Transcript IBC training for PIs..

Research & Teaching
• Various sections of the NIH Guidelines including:
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NIH Overview
Calvin’s Institutional Biosafety Committee (IBC)
Recombinant DNA (rDNA) & Synthetic Nucleic Acid Molecule guidelines
Animal guidelines
Plant guidelines
Roles & Responsibilities
Resources
• For the purposes of this training, Principal Investigator (PI)
includes any faculty or researchers conducting research or
teaching coursework at the college
• Details procedures and practices for the containment and safe
conduct of various forms of rDNA & SNA research.
• First drafted in 1976 as an outcome of a meeting of scientists
concerned about addressing the potential public health and
environmental risks associated with rDNA.
• Frequently amended to reflect evolving scientific understanding
of rDNA and its applications.
• A core responsibility of OBA is to promote awareness of, and
adherence to, the standards and practices set forth in the NIH
Guidelines.
• Provide guidance to IBCs in the oversight of r/sNA research
• Disseminate information on technical and policy matters
concerning r/sNA research
• Develop and contribute to public policy on r/sNA research
• According to the NIH Guidelines
• “The institution is responsible for ensuring that the Principal Investigator (PI)
has sufficient training” regarding laboratory safety and implementation
of the NIH Guidelines.
• “The PI is responsible for ensuring that laboratory staff are appropriately
trained.”
• We have developed this online training course to fulfill the
training requirements for PIs; this will be tracked by the
Biosafety Officer (BSO, Lori Keen) in the IBC database.
• PIs will be responsible for training their staff and will have
access to a downloadable ppt.
• Upon completion of this course, participants will have a better
understanding of:
• The IBC review and approval processes that apply to various forms of
research and teaching
• The biosafety levels of the NIH Guidelines
• The various types of research & teaching covered by the NIH Guidelines
• The roles and responsibilities of investigators under the NIH Guidelines
Institutional Biosafety Committee
Training
• IBCs were established under the NIH Guidelines to provide local
review and oversight of research using r/sNA.
• They ensure that r/sNA research conducted at or sponsored by
the institution is in compliance with the NIH Guidelines.
• Many institutions, including Calvin, have chosen to assign their
IBCs the responsibility of reviewing other research & teaching
involving other biohazardous risks (e.g. infectious agents and
human samples).
• Made up of faculty, staff and community members
• Members include representatives from:
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Biology and/or Biochemistry- Dave Benson, Curt Blankespoor, John Ubels
Biology Lab Manager - Lori Keen
Environmental Health & Safety – Heather Chapman
2 community members – David LaGrand, Bob Leunk
• IBC Coordinator, Lori Keen
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Liaison between the investigators & the IBC
Assists faculty with the protocol review process
Notifies investigators of IBC review outcome
Ensures committee operations comply with federal and state regulations
PIs must notify the IBC prior to commencing your research or
teaching, if you plan to use:
• Recombinant DNA or Synthetic Nucleic Acid molecules
• Infectious agents (BSL2)
• Human body fluids or tissues
• If your research or teaching is non-exempt, you must complete
the Biosafety Application
• If your research or teaching is exempt, you must complete the
IBC First Assessment Form (keep in mind that you may have
already completed this)
• See next slide for definitions of exempt vs non-exempt
• Both forms are to be submitted to the IBC Coordinator, Lori
Keen who will ensure the appropriate review process
Per Section III-F of the NIH Guidelines, experiments are exempt when they involve
recombinant DNA or SNA that:
• Is not in organisms or viruses;
• Uses a host vector system such as: E. coli K 12, Saccharomyces cerevisiae, Saccharomyces
uvarum or Bacillus subtilis; and their plasmids;
• Uses rDNA molecules containing less than one-half of any eukaryotic genome that are
propagated and maintained in cells in tissue culture;
• Consist entirely of DNA segments from a single nonchromosomal or viral DNA source;
though one or more of the segments may be a synthetic equivalent;
• Consist entirely of DNA from a prokaryotic host including its indigenous plasmids or viruses
when propagated only in that host (or a closely related strain of the same species); or
when transferred to another host by well-established physiological means;
• Consist entirely of DNA from a eukaryotic host including its chloroplasts, mitochondria, or
plasmids (but excluding viruses) when propagated only in that host (or a closely related
strain of the same species).
• Details on certain other experiments that may be exempt, as well as exceptions, can be
found in Appendix C of the NIH Guidelines
(http://oba.od.nih.gov/oba/rac/Guidelines/APPENDIX_C.htm)
Per Section III of the NIH Guidelines , research or teaching that meet any of the criteria below must
submit a proposal to the IBC and receive IBC approval:
• Experiments involving the introduction of rDNA or SNA into risk group 2 organisms (includes adenovirus &
murine retroviral vectors) or higher
• Experiments in which DNA from human or animal pathogens (risk group 2 or higher) is introduced into a
non-pathogenic host vector system
• Experiments involving the use of infectious DNA or RNA viruses or defective DNA or RNA viruses (risk
group 2 or higher) in the presence of helper virus in tissue culture systems
• Experiments involving formation of rDNA molecules containing no more than 2/3 of the genome of only
eukaryotic virus (with some restrictions). It must be demonstrated that cells lack helper virus
• The deliberate transfer of a drug resistance trait to microorganisms that are not known to acquire the trait
naturally, if such acquisition could compromise the use of the drug to control disease agents in humans,
veterinary medicine or agriculture.
• Cloning of toxic molecules with LD50 of less than 100 nanograms/kg body weight
• Experiments involving cultures of more than 10 liters
• Whole animals in which the animal’s genome has been altered by the stable introduction of rDNA, or RNA
derived therefrom, into the germline (transgenic animals)
• Experiments involving whole plants
• Gene transfer experiments in humans
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For more information, you may view Section III at: http://oba.od.nih.gov/oba/rac/Guidelines/NIH_Guidelines.htm
• The Biosafety Officer can review and approve research or
teaching involving:
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BSL1 agents, <10 L
Human blood and/or tissue (requires consult with the BSO)
Already approved infectious agents
Environmental swabbing for culturing
• If any of the following criteria are met, the research or teaching
must be reviewed by the full IBC at a convened meeting:
• BSL 2 or higher agents
• > 10 L of an agent
• Recombinant DNA that is NOT exempt
• Four possible outcomes:
• Approved as is
• Approved with conditions
• Minor corrections required
• Tabled
• More information required
• Denied
• Major corrections and/or information needed. PI generally instructed
to consult BSO and re-submit application.
• Due to the low volume of Non-exempt work at the College, the
IBC meets as necessary, but at least annually to review
protocols and annual reports.
• If you submit an application, the IBC will convene within 2 weeks to review
your application
• Applications that do not require full committee review may be
submitted to the IBC Coordinator or the IBC Chairperson at any
time.
• PIs must submit annual reports for projects falling within the NIH
Guidelines
• The PI will receive a reminder email at least 30 days prior to
the report deadline
• Approved non-exempt long-term projects must be renewed
every 3 years
• The BSO can review and approve:
• Closures
• Renewals without change
• Renewals with minor change
• Such as personnel changes or changing project titles
• The IBC reviews and approves:
• Renewals with major changes
• Such as an adding an agent to a project, going from in vitro to in vivo
• 3-year renewals
• Section I –Scope of the Guidelines
• Section II –Safety Considerations for r/sNA research
• Section III –Types of Experiments Covered by the NIH
Guidelines and the levels of review these experiments require
• Section IV –Roles and Responsibilities of individuals and entities
involved in the conduct and oversight of r/sNA research
• Appendices –large number of appendices covering particular
topics in greater detail
• To specify the practices for constructing and handling:
• (i) recombinant nucleic acid molecules,
• (ii) synthetic nucleic acid molecules, including those that are chemically or
otherwise modified but can base pair with naturally occurring nucleic acid
molecules, and
• (iii) cells, organisms, and viruses containing such molecules
• In the context of the NIH Guidelines, recombinant and synthetic
nucleic acids are defined as:
• (i) molecules that a) are constructed by joining nucleic acid molecules and
b) that can replicate in a living cell, i.e., recombinant nucleic acids;
• (ii) nucleic acid molecules that are chemically or by other means
synthesized or amplified, including those that are chemically or otherwise
modified but can base pair with naturally occurring nucleic acid molecules,
i.e., synthetic nucleic acids, or
• (iii) molecules that result from the replication of those described in (i) or (ii)
above.
• All institutions that receive NIH funding for r/sD research must
comply with the NIH Guidelines.
• All research & teaching at an institution that are subject to the
NIH Guidelines must comply with the requirements even if their
individual projects are not funded by NIH.
• Compliance with the NIH Guidelinesis mandatory as a condition
of receiving NIH funding.
• “Guidelines” does not mean “optional”
 Safety Considerations
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Risk assessments: (Appendix B) - Appendix B lists human etiologic
agents and zoonotic agents based on RG
RG 1
Agents that are
not associated
with disease in
healthy adult
humans
RG 2
Agents that are
associated with
human disease
which is rarely
serious and for
which preventive
or therapeutic
interventions are
often available
RG 3
Agents that are
associated with
serious or lethal
human disease
for which
preventive or
therapeutic
interventions
may be available
(high individual
risk but low
community risk)
RG 4
Agents that are
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)
• Physical Containment
• Defined by 4 Biosafety Levels
• BSL1, the least stringent; BSL4, the most stringent
• These biosafety levels consist of a combination of
• Lab practices and techniques,
• Safety equipment, and
• Lab facilities appropriate for the operations being performed
• Consistent with the CDC Biosafety in Microbiological and
Biomedical Laboratories
• Described in detail in Appendix G
BSL
Agents
Practices
Barriers & Safety
Equipment
Facilities
1
Not known to cause disease in
healthy adults
Standard microbiological practices
None required
Lab bench and sink
required
2
• Associated with human
disease
• Routes of transmission
include percutaneous injury,
ingestion, mucous
membrane exposure
BSL-1 practice plus:
• Limited access
• Biohazard warning signs
• Sharps precautions
• Biosafety manual defining any
needed waste decontamination
or medical surveillance policies
Primary barriers:
• Class I or II BSCs or other
physical containment devices
used for manipulations of
agents that cause splashes or
aerosols of infectious materials
• PPE:
• Lab coat, gloves,
respirator as needed
BSL-1 plus:
• Autoclave available
3
• Indigenous or exotic agents
with potential for aerosol
transmission
• Disease may have serious
or lethal consequences
BSL-2 practices plus:
• Controlled access
• Decontamination of all waste
• Decontamination of lab clothing
before laundering
• Baseline serum
Primary barriers:
• Class I or II BSCs or other
physical containment devices
used for manipulations of
agents that cause splashes or
aerosols of infectious materials
• PPE:
• Lab coat, gloves,
respirator as needed
BSl-2 plus:
• Physical separation
from access corridors
• Self-closing, doubledoor access
• Exhaust air not
recirculated
• Negative air flow into
lab
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• Dangerous/exotic agents
which pose high risk of life
threatening disease
• Aerosol-transmitted lab
infections have occurred; or
related agents with
unknown risk of transmission
BSL -3 practices plus:
• Clothing change before
entering
• Shower on exit
• All material decontaminated on
exit from facility
Primary barriers:
• All procedures conducted in
class III BSCs or Class I or II
BSCs in combination with fullbody, air-supplied positive
pressure personnel suit
BSL-3 plus:
• Separate building or
isolated zone
• Dedicated supply and
exhaust vacuum, and
decon systems
• Other requirements
may apply
• Select Agents are pathogens or toxins considered to have
potential as bioweapons. They are regulated by CDC and/or
USDA and require approval from those organizations to
possess, use, receive or ship them.
• A list of Select Agents, and information on the Select Agent
Program is available at http://www.selectagents.gov/
• Biological Containment
• Refers to the application of highly specific biological barriers (appendix I)
• Limit infectivity of a vector for specific hosts
• Limits dissemination and survival in the environment
• Example – genetically designed to be replication defective outside of
host
• Risk Group (RG) is a stable comparative descriptor of the
inherent pathogenic nature of a given microorganism. RG
designation is based on how a particular organism is associated
with disease in a “healthy” adult and whether prevention or
intervention exists for that organism. RG does not change based
on how or where the agent is used.
• Biosafety Level (BSL) is a variable comparative descriptor of
the facility, equipment, practices that serve to “contain” a
microorganism, and to ensure the safe use of that organism,
while it is being handled. BSL is based on risk assessment and
technical judgment and may vary with the use of the agent.
• Six categories of experiments involving r/sNA based on the
level of review required (III-A, III-B, III-C, III-D, III-E, III-F)
• Experiments which pose great risk to human health require the
highest level of review (category III-A), such as the deliberate
transfer of antibiotic resistance into a pathogen, that would then
compromise the use of that drug to treat the disease.
• Experiments that are not considered to pose a risk to human
health or the environment are exempt from the
Guidelines(category III-F) and do not require review (e.g., the
purchase of transgenic animals that can be housed at BSL1).
Level of Review
Example of r/sNA Research
Relevant section(s) of the
NIH Guidelines
IBC, RAC review, & NIH Director
review and approval – Major Action
Experiments that compromise the 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 rDNA modified
restricted agent in a whole animal
III-B
IBC & IRB approval and NIH review
before research participant
enrollment
Experiments involving the deliberate transfer of
rDNA into a human research participant
III-C
IBC approval before initiation
Creating stable germline alterations of an animal’s
genome, or testing viable rDNA modified
microorganisms on whole animals; experiments in
which whole plants are genetically engineered or
used with rDNA modified insects; generally require
BSL-2 containment or greater
III-D
IBC notice at initiation
Creating stable germline alterations of rodents using
rDNA; experiments involving rDNA modified whole
plants that are not noxious weeds; require only BSL 1
containment
III-E
Exempt from the NIH Guidelines
Purchase or transfer of transgenic rodents
III-F
Life sciences research that yields information or technologies with the potential
to be misused to threaten public health or national security.
• The National Science Advisory Board for Biosecurity (NSABB) has identified
seven categories of experiments that have the potential to fall under Dual
Use Research of Concern:
• Enhance the harmful consequences of a biological agent or toxin.
• Disrupt immunity or the effectiveness of an immunization without clinical and/or
agricultural justification.
• Confer resistance to prophylactic or therapeutic interventions, or facilitate the ability of
an agent or toxin to evade detection methodologies.
• Increase the stability, transmissibility, or the ability to disseminate a biological agent or
toxin.
• Alter the host range or tropism of a biological agent or toxin.
• Enhance the susceptibility of a host population.
• Generate a novel pathogenic agent or toxin or reconstitute an eradicated or extinct
biological agent.
• IBC and Institutional Animal Care & Use Committee (IACUC)
Approval Before Initiation
• Includes Experiments in which:
• the animal’s genome has been altered by stable introduction of r/sNA into
germline (i.e., transgenic animals)
• applies to both the generation and use of transgenic animals (including
arthropods)
• r/sNA modified microorganisms are tested on whole animals
• BSL2 or BSL2-N or greater containment
• IBC and IACUC Approval Before Initiation at Calvin
• Includes Experiments in which:
• Rodent’s genome has been altered by stable introduction of recombinant
or synthetic nucleic acid into germline
• applies only to the generation of transgenic rodents
• BSL1 containment is appropriate
• The purchase or transfer of transgenic rodents that require BSL1 containment
• Further manipulations of these animals with r/sNA are not
necessarily exempt from the NIH Guidelines
• Joint purview and collaborative review over certain types of
research
• Transgenic or cloned animals
• Use of recombinant or synthetic nucleic acid molecules in animals
• Pre-clinical studies and data assessment for human gene transfer protocols
• At Calvin, the EHS Officer is a member of both committees
IACUC Review
IBC Review
Animal Welfare
Risks to Human Health
o Pain & distress from adverse
o Transfer of genetically altered
phenotypes (behavioral,
material, viral vectors, etc
anatomical & physiological
abnormalities)
Risks to the Environment
o Risks to other animals in the facility
o Escape & establishment in the wild
from the inadvertent spread of
o Interbreeding with wild stock
vectors
o Consumption by other animals
• Containment procedures (SOPs)
• Physical and biological
• Plans for recapture of escapees
• Consequences should containment fail
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Procedures for transfer and transportation of animals
Disposal and destruction methods
Breeding SOPs
Occupational biosafety concerns
• Personal protective equipment
• Decontamination
• Applies when research animals are of a size or have growth
requirements that preclude laboratory containment
• For example, cattle, swine, sheep, goats, horses, poultry, etc.
• Addresses containment and confinement practices in animal
facilities (BL1-N to BL4-N)
• Applies to animals:
• In which genome is altered by stable introduction of rDNA or SNA; or
• On which rDNA or SNA-modified microorganisms are being tested
• IBC Approval Before Initiation
• Includes Experiments in which:
• Plants are genetically engineered by r/sNA or synthetic biology methods,
or
• Plants are used with r/sNA modified insects
• Generally BL1-P through BL4-P, depending on risk
• IBC Approval Before Initiation
• Includes Experiments:
• Involving r/sNA-modified whole plants
• That are not noxious weeds and will not hybridize with noxious weeds,
and
• For which BL1-P containment is appropriate
• Defines physical containment levels for r/sNA research involving
plants
• Describes the four plant Biosafety Levels BL1-P through BL4-P and
provides details on the standard practices and any special procedures
that should be followed
• Describes biological containment practices for r/sNA-containing
plants, plant-associated microorganisms, and plant-associated
small animals.
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Institution
Institutional Biosafety Committee (IBC)
Biological Safety Officer (BSO)
Principal Investigator (PI)
NIH
• Establish and implement policies for the safe conduct of
recombinant or synthetic nucleic acid research
• Establish an IBC
• Ensure compliance with the NIH Guidelines by investigators
• Ensure appropriate training for IBC members and staff, PIs, and
laboratory staff
• Determine necessity for health surveillance of personnel
• Report any significant incidents or violations to the NIH
Guidelines to OBA within 30 days
• Assessment of r/sNA research
• Conformity with the NIH Guidelines
• Potential risk to environment and public health
• Containment levels per NIH Guidelines
• Adequacy of facilities, SOPs, PI and lab personnel training
• Institutional and investigator compliance; e.g., adverse event reports
• Periodically review r/sNA use for compliance
• This may include periodic unannounced inspections
• Adopt emergency plans covering spills, contamination, other accidents
• The IBC may not authorize initiation of r/sNA experiments not
explicitly covered by the NIH Guidelines until NIH establishes the
containment requirement
• Membership requirements
• At least 5 individuals
• Appropriate r/sNA expertise
• Plant and animal experts if needed, biosafety officer as appropriate
• At least two members not affiliated with the institution
• represent the interest of the surrounding community with respect to
health and protection of the environment
• Laboratory technical staff (recommended)
• Expertise in assessment of risk to environment and public health
• Knowledge biological safety and physical containment
• The Biosafety Officer’s (BSO) duties include:
• Reporting to the IBC and institution of any problems, violations, researchrelated accidents or illnesses
• Advice on lab security
• Technical advice to PIs and IBCs on research safety procedures
• The BSO shares certain responsibilities including:
• Periodic inspection of labs
• Developing emergency plans for handling accidental spills and personnel
contamination
• Full compliance with the NIH Guidelines
• PIs must:
• Be familiar with institutional policies which may go above and beyond the
NIH Guidelines
• Not initiate or modify r/sNA research prior to IBC approval
• Be adequately trained in good microbiological techniques
• Inform and train laboratory staff
• Risk assessment
• Containment Practices
• Procedures for dealing with accidents
• Occupational health
• Supervise r/sNA research
• Adhere to all approval conditions imposed by the IBC
• Correct work errors and conditions that may result in the release of rDNA
materials
• Ensure the integrity of containment
• Comply with permit and shipping requirements
• Adhere to IBC-approved emergency plans
• Report any significant problems, violations of the NIH
Guidelines, or any significant research-related accidents and
illnesses to the BSO
• Know the Calvin IBC Policy on reporting incidents involving r/sNA to the
NIH OBA
• Recombinant and Synthetic nucleic acid experiments requiring
review by NIH OBA
• Deliberate transfer of drug resistance to microorganisms, if it could
compromise disease control
• Cloning of toxin molecules with LD50 <100 ng/Kg bodyweight
• DNA from restricted agents transferred to nonpathogenic prokaryotes or
lower eukaryotes
• The term restricted agent in the NIH Guidelines is used specifically to refer to
the pox viruses, small pox and white pox, and should not be confused with
“select agents”
• DNA from nonpathogenic prokaryotes or lower eukaryotes
transferred to restricted agents
• Use of infectious or defective restricted poxviruses in presence
of helper virus
• There are 15 appendices. Those highlighted are the ones you
are most likely to consult.
• Appendix A –Exemptions: Natural Exchangers
• Appendix B –Classification of Etiologic Agents
• Appendix C –Exemptions under III-F
• Appendix D –Major Actions
• Appendix E –Certified Host-Vector Systems
• Appendix F –Biosynthesis of Toxic Molecules
• Appendix G –Physical Containment
• Appendix H –Shipment
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Appendix I –Biological Containment
Appendix J –Biotechnology Research Subcommittee
Appendix K –Large Scale Physical Containment
Appendix L –Gene Therapy Policy Conferences
Appendix M –Points to Consider in Human Gene Transfer
Research
• Appendix P –Physical and Biological Containment: Plants
• Appendix Q –Physical and Biological Containment: Animals
“The NIH Guidelines will never be complete or final since all
conceivable experiments involving recombinant DNA cannot
be foreseen. Therefore, it is the responsibility of the institution
and those associated with it to adhere to the intent of the NIH
Guidelines as well as to the specifics.”
• Ensure that you are working with infectious agents, human
samples, and rDNA/SNA safely
• Meet all compliance requirements for use of rDNA & SNA
• Meet all compliance requirements
• Avoid preventable accidents and incidents that might cause
harm or undermine public confidence in your research/teaching
activities
• With lab safety issues
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Personal protective equipment for personnel
Disposal of waste
Decontamination of laboratory and equipment
Containment facilities
Accidents (emergency plans and response)
• NIH Guidelines for Research Involving Recombinant DNA Molecules
(http://oba.od.nih.gov/rdna/nih_guidelines_oba.html)
• Biosafety in Microbiological and Biomedical Laboratories(BMBL) 5th
Edition (http://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm)
• National Select Agent Registry (http://www.selectagents.gov/) Select
Agent and Toxins list
(http://www.selectagents.gov/Select%20Agents%20and%20Toxins%
20List.html)
• American Biological Safety Association (ABSA) Resources
(http://absa.org/resmenu.html)
• Contact
• IBC Coordinator & BSO, Lori Keen
• 526.6080
• [email protected]
• IBC Chairperson, John Ubels
• 526.6219
• [email protected]
• Environmental Health & Safety Officer, Heather Chapman
• 526.8591
• [email protected]
I acknowledge that I have read and understand the IBC training
module.
I didn’t quite get it and would like the BSO to contact me to
discuss further
• Please select a box above and then print and send to the BSO.
NAME: ___________________________________________
DATE: ____________________________________________