CLIENT NAME / DATE

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 – the physical containment of

pathogenic organisms or agents to prevent accidental infection of workers or release into the surrounding community .

Class III cabinets at the U.S. Biological Warfare Laboratories, Camp Detrick, Maryland (Photo, 1940s)

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

Pathogen is virulent

Sufficient numbers of organisms

Portal of entry

Susceptible host

CLIENT NAME / DATE

Infectious Dose Agent

• Ebola virus • TB • Tularemia • Anthrax (inhalational) • Cholera • Salmonella typhi • E. coli (enteropathogenic) • Shigella • Norovirus

Dose • 1 • 1 - 10 • 10 • 8,000-50,000 est. • 108

• 105

• 108 – 1010 • 10 – 200

• 18

Salmonella, NIH

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.

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

CDC/James Gathany

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-2 BSL-1

CLIENT NAME / DATE

Provides “Zone Control” of hazards and odors

Air flow from lowest to highest hazard

Directional Airflow

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

A – disinfectant containing flask B – overflow flask C – in-line HEPA filter D – vacuum system

Flasks should be plastic, plastic-coated glass or covered with netting

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 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

Fill line

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

front grille • Do not place items on the

front grille or block rear vent

• Wipe all materials going in and out of BSC with disinfectant (depending)

• Place discard containers inside BSC

• Load only those materials needed inside cabinet – Avoid withdrawing hands for

discard or supplies • Wait 5 minutes after loading

BSC before working • Avoid rapid sweeping arm

movements • Clean trough under work

surface regularly • No open flames inside

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

for a splash or spray – Filtering under pressure – Opening blood tubes – Running a peristaltic pump

• Wear additional mucous membrane protection – Face shield – Mask and goggles – Visor/mask combo – Plexiglas shield – Work inside biological

safety cabinet (BSC)

Disposable face shield

Fluid resistant mask/visor

Molded face mask

CLIENT NAME / 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 http://wwwnc.cdc.gov/eid/article/12/1/05-1126_article.htm

CLIENT NAME / DATE

Laundry Requirements Laundry must be collected near where it is

removed Spill on a lab coat?

– Remove – Spray with disinfectant – Rinse with water – Place in laundry bag or discard if disposable

The bin will be labeled “Soiled Laundry, Use Universal Precautions”

Lab coats must not be taken home for laundering

Soiled Laundry Use Universal Precautions

Biohazard

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

Solids

Bulk Liquids

10% bleach in waste for 30 minutes

Sewer

Sharps

Sharps container

Biohazard waste bin (with cover)

Syringes, broken glass, Pasteur

pipets, needles, etc.

Vials, centrifuge

tubes, gloves, etc.

Pipets Pipet tips

Plastic bottle or “Benchtop Keeper”

Pipet keeper or sharps container

Stericycle Box

Pipets/tubes/tips in BSC

Disinfectant filled beaker or pan

Pour off disinfectant (colander)

Regular trash (plastics) Glass Bin (glass)

+

CLIENT NAME / DATE

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

UNCCEquipmentDecontamination Verification

Serial No.:_______________ Date__________Asset No.:_________________Prior to service of this equipment that may becontaminated with potentiallybiohazardous materials, it MUST BE DECONTAMINATED by the user. Thisdocumentation procedure will include thefollowing as appropriate:

1. Removal of all contaminated materials from the unit.

YES___

NO___

NA__

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.

___ ___ __

Name (Print):____________________________________Signature:_______________________________________Phone No.:__________________By signing the decontamination verification card, theowner assumes the responsibility of completing thedecontamination procedure as indicated on the frontof this card.

List any areas that could not be decontaminated:_____

____________________________________________

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

• Label vials, tubes, etc. – Biohazard label

• Or, label box or carrier • Transfer internally in a zip lock

bag with absorbent inside or in a labeled cooler with absorbent inside – Decon outside – no gloves

• Need to ship? – Only trained employees

allowed to package materials for shipping

• Renewed every 2 years – Know status of material to be

shipped • Most UNCC materials will

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”

Labeling and Shipping

CLIENT NAME / DATE

SPILLS AND EMERGENCY PROCEDURES

CLIENT NAME / DATE

Spills Clean up and report spills

per Spill Operating Procedure

Employees must be able/equipped to handle spills of biological material

Absorb liquid, preclean with detergent (to remove organic materials), then wipe with an approved disinfectant

Use disinfectant appropriate for agent

Use full strength disinfectant on large spills (dilution effect)

NEVER pick up broken sharps with fingers

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 – Blood, serum – Human cell lines – Sputum

• Viruses – VSV – HRSV – HPIV3 – Adenovirus – Rhinovirus

• Bacteria – Vibrio spp. – Pseudomonas aeruginosa – Staphylococcus aureus – Klebsiella pneumoniae

• Teaching lab – Salmonella typhimurium – Shigella flexneri – Streptococcus pyogenes – 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

– Include HBIG and vaccine

• HCV – No post-exposure

prophylaxis currently recommended

– Post-exposure testing

• Analyze risk of source • HIV recommendations

– Use of ZDV, Lamivudine, protease inhibitors

– Can lower seroconversion rate by 79%

http://www.nccc.ucsf.edu/hiv_clinical_resources/pepline_guidances_for_occupational_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

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

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

4 Likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available (high individual risk and high community risk)

CLIENT NAME / DATE

Guidelines – Section III Levels Of Review

Level of Review Example of Recombinant DNA Research Involving Animals

Relevant Sections of the NIH Guidelines

IBC, RAC review, & NIH Director review & approval

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

III-A

IBC approval & NIH review for containment determinations

Experiments conducted with a recombinant DNA modified restricted agent in a whole animal

III-B

IBC & IRB approval & NIH review before research participant enrollment

Not applicable III-C

Continued on next slide

CLIENT NAME / DATE

Guidelines – Section III

Level of Review Example of Recombinant DNA Research Involving Animals

Relevant Sections of the NIH Guidelines

IBC approval before initiation

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

III-D

IBC notice at initiation

Creating stable germline alterations of rodents using recombinant DNA when these experiments require only BL-1 containment

III-E

Exempt from NIH Guidelines. IBC registration not required if experiment not covered by Sections III-A, III-B, or III-C

Purchase or transfer of transgenic rodents III-F

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

http://osp.od.nih.gov/sites/default/files/resources/InvestigatorEducationalBrochureRecombinant%20DNA_0.pdf

CLIENT NAME / DATE

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, FDA, etc.)

CLIENT NAME / 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: Confronting the Dual Use Dilemma.”

CLIENT NAME / DATE

Questions?