Presentation on theme: "Institutional Biosafety Committee Member Training"— Presentation transcript:
1 Institutional Biosafety Committee Member Training October 2014
2 BackgroundRecombinant DNA work covered under NIH Office of Biotechnology Activities (NIH OBA) in:NIH GUIDELINES FOR RESEARCH INVOLVINGRECOMBINANT 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.
3 IBC Institutional Biosafety Committee (IBC) Reviews all research that involves the use of rDNANIH/OBA rDNA Guidelines as reference documentReviews research involving the use of infectious agents NOT rDNAInclusive of subcommittees-needlestick and healthcareBMBL as a reference document
4 Biosafety LevelsBiosafety 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
5 Risk Assessment Factors PathogenicityRoute of TransmissionAgent StabilityInfectious DoseConcentrationAvailability of effective prophylaxis, treatmentAvailability of medical surveillanceHost susceptibility
6 Risk Assessment Organism Hosts Vector Expression of foreign gene Protein producedContainmentFacilityLaboratory-specific protocolTraining & expertise of personnel
7 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.
8 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.
9 Section II: Safety Considerations Risk Assessment Risk 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 .
10 Section II: Safety Considerations Containment Containment 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 GuidelinesLaboratory Safety Monograph (historical document)Biosafety in Microbiological and Biomedical Laboratories (BMBL)
11 Section III: Experiments covered by the NIH Guidelines III-A: transfer of drug resistanceIII-B: cloning of lethal toxinsIII-C: human gene transfer researchIII-D: infectious agents as vectors & transgenic animalsIII-E: generation of transgenic rodentsIII-F: exemptions
12 Experiments Covered by the NIH Level of ReviewSectionResearch ExampleIBC, RAC review and NIH Director review and approvalIII-ACipro resistant Bacillus anthracisIBC approval and NIH review for containment determinationIII-BCloning botulinum toxin expression into adenovirusIBC and IRB approval and NIH review before research particpant enrollmentIII-CHuman gene transferIBC approval before initiationIII-DExpression of a nonnative protein in Staphylococcus aureusIBC notification at initiationIII-EGermline alteration of rodents which may be housed in BL-1ExemptIII-FPurchased transgenic rodents
13 III-A: Major ActionsRequires: IBC Approval, RAC Review, NIH Director Approval Before Initiation of WorkTransfer of therapeutically useful drug resistance to organisms which may compromise human health/agriculture/medicine
14 III-B: Toxin TransferRequires: NIH/OBA, IBC Review and Approval Before Initiation of WorkDeliberate 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
15 III-C: (Deliberate Transfer of rDNA into Research Participants, ex III-C: (Deliberate Transfer of rDNA into Research Participants, ex. Gene Therapy)Requires: RAC Review, IBC and IRB Approval Before Participant EnrollmentHuman gene transfer (HGT) protocolsAll 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.
16 III-D: General WorkRequires: IBC Review and Approval Prior to the Initiation of WorkInvolves RG 2-4 agents, host/vector systemCloned DNA from RG 2-4 agents into non-pathogenic prokaryotesRG 2-4 agents into whole animals, usually transgenicRecombinant plantsLarge scale experiments greater than 10LGeneration of any transgenic animal other than BSL-1 rodents
17 III-E: Less Restrictive Work Requires: IBC Notification at the Initiation of Work (BSL-1 Containment), and Subsequent IBC Review and ApprovalrDNA molecules that contains less than 2/3 of any eukaryotic viral genomeTransgenic rodents with BSL-1 containment(crossbreeding of transgenics now exempt at BSL-1)Whole plants that require minimal containmentAnything else NOT covered under sections III-A through III-D & III-F
18 III-F: ExemptionsExempt from the NIH Guidelines and Does Not Require IBC Review or ApprovalrDNA molecules that are:Not in organisms or virusesNot a risk to health or the environment-See Appendix CNote: exceptions to exemptions!
19 FAQ Review process for human gene transfer protocols Vaccine exemptionsMajor actions under the guidelinesTransgenic animals
20 FAQ IBC committee minutes Experiments that are exempt
21 Section IV: Roles and Responsibilities Responsibilities of the Institution:Ensure compliance with NIH GuidelinesEstablish IBCAppoint a Biosafety Officer if conducting BSL-3, BSL-4, or large-scale workEnsure IBC has expertise in the research that is reviewedEstablish a medical surveillance program as neededReport all incidents to the NIH OBA
22 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.
23 Section IV: Roles and Responsibilities Responsibilities 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.
24 Section IV: Roles and Responsibilities Responsibilities 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.
25 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.
26 Section IV: Roles and Responsibilities Responsibilities 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).
27 Section IV: Roles and Responsibilities Responsibilities 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; andEnsure the integrity of the physical containment (e.g., biological safety cabinets) and the biological containment (e.g., purity and genotypic and phenotypic characteristics).
28 No fewer than 5 members who exhibit: IBC RequirementsNo fewer than 5 members who exhibit:rDNA KnowledgeCommunity interestResearch expertiseRequired to annually submit IBC roster update including curriculum vitae of new members, brief biographical sketch and any significant updates of existing members to OBA
29 Dual Use Consider dual use if any agents/toxins from the below list: a) Avian influenza virus (highly pathogenic)b) Bacillus anthracisc) Botulinum neurotoxind) Burkholderia malleie) Burkholderia pseudomalleif) Ebola virusg) Foot-and-mouth disease virush) Francisella tularensisi) Marburg virusj) Reconstructed 1918 Influenza virusk) Rinderpest virusl) Toxin-producing strains of Clostridium botulinumm) Variola major virusn) Variola minor viruso) Yersinia pestis
30 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 toxinb) Disrupts immunity or the effectiveness of an immunization against the agent or toxinwithout clinical and/or agricultural justificationc) Confers to the agent or toxin resistance to clinically and/or agriculturally usefulprophylactic or therapeutic interventions against that agent or toxin or facilitatestheir ability to evade detection methodologiesd) Increases the stability, transmissibility, or the ability to disseminate the agent ortoxine) Alters the host range or tropism of the agent or toxinf) Enhances the susceptibility of a host population to the agent or toxing) Generates or reconstitutes an eradicated or extinct agent or toxin listed in 6.2.1
31 UTHealth IBC Membership Full MembersServe staggered two year terms (FY 14-16)3+ faculty members with rDNA experience and/or biological safety and containment2 individuals not associated with the institution (community member)At least 1 member from each schoolAt least 1 with animal containmentAt least 1 with infectious disease expertise1 student memberEx-Officio MembersRepresentative from Risk Management/Legal AffairsRepresentative from Health ServicesDirector, Environmental Health & SafetyVP, SHERMExecutive Vice President for ResearchRepresentative from HCPC
32 Expectations: Members Active participation on the CommitteeSharing expertise and experienceQuestion and scrutinize protocolsEnsure protocols meet requirements of NIH Guidelines, BMBL and other biosafety guidelinesParticipate as a member of a Subcommittee during preliminary reviewsTimely response as a member of a SubcommitteeParticipate in member training, at least annually
33 UTHealth Protocol Review Submitted to Biosafety for assessmentCommunication with PI to produce protocolSubmitted to Subcommittee for reviewSubmit protocol to IBC for full reviewProtocol acceptedProtocol rejected, tabled or pending
34 Approval MemosOnce a protocol is approved the appropriate memo is sent outApproval memoConditional approval memo
35 Conditionally Exempt Protocols To be a conditionally exempt protocol, proposed work must meet the following conditions:No work that falls under the NIH GuidelinesOnly involves the collection of human samples (i.e. blood, urine, tissue, etc.)Sample processing limited to:CentrifugationStorageBiological safety office reviews and approves protocolsProtocols appear in meeting packets
36 IBC ResourcesNIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid MoleculesOffice of Biotechnology ActivitiesCDC/NIH Biosafety in Microbiological and Biomedical Laboratories (BMBL)