key definitions and acronyms

Overview of the Roles, Overview of the Roles, Responsibilities and Interactions Responsibilities and Interactions of the Principal Investigator with of the Principal Investigator with the MSSM Institutional Biosafety the MSSM Institutional Biosafety

Committee (IBC)Committee (IBC)

pgh/ 10/2004pgh/ 10/2004

Key Definitions and AcronymsKey Definitions and Acronyms

Biosafety Level (BL)Biosafety Level (BL): :

A description of the degree of physical A description of the degree of physical containment being employed to confine containment being employed to confine organisms containing recombinant DNA organisms containing recombinant DNA molecules and to reduce the potential for molecules and to reduce the potential for exposure of laboratory workers, persons outside exposure of laboratory workers, persons outside of the laboratory, and the environment. In of the laboratory, and the environment. In Appendix G Appendix G of the of the NIH GuidelinesNIH Guidelines, these are , these are graded from BL-1 (the least stringent) to BL-4 graded from BL-1 (the least stringent) to BL-4 (the most stringent). (the most stringent).


Biological Safety Officer (BSO)Biological Safety Officer (BSO)::

An individual appointed by an institution to An individual appointed by an institution to oversee management of biosafety risks. Theoversee management of biosafety risks. The NIH GuidelinesNIH Guidelines require that a BSO be appointed require that a BSO be appointed when the institution is engaged in large-scale when the institution is engaged in large-scale research or production activities, or in research research or production activities, or in research requiring containment at BL-3 or BL-4. The requiring containment at BL-3 or BL-4. The duties of the BSO are described in section IV-B-duties of the BSO are described in section IV-B-3 of the 3 of the NIH GuidelinesNIH Guidelines. .


Institutional Biosafety Committee (IBC)Institutional Biosafety Committee (IBC): : An institutional committee created under An institutional committee created under thethe NIH GuidelinesNIH Guidelines to review research to review research involving recombinant DNA. The involving recombinant DNA. The role of role of IBCsIBCs has evolved over time, and many has evolved over time, and many committees also review other forms of committees also review other forms of research that entail biohazardous risks as research that entail biohazardous risks as part of their institutionally assigned part of their institutionally assigned responsibilities. responsibilities.


National Institutes of Health(NIH):National Institutes of Health(NIH):

One of the world's foremost medical research institutions and the One of the world's foremost medical research institutions and the preeminent federal funder of medical research in the U.S.preeminent federal funder of medical research in the U.S.

The NIH, comprised of 27 separate Institutes and Centers, is one of The NIH, comprised of 27 separate Institutes and Centers, is one of eight health agencies within the Public Health Service, which is an eight health agencies within the Public Health Service, which is an agency within the U.S. Department of Health and Human Services. agency within the U.S. Department of Health and Human Services.

The goal of NIH research is to acquire new knowledge to help The goal of NIH research is to acquire new knowledge to help prevent, detect, diagnose, and treat disease and disability. The NIH prevent, detect, diagnose, and treat disease and disability. The NIH mission is to uncover new knowledge that will lead to better health mission is to uncover new knowledge that will lead to better health for everyone. for everyone.


NIH Guidelines for Research Involving Recombinant DNANIH Guidelines for Research Involving Recombinant DNAMolecules (NIH Guidelines)Molecules (NIH Guidelines): :

A document created in 1976 that outlines Principals for the safe A document created in 1976 that outlines Principals for the safe conduct of research employing recombinant DNA technology. conduct of research employing recombinant DNA technology.

http://www4.od.nih.gov/oba/rac/guidelines/guidelines.htmlhttp://www4.od.nih.gov/oba/rac/guidelines/guidelines.html

The The NIH GuidelinesNIH Guidelines detail practices and procedures for the detail practices and procedures for the containment of various forms of recombinant DNA research, for the containment of various forms of recombinant DNA research, for the proper conduct of research involving genetically modified plants and proper conduct of research involving genetically modified plants and animals, and for the safe conduct of human gene transfer research. animals, and for the safe conduct of human gene transfer research. As a “living” document, it is periodically revised to keep pace with As a “living” document, it is periodically revised to keep pace with the changing state of science. the changing state of science.


Office of Biotechnology Activities (OBA)Office of Biotechnology Activities (OBA): :

The NIH office responsible for developing, The NIH office responsible for developing, implementing, and monitoring NIH policies implementing, and monitoring NIH policies and procedures for the safe conduct of and procedures for the safe conduct of recombinant DNA activities, including recombinant DNA activities, including human gene transfer. human gene transfer.

Key Definitions and AcronymsKey Definitions and Acronyms Recombinant DNA Advisory Committee (RAC)Recombinant DNA Advisory Committee (RAC): :

An NIH advisory committee whose principal role is to provide An NIH advisory committee whose principal role is to provide advice and recommendations to the NIH Director on advice and recommendations to the NIH Director on

(1) the conduct and oversight of research involving (1) the conduct and oversight of research involving recombinant DNA, including the content and implementation of the recombinant DNA, including the content and implementation of the NIH Guidelines,NIH Guidelines, and and

(2) other NIH activities pertinent to recombinant DNA (2) other NIH activities pertinent to recombinant DNA technology. A major element of this role is to examine the science, technology. A major element of this role is to examine the science, safety, and ethics of clinical trials that involve the transfer of safety, and ethics of clinical trials that involve the transfer of recombinant DNA to humans. recombinant DNA to humans.

More details about RAC membership and responsibilities can be More details about RAC membership and responsibilities can be found on the found on the RAC pageRAC page of the OBA Website, as well as in its of the OBA Website, as well as in its CharterCharter. .


Recombinant DNA moleculesRecombinant DNA molecules: :

Under the current Under the current NIH GuidelinesNIH Guidelines, these , these are molecules constructed outside of living are molecules constructed outside of living cells by joining natural or synthetic DNA cells by joining natural or synthetic DNA segments to DNA molecules that can segments to DNA molecules that can replicate in a living cell, or molecules that replicate in a living cell, or molecules that result from their replicationresult from their replication..

Perview of the MSSM-IBC CommitteePerview of the MSSM-IBC Committee

Review all R - DNA Projects with respect to Health and Safety IssuesReview all R - DNA Projects with respect to Health and Safety Issues

Assist Principal Investigators in establishing the proper BioSafetyAssist Principal Investigators in establishing the proper BioSafetyLevels at which research projects involving R-DNA or other biohazards will Levels at which research projects involving R-DNA or other biohazards will proceedproceed

Interface with the NIH, ORDA, and OBA as required under the Interface with the NIH, ORDA, and OBA as required under the NIH NIH GuidelinesGuidelines

Review new Laboratory design and construction for projects requiring Review new Laboratory design and construction for projects requiring containment higher than BSL-2 / ABSL-1containment higher than BSL-2 / ABSL-1

Interface with MSSM-IACUC and MSSM-IRB on issues involving Animal or Interface with MSSM-IACUC and MSSM-IRB on issues involving Animal or Human Subject use in R-DNA-related studiesHuman Subject use in R-DNA-related studies

Provide oversight on any biosafety issues arising out of development or use Provide oversight on any biosafety issues arising out of development or use of R-DNA, or other Biologically- derived materials. (i.e. Toxins, Proteins etc.)of R-DNA, or other Biologically- derived materials. (i.e. Toxins, Proteins etc.)

Principal Investigator (PI)Principal Investigator (PI)On behalf of Mt Sinai School of Medicine, the On behalf of Mt Sinai School of Medicine, the Principal Principal InvestigatorInvestigator is responsible for is responsible for full compliancefull compliance with the with the NIH GuidelinesNIH Guidelines in the conduct of recombinant DNA in the conduct of recombinant DNA research. research.

A Principal Investigator engaged in human gene transfer A Principal Investigator engaged in human gene transfer research may delegate to another party, such as a research may delegate to another party, such as a corporate sponsor, the reporting functions set forth in corporate sponsor, the reporting functions set forth in Appendix MAppendix M, with written notification to the NIH OBA of , with written notification to the NIH OBA of the delegation and of the name(s), address, telephone, the delegation and of the name(s), address, telephone, and fax numbers of the contact. and fax numbers of the contact.

The Principal Investigator is responsible for ensuring that The Principal Investigator is responsible for ensuring that the reporting requirements are fulfilled and will be held the reporting requirements are fulfilled and will be held accountable for any reporting lapses.accountable for any reporting lapses.

General Responsibilities of the PI General Responsibilities of the PI

As part of his/her general responsibility, the Principal Investigator shall:As part of his/her general responsibility, the Principal Investigator shall:

Initiate or modify no recombinant DNA research which requires Institutional Initiate or modify no recombinant DNA research which requires Institutional Biosafety Committee approval prior to initiation (see Sections Biosafety Committee approval prior to initiation (see Sections III-AIII-A, , III-BIII-B, , III-CIII-C, , III-DIII-D, and , and III-EIII-E, , Experiments Covered by the NIH GuidelinesExperiments Covered by the NIH Guidelines) until that ) until that research or the proposed modification thereof has been approved by the research or the proposed modification thereof has been approved by the Institutional Biosafety Committee and has met all other requirements of the Institutional Biosafety Committee and has met all other requirements of the NIH GuidelinesNIH Guidelines;;

Determine whether experiments are covered by Determine whether experiments are covered by Section III-ESection III-E, , Experiments Experiments

that Require Institutional Biosafety Committee Notice Simultaneous with that Require Institutional Biosafety Committee Notice Simultaneous with InitiationInitiation, and ensure that the appropriate procedures are followed;, and ensure that the appropriate procedures are followed;

Report any significant problems, violations of the Report any significant problems, violations of the NIH GuidelinesNIH Guidelines, or any , or any

significant research-related accidents and illnesses to the Biological Safety significant research-related accidents and illnesses to the Biological Safety Officer, 241 5169 (where applicable), Institutional Biosafety Committee, Officer, 241 5169 (where applicable), Institutional Biosafety Committee, NIH/OBA, and other appropriate authorities (if applicable) NIH/OBA, and other appropriate authorities (if applicable) within 30 dayswithin 30 days. .

Reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, Reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, National Institutes of Health.National Institutes of Health.

General Responsibilities of the PI General Responsibilities of the PI

Report any new information bearing on the Report any new information bearing on the NIH NIH GuidelinesGuidelines to the Institutional Biosafety Committee and to the Institutional Biosafety Committee and to NIH/OBA (reports to NIH/OBA shall be sent to the to NIH/OBA (reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, National Institutes of Office of Biotechnology Activities, National Institutes of HealthHealth

Be adequately trained in good microbiological techniquesBe adequately trained in good microbiological techniques Adhere to Institutional Biosafety Committee approved Adhere to Institutional Biosafety Committee approved

emergency plans for handling accidental spills and emergency plans for handling accidental spills and personnel contamination personnel contamination

Comply with shipping requirements for recombinant DNA Comply with shipping requirements for recombinant DNA

molecules (see molecules (see Appendix HAppendix H, , ShipmentShipment, for shipping , for shipping requirements and the requirements and the Laboratory Safety MonographLaboratory Safety Monograph for for technical recommendations).technical recommendations).

Guide to the NIH Guidelines for Guide to the NIH Guidelines for Recombinant DNA ResearchRecombinant DNA Research

This outline is intended only to serve as a guide to the NIH This outline is intended only to serve as a guide to the NIH Guidelines for Recombinant DNA ResearchGuidelines for Recombinant DNA Research. .

It is the responsibility of each NIH-funded investigator to make sure It is the responsibility of each NIH-funded investigator to make sure that his/her laboratory is in compliance. If your experiments require that his/her laboratory is in compliance. If your experiments require registration, check the Guidelines for the appropriate biosafety level registration, check the Guidelines for the appropriate biosafety level and relevant section. If you are unsure in which category your and relevant section. If you are unsure in which category your experiments fall, register them.experiments fall, register them.

Many, Many, but not allbut not all, recombinant DNA experiments currently , recombinant DNA experiments currently allowable by the Guidelines must be registered as follows:allowable by the Guidelines must be registered as follows:

Source: NIH Institutional Biosafety Committee February, 1999Source: NIH Institutional Biosafety Committee February, 1999


Experiments WhichExperiments Which Must be Must be Registered & ApprovedRegistered & Approved by the MSSM IBC by the MSSM IBC PRIORPRIOR to to Initiation:Initiation:

Cloning of DNA encoding molecules toxic to vertebrates with Cloning of DNA encoding molecules toxic to vertebrates with an LD50 <100ng/kg an LD50 <100ng/kg body weight. body weight.

Cloning of DNA from all Cloning of DNA from all Risk Group 2, 3, or 4Risk Group 2, 3, or 4 human or animal pathogens (including human or animal pathogens (including HIV and related viruses, and human tumor viruses). HIV and related viruses, and human tumor viruses).

Experiments using as vectors Experiments using as vectors more than two-thirdsmore than two-thirds of the genome of infectious of the genome of infectious animal or plant viruses or defective recombinant viruses grown in the presence of a animal or plant viruses or defective recombinant viruses grown in the presence of a helper virus. helper virus.

Cloning using Cloning using human or animal pathogenshuman or animal pathogens as host-vector systems. as host-vector systems.

All experiments that may All experiments that may generate transgenic animalsgenerate transgenic animals or plants which may or plants which may extend extend the host-range of human or animal pathogenthe host-range of human or animal pathogen, or that , or that require BL-2 or greater require BL-2 or greater containment. containment.

All human gene transfer experimentsAll human gene transfer experiments. .

Experiments that Require Institutional MSSM Biosafety Experiments that Require Institutional MSSM Biosafety

Committee Approval Before InitiationCommittee Approval Before Initiation PriorPrior to the initiation of an experiment that falls into this category, the Principal to the initiation of an experiment that falls into this category, the Principal Investigator must submit a registration documentInvestigator must submit a registration document**** to the Institutional Biosafety to the Institutional Biosafety Committee which contains the following information: Committee which contains the following information:

(i) the source(s) of DNA(i) the source(s) of DNA (ii) the nature of the inserted DNA sequences(ii) the nature of the inserted DNA sequences (iii) the host(s) and vector(s) to be used(iii) the host(s) and vector(s) to be used (iv) if an attempt will be made to obtain expression of a foreign gene, and indicate the (iv) if an attempt will be made to obtain expression of a foreign gene, and indicate the

protein that will be producedprotein that will be produced (v) the containment conditions that will be implemented as specified in the (v) the containment conditions that will be implemented as specified in the NIH NIH

GuidelinesGuidelines..

For experiments in this category, the Certificate of Registration document shall be For experiments in this category, the Certificate of Registration document shall be dated, signed by the Principal Investigator, and filed with the MSSM Institutional dated, signed by the Principal Investigator, and filed with the MSSM Institutional Biosafety Officer. The MSSM Institutional Biosafety Committee shall review and Biosafety Officer. The MSSM Institutional Biosafety Committee shall review and approve all experiments in this category approve all experiments in this category prior to their initiationprior to their initiation. .

****Forms for this registration can be obtained by going to:Forms for this registration can be obtained by going to: http://www.mssm.edu/biosafety/forms/10-2001.dochttp://www.mssm.edu/biosafety/forms/10-2001.doc and and http://www.mssm.edu/iacuc/forms/IACUC3_safety_forms.dochttp://www.mssm.edu/iacuc/forms/IACUC3_safety_forms.doc


Experiments Which Require Experiments Which Require Registration with the MSSM IBC Registration with the MSSM IBC SimultaneousSimultaneous with Initiation: with Initiation:

Experiments using as vectors Experiments using as vectors less than two-thirdsless than two-thirds of the genome of of the genome of defective animal or plant viruses, free of helper virus. defective animal or plant viruses, free of helper virus.

Cloning of DNA for more Cloning of DNA for more than one-half of the genomethan one-half of the genome of Class 1 or of Class 1 or Class 2 human or animal pathogens, or Class 2 human or animal pathogens, or cloning of known oncogenes. cloning of known oncogenes.

Generation of Generation of transgenic animals requiring ABL-1 containmenttransgenic animals requiring ABL-1 containment. .

Experiments involving whole plants. Experiments involving whole plants.

Experiments not specified. Experiments not specified.


Are Exempt and Do Not Require Registration (by the NIH)**:Are Exempt and Do Not Require Registration (by the NIH)**:

Cloning of all other DNA in Cloning of all other DNA in E. coliE. coli K12, K12, S. cervisiaeS. cervisiae, and , and B. subtilisB. subtilis host-vector host-vector systems (with the exception of DNA from Class 2, 3, or 4 pathogens). systems (with the exception of DNA from Class 2, 3, or 4 pathogens).

Introduction into cultured cells of any recombinant DNA containing less than half Introduction into cultured cells of any recombinant DNA containing less than half of a eukaryotic viral genome (with the exception of Class 2, 3, or 4 pathogens). of a eukaryotic viral genome (with the exception of Class 2, 3, or 4 pathogens).

Purchase or transfer of transgenic rodents.Purchase or transfer of transgenic rodents.

**All laboratories working with recombinant DNA Molecules, zoonotic or human **All laboratories working with recombinant DNA Molecules, zoonotic or human pathogenic material or potentially pathogenic material (human tissue and blood pathogenic material or potentially pathogenic material (human tissue and blood products) as products) as per MSSM policyper MSSM policy, , must register withmust register with the Institutional Biosafety the Institutional Biosafety Committee by forwarding a Registration to the MSSM BSO. Committee by forwarding a Registration to the MSSM BSO.

Appropriate forms for this registration can be obtained by going to: Appropriate forms for this registration can be obtained by going to: http://www.mssm.edu/biosafety/forms/10-2001.dochttp://www.mssm.edu/biosafety/forms/10-2001.doc and and

http://www.mssm.edu/iacuc/forms/IACUC3_safety_forms.dochttp://www.mssm.edu/iacuc/forms/IACUC3_safety_forms.doc

NIH Offices and CommitteesNIH Offices and Committees

The following offices and committees require The following offices and committees require specific reports from the P Ispecific reports from the P I

Gene Therapy Submissions require Gene Therapy Submissions require notification to both the NIH and the FDA, if a notification to both the NIH and the FDA, if a novel Investigational New Drug (IND) is being novel Investigational New Drug (IND) is being developeddeveloped

Recombinant DNA Advisory Committee (RAC) Recombinant DNA Advisory Committee (RAC)

RAC shall be responsible for:RAC shall be responsible for: Advising the NIH Director on the following actions:Advising the NIH Director on the following actions:

(1) Adopting changes in the (1) Adopting changes in the NIH GuidelinesNIH Guidelines. .

(2) Assigning containment levels, changing containment levels, (2) Assigning containment levels, changing containment levels, and and approving experiments considered as approving experiments considered as Major ActionsMajor Actions under the under the NIH NIH GuidelinesGuidelines, i.e., the deliberate transfer of a drug resistance trait to , i.e., the deliberate transfer of a drug resistance trait to

microorganisms that are not known to acquire the trait naturally, microorganisms that are not known to acquire the trait naturally, if if such acquisition could compromise the use of the drug to control such acquisition could compromise the use of the drug to control

disease agents in humans, veterinary medicine, or agriculture. disease agents in humans, veterinary medicine, or agriculture.

(3) Promulgating and amending lists of classes of recombinant (3) Promulgating and amending lists of classes of recombinant DNA DNA molecules to be exempt from the molecules to be exempt from the NIH GuidelinesNIH Guidelines because they because they consist entirely of DNA segments from species that exchange consist entirely of DNA segments from species that exchange DNA by DNA by known known physiological processes or otherwise do not physiological processes or otherwise do not present a present a significant risk to health or the environment. significant risk to health or the environment.

(4) Certifying new host-vector systems.(4) Certifying new host-vector systems.

Recombinant DNA Advisory Committee (RAC)Recombinant DNA Advisory Committee (RAC)

RAC shall be responsible for:RAC shall be responsible for:

Identifying novel human gene transfer experiments Identifying novel human gene transfer experiments deserving of public discussion by the full RAC;deserving of public discussion by the full RAC;

Transmitting to the NIH Director specific comments/ Transmitting to the NIH Director specific comments/

recommendations about: recommendations about: (i) a specific human gene transfer experiment, or (i) a specific human gene transfer experiment, or (ii) a category of human gene transfer experiments;(ii) a category of human gene transfer experiments;

Experiments that fall under formal RAC review must Experiments that fall under formal RAC review must be sent to RAC before obtaining MSSM IBC approvalbe sent to RAC before obtaining MSSM IBC approval

Recombinant DNA Advisory Committee (RAC)Recombinant DNA Advisory Committee (RAC)

RAC shall be responsible for:RAC shall be responsible for: Publicly reviewing human gene transfer clinical trial data and relevant Publicly reviewing human gene transfer clinical trial data and relevant

information evaluated and summarized by NIH/OBA in accordance with information evaluated and summarized by NIH/OBA in accordance with the annual data reporting requirements;the annual data reporting requirements;

Identifying broad scientific, safety, social, and ethical issues relevant to Identifying broad scientific, safety, social, and ethical issues relevant to

gene therapy research as potential Gene Therapy Policy Conference gene therapy research as potential Gene Therapy Policy Conference topics;topics;

Identifying novel social and ethical issues relevant to specific human Identifying novel social and ethical issues relevant to specific human

applications of gene transfer and recommending appropriate applications of gene transfer and recommending appropriate modifications to the modifications to the Points to ConsiderPoints to Consider that will provide guidance in the that will provide guidance in the preparation of relevant Informed Consent documents; andpreparation of relevant Informed Consent documents; and

Identifying novel scientific and safety issues relevant to specific human Identifying novel scientific and safety issues relevant to specific human

applications of gene transfer and recommending appropriate applications of gene transfer and recommending appropriate modifications to the modifications to the Points to ConsiderPoints to Consider that will provide guidance in the that will provide guidance in the design and submission of human gene transfer clinical trials.design and submission of human gene transfer clinical trials.

Office of Biotechnology Activities (OBA)Office of Biotechnology Activities (OBA)

OBA shall serve as a focal point for information on recombinant DNA activitiesOBA shall serve as a focal point for information on recombinant DNA activitiesand provide advice to all within and outside NIH including institutions, Biologicaland provide advice to all within and outside NIH including institutions, BiologicalSafety Officers, Principal Investigators, Federal agencies, state and localSafety Officers, Principal Investigators, Federal agencies, state and localgovernments, and institutions in the private sector. OBA shall carry out suchgovernments, and institutions in the private sector. OBA shall carry out suchother functions as may be delegated to it by the NIH Director. OBA'sother functions as may be delegated to it by the NIH Director. OBA'sresponsibilities include (but are not limited to) the following:responsibilities include (but are not limited to) the following:

Serving as the focal point for public access to summary information pertaining to Serving as the focal point for public access to summary information pertaining to human gene transfer experiments;human gene transfer experiments;

Serving as the focal point for data management of human gene transfer Serving as the focal point for data management of human gene transfer

experiments;experiments; Administering the annual data reporting requirements (and subsequent review) Administering the annual data reporting requirements (and subsequent review)

for human gene transfer experiments (see for human gene transfer experiments (see Appendix M-I-CAppendix M-I-C, , Reporting Reporting RequirementsRequirements););


Transmitting comments/recommendations arising from public RAC discussion of Transmitting comments/recommendations arising from public RAC discussion of a novel human gene transfer experiment to the NIH Director. a novel human gene transfer experiment to the NIH Director. RAC recommendations shall be forwarded to the Principal Investigator, the RAC recommendations shall be forwarded to the Principal Investigator, the sponsoring institution, and other DHHS components, as appropriate.sponsoring institution, and other DHHS components, as appropriate.

Collaborating with Principal Investigators, Institutional Biosafety Committees, Collaborating with Principal Investigators, Institutional Biosafety Committees,

Institutional Review Boards, and other Institutional Review Boards, and other DHHSDHHS components (including components (including FDAFDA and and the the Office for Human Research ProtectionsOffice for Human Research Protections), to ensure human gene transfer ), to ensure human gene transfer experiment registration compliance in accordance with experiment registration compliance in accordance with Appendix M-IAppendix M-I, , Requirements for Protocol Submission, Review, and Reporting-Human Gene Requirements for Protocol Submission, Review, and Reporting-Human Gene Transfer ExperimentsTransfer Experiments of the of the NIH GuidelinesNIH Guidelines..

Administering Gene Therapy Policy Conferences as deemed appropriate by the Administering Gene Therapy Policy Conferences as deemed appropriate by the

NIH Director.NIH Director. Reviewing and approving experiments in conjunction with Reviewing and approving experiments in conjunction with ad hocad hoc experts experts

involving the cloning of genes encoding for toxin molecules that are lethal for involving the cloning of genes encoding for toxin molecules that are lethal for vertebrates at an LD50 of less than or equal to 100 nanograms per kilogram vertebrates at an LD50 of less than or equal to 100 nanograms per kilogram body weight in organisms other than body weight in organisms other than EscherichiaEscherichia colicoli K-12 K-12


Serving as the executive secretary of RAC;Serving as the executive secretary of RAC; Publishing in the Publishing in the Federal RegisterFederal Register::

Announcements of RAC meetings and tentative agendas at least 15 days in Announcements of RAC meetings and tentative agendas at least 15 days in advance (Note: If the agenda for a RAC meeting is modified, OBA shall make advance (Note: If the agenda for a RAC meeting is modified, OBA shall make the revised agenda available to anyone upon request in advance of the meeting);the revised agenda available to anyone upon request in advance of the meeting);

Announcements of Gene Therapy Policy Conferences and tentative agendas at Announcements of Gene Therapy Policy Conferences and tentative agendas at least 15 days in advance;least 15 days in advance;

Proposed Proposed Major ActionsMajor Actions at least 15 days prior to the RAC meeting; and at least 15 days prior to the RAC meeting; and Reviewing and approving the membership of an institution's Institutional Reviewing and approving the membership of an institution's Institutional

Biosafety Committee, and where it finds the Institutional Biosafety Committee Biosafety Committee, and where it finds the Institutional Biosafety Committee meets the requirements set forth in meets the requirements set forth in Section IV-B-2Section IV-B-2, , Institutional Biosafety Institutional Biosafety Committee (IBC)Committee (IBC), giving its approval to the Institutional Biosafety Committee , giving its approval to the Institutional Biosafety Committee membership.membership.

PI Reporting Requirements to PI Reporting Requirements to OBAOBA

Safety Reporting: Time frames for Expedited Reports

Any serious adverse event that is fatal or life-threatening, that is unexpected, and associated with the use of the gene transfer product must be reported to the NIH OBA as soon as possible, but not later than 7 calendar days after the sponsor’s initial receipt of the information (i.e., at the same time the event must be reported to the FDA).

Serious adverse events that are unexpected and associated with the use of the gene transfer product, but are not fatal or life-threatening, must be reported to the NIH OBA as soon as possible, but not later than 15 calendar days after the sponsor’s initial receipt of the information (i.e., at the same time the event must be reported to the FDA).

PI Reporting Requirements to PI Reporting Requirements to OBAOBA

Changes in this schedule are permitted only where, under the FDA IND regulations [21 CFR 312(c)(3)], changes in this reporting schedule have been approved by the FDA and are reflected in the protocol.

If, after further evaluation, an adverse event initially considered not to be associated with the use of the gene transfer product is subsequently determined to be associated, then the event must be reported to the NIH OBA within 15 days of the determination.

Relevant additional clinical and laboratory data may become available following the initial serious adverse event report. Any follow-up information relevant to a serious adverse event must be reported within 15 calendar days of the sponsor’s receipt of the information. If a serious adverse event occurs after the end of a clinical trial and is determined to be associated with the use of the gene transfer product, that event shall be reported to the NIH OBA within 15 calendar days of the determination.

Any finding from tests in laboratory animals that suggests a significant risk for human research participants including reports of mutagenicity, teratogenicity, or carcinogenicity must be reported as soon as possible, but not later than 15 calendar days after the sponsor’s initial receipt of the information (i.e., at the same time the event must be reported to the FDA).

Information to Be Submitted by the Information to Be Submitted by the Principal Investigator to NIH OBAPrincipal Investigator to NIH OBA

The Principal Investigator shall:The Principal Investigator shall:

Submit information to NIH/OBA for certification of new host-Submit information to NIH/OBA for certification of new host-vector systems;vector systems;

Petition NIH/OBA, with notice to the MSSM IBC, for proposed Petition NIH/OBA, with notice to the MSSM IBC, for proposed

exemptions to the exemptions to the NIH GuidelinesNIH Guidelines;; Petition NIH/OBA, with concurrence of the MSSM IBC, for Petition NIH/OBA, with concurrence of the MSSM IBC, for

approval to conduct experiments specified in approval to conduct experiments specified in Sections III-A-1Sections III-A-1, , Major Actions Under the NIH GuidelinesMajor Actions Under the NIH Guidelines, and III-B, , and III-B, Experiments that Require NIH/OBA and Institutional Experiments that Require NIH/OBA and Institutional Biosafety Committee Approval Before InitiationBiosafety Committee Approval Before Initiation;;

Information to Be Submitted by the Information to Be Submitted by the Principal Investigator to NIH OBA Principal Investigator to NIH OBA

Petition NIH/OBA for determination of containment for experiments requiring case-by-case Petition NIH/OBA for determination of containment for experiments requiring case-by-case review; andreview; and

Petition NIH/OBA for determination of containment for experiments not covered by the Petition NIH/OBA for determination of containment for experiments not covered by the NIH NIH

GuidelinesGuidelines.. Ensure that all aspects of Appendix M have been appropriately addressed prior to Ensure that all aspects of Appendix M have been appropriately addressed prior to

submission of a human gene transfer experiment to NIH OBA, and provide a letter signed by submission of a human gene transfer experiment to NIH OBA, and provide a letter signed by the Principal Investigator(s) on institutional letterhead acknowledging that the documentation the Principal Investigator(s) on institutional letterhead acknowledging that the documentation being submitted to NIH OBA complies with the requirements set forth in Appendix M. No being submitted to NIH OBA complies with the requirements set forth in Appendix M. No research participant shall be enrolled (see definition of enrollment in Section I-E-7) in a research participant shall be enrolled (see definition of enrollment in Section I-E-7) in a human gene transfer experiment until the RAC review process has been completed (see human gene transfer experiment until the RAC review process has been completed (see Appendix M-I-B, Appendix M-I-B, RAC Review RequirementsRAC Review Requirements););MSSMMSSM IBC approval (from the clinical trial IBC approval (from the clinical trial site) has been obtained; Institutional Review Board (MSSMsite) has been obtained; Institutional Review Board (MSSM IRB) approval has been IRB) approval has been obtained; and all applicable regulatory authorization(s) have been obtained.obtained; and all applicable regulatory authorization(s) have been obtained.

For a clinical trial site that is added after the RAC review process, no research participant For a clinical trial site that is added after the RAC review process, no research participant

shall be enrolled (see definition of enrollment in Section I-E-7) at the clinical trial site until the shall be enrolled (see definition of enrollment in Section I-E-7) at the clinical trial site until the following documentation has been submitted to NIH OBA: (1) IBC approval (from the following documentation has been submitted to NIH OBA: (1) IBC approval (from the clinical trial site); (2) IRB approval; (3) IRB-approved informed consent document; (4) clinical trial site); (2) IRB approval; (3) IRB-approved informed consent document; (4) curriculum vitae of the principal investigator(s) (no more than two pages in biographical curriculum vitae of the principal investigator(s) (no more than two pages in biographical sketch format); and (5) NIH grant number(s) if applicable.sketch format); and (5) NIH grant number(s) if applicable.

Submissions by the Principal Submissions by the Principal Investigator to the MSSM Institutional Investigator to the MSSM Institutional

Biosafety CommitteeBiosafety Committee


Make an initial determination of the required levels of physical and Make an initial determination of the required levels of physical and biological containment in accordance with the biological containment in accordance with the NIH GuidelinesNIH Guidelines;;

Select appropriate microbiological practices and laboratory Select appropriate microbiological practices and laboratory

techniques to be used for the research;techniques to be used for the research;

Submit the initial research protocol and any subsequent changes Submit the initial research protocol and any subsequent changes (e.g., changes in the source of DNA or host-vector system), if (e.g., changes in the source of DNA or host-vector system), if covered under Sections III-A, III-B, III-C, III-D, or III-E (covered under Sections III-A, III-B, III-C, III-D, or III-E (Experiments Experiments Covered by the NIH GuidelinesCovered by the NIH Guidelines), to the Institutional Biosafety ), to the Institutional Biosafety Committee for review and approval or disapproval; andCommittee for review and approval or disapproval; and

Remain in communication with the Institutional Biosafety Committee Remain in communication with the Institutional Biosafety Committee

throughout the conduct of the project.throughout the conduct of the project.

Responsibilities of the Principal Responsibilities of the Principal Investigator Prior to Initiating Investigator Prior to Initiating

ResearchResearch


Make available to all laboratory staff the protocols that describe Make available to all laboratory staff the protocols that describe the potential biohazards and the precautions to be taken;the potential biohazards and the precautions to be taken;

Instruct and train laboratory staff in: (i) the practices and Instruct and train laboratory staff in: (i) the practices and

techniques required to ensure safety, and (ii) the procedures for techniques required to ensure safety, and (ii) the procedures for dealing with accidents; anddealing with accidents; and

Inform the laboratory staff of the reasons and provisions for any Inform the laboratory staff of the reasons and provisions for any

precautionary medical practices advised or requested (e.g., precautionary medical practices advised or requested (e.g., vaccinations or serum collection).vaccinations or serum collection).

Responsibilities of the Principal Investigator Responsibilities of the Principal Investigator During the Conduct of the Research During the Conduct of the Research


Supervise the safety performance of the laboratory staff to ensure that the Supervise the safety performance of the laboratory staff to ensure that the required safety practices and techniques are employed;required safety practices and techniques are employed;

Investigate and report any significant problems pertaining to the operation and Investigate and report any significant problems pertaining to the operation and

implementation of containment practices and procedures in writing to the implementation of containment practices and procedures in writing to the Biological Safety Officer, 241-1451 MSSM Institutional Biosafety Committee, Biological Safety Officer, 241-1451 MSSM Institutional Biosafety Committee, NIH/OBA, and other appropriate authorities (if applicable) NIH/OBA, and other appropriate authorities (if applicable) (reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, National Institutes of Health, (reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD 20892-7985 (20817 for non-USPS mail), 301-6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD 20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax);496-9838, 301-496-9839 (fax);

Correct work errors and conditions that may result in the release of recombinant Correct work errors and conditions that may result in the release of recombinant

DNA materials; andDNA materials; and Ensure the integrity of the physical containment (e.g., biological safety cabinets) Ensure the integrity of the physical containment (e.g., biological safety cabinets)

and the biological containment (e.g., purity and genotypic and phenotypic and the biological containment (e.g., purity and genotypic and phenotypic characteristics).characteristics).

Comply with reporting requirements for human gene transfer experiments Comply with reporting requirements for human gene transfer experiments

conducted in compliance with theconducted in compliance with the NIH Guidelines NIH Guidelines (see Appendix M-I-C, (see Appendix M-I-C, Reporting RequirementsReporting Requirements).).


Experiments that Require MSSM Institutional Biosafety Committee Experiments that Require MSSM Institutional Biosafety Committee Approval, RAC Review, and NIH Director Approval Approval, RAC Review, and NIH Director Approval Before InitiationBefore Initiation

Major Actions under the Major Actions under the NIH GuidelinesNIH Guidelines

Experiments considered as Experiments considered as Major ActionsMajor Actions under the under the NIH GuidelinesNIH Guidelines cannot be cannot be initiatedinitiated without submission of relevant information on the proposed experiment without submission of relevant information on the proposed experiment to the Office of Biotechnology Activities (OBA), National Institutes of Health, nor to the Office of Biotechnology Activities (OBA), National Institutes of Health, nor without the publication of the proposal in the without the publication of the proposal in the Federal RegisterFederal Register for 15 days of for 15 days of comment, followed by review by RAC, and specific approval by NIH. comment, followed by review by RAC, and specific approval by NIH.

The containment conditions or stipulation requirements for such experiments will The containment conditions or stipulation requirements for such experiments will be recommended by RAC and set by NIH at the time of approval. Such be recommended by RAC and set by NIH at the time of approval. Such experiments require MSSM Institutional Biosafety Committee experiments require MSSM Institutional Biosafety Committee approval before approval before initiationinitiation. Specific experiments already approved are included in Appendix D, . Specific experiments already approved are included in Appendix D, Major Actions Taken under the NIH Guidelines.Major Actions Taken under the NIH Guidelines.

The deliberate transfer of a drug resistance trait to microorganisms that are not The deliberate transfer of a drug resistance trait to microorganisms that are not known to acquire the trait naturally (see Section V-B, known to acquire the trait naturally (see Section V-B, Footnotes and References Footnotes and References of Sections I-IVof Sections I-IV), if such acquisition could compromise the use of the drug to ), if such acquisition could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture, will be control disease agents in humans, veterinary medicine, or agriculture, will be reviewed by RAC as a reviewed by RAC as a Major Action.Major Action.

CONCLUSIONCONCLUSION

This presentation is a brief overview of the This presentation is a brief overview of the requirements that PIs must meet while requirements that PIs must meet while working with recombinant DNA molecules.working with recombinant DNA molecules.

If you require further clarification or If you require further clarification or assistance in contacting the MSSM IBC, assistance in contacting the MSSM IBC, please contact the Biosafety Officer at please contact the Biosafety Officer at

241-5169 or [email protected] or [email protected]

key definitions and acronyms

Documents

goal of nih research

acronyms nih guidelines

nih director

nih mission

nih advisory committee

forms of research

safe conduct of research

key definitions