NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules

________________________ that now provides recommendations to the NIH Director and a public forum for the discussion of the scientific, safety and ethical issues associated with emerging biotechnologies.

Novel and Exceptional Technology and Research Advisory Committee (NExTRAC)

Recombinant and Synthetic Nucleic Acid Molecules per NIH Guidelines

(i) molecules that a) are constructed by joining nucleic acid molecules and b) 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.

IBC approval is required for transfer of recombinant or synthetic nucleic acid molecules into _____ recipients

human

Who must follow NIH guidelines?

• all recombinant or synthetic nucleic acid research within the US

• Research involving testing human of materials containing recombinant or synthetic nucleic acids developed with NIH funds if the institution that developed those materials sponsors or participates in these projects - must have research collaboration or contractual agreements

• Research performed abroad if if it’s one of the above

• research supported by NIH funds

• If host country has rules for conduct of recombinant or synthetic nucleic acid molecules research - must be in compliance with those rules, if those don’t exist, NIH approved IBC must review it & that must be accepted in writing by an appropriate national governmental authority

Who sends the report to NIH if there's noncompliance regarding the use of recombinant or synthetic nucleic acid molecules (rsNA)

The institution, generally the IBC, takes appropriate action and sends report to NIH/OSP (Office of Science Policy)

What can noncompliance regarding the use of recombinant or synthetic nucleic acid molecules (rsNA) result in?

May result in suspension, limitation, or termination of NIH funds for rsNA research or a requirement for prior NIH approval for rsNA work (not the specific project that was affected, but ALL projects at the institution).

any public or private entity (including Federal, state, and local government agencies).

institution

Purpose of IBC

committee that:

(i) meets the requirements for membership

(ii) reviews, approves, and oversees projects

Office within the NIH that is responsible for: (i) reviewing and coordinating all activities relating to the NIH Guidelines, and (ii) performing other duties as

defined

Office of Science Policy

introduction of recombinant or synthetic nucleic acid molecules into organisms, cells, or viruses.

initiation

the Director of the National Institutes of Health, or any other officer or employee of NIH to whom authority has been delegated.

NIH Director

defined as a planned introduction of recombinant or synthetic nucleic acid molecule-containing microorganisms, plants, or animals into the environment.

Deliberate release

defined as a technology whereby a particular heritable element biases inheritance in its favor, resulting in the heritable element becoming more prevalent than predicted by Mendelian laws of inheritance in a population over successive generations.

Gene drive

Novel and Exceptional Technology and Research Advisory Committee (NExTRAC): how many members?

No longer reviews human gene transfer studies

Up to 25 members

Designated Federal Officer

Other members not employees of a federal agency

Within how many days does IBC need to report noncompliance to NIH/OSP?

Report any significant problems/violations to NIH/OSP within 30 days

What is the association of Office of Science Policy (OSP) to NIH?

OSP coordinates the NIH Guidelines (part of the NIH)

-Provides oversight, guidance, and resources to IBCs

-Approves IBC membership

Who is responsible for ensuring research is being conducted according to the NIH Guidelines?

Principal Investigator

What should be taken into consideration when assigning an recombinant or synthetic molecules to a risk group?

virulence, pathogenicity, infectious dose, environmental stability, route of spread, communicability, operations, quantity, availability of vaccines or treatment and gene product effects such as toxicity, physiological activity, and allergenicity

a) Function or intended function of the genetic/gene drive construct (i.e., a designed or

engineered assembly of sequences);

b) Source of the genetic material (e.g., sequences of transgenes) in the construct;

c) The modifications to the construct;

d) Whether it is possible to predict the consequences of a construct, including the

recognition of an unintended gene drive (i.e., construct not specifically designed as a

gene drive but nonetheless having properties of a gene drive) and the possible

consequences of escape into the environment;

e) The potential ability of the gene drive to spread or persist in local populations;

Some risk group agents can be cultured at corresponding BSL level, but if agent is inoculated in an animal or used to study transmission, the BSL level may raise. What are some examples

Dengue virus is RG2 and thus BSL2, but must be ABLS3 when used in animals

Venezuelan equine encephalomyelitis and yellow fever virus are RG3 and BSL3, but become ABSL4 when inoculated in animals

BSL2 is recommended for all activities involving what in regards to humans?

all blood-contaminated clinical specimens, body fluids, and tissues from all humans, or from HIV- or HBV-infected or inoculated laboratory animals

production of research-laboratory scale quantities of HIV or other bloodborne pathogens, manipulating concentrated virus preparations, or conducting procedures that may produce droplets or aerosols, are performed in a ____ facility using the additional practices and containment equipment recommended for

___.

BL2 with BL3

involving industrial scale volumes or preparations of concentrated HIV are conducted in a ___ facility, or ___ Large Scale if appropriate, using ___ practices and containment equipment.

BL3, BL3, BL3

When might a strain be increased or decreased in containment level?

-increased - more virulent than parent or wild type strain

-decreased - attenuated to have irreversibly lost known virulence factors

When does a project require IBC approval alone?

NIH Director Approval and IBC approval?

NIH OSP and IBC approval?

Human Gene Transfer that requires IBC approval

Experiments that require IBC approval before initiation

Risk Group 1 (RG1):

agents not associated with disease in healthy adult humans

-Bacillus subtilis or Bacillus lichenformis Host-Vector Systems

-Adeno-associated virus (AAV) - all serotypes

-Recombinant or synthetic AAV constructs

-Avirulent E. coli

-Simian virus 40

-Mouse mammary tumor virus

Risk Group 2 (RG2):

agents associated with human disease which is rarely serious and for which preventative or therapeutic interventions are often available

-Leptospira interrogans - all serotypes

-Salmonella spp.

-Adenovirus, human - all types

-Herpesviruses - except Herpes B

Risk Group 3 (RG3):

agents associated with serious or lethal human disease for which preventative or therapeutic interventions may be available

-Mycobacterium bovis and M. tuberculosis

-Influenza viruses 1918 H1N1, H2N2 (1957-1968) and HPAI H5N1 strains

-HIV and SIV

-Coccidioides immitis and Histoplasma capsulatum

-SARS-CoV and MERS-CoV (added in since 2019)

Risk Group 4 (RG4):

agents likely to cause serious or lethal human disease for which preventative or therapeutic interventions are not usually available

-Filoviruses

-Herpes B virus

No bacterial, fungal or parasitic agents are listed

What are BL-N levels?

for research involving animals which are of a size or have growth requirements that preclude use of conventional primary containment systems used for small laboratory animals

BL1-N

containment to prevent only vertical transmission of viable rDNA or synthetic DNA microorganisms among transgenic animals

BL2-N:

containment to prevent vertical or horizontal transmission (including by arthropods) of rDNA or synthetic DNA microorganisms in transgenic animals

BL3-N or BL4-N:

higher levels of containment for research with certain transgenic animals with hazardous agents

For boards you need to know which projects need ___ approval and ____ approval simultaneous with ____.

IBC approval

IBC approval with notification of initiation

Experiments that require only IBC approval before initiation

-Using RG2, RG3, RG4 or Restricted Agents as Host-Vector Systems

-DNA From RG2, RG3, RG4 or restricted agents is cloned into non-pathogenic prokaryotic or lower eukaryotic host-vector systems

-Using DNA or RNA viruses in the presence of helper virus in tissue culture systems

-Whole animals or plants

-More than 10L of culture

-Influenza viruses

Experiments that require IBC notice simultaneous with initiation

• For experiments not in other Section II subsections

• May all be conducted at BL1

• Formation of rsNA molecules with no more than 2/3 of the genome of any eukaryotic virus

• Experiments Involving transgenic rodents (BL1 only)

Experiments that require IBC and IRB approval before initiation or enrollment

1) "Major Actions": work involved drug resistant gene

2) Cloning toxin molecules with LD50 less than 100 ng/kg body weight

3) human gene transfer or work involved synthetic DNA into human

Experiments involving _____ or ___ , except for viruses that are transmitted vertically, may only be conducted at a minimum containment level of ___.

• gene drive modified animals

• OR viable recombinant or synthetic nucleic acid molecule modified organisms

• BL-2 or BL2-N

When can work be conducted in animals at BL-1 or BL1-N level?

-DNA/RNA derived from LESS than 2/3 of eukaryotic genome can be transferred to non human vertebrate and propagated

-sequences of viral vectors do not lead to transmissible infection either directly or indirectly (as result of complementation or recombination in animals)

An investigator must demonstrate that the fraction of viral genome being utilized does not lead to ____.

productive infection

When is a US Deptartment of Ag permit required?

plant or animal pathogens

For what projects does the IBC decide containment level?

-if molecule source has greater than 2/3 of eukaryotic viral genome and transferred to non-human vertebrate or invertebrate

-Uses Human or Animal Pathogen that is risk group 2, 3, 4, or restricted agents as host vector systems

-gene drive modified animals are at LEAST BL2/BL2-N

Generation or use of rodents in which their genome has been altered by stable introduction of recombinant or synthetic nucleic acid molecules or molecules derived from them in the germ line required ____ practices.

BL1

Experiments involving breeding of certain ____ transgenic rodents are exempt from NIH guidelines.

BSL1

What project are exempt from NIH Guidelines?

• Synthetic nucleic acids that

  • (1) can neither replicate nor generate nucleic acids that can replicate in any living cell AND

  • (2) are not designed to introduce a stable genetic modification, AND

  • (3) do not produce a toxin that is lethal for vertebrates at an LD50 of less than 100 nanograms per kilogram body weight.

• not in organisms, cells, or viruses that have not been modified or manipulated to render them capable of penetrating cellular membranes

• consist of exact recombinant or synthetic nucleic acid sequence from single source that exists contemporaneously in nature

• consist entirely of nucleic acids from prokaryotic host, including its indigenous plasmids or viruses when propagated only in that host (or closely related strain of same species) or when transferred to another host by well established physiological means

• consisten entirely of nucleic acids from eukaryotic hosti ncluding it’s chloroplasts, mitochondira, or plasmids (but excluding viruses) when propagated only in that host (or closely related strain of same species) or when transferred to another host by well established physiological means

• consist entirely of DNA segments from different species that exchange DNA by known physiological processes

• genomic DNA molceules that have acquired a transposable element provided the transposable element does not contain any recombinant or synthetic DNA

• do not present a significant risk to health or the environment as determined by NIH director folllowing appropriate notice and opportunity for public comment

All genetically engineered neonates must be permanently marked within ________ after birth if their size permits

72 hours

What does Institutional Biosafety Committee (IBC) review?

Established at an institute under the NIH Guidelines to review research involving recombinant or synthetic nucleic acid molecules

May be assigned additional review responsibilities at the Institution's discretion

• -Select agents and toxins

• -Blood borne pathogens

• -Xenotransplantation

• -Stem cell research

• -"Dual Use" research

• -Nanotechnology

What are the responsibilities of the institution?

• establish policies and guidelines to implement NIH guidelines

• establish IBC

• Appoint BSO if necessary

• Appoint one individual with expertise in plants stuff to IBC

• appoint one individual with expertise in animal stuff to IBC

• Ensure no research involving human participants is initiated until IBC has approved it

• Assist and ensure compliance with NIH Guidelines by PIs

• Ensure appropriate training

• Ensure health surveillance program for personnel engaged in large scale research or production that require BL3 containment or animal research with molecules that are BL3

• Report significant problems, violations, significant research accidents or illneses to NIH OSP within 30d

The institution is responsible for ensuring appropriate training for ____.

• Institutional Biosafety Committee Chair and members

• Biological Safety Officer and other containment experts (when applicable)

• Principal Investigators, and laboratory staff - responsibility can be delegated to IBC

• regarding laboratory safety and implementation of the NIH Guidelines.

What is the membership requirement for Institutional Biosafety Committee (IBC) ?

• at least 5 individuals

  • 2 members must be non-affiliated with the Institution

  • "Appropriate recombinant and synthetic nucleic acid expertise collectively"

  • Animal Expert

  • Plant Expert

  • Appoint a Biosafety Officer (BSO) if indicated

How often does IBC update OSP? What should be included in the membership updates?

Register the IBC with OSP and file annual membership updates

A roster of IBC members

Clearly indicate chair, contact person, and special expertise as appropriate (BSO, animal, plant, human gene transfer)

Biographical sketches of all members

Can IBC records be made public?

Yes

In a nutshell, what must IBCs review?

Research involving recombinant or synthetic nucleic acid molecules for conformity with the NIH Guidelines

• 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 recombinant or synthetic nucleic acid molecule research

• (iii) for recombinant or synthetic nucleic acid molecule research involving human research participants assessment focused on biosafety issues

Functions of the IBC

• Review recombinant research

• Notify PI results of IBC review and approval

• Can lower containment levels for certain experiments in which nucleic acid from Risk Group 2-4 or Restricted agents Is Cloned in Non-pathogenic organisms

• Set containment levels for experiments involving whole plants and animals

• Review periodically institutional compliance with NIH Guidelines

• Adopt emergency plans covering spills, contamination, other accidents

• Report significant problems or violations of NIH guidelines and significant research related accidents or illnesses to NIH OSP in 30d

What can the IBC not do?

cannot authorize initiation of experiments not covered by NIH Guidelines until NIH establishes the containment requirement

When is a Biological Safety Officer (BSO) required?

institution conducts recombinant or synthetic nucleic acid research at:

• Large scale (>10 L)

• High containment (BL-3 or BL-4)

• gene drive modified organisms (BSL2 or higher)

What are the duties of Biological Safety Officer (BSO)?

• Must be apart of IBC

• Periodic inspection of labs

• Reporting to the IBC and institution of any problems, violations, research-related accidents or illnesses

• Developing emergency plans for handling accidental spills and personnel contamination

• Advice on lab security

• Technical advice to PIs and the IBC on research safety procedures

Responsibilities of Principal Investigator

• Do not initiate or modify recombinant molecules until IBC approval and met requirements of NIH Guidelines

• Determine if experiments require IBC notice with initiaition

• Report significant problems, violations, or accidents or illnesses to BSO, IBC, NIH OSP, and appropriate authorities within 30d

• Report new info bearing on NIH guidelines to IBC and NIH OSP

• trained in good microbiological techniques

• Adhere to IBC emergency plans

• comply with shipping requirements for

Information to be submiited by PI to NIH OSP

• submit certification of new host vector systems

• Petition with notice to IBC for proposed exemptions to NIH Guidlines

• Petition with concurrence of IBC for approval to conduct experiments specified in major actions under the NIG and experiments that require NIH OSP and IBC approval before initiaition

• Petition for determination of containment for experiments requiring case by case review

• Peitition for determinitiation of containment for experiments not covered by NIH Guidelines

Information to be submitted by PI to IBC

• Make initial determination of required levels of physical and biological containment

• select appropriate microbiological practices and lab techniques

• submit initial protocol and subsequent changes to IBC

• remain in communication with IBC

Responsibilities of PI prior to initiation research

• Supervise safety performance of lab staff to ensure they are following procedures

• investigate and report significant problems pertaining to operation and omplementation of containment practices and procedures in WRITING to BSO, IBC, NIH OSP, and other appropriate authorities

• correct work error and conditions that may result in release of molecules

• ensure integrity of the physical containment (e.g., biological safety cabinets) and the biological containment (e.g., purity and genotypic and phenotypic characteristics).

What does IRB - Institutional Review Board review?

human experiments

The IBC chair is responsible for ensuring that ____ are trained

IBC committee members

The PI is responsible for ensuring ____ are trained

lab staff

What should the IBC do if there are projects that involve animals

-one scientist with expertise in animal containment principles

-institute establish and maintain a health surveillance program for personell if BL3 or higher containment necessary

How should animals be disposed of BL1-N through BL4-N

carcass disposed of to avoid its use as food for human beings or animals unless food use is psecifically authorized by an appropriate federal agency

permanent record shal be maintained of the experimental use and disposal of each animal or group of animals

BL1-N Standard Practices

General

• containment area is locked

• access is limited or restricted when experimental animals being held

• containment shall be patrolled or monitored at frequent intervals

Other

• GE neonates marked within 72 hours after birth if size permits

  • if it doesn’t permit - containers should be marked

  • transgenic animals should contain distinct assayable DNA that allows identification of transgenic animals from non-transgenic animals

• double barrier to seperate male and female animals unless reproductive studies are apart of experiment or other measures taken to avoid reproductive transmission (reproductive incapacitation may be used)

Animal Facility

• containment area in accorance with federal laws and animal care requirements

• Animals contained to securely fences areas or be in enclosured structures

BL2-N

BL1-N +

General

• Animal facility director establish policies and porcedures where only persons adivsed on potential hazard and meet requirements may enter lab animal rooms

• animals of same or different species not involved in work are not permitted in animal area

• contaminated material decontaminated at site awar from lab - placed in durable leak proof container prior to removal from facility

• needles & syringes placed in puncture resistant container - preferably autoclaved before discard or reuse

• IF special provision required for entry - need sign to indicate - agent, animal species, anme and telephone number of Animal Facility Director or other responsible, and special requirements for entering lab

• Lab coats, gowns, smocks, or uniforms worn while in animal area or attached lab, remove protective clothing before leaving

• impervious/protective gloves when handling naimals and when skin contact with infectious agent unavoidable

• Any incident with spills or environmental release of animals - report to Animal Facility Director, IBC, NIH OSP, other appropriate authorities

• Baseline serum samples collected and stored for animal care and at risk personnel - collect additional periodically depending on agent handled

• Biological material removed from animal containment - non breakable sealed primary container then enclosed in non breakable sealed secondary container - disinfect before removal, advance approval from Animal Facility Director, only open in faciltities with adequate containment faciltities unless sample is bilogically inactivated or uncapable of reproduction

Other

• Mark in 72hr

• needles and syringes - can only be needle locking suringes or syringe needle unit - the npuncture resistant plastic and autoclave

• prevent horizontal transmission - if agent used is vector known to be transmitted by particular route, special attention to prevent spread by this route, in absence of specific knowledge - all potential means should be prevented

• no eating, drinking, smoking, or applying cosmetics

• wash hands before exiting area

• double barrier to keep males and females separate

• containment in accordance with federal laws

• biosafety manual prepared and adopted

Animal Facility

• enclosed structure

• surfaces ipervious to water and resistant to acids, alkalis, organic solvents, and moderate heat

• animal containment shall be easily cleaned

• windows that open fitted with fly screens

• autoclave available for decontamination

• athropods used or can be transmitted to arthropod - interior work areas appropriated screen (52 mesh) - all permiter joints and openins sealed and additional athropod control measures

BL3- N General, other, animal faciltities

BL2-N+

General

• Containment building controlled and locking access

• animal room doors, gates, other closures kept closed when experiments in progress

• decontaiminate work surgfaces - plasttic backed paper toweling on nonporous surfaces

• euthanize animals at end of experimental usefulness and carcasseses decontaminated before disposal

• safety testing, decontamination and IBC approval to transfer agents or tissues from BL3-N animal facility to facility with lower containment

• Liquid effluent - decontaminated by heat treatment before release into sanitary system - monitor with recording thermometer - effectiveness validated on yearly basis with indicator oganism - more frequent if decided by IBC

• full protectice clothing (scrub suits, coverall, unifroms), not worn outside animal containement and decontaminate before laundering or disposal

• shower before exiting and wearing personal clothing

• appropriate respiratory protection

Other

• experiments with organisms lower than BL3-N can be performed in the same area if conducted in accordance with BL3-N practices

• animal holding cleaned once a day and decontaminated immediately following any spill

• minimize creation of aerosols

Animal Facility

• interior walls, floors, and cielding impervious to water and resistant to chemicals - penetrations shall be sealed

• windows closed, sealed, and breakage resistant (double pane tempered glass)

• negative pressure necessary

• access doors to containment area are self closing

• animal area seperate from all other areas - passage through 2 sets of doors

• animal containment area physically separated from access corridors and oter labs or areas by double door clothes change room equiped with showers and airlock

• exhaust air ventilation provided - directional airflow draws air into animal room

• exhaust air discharged to outside and dispersed away from occupied areas and air intakes

• aerosol transmission possible - exhaust air through HEPA

• vacuum lines w/ HEPA filters and liquid disinfectant traps

• can house in partial containment caging (horsfall units, gnotobiotic systems, other special)

• automatic, foot, or elbow operated sink located near exit door

• restraining develioces may be required to avoid damage to animal facility

BL4-N General, other, animal faciltities

BL3-N +

General

• individuals under 16yr of age not permitted to enter animal area

• enter and exit animal facilit only through clothing change and shower rooms

• airlocks to enter or exit laboratory only in an emergency

• all contaiminated liquid or solid waste is decontaminated before disposal

• no material, except biological material that are to remain in a vaible or intact state, shall be removed from the lab unless they have been autoclaved or decontaminated

  • if it gets damaged at high temps then gaseous or vapor decontamination in airlock or chamber designed for this purpose

• ventilated suite required - shower entrance and exit area equipped with chemical disinfectant shower to decontaminate surface of suit before exiting, neutralization or water dilution integral with chemica disinfectanct discharge piping before entering heat sterilization system, entry into this area though airlock fitted with airtight doors

• supplies and materials brought in by double door autoclave, fumigation chamber, or airlocked decontaminated between each use

• autoclave, incenerator in containment area for decontamination - double door autoclave preferred

• For liquid effluent heat treatment 0 if required liquid wastes from showe shall be chemically decontaminated using EPA aproved germicide, efficacy should be validated with indicator oganism, chemical disingectant neutralized or diluted before release into general wastes

• Entering facxility - remove street clothing in outer clothing change room, complete lab clothing (including undergarments) provided,

• Exiting facility - before going to shower area - remove lab clothing in inner change room, lab clothing autoclaves before laundering - shower each time they exit facility

• Ventilated head hood or pone piece positive pressure suit with ventilated life support system worn by personnel entering rooms that contain experimental animals when appropriate

• if ventilated suite - chemical disingectant shower to decontaminate surface of suit before exiting - neutralization water dilution device and airlock

• system shall be established for: (i) reporting laboratory accidents and exposures that are a result of overt exposures to organisms containing recombinant or synthetic nucleic acid molecules, (ii) employee absenteeism, and (iii) medical surveillance of potential laboratory associated illnesses.

• permanent record book indicating date and time of each entry and exit signed by all personnel

• If biological material needs to be taken out intact - non breakable sealed primary container enclosed in non breaklable sealed secondary container removed thorugh disinfectant dunk tank, fumigation chamber w/ approval from Animal facilit director

  • can only be opened in another BL4-N facility

• Anything entering must be through double door autoclave, fumigation chmaber, or airlock decontaminated between uses

Other

• essential adjunt to reporting surveillance system is the availability of a facility for quarantine, isolation, and medical care of personnel with potential or known laboratory associated illness

Animal Faciltities

• Double barrier - if inner facility is breached, outer barrier will prevent release into environment

• necropsy room for BL4-N area

• ducted air exhaust to provide directional airflow

• exhaust air is not recurculated at all - discharge to outside away from occupied and air intakes

• exhaust air double HEPA filtered or treated by passing through HEPA and air incinerator before release

  • must biologically challange to prove air incenerator viable - biological challenge must be minimally 1x108 organisms per cubic foot of airflow through the incinerator. It is universally accepted if bacterial spores are used like Bacillus subtilis var. niger or Bacillus stearothermophilus.

• supply air is double HEPA filtered

• all HEPA filters confirmed to have no detectable smoke (dioctyl phthalate) leaks when the exit face (direction of flow) of filter is scanned above 0.01% whe nmeasured by linear or logarithmic photometer

  • The instrument must demonstrate a threshold sensitivity of at least 1x10-3 micrograms per liter for 0.3 micrometer diameter dioctyl phthalate particles and a challenge concentration of 80-120 micrograms per liter. The air sampling rate should be at least 1 cfm (28.3 liters per minute).

• All equipment and floor drains equipped with deep traps (at least 5in) - fitted with isolation plugs or fitted with automatic water fill devices

• supply water fitted with back flow preventor or break tank

• all ultities provided shall be protected with devices that avoid back flow (liquid, gas, etc)

• Sewer or other atmospheric ventilation lines eqipped with HEPA filter

  • Condensate drains from these type housings shall be appropriately connected to a contaminated or sanitary drain system. The drain position in the housing dictates the appropriate system to be used.

Which institutions are required to appoint a biological safety officer?

A) Every institution that works with biological hazards requires a biological safety officer

B) Institutions that engage in large-scale research or production activities involving viable organisms containing recombinant DNA molecules

C) Institutions that engage in recombinant DNA research at BSL 2 or higher regardless of program scale

D) Any institution utilizing recombinant DNA molecules in research

B) Institutions that engage in large-scale research or production activities involving viable organisms containing recombinant DNA molecules

According to NIH Guidelines for Research Involving Recombinant DNA Molecules, membership of the Institutional Biosafety Committee must include a minimum of:

A. 3 individuals, with no requirement for unaffiliated members

B. 3 individuals, including 1 unaffiliated community member

C. 5 individuals, with no requirement for unaffiliated members

D. 5 individuals, including 1 unaffiliated community member

E. 5 individuals, including 2 unaffiliated community members

E. 5 individuals, including 2 unaffiliated community members

The transfer and breeding of BL-1 transgenic mice are ______ from NIH Guidelines

exempt