work Practice Controls Protection of: . yourself . ”work products" . co-workers . lab support personnel . community . environment

CLIENT NAME / DATE Safe Work Practices

. Wash hands frequently Fill line . Do not bend or recap needles . Place sharps in the appropriate container . Do not eat, drink, smoke, apply cosmetics or handle contact lenses in the work areas

CLIENT NAME / DATE Safe Work Practices . Minimize splashing, spraying, generation of droplets . Do not reach into trash/sharps containers . Minimize glassware/sharps hazards . Never pipette by mouth – use pipet aids . Wipe down work area with a disinfectant

CLIENT NAME / DATE Proper Use of the BSC

• Work 4” back from the • Load only those materials front grille needed inside cabinet – Avoid withdrawing hands for • Do not place items on the discard or supplies front grille or block rear • Wait 5 minutes after loading vent BSC before working • Wipe all materials going • Avoid rapid sweeping arm in and out of BSC with movements disinfectant (depending) • Clean trough under work surface regularly Place discard containers • • No open flames inside inside BSC cabinet

CLIENT NAME / DATE Minimize use of sharps– use alternatives . Hypodermic needles . Use safety needles / syringes . Pasteur pipet . Use plastic transfer pipet . Scissors . Use blunt-tipped safety scissors . Box Cutters . Use self-retracting utility knife . Document consideration of safer devices annually

CLIENT NAME / DATE Biohazard Door Signage for BSL-2 . Biohazard Symbol . Word “Biohazard” . Orange or orange-red in color . BSL-2 . List materials/agents in use – E.g., human tissue, human cell culture . List emergency contact names and phone numbers . List any special applicable entry requirements – E.g., safety glasses, lab coats, etc.

CLIENT NAME / DATE Labeling Requirements . What needs a biohazard label? » Room doors if work with potentially biohazardous materials » Freezers/Refrigerators used to store potentially biohazardous materials » Biowaste containers (cans, sharps containers, pipet boxes) » Shipping/transport containers for potentially biohazardous materials » Materials for storage

CLIENT NAME / DATE Administrative Controls

. Biosafety Manual – Spill and emergency procedures, use of a BSC, list of appropriate disinfectants, training requirements, reporting procedures for incidents, PI responsibilities, waste handling guidelines, etc. . Laboratory SOPs – For specific lab procedures (ultracentrifuge operation, cell sorter, etc.) . Housekeeping – Cleaning and disinfection procedures . Training – Annually (BBP) or whenever agents or procedures change – Documented training on SOPs

CLIENT NAME / DATE PERSONAL PROTECTIVE EQUIPMENT (PPE)

CLIENT NAME / DATE Personal Protective Equipment (PPE)

. Safety glasses with side shields – Wear when entering the work area . Lab coats – Leave in the work area – If contaminated, decontaminate before placing in laundry bag – Wear buttoned with sleeves rolled down

CLIENT NAME / DATE Personal Protective Equipment (PPE)

. Gloves • Check for pinholes before wearing • Do not touch common items with gloved hands (e.g., door knobs, phones) • Consider chemical compatibility if applicable • Don’t reuse disposable gloves • Waterproof needed for working with human-sourced materials • NOTE: if double gloving, can combine different types (like latex and nitrile) • Wash hands after removing • DO NOT wear outside the lab!

CLIENT NAME / DATE Additional PPE

. Activity with the potential • Wear additional mucous for a splash or spray membrane protection – Filtering under pressure – Face shield – Opening blood tubes – Mask and goggles – Running a peristaltic pump – Visor/mask combo – Plexiglas shield

Fluid resistant mask/visor – Work inside biological safety cabinet (BSC)

Molded face mask

DisposableCLIENT faceNAME shield / DATE Remember:

. Most infectious agents can be transmitted via a cut or needlestick . Most infectious agents can be transmitted via an eye exposure – Either systemic or a localized eye infection can occur

CDC Ocular Vaccinia in a Laboratory Worker CLIENT NAME / DATE http://wwwnc.cdc.gov/eid/article/12/1/05-1126_article.htm Laundry Requirements

. Laundry must be collected near where it is removed . Spill on a lab coat? Remove – Soiled Laundry – Spray with disinfectant Use Universal Precautions – Rinse with water Place in laundry bag or discard if disposable – Biohazard . The bin will be labeled “Soiled Laundry, Use Universal Precautions” . Lab coats must not be taken home for laundering

CLIENT NAME / DATE WASTE HANDLING AND DISINFECTION PRACTICES

CLIENT NAME / DATE Waste Treatment at UNCC

. Medical Waste definition in NC: – blood and body fluids in individual containers, microbiological waste, and pathological wastes that have not been treated . Sharps will also be treated as Medical Waste . Medical waste can be: – Handled by Stericycle without pretreatment – “Pretreated” by autoclaving (if an autoclave is available) and then placed in Stericycle bins . This waste is NOT to be placed in general solid waste bins – Sharps (needles, razor blades, scalpels, etc.) will be handled by Stericycle CLIENT NAME / DATE Solid Waste Decontamination . In order to place autoclaved waste in the general trash: – Laboratory personnel autoclave waste in a decontamination autoclave which is: . tested weekly with biological indicators and tests are logged . records for autoclave runs (tape or charts) are checked for each run and maintained . all users are trained on the procedures . If sharps are autoclaved as above, they still go in the Stericycle bin

CLIENT NAME / DATE Liquid & Solid Biohazardous Waste

. Small quantities of liquid waste (in tubes) can be placed in the biohazard waste bag . Larger quantities of liquid waste should be chemically decontaminated – Use a final dilution of 0.5% sodium hypochlorite (~10% bleach final dilution) in waste, allow to sit 30 minutes and sewer – Autoclaving large quantities of liquid waste is not recommended due to the risk of scalds and burns to the operator . Solid waste (e.g., pipettes, tips) can be chemically decontaminated by submerging in a 0.1% or stronger solution of sodium hypochlorite (~2% bleach) and discarding into regular trash

CLIENT NAME / DATE Disposal/Handling of Contaminated Items

Sharps Pipets/tubes/tips Pipets Bulk Syringes, broken in BSC Pipet tips glass, Pasteur Liquids pipets, needles, etc.

Sharps Pipet keeper or container sharps + container Plastic bottle or “Benchtop Keeper” Solids Disinfectant filled beaker or pan Vials, centrifuge tubes, gloves, etc. Pour off disinfectant (colander) 10% bleach in waste for 30 minutes Biohazard waste bin (with cover)

Regular trash (plastics) Glass Bin (glass)

CLIENT NAME / DATE Stericycle Box Sewer Disinfectants

. For human specimens, must use a disinfectant effective for bloodborne pathogens – 0.1% sodium hypochlorite (bleach) made fresh daily – Or see list on next slide . Must follow manufacturer’s label instructions . Disinfect bench tops at least daily . Decontaminate equipment sent for repair or disposal – Use Decontamination Verification Tag . Alcohol solutions are for cleaning and control of environmental contaminants. – Not approved by OSHA for use with BBP . See Disinfection Appendix document CLIENT NAME / DATE New UNCC Disinfection Appendix Document UNCC Equipment Decontamination Verification

Serial No.:______Date______Asset No.:______Prior to service of this equipment that may be contaminated with potentially biohazardous materials, it MUST BE DECONTAMINATED by the user. This documentation procedure will include the following as appropriate:

1. Removal of all contaminated YES NO NA materials from the unit. ______2. Flushing/decontamination of any fluid pathways and ______contaminated surfaces. 3. Surface wipedown of unit with a detergent, followed by a wipedown with a tuberculocidal disinfectant. ______List any areas that could not be decontaminated:_____

______

Name (Print):______Signature:______Phone No.:______By signing the decontamination verification card, the owner assumes the responsibility of completing the decontamination procedure as indicated on the front of this card.

CLIENT NAME / DATE Other Disinfectants

. Tuberculocidal . Heed expiration dates – Cavicide/Envirocide – Caviwipes – Clorox Cleanup with Bleach . Stabilized bleach with detergent . One step cleaning – Clorox Healthcare Bleach Germicidal Cleaner – Super Sani-Cloth Germicidal Wipes . Visibly soiled surfaces must be precleaned with an aqueous detergent before

disinfection CLIENT NAME / DATE SHIPPING AND TRANSPORT

CLIENT NAME / DATE Labeling and Shipping

• Label vials, tubes, etc. • Need to ship? – Biohazard label – Only trained employees allowed to package materials • Or, label box or carrier for shipping • Transfer internally in a zip lock • Renewed every 2 years bag with absorbent inside or in – Know status of material to be a labeled cooler with shipped absorbent inside • Most UNCC materials will – Decon outside – no gloves be shipped as “Biological Substance, Category B”

– Most RG 2 agents – Diagnostic and clinical specimens from a person with a disease • Non-infectious clinical specimens are “exempt human specimens”

CLIENT NAME / DATE SPILLS AND EMERGENCY PROCEDURES

CLIENT NAME / DATE Spills

. Clean up and report spills . Use disinfectant per Spill Operating appropriate for agent Procedure . Use full strength . Employees must be disinfectant on large spills able/equipped to handle (dilution effect) spills of biological . NEVER pick up broken material sharps with fingers . Absorb liquid, preclean with detergent (to remove organic materials), then wipe with an approved disinfectant

CLIENT NAME / DATE Emergency Procedures . Remove PPE and provide immediate care to the exposure site: − Wash wounds and skin with soap and water for 15 minutes. − Flush mucous membranes with water for 15 minutes . Notify your supervisor and BSO of the incident . Visit Occupational Health Provider or Emergency Room for evaluation. . Seek medical attention and have the incident evaluated immediately (within 1-2 hours). CLIENT NAME / DATE

OSHA BLOODBORNE PATHOGEN STANDARD

CLIENT NAME / DATE OSHA Bloodborne Pathogen Standard (29 CFR 1910.1030)

. The Federal OSHA Bloodborne Pathogen Standard was instituted in 1991.

. It was designed to reduce and minimize the potential for occupational exposure to the Human Immunodeficiency Virus (HIV), the Hepatitis B Virus (HBV) and other human bloodborne pathogens.

CLIENT NAME / DATE Who is Covered Under the Bloodborne Pathogen Standard?

• All workers occupationally exposed to blood or other potentially-infectious materials (OPIM) • Occupationally exposed: reasonably anticipated contact with blood or other potentially infectious material that may result from the normal performance of an employee's job duties

CLIENT NAME / DATE Requirements of the Standard

. Have an Exposure Control Plan . Identify employees who may have exposure while performing their job . Provide annual training and Hepatitis B Vaccination to all employees at risk . Provide Post-Exposure Follow-Up to employees who have had exposure to a bloodborne pathogen

CLIENT NAME / DATE Occupations at Risk

. Titles of employees who WILL have exposure to human-sourced materials – e.g., Laboratory Technician, Research Assistant, Research Scientist, Occupational Health Nurse . Titles of employees who MAY have exposure – e.g., Applications Engineer, Housekeeping, Emergency Response Team member – The tasks that may cause them to have exposure . e.g., troubleshooting contaminated equipment, safety audit team, etc. . Many employees will have no exposure – e.g., Accountant, Administrative Assistant CLIENT NAME / DATE Materials covered under the OSHA Standard include:

Blood • Human Blood • Blood Products • Blood Components Other Potentially Infectious Materials (OPIMs) • Unfixed Human Tissue or Organs – Human cell lines • Cells containing a BBP • Saliva in dental procedures • Any fluid that is visibly contaminated with blood – Not urine (unless bloody) • Human body fluids – Body cavity fluids – Semen and vaginal secretions CLIENT NAME / DATE

Occupational Route of Transmission for Bloodborne Pathogens

• Skin puncture • Needle stick or sharp objects Most common in health care workers

• Broken or non-intact skin • Rashes, hang nails, cuts, punctures, abrasions, acne, cold sores

• Contact with mucous membranes of eyes, nose, and mouth • Spills, splashes, sprays of infectious materials • Less common route of transmission, but many documented cases exist

CLIENT NAME / DATE Protection

. Hepatitis B vaccine . Universal Precautions . Protection from percutaneous exposures . Protection from mucous membrane/non-intact skin exposures . Signs and labels used to identify potential presence of bloodborne pathogens

CLIENT NAME / DATE Hepatitis B Vaccine

. Available free of charge to employees who are occupationally exposed to bloodborne pathogens. . Provided in a 3 shot series (initial shot, 1 month later, and 6 months after initial . May be declined with a signed waiver and available later if you decide you want it . Effective in 90-95% of people receiving the 3 shots – Boosters generally considered unnecessary

CLIENT NAME / DATE Incident Follow-up (OSHA Law)

. Documentation of: – Route of exposure – Circumstances – Source individual . Unless unfeasible or prohibited by local law . Source tested for HIV, HBV, (HCV) – Disclose results to exposed employee . Collect baseline on exposed employee – With consent – Test for HIV, HCV, HBV, others as appropriate . Post-exposure prophylaxis as recommended by Public Health Service – May include antiviral drugs for a serious exposure . Counseling . Evaluation of reported illness . Healthcare professional’s written opinion CLIENT NAME / DATE AGENTS IN USE AT UNCC

CLIENT NAME / DATE Examples of Materials/Agents Used at UNCC All handled at BSL-2

• Human-sourced • Bacteria – Blood, serum – Vibrio spp. – Human cell lines – Pseudomonas aeruginosa – Sputum – Staphylococcus aureus • Viruses – Klebsiella pneumoniae – VSV • Teaching lab – HRSV – Salmonella typhimurium – HPIV3 – Shigella flexneri – Adenovirus – Streptococcus pyogenes – Rhinovirus – Proteus mirabilis

CLIENT NAME / DATE OCCUPATIONAL HEALTH CONSIDERATIONS

CLIENT NAME / DATE BMBL Occupational Health Recommendations

. Risk Assessment for agents and activities . Prophylaxis protocols in place before work begins (with PI input) . Training and education of workers – Agents, signs and symptoms, risk of infection, routes of transmission . Programs cover all exposed, including contract, students, and visitors . Annual review of training and exposure incidents

CLIENT NAME / DATE

BSL-2 – Not a Big Deal, Right?

. Risk Group 2 organisms are generally able to be safely handled with good microbiological practices – Includes wearing PPE, hand washing, reporting exposures, etc. – There is often treatment or vaccine available . However – Immune suppressed individuals will be at increased risk – If exposures are not reported or correctly diagnosed, treatment will not be initiated . Plague case at University of Chicago – Samples of HCV and HIV are handled at BSL-2 . Serious diseases with long term implications

CLIENT NAME / DATE Special Employee Circumstances that Should Prompt a Consultation with a Medical Professional

. Pregnancy or contemplating pregnancy – Work with Rubella, Toxoplasma, Cytomegalovirus, Chagas, Parvovirus B-19, syphilis . Immunosuppression – Immune-suppressive drugs, Lupus, steroid therapy – Employee infected with HIV, splenectomized, etc. . Increased susceptibility – HBV carrier (to HBV infection) . Conditions that may affect ability to work in a laboratory – Uncontrolled diabetes, medications that affect ability to use machinery

CLIENT NAME / DATE Pregnant HCW and Vaccination

. Consult most current recommendations before proceeding – OK to vaccinate: HAV, HBV, Tetanus, Rabies, influenza (trivalent inactivated) – Contraindicated: Rubella, Varicella, Anthrax, Yellow Fever . Obviously, wise to get vaccines before become pregnant (training issue) . For many diseases (CMV, TB), protection relies on using standard precautions

CLIENT NAME / DATE Special Employee Circumstances

. Occupational Health discussions covered under HIPAA Law. – Decisions made by Occ Health medical professional, employee physician and employee . Legally, cannot restrict an employee from job duties because of gender, concern for unborn children, etc. – Johnson Controls Case . Provide mechanism for “Acknowledgment of Risk” – Make sure employee is aware of the risks associated with their condition relative to the job

CLIENT NAME / DATE Post Exposure Recommendations

• HBV • Analyze risk of source • HIV recommendations – Include HBIG and vaccine – Use of ZDV, Lamivudine, • HCV protease inhibitors – No post-exposure – Can lower seroconversion prophylaxis currently rate by 79% recommended – Post-exposure testing

http://www.nccc.ucsf.edu/hiv_clinical _resources/pepline_guidances_for_oc cupational_exposures/

CLIENT NAME / DATE Questions?

CLIENT NAME / DATE NIH Guidelines for Principal Investigators Training

UNIVERSITY OF NORTH CAROLINA - CHARLOTTE/ APRIL 30, 2014

CLIENT NAME / DATE Agenda

. Why are we concerned about IBC training? . Orientation to the NIH Guidelines – Review of applicable sections . Expectations for PIs – Implicit and implied . Overview of the IBC and its function . Pending U.S. legislative activities . What sections and appendices are applicable to research

CLIENT NAME / DATE NIH Guidelines

. Apply to rDNA research that is – Funded by NIH – Performed at or sponsored by an institution that receives any NIH funding for rDNA research . Are the NIH Guidelines optional? NO. – Potential consequences for non- compliance: . Suspension, limitation or termination of NIH funds for rDNA research at the institution (and not just for the offending researcher!) . A requirement for prior NIH approval of any or all rDNA projects at the institution

CLIENT NAME / DATE Non-Compliance Consequences UW-Madison fined $40K by NIH in 2010

– “Major Action Violation”

– UW-Madison professor barred from lab for 5 years (by University)

– Research involved a select agent (Brucella) . Graduate students working with antibiotic-resistant strains . One case of Brucella in laboratory staff

– Principal Investigator (PI) claimed inadequate biosafety training and support . He had been an IBC member for many years!

CLIENT NAME / DATE Guidelines – Section II (Safety) Risk Assessment

Risk Group Agents

1 Not associated with disease in healthy adult humans

Associated with human disease which is rarely serious and 2 for which preventive or therapeutic interventions are often available

Associated with serious or lethal human disease for which 3 preventive or therapeutic interventions may be available (high individual risk but low community risk)

Likely to cause serious or lethal human disease for which 4 preventive or therapeutic interventions are not usually available (high individual risk and high community risk) CLIENT NAME / DATE Guidelines – Section III Levels Of Review

Example of Recombinant DNA Relevant Sections of Level of Review Research Involving Animals the NIH Guidelines Experiments that compromise control of IBC, RAC review, & disease agents in medicine through NIH Director review deliberate transfer of a drug resistance III-A & approval trait

IBC approval & NIH Experiments conducted with a review for recombinant DNA modified restricted III-B containment agent in a whole animal determinations

IBC & IRB approval & NIH review before Not applicable III-C research participant enrollment CLIENT NAME / DATE Continued on next slide Guidelines – Section III

Example of Recombinant DNA Relevant Sections of Level of Review Research Involving Animals the NIH Guidelines

Creating stable germline alterations of IBC approval before an animal’s genome, or testing viable III-D initiation rDNA modified microorganisms on whole animals, where BL-2 containment or greater is necessary

Creating stable germline alterations of IBC notice at initiation rodents using recombinant DNA when III-E these experiments require only BL-1 containment Exempt from NIH Guidelines. IBC registration not Purchase or transfer of transgenic required if experiment III-F rodents not covered by Sections III-A, III-B, or III-C CLIENT NAME / DATE Animal Research Sections

. Section III-D-4 Experiments involving whole animals – Requires IBC approval BEFORE initiation – Experiments in which . The animal’s genome has been altered by stable introduction of rDNA into germline, or . rDNA modified microorganisms are tested on whole animals . BSL-2 or greater containment

CLIENT NAME / DATE Animal Research Sections

. Section III-E-3 Experiments involving the generation of transgenic rodents – Requires IBC notice AT initiation – Experiments in which . Rodent’s genome has been altered by stable introduction of rDNA into germline . BL-1 containment is appropriate

CLIENT NAME / DATE Animal Research Sections

. Section III-F (and Appendix C-VI) Exempt Experiments – The purchase or transfer of rodents for experiments that require BL-1 containment – Further manipulation of these animals with recombinant DNA are not necessarily exempt from the NIH Guidelines

CLIENT NAME / DATE Key Portions of the Guidelines

. Appendix B – Actual lists of etiologic agents . Recently added Pseudomonas aeruginosa (RG2) and MERS-CoV (RG3) . Appendix G – Specifies details of containment and confinement for standard laboratory work – Defines BL-1 through BL-4 – Appropriate for animals that are handled in a laboratory setting

CLIENT NAME / DATE Key Portions of the Guidelines

. Appendix Q – Applies to research animals that are not handled in a laboratory setting (cattle, sheep, swine, goats, horses, poultry) – Addresses containment/confinement practices in animal facilities (BL1-N to BL4-N) – Primates could be under Appendix G or Q, depending on study and use – Applies to: . Animals in which genome is altered by stable introduction of rDNA, or . Animals on which rDNA-modified microorganisms are being tested

CLIENT NAME / DATE

Per the NIH Guidelines (Section IV-B) the PI will: . Register all rDNA protocols with the IBC – Petition NIH/OBA for proposed exemptions – Submit info for new host-vector systems to NIH/OBA – Ensure any human gene transfer experiments are handled according to the Guidelines . Report any significant problems/violations, accidents, illnesses to BSO, IBC, NIH/OBA (30 days) . Be proficient in the laboratory procedures involved

CLIENT NAME / DATE PI responsibilities (cont):

. Adhere to IBC approved emergency plans . Comply with shipping requirements for rDNA materials . Make the initial determination of biosafety level and biological containment . Select appropriate microbiological practices . Stay in contact with IBC throughout the life of the project

CLIENT NAME / DATE PI Responsibilities (cont):

. Provide the staff with copies of the protocol . Instruct and train laboratory staff – Emergency procedures and safety practices . Inform staff of advised or required medical provisions – Vaccines, prophylaxis . Ensure continued safe practices in the lab . Ensure integrity of the physical and biological containment measures – BSCs certified, purity and genotypic and phenotypic characteristics CLIENT NAME / DATE When/if OBA visits your facility: . They will interview random PIs – For certain: any area with lab associated infections, significant violations . PIs must : – Know what section of the NIH Guidelines their research falls into (Section III-A through III-F) – Be familiar with their responsibilities (Section IV-B) – Be familiar with BMBL, regarding biosafety level of their work . PIs will be expected to have had training on the NIH Guidelines . Be able to provide laboratory training records, SOPs, emergency procedures CLIENT NAME / DATE OBA Handout

CLIENT NAME / DATE http://osp.od.nih.gov/sites/default/files/resources/InvestigatorEducationalBrochureRecombinant%20DNA_0.pdf Reporting Adverse Events

. Reporting of spills, releases, illnesses, adverse events to NIH, CDC, etc. – Spills/accidents in BSL-2 labs resulting in an overt exposure to rDNA material must be reported immediately to OBA – BSL-3 spills/accidents resulting in overt or potential exposure must be immediately reported to OBA . Therefore, PI must ensure students/employees are trained to report incidents and illnesses associated with working in the lab – PI to contact BSO and/or Research Compliance staff ASAP to begin assessment and reporting process

CLIENT NAME / DATE IBC Charter

. Established under the NIH Guidelines specifically for the review of rDNA research . Often review other biohazardous research – Infectious agents, Select Agents, toxins, etc. – Broader purview is a matter of institutional discretion . However, there is an expectation by government that Select Agent/toxin work will be reviewed by an institutional body . Membership – > 5 members, including > 2 outside members – BSO (Biological Safety Officer) member if research is large scale or BSL-3/4. – Laboratory technical staff person (recommended)

CLIENT NAME / DATE IBC Expertise

. Expertise in – rDNA technology (collectively) – Infectious agents in use on campus – Assessment of risk to environment and public health – Biological safety and physical containment systems – Plant and animal use, if appropriate . Knowledge of – Institutional commitments and policies – Applicable law – Professional standards – Community attitudes

CLIENT NAME / DATE Membership

. Outside members – Representatives of community interests with respect to health and protection of the environment – Individuals who “represent community attitudes” . Officials of health or environmental authorities . Persons with medical, occupational or environmental expertise . Ad hoc consultants – May be used when reviewing research outside the expertise of the IBC membership – Often used for human gene transfer research CLIENT NAME / DATE Growing significance of IBCs

. IBCs are increasingly being assigned additional review tasks: – Select Agents – Research utilizing non-rDNA infectious agents – Xenotransplantation (cross species transplantation) – Stem cell research – Possible role in “Dual Use” research oversight – Engineers and chemists using biological agents as “tools” CLIENT NAME / DATE Interactions in protocol review

. Principal Investigator (PI) initiates risk review via protocol submission

. Biosafety Officer (assists PI)

. Institutional Biosafety Committee (must review and approve PI’s submission)

. Assistance through – published listings, guidelines (U.S. and abroad) – other experts at host institution, local public health – other institutions working with same agents – Government entities (CDC, NIH, USDA,CLIENT FDA, NAME /etc.) DATE

For rDNA research involving animals:

. IACUC Review – Animal welfare . Pain and distress from adverse phenotypes (behavioral, anatomical and physiological abnormalities) . Risks to other animals in the facility from the inadvertent spread of vectors . IBC Review – Risk to human health . Transfer of genetically altered material, viral vectors, etc. . Safety issues for animal staff and researchers re: shedding, bedding, wastes, etc. . Recommendations for PPE for animal handlers – Risk to the environment . Escape and establishment in the wild . Interbreeding with wild stock . Consumption with other animals . Appropriate disposal of wastes

CLIENT NAME / DATE The importance of IBCs/BSOs to PIs

. The IBC and BSO can help: – Ensure that rDNA is being safely handled and discarded – Meet all compliance requirements associated with NIH funding for research involving rDNA – Help avoid withdrawal of funding for the PI and/or the institution – Help avoid preventable accidents and incidents that may cause harm or undermine public confidence in your research . Tularemia incidents at Boston University 2004 . Texas A&M Brucella infections with “Madison” chamber 2007 – Obtain biosafety advice on an ongoing basis

CLIENT NAME / DATE Typical Dual Use Questions to Consider*

Will the proposed research: 1. Enhance the harmful consequences of a biological agent or toxin. 2. Disrupt immunity or effectiveness of an immunization without clinical and/or agricultural justification. 3. Confer to a biological agent or toxin resistance to clinically and/or agriculturally useful prophylactic or therapeutic interventions against agent or toxin. 4. Facilitate their ability to evade detection methodologies. 5. Increase the stability, transmissibility, or the ability to disseminate a biological agent or toxin. 6. Alter the host range or tropism of a biological agent or toxin. 7. Enhance the susceptibility of a host population. 8. Generate a novel pathogenic agent or toxin, or reconstitute an eradicated or extinct biological agent.

*based on the National Research Council report “Biotechnology Research in An Age of Terrorism: CLIENT NAME / DATE Confronting the Dual Use Dilemma.” Questions?

CLIENT NAME / DATE