institutional biosafety committee member training
DESCRIPTION
October 2014. Institutional Biosafety Committee Member Training. Background. Recombinant DNA work covered under NIH Office of Biotechnology Activities (NIH OBA) in: NIH GUIDELINES FOR RESEARCH INVOLVING RECOMBINANT OR SYNTHETIC NUCLEIC ACID MOLECULES (March 2013) Purpose of Guidelines: - PowerPoint PPT PresentationTRANSCRIPT
Institutional Biosafety Committee Member TrainingOctober 2014
Background
Recombinant DNA work covered under NIH Office of Biotechnology Activities (NIH OBA) in:
• NIH GUIDELINES FOR RESEARCH INVOLVING • RECOMBINANT OR SYNTHETIC NUCLEIC ACID
MOLECULES (March 2013)
Purpose of Guidelines: • 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,
• (iii) cells, organisms, and viruses containing such molecules.
IBC
Institutional Biosafety Committee (IBC)• Reviews all research that involves the use of rDNA
NIH/OBA rDNA Guidelines as reference document• Reviews research involving the use of infectious
agents NOT rDNA• Inclusive of subcommittees-needlestick and
healthcare• BMBL as a reference document
Biosafety Levels
Biosafety levels are a combination of facilities, equipment and practices.
Level 1: basic lab, good lab practicesLevel 2: limited lab access, specific training and practicesLevel 3: containment (biosafety cabinet), specific training and practicesLevel 4: full containment; specific facility, training and practices
Risk Assessment Factors
•Pathogenicity
•Route of Transmission
•Agent Stability
•Infectious Dose
•Concentration
•Availability of effective prophylaxis,
treatment
•Availability of medical surveillance
•Host susceptibility
Risk Assessment
Organism
Hosts
Vector
Expression of foreign gene
Protein produced
Containment
Facility
Laboratory-specific protocol
Training & expertise of personnel
History of the Guidelines
The NIH Guidelines were
implemented in response to
public and scientific concern
over the emerging science of
rDNA technologies in the early
1970’s. By 1976, NIH had
published the first set of
guidelines which have been
amended over time to allow for
greater public access and a
greater emphasis on safety.
Section I: Scope and Applicability
If your institution receives NIH funding for
rDNA research, then it must comply with the
NIH Guidelines.
Even if a project is privately sponsored, that
research must still be conducted in
accordance with the NIH Guidelines if
conducted at an institution subject to the NIH
Guidelines.
Section II: Safety Considerations Risk
AssessmentRisk Group 1 (RG1) agents are not associated with disease in healthy adult humans.
Risk Group 2 (RG2) agents are associated with human disease which is rarely serious and for which preventive or therapeutic interventions are often available.
Risk Group 3 (RG3) agents are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available.
Risk Group 4 (RG4) agents are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available .
Section II: Safety Considerations
ContainmentContainment should be a combination of standard microbiology practices, engineering controls, laboratory facilities and design.
Containment is defined in:• Appendices G, P, & Q of the NIH Guidelines• Laboratory Safety Monograph (historical
document)• Biosafety in Microbiological and Biomedical
Laboratories (BMBL)
Section III: Experiments covered by the NIH GuidelinesIII-A: transfer of drug resistance
III-B: cloning of lethal toxins
III-C: human gene transfer research
III-D: infectious agents as vectors &
transgenic animals
III-E: generation of transgenic rodents
III-F: exemptions
Experiments Covered by the NIHLevel of Review Section Research Example
IBC, RAC review and NIH Director review and approval III-A Cipro resistant Bacillus anthracis
IBC approval and NIH review for containment determination III-B Cloning botulinum toxin expression into adenovirus
IBC and IRB approval and NIH review before research particpant enrollment III-C Human gene transfer
IBC approval before initiation III-DExpression of a nonnative protein in Staphylococcus aureus
IBC notification at initiation III-EGermline alteration of rodents which may be housed in BL-1
Exempt III-F Purchased transgenic rodents
III-A: Major Actions
Requires: IBC Approval, RAC Review, NIH Director Approval Before Initiation of Work
Transfer of therapeutically useful drug resistance to organisms which may compromise human health/agriculture/medicine
III-B: Toxin Transfer
Requires: NIH/OBA, IBC Review and Approval Before Initiation of Work
Deliberate cloning of toxin molecules lethal to vertebrates at an LD50 of less than 100 nanograms/Kg of body weight (e.g., botulinum toxin)
Containment determined by NIH/OBA
III-C: (Deliberate Transfer of rDNA into Research Participants, ex. Gene Therapy)
Requires: RAC Review, IBC and IRB Approval Before Participant Enrollment
Human gene transfer (HGT) protocols• All HGT trials except those covered under
vaccine exemption require RAC registration. • 20-30% will be publicly reviewed and may
require public review prior to participant enrollment.
III-D: General WorkRequires: IBC Review and Approval Prior to the Initiation of Work
•Involves RG 2-4 agents, host/vector system
•Cloned DNA from RG 2-4 agents into non-
pathogenic prokaryotes
•RG 2-4 agents into whole animals, usually
transgenic
•Recombinant plants
•Large scale experiments greater than 10L
•Generation of any transgenic animal other than
BSL-1 rodents
III-E: Less Restrictive WorkRequires: IBC Notification at the Initiation of Work (BSL-1 Containment), and Subsequent IBC Review and Approval
•rDNA molecules that contains less than 2/3 of any
eukaryotic viral genome
•Transgenic rodents with BSL-1 containment
• (crossbreeding of transgenics now exempt at
BSL-1)
•Whole plants that require minimal containment
•Anything else NOT covered under sections III-A
through III-D & III-F
III-F: Exemptions
Exempt from the NIH Guidelines and Does Not Require IBC Review or Approval
rDNA molecules that are:
•Not in organisms or viruses
•Not a risk to health or the environment
-See Appendix C
•Note: exceptions to exemptions!
FAQReview process for human gene transfer protocols
http://
osp.od.nih.gov/office-biotechnology-activities/biom
edical-technology-assessment/hgt
Vaccine exemptions
http://
osp.od.nih.gov/faq/faqs-about-vaccine-exemption-ni
h-guidelines-research-involving-recombinant-dna-m
olecules
Major actions under the guidelines
http://
osp.od.nih.gov/sites/default/files/resources/Major_A
ction_FAQs_March_2013.pdf
Transgenic animalshttp://osp.od.nih.gov/sites/default/files/Animals_NA_0.pdf
FAQ
IBC committee minuteshttp://osp.od.nih.gov/sites/default/files/resources/IBC_Meetings_and_Minutes_FAQs.pdf
Experiments that are exempthttp://osp.od.nih.gov/sites/default/files/Experiments_that_are_Exempt_from_the_NIH_Guidelines.pdf
Section IV: Roles and ResponsibilitiesResponsibilities of the Institution:
• Ensure compliance with NIH Guidelines
• Establish IBC
• Appoint a Biosafety Officer if conducting BSL-3,
BSL-4, or large-scale work
• Ensure IBC has expertise in the research that is
reviewed
• Establish a medical surveillance program as
needed
• Report all incidents to the NIH OBA
Section IV: Roles and Responsibilities
Responsibilities of the IBC:• Review rDNA research, and approve those research projects that are found to
conform with the NIH Guidelines. This review shall include: -(i) independent assessment of the containment levels required by the NIH Guidelines for the proposed research; (ii) assessment of the facilities, procedures, practices, and training and expertise of personnel involved in rDNA research; (iii) ensuring that all aspects of Appendix M have been appropriately addressed by the PI; (vii) ensuring compliance with all surveillance, data reporting, and adverse event reporting requirements set forth in the NIH Guidelines.
• Notify the PI of the results of the IBC’s review and approval.• Lower containment levels for certain experiments as specified in Section III-D-
2-a, Experiments in which DNA from Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents is Cloned into Nonpathogenic Prokaryotic or Lower Eukaryotic Host-Vector Systems.
• Set containment levels as specified in Sections III-D-4-b, Experiments Involving Whole Animals.
Section IV: Roles and ResponsibilitiesResponsibilities of the IBC:
• Periodically review rDNA research conducted at the institution to ensure compliance with the NIH Guidelines.
• Adopt emergency plans covering accidental spills and personnel contamination resulting from rDNA research.
• Report any significant problems with or violations of the NIH Guidelines and any significant research-related accidents or illnesses to the appropriate institutional official and NIH/OBA within 30 days.
• The IBC may not authorize initiation of experiments which are not explicitly covered by the NIH Guidelines until NIH establishes the containment requirement.
• Perform such other functions as may be delegated to the IBC.
Section IV: Roles and ResponsibilitiesResponsibilities of the Biological Safety Officer (BSO)
• Periodic inspections to ensure that laboratory standards are rigorously followed;
• Report to the IBC and the institution any significant problems, violations of the NIH Guidelines, and any significant research-related accidents or illnesses of which the BSO becomes aware;
• Develop emergency plans for handling accidental spills and personnel contamination and investigating laboratory accidents involving rDNA research;
• Provide advice on laboratory security; • Provide technical advice to PIs and the IBC on
research safety procedures.
Section IV: Roles and Responsibilities
Responsibilities of the Principal Investigator (PI)• Initiate or modify no recombinant DNA research which requires IBC approval
prior to initiation until that research or the proposed modification thereof has been approved by the IBC and has met all other requirements of the NIH Guidelines;
• Determine whether experiments are covered by Section III-E, and ensure that the appropriate procedures are followed;
• Report any significant problems, violations of the NIH Guidelines, or any significant research-related accidents and illnesses to the BSO, Animal Facility Director (where applicable), IBC, NIH/OBA, and other appropriate authorities (if applicable) within 30 days;
• Report any new information bearing on the NIH Guidelines to the Institutional Biosafety Committee and to NIH/OBA
• Be adequately trained in good microbiological techniques; • Adhere to IBC approved emergency plans for handling accidental spills and
personnel contamination; • Comply with shipping requirements for rDNA molecules.
Section IV: Roles and ResponsibilitiesResponsibilities of the PI:
• Responsible for full compliance with the NIH Guidelines in the conduct of rDNA research.
• Responsible for ensuring that the reporting requirements are fulfilled and will be held accountable for any reporting lapses.
• Prior to initiating research:-Make available to all laboratory staff the protocols that describe the potential biohazards and the precautions to be taken; -Instruct and train laboratory staff in: (i) the practices and techniques required to ensure safety, and (ii) the procedures for dealing with accidents; and -Inform the laboratory staff of the reasons and provisions for any precautionary medical practices advised or requested (e.g., vaccinations).
Section IV: Roles and ResponsibilitiesResponsibilities of the PI:
During conduct of research: • Supervise the safety performance of the laboratory staff to
ensure that the required safety practices and techniques are employed;
• Investigate and report any significant problems pertaining to the operation and implementation of containment practices and procedures in writing to the BSO, Animal Facility Director (where applicable), IBC, NIH/OBA, and other appropriate authorities (if applicable)
• Correct work errors and conditions that may result in the release of rDNA materials; and
• Ensure the integrity of the physical containment (e.g., biological safety cabinets) and the biological containment (e.g., purity and genotypic and phenotypic characteristics).
IBC Requirements
Required to annually submit IBC roster update including curriculum vitae of new members, brief biographical sketch and any significant updates of existing members to OBA
rDNA Knowledge
Community interest
Research expertise
No fewer than 5 members who exhibit:
Dual UseConsider dual use if any agents/toxins from
the below list:a) Avian influenza virus (highly pathogenic) b) Bacillus anthracis c) Botulinum neurotoxind) Burkholderia mallei e) Burkholderia pseudomallei f) Ebola virus g) Foot-and-mouth disease virus h) Francisella tularensis i) Marburg virus j) Reconstructed 1918 Influenza virus k) Rinderpest virus l) Toxin-producing strains of Clostridium botulinum m) Variola major virus n) Variola minor virus o) Yersinia pestis
Dual UseConsider dual use if any agents/toxins from the previous list are used in the below categories of experiments:a) Enhances the harmful consequences of the agent or toxin b) Disrupts immunity or the effectiveness of an immunization against the agent or toxin without clinical and/or agricultural justification c) Confers to the agent or toxin resistance to clinically and/or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin or facilitates their ability to evade detection methodologies d) Increases the stability, transmissibility, or the ability to disseminate the agent or toxin e) Alters the host range or tropism of the agent or toxin f) Enhances the susceptibility of a host population to the agent or toxin g) Generates or reconstitutes an eradicated or extinct agent or toxin listed in 6.2.1
UTHealth IBC Membership
Full MembersServe staggered two year terms (FY 14-16)
3+ faculty members with rDNA experience and/or biological safety and containment
2 individuals not associated with the institution (community member)
At least 1 member from each school
At least 1 with animal containment
At least 1 with infectious disease expertise
1 student member
Ex-Officio MembersRepresentative from Risk Management/Legal Affairs
Representative from Health Services
Director, Environmental Health & Safety
VP, SHERM
Executive Vice President for Research
Representative from HCPC
Expectations: Members
Active participation on the Committee
Sharing expertise and experience
Question and scrutinize protocols
Ensure protocols meet requirements of NIH
Guidelines, BMBL and other biosafety
guidelines
Participate as a member of a Subcommittee
during preliminary reviews
Timely response as a member of a
Subcommittee
Participate in member training, at least
annually
UTHealth Protocol ReviewSubmitted to Biosafety for assessment
Communication with PI to produce protocol
Submitted to Subcommittee for review
Submit protocol to IBC for full review
Protocol accepted Protocol rejected, tabled or pending
Approval Memos
Once a protocol is approved the appropriate memo is sent out
• Approval memo
• Conditional approval memo
Conditionally Exempt ProtocolsTo be a conditionally exempt protocol, proposed work must meet the following conditions:
• No work that falls under the NIH Guidelines• Only involves the collection of human samples
(i.e. blood, urine, tissue, etc.)• Sample processing limited to:
• Centrifugation• Storage
• Biological safety office reviews and approves protocols
• Protocols appear in meeting packets
IBC Resources
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules
http://osp.od.nih.gov/sites/default/files/NIH_Guidelines_0.pdf
Office of Biotechnology Activitieshttp://www4.od.nih.gov/oba/
CDC/NIH Biosafety in Microbiological and Biomedical Laboratories (BMBL)
http://www.cdc.gov/biosafety/publications/bmbl5/BMBL.pdf
Questions?