41082 Federal Register / Vol. 83, No. 160 / Friday, August 17, 2018 / Notices 

humans or animal models that could be 

addressed with new technologies. 

• Considerations for data sharing 

infrastructure and policies. 

• Areas and topics for research on the 

ethical implications of BRAIN Initiativesupported emerging neurotechnologies 

and advancements and their 

applications. 

• Approaches for disseminating new 

tools and technologies as well as 

training the broader neuroscience 

research community. 

• Any other topic relevant to the 

strategic plan of the BRAIN Initiative. 

Responses to this RFI are voluntary. 

Any personal identifiers will be 

removed when responses are compiled. 

Individual feedback will not be 

provided to any responder. Proprietary, 

classified, confidential, or sensitive 

information should not be included in 

your response. This Request for 

Information (RFI) is for planning 

purposes only and is not a solicitation 

for applications or an obligation on the 

part of the United States (U.S.) 

Government to provide support for any 

ideas identified in response to it. Please 

note that the U.S. Government will not 

pay for the preparation of any comment 

submitted or for its use of that comment. 

Dated: August 10, 2018. 

Lawrence A. Tabak, 

Deputy Director, National Institutes of Health. 

[FR Doc. 2018–17759 Filed 8–16–18; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institutes of Health (NIH) 

Office of Science Policy (OSP) 

Recombinant or Synthetic Nucleic Acid 

Research: Proposed Changes to the 

NIH Guidelines for Research Involving 

Recombinant or Synthetic Nucleic Acid 

Molecules (NIH Guidelines) 

AGENCY: National Institutes of Health, 

HHS. 

ACTION: Notice. 

SUMMARY: The National Institutes of 

Health (NIH) seeks public comment on 

its proposal to amend the NIH 

Guidelines for Research Involving 

Recombinant or Synthetic Nucleic Acid 

Molecules (NIH Guidelines) to 

streamline oversight for human gene 

transfer clinical research protocols and 

reduce duplicative reporting 

requirements already captured within 

the existing regulatory framework. 

Specifically, NIH proposes amendments 

to: Delete the NIH protocol registration 

submission and reporting requirements 

under Appendix M of the NIH 

Guidelines, and modify the roles and 

responsibilities of entities that involve 

human gene transfer or the Recombinant 

DNA Advisory Committee (RAC). 

DATES: To ensure consideration, 

comments must be submitted in writing 

by October 16, 2018. 

ADDRESSES: Comments may be 

submitted electronically by visiting: 

https://osp.od.nih.gov/comment-formnih-guidelines/. Comments may also be 

sent via fax to 301–496–9839, or by mail 

to the Office of Science Policy, National 

Institutes of Health, 6705 Rockledge 

Drive, Suite 750, Bethesda, Maryland 

20892–7985. All written comments 

received in response to this notice will 

be available for public inspection at NIH 

Office of Science Policy (OSP), 6705 

Rockledge Drive, Suite 750, Bethesda, 

MD 20892–7985, weekdays between the 

hours of 8:30 a.m. and 5 p.m. and may 

be posted without change, including 

any personal information, to the NIH 

OSP website. 

FOR FURTHER INFORMATION CONTACT: If 

you have questions, or require 

additional background information 

about these proposed changes, please 

contact the NIH by email at 

SciencePolicy@od.nih.gov, or telephone 

at 301–496–9838. You may also contact 

Jessica Tucker, Ph.D., Director of the 

Division of Biosafety, Biosecurity, and 

Emerging Biotechnology Policy, Office 

of Science Policy, NIH, at 301–451–4431 

or Jessica.Tucker@nih.gov. 

SUPPLEMENTARY INFORMATION: NIH is 

proposing a series of actions to the NIH 

Guidelines for Research Involving 

Recombinant or Synthetic Nucleic Acid 

Molecules (NIH Guidelines) to 

streamline oversight of human gene 

transfer research (HGT), and to focus the 

NIH Guidelines more specifically on 

biosafety issues associated with research 

involving recombinant or synthetic 

nucleic acid molecules. The field of 

HGT has recently experienced a series 

of advances that have resulted in the 

translation of research into clinical 

practice, including U.S. Food and Drug 

Administration (FDA) approvals for 

licensed products. Additionally, 

oversight mechanisms for ensuring HGT 

proceeds safely have sufficiently 

evolved to keep pace with new 

discoveries in this field. 

At this time, there is duplication in 

submitting protocols, annual reports, 

amendments, and serious adverse 

events for HGT clinical protocols to 

both NIH and FDA that does not exist 

for other areas of clinical research. 

Historically, this duplication was 

conceived as harmonized reporting, 

enabling FDA to provide regulatory 

oversight while NIH provided a forum 

for open dialogue and transparency. 

However, since these complementary 

functions were first envisioned, we have 

now seen several converging systems 

emerge that provide some of these 

functions. For instance, 

ClinicalTrials.gov has been instituted, 

which provides a transparent and 

searchable database for clinical trials. In 

addition, the protection of human 

research subjects was improved through 

changes that updated provisions of the 

Common Rule. In 2018, FDA released a 

suite of draft guidance documents 

pertaining to gene therapy that includes 

new guidance on manufacturing issues, 

long-term follow-up, and pathways for 

clinical development in certain areas, 

including hemophilia, ophthalmologic 

indications, and rare diseases. 

While the science and oversight 

system have evolved, HGT protocols 

continue to receive special oversight 

that is not afforded to other areas of 

clinical research. This observation was 

also noted in a 2014 Institute of 

Medicine of the National Academies 

report, Oversight and Review of Clinical 

Gene Transfer Protocols: Assessing the 

Role of the Recombinant DNA Advisory 

Committee, in which it was 

recommended that NIH begin to limit 

RAC review to only exceptional HGT 

protocols that meet certain criteria and 

that would significantly benefit from 

RAC review. As very few protocols have 

been assessed by NIH to merit review 

under this new system, NIH asserts it is 

an opportune time to make changes to 

the NIH Guidelines to make oversight of 

HGT commensurate with oversight 

afforded to other areas of clinical 

research given the robust infrastructure 

in place to oversee this type of research. 

Briefly to summarize, NIH proposes 

amending the NIH Guidelines to: 

1. Eliminate RAC review and 

reporting requirements to NIH for HGT 

protocols. 

2. Modify roles and responsibilities of 

investigators, institutions, IBCs, the 

RAC, and NIH to be consistent with 

these goals including: 

a. Modifying roles of IBCs in 

reviewing HGT to be consistent with 

review of other covered research, and 

b. Eliminating references to the RAC, 

including its roles in HGT and biosafety. 

NIH suggests that the series of 

changes proposed in this Notice is a 

rational next step in the process of 

considering appropriate oversight of 

HGT. Consistent with these proposed 

changes to the NIH Guidelines, Section 

I–A, the Purpose of the NIH Guidelines, 

is proposed to be amended to clarify 

that the focus of the policy is biosafety 


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oversight of research involving 

recombinant or synthetic nucleic acid 

molecules. NIH notes that some of the 

duties of Institutional Biosafety 

Committees (IBCs) as currently written 

in the NIH Guidelines (e.g., review of 

informed consent documents) are 

duplicative with the oversight provided 

by FDA or Institutional Review Boards 

(IRBs). NIH proposes that IBCs retain 

responsibility to review and approve 

HGT protocols; however, NIH proposes 

that these responsibilities be modified 

to be similar to those responsibilities 

IBCs currently have for review and 

approval of other research subject to the 

NIH Guidelines. 

With the proposed elimination of the 

requirements for safety reporting under 

Appendix M, IBC oversight should be 

completed immediately after the last 

participant is administered the final 

dose of product. Additionally, the role 

of IBC review is proposed to be 

amended to be consistent with FDA’s 

current guidance regarding individual 

patient expanded access to 

investigational drugs. In this way, the 

role of the IBCs will be focused on 

providing local biosafety oversight of 

basic and clinical research involving 

recombinant or synthetic nucleic acids. 

In particular, NIH seeks comment on 

whether the expectations of IBCs, in 

light of these proposed changes, have 

been articulated clearly in the proposed 

revisions to the NIH Guidelines. 

Notably, the roles and responsibilities 

of the RAC are proposed to be removed 

from the NIH Guidelines. NIH 

recognizes the value of the RAC in 

discussions of science, safety, and 

ethics. In an effort to use the RAC as a 

public forum to advise on issues 

associated with emerging 

biotechnologies, the RAC’s charter will 

be modified to change the committee’s 

focus from research solely involving 

recombinant or synthetic nucleic acids 

to emerging biotechnologies research. In 

light of this modification to the 

committee, NIH proposes eliminating 

references to the RAC in the NIH 

Guidelines, though NIH may continue to 

seek advice from the RAC on biosafety 

issues that fall under the purview of the 

NIH Guidelines. Similarly, NIH may 

choose to seek advice from internal 

working groups or Federal Advisory 

Committees on a variety of issues, when 

warranted. 

The proposed changes outlined above 

will require amendment of multiple 

portions of the NIH Guidelines. Sections 

and appendices proposed to be deleted 

from the current NIH Guidelines may be 

accessed at https://osp.od.nih.gov/ 

biotechnology/nih-guidelines/. 

Following deletions, sections and 

appendices will be relabeled to proceed 

consecutively throughout the NIH 

Guidelines. 

Proposed Amendments to the NIH 

Guidelines 

Section I–A currently states: 

Section I–A. Purpose 

The purpose of the NIH Guidelines is 

to specify the practices for constructing 

and handling: (i) Recombinant nucleic 

acid molecules, (ii) synthetic nucleic 

acid molecules, including those that are 

chemically or otherwise modified but 

can base pair with naturally occurring 

nucleic acid molecules, and (iii) cells, 

organisms, and viruses containing such 

molecules. 

Section I–A is proposed to be 

amended as follows: 

Section I–A. Purpose 

The purpose of the NIH Guidelines is 

to specify the biosafety practices and 

containment principles for constructing 

and handling: (i) Recombinant nucleic 

acid molecules, (ii) synthetic nucleic 

acid molecules, including those that are 

chemically or otherwise modified but 

can base pair with naturally occurring 

nucleic acid molecules, and (iii) cells, 

organisms, and viruses containing such 

molecules. 

Section I–A–1 currently states: 

Section I–A–1. Any nucleic acid 

molecule experiment, which according 

to the NIH Guidelines requires approval 

by NIH, must be submitted to NIH or to 

another federal agency that has 

jurisdiction for review and approval. 

Once approvals, or other applicable 

clearances, have been obtained from a 

federal agency other than NIH (whether 

the experiment is referred to that agency 

by NIH or sent directly there by the 

submitter), the experiment may proceed 

without the necessity for NIH review or 

approval. (See exception in Section I– 

A–1-a regarding requirement for human 

gene transfer protocol registration.) 

Section I–A–1 is proposed to be 

amended as follows: 

Section I–A–1. Any nucleic acid 

molecule experiment, which according 

to the NIH Guidelines requires approval 

by NIH, must be submitted to NIH or to 

another federal agency that has 

jurisdiction for review and approval. 

Once approvals, or other applicable 

clearances, have been obtained from a 

federal agency other than NIH (whether 

the experiment is referred to that agency 

by NIH or sent directly there by the 

submitter), the experiment may proceed 

without the necessity for NIH review or 

approval. 

Section I–A–1–a currently states: 

Section I–A–1–a. For experiments 

involving the deliberate transfer of 

recombinant or synthetic nucleic acid 

molecules, or DNA or RNA derived from 

recombinant or synthetic nucleic acid 

molecules, into human research 

participants (human gene transfer), no 

research participant shall be enrolled 

(see definition of enrollment in Section 

I–E–7) until the NIH protocol 

registration process has been completed 

(see Appendix M–I–B, Selection of 

Individual Protocols for Public RAC 

Review and Discussion); Institutional 

Biosafety Committee (IBC) approval 

(from the clinical trial site) has been 

obtained; Institutional Review Board 

(IRB) approval has been obtained; and 

all applicable regulatory 

authorization(s) have been obtained. 

For a clinical trial site that is added 

after the completion of the NIH protocol 

registration process, no research 

participant shall be enrolled (see 

definition of enrollment in Section I–E– 

7) at the clinical trial site until IBC 

approval and IRB approval from that 

site have been obtained. Within 30 days 

of enrollment (see definition of 

enrollment in Section I–E–7) at a 

clinical trial site, the following 

documentation shall be submitted to 

NIH OSP: (1) Institutional Biosafety 

Committee approval (from the clinical 

trial site); (2) Institutional Review Board 

approval; (3) Institutional Review 

Board-approved informed consent 

document(s); and (4) NIH grant 

number(s) if applicable. 

Section I–A–1–a is proposed to be 

amended as follows: 

Section I–A–1–a. For experiments 

involving the deliberate transfer of 

recombinant or synthetic nucleic acid 

molecules, or DNA or RNA derived from 

recombinant or synthetic nucleic acid 

molecules, into human research 

participants (human gene transfer), no 

human gene transfer experiment shall 

be initiated (see definition of initiation 

in Section I–E–7) until Institutional 

Biosafety Committee (IBC) approval 

(from the clinical trial site) has been 

obtained; and all other applicable 

institutional and regulatory 

authorization(s) and approvals have 

been obtained. 

Section I–E. General Definitions is 

proposed to be amended to delete the 

current definitions I–E–4, I–E–7 through 

I–E–12 and to include a new definition 

for ‘‘initiation.’’ 

Section I–E–4 is proposed to be 

amended to define initiation as the 

following: ‘‘Initiation’’ of research is the 

introduction of recombinant or 

synthetic nucleic acid molecules into 

organisms, cells, or viruses. 

Section III currently states: 


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Section III. Experiments Covered by the 

NIH Guidelines 

This section describes six categories 

of experiments involving recombinant 

or synthetic nucleic acid molecules: (i) 

Those that require Institutional 

Biosafety Committee (IBC) approval, 

RAC review, and NIH Director approval 

before initiation (see Section III–A), (ii) 

those that require NIH OSP and 

Institutional Biosafety Committee 

approval before initiation (see Section 

III–B), (iii) those that require 

Institutional Biosafety Committee and 

Institutional Review Board approvals 

and RAC review before research 

participant enrollment (see Section III– 

C), (iv) those that require Institutional 

Biosafety Committee approval before 

initiation (see Section III–D), (v) those 

that require Institutional Biosafety 

Committee notification simultaneous 

with initiation (see Section III–E), and 

(vi) those that are exempt from the NIH 

Guidelines (see Section III–F). 

Note: If an experiment falls into Sections 

III–A, III–B, or III–C and one of the other 

sections, the rules pertaining to Sections III– 

A, III–B, or III–C shall be followed. If an 

experiment falls into Section III–F and into 

either Sections III–D or III–E as well, the 

experiment is considered exempt from the 

NIH Guidelines. 

Any change in containment level, 

which is different from those specified 

in the NIH Guidelines, may not be 

initiated without the express approval 

of NIH OSP (see Section IV–C–1–b–(2) 

and its subsections, Minor Actions). 

Section III is proposed to be amended 

as follows: 

Section III. Experiments Covered by the 

NIH Guidelines 

This section describes six categories 

of experiments involving recombinant 

or synthetic nucleic acid molecules: (i) 

Those that require Institutional 

Biosafety Committee (IBC) approval and 

NIH Director approval before initiation 

(see Section III–A), (ii) those that require 

NIH OSP and Institutional Biosafety 

Committee approval before initiation 

(see Section III–B), (iii) those that 

require Institutional Biosafety 

Committee approval before initiation of 

human gene transfer (see Section III–C), 

(iv) those that require Institutional 

Biosafety Committee approval before 

initiation (see Section III–D), (v) those 

that require Institutional Biosafety 

Committee notification simultaneous 

with initiation (see Section III–E), and 

(vi) those that are exempt from the NIH 

Guidelines (see Section III–F). 

Note: If an experiment falls into Sections 

III–A, III–B, or III–C and one of the other 

sections, the rules pertaining to Sections III– 

A, III–B, or III–C shall be followed. If an 

experiment falls into Section III–F and into 

either Sections III–D or III–E as well, the 

experiment is considered exempt from the 

NIH Guidelines. 

Any change in containment level, 

which is different from those specified 

in the NIH Guidelines, may not be 

initiated without the express approval 

of NIH OSP (see Section IV–C–1–b–(2) 

and its subsections, Minor Actions). 

Section III–A currently states: 

Section III–A. Experiments That 

Require Institutional Biosafety 

Committee Approval, RAC Review, and 

NIH Director Approval Before 

Initiation (See Section IV–C–1–b–(1), 

Major Actions). 

Experiments considered as Major 

Actions under the NIH Guidelines 

cannot be initiated without submission 

of relevant information on the proposed 

experiment to the Office of Science 

Policy, National Institutes of Health, 

preferably by email to: NIHGuidelines@

od.nih.gov, the publication of the 

proposal in the Federal Register for 15 

days of comment, review by RAC, and 

specific approval by NIH. The 

containment conditions or stipulation 

requirements for such experiments will 

be recommended by RAC and set by 

NIH at the time of approval. Such 

experiments require Institutional 

Biosafety Committee approval before 

initiation. Specific experiments already 

approved are included in Appendix D, 

Major Actions Taken under the NIH 

Guidelines, which may be obtained from 

the Office of Science Policy, National 

Institutes of Health, preferably by 

submitting a request for this information 

to: NIHGuidelines@od.nih.gov; 

additional contact information is also 

available here and on the OSP website 

(www.osp.od.nih.gov). 

Section III–A–1–a. The deliberate 

transfer of a drug resistance trait to 

microorganisms that are not known to 

acquire the trait naturally (see Section 

V–B, Footnotes and References of 

Sections I–IV), if such acquisition could 

compromise the ability to control 

disease agents in humans, veterinary 

medicine, or agriculture, will be 

reviewed by the RAC. 

Consideration should be given as to 

whether the drug resistance trait to be 

used in the experiment would render 

that microorganism resistant to the 

primary drug available to and/or 

indicated for certain populations, for 

example children or pregnant women. 

At the request of an Institutional 

Biosafety Committee, NIH OSP will 

make a determination regarding whether 

a specific experiment involving the 

deliberate transfer of a drug resistance 

trait falls under Section III–A–1-a and 

therefore requires RAC review and NIH 

Director approval. An Institutional 

Biosafety Committee may also consult 

with NIH OSP regarding experiments 

that do not meet the requirements of 

Section III–A–1–a but nonetheless raise 

important public health issues. NIH 

OSP will consult, as needed, with one 

or more experts, which may include the 

RAC. 

Section III–A is proposed to be 

amended as follows: 

Section III–A. Experiments That 

Require Institutional Biosafety 

Committee Approval and NIH Director 

Approval Before Initiation (See Section 

IV–C–1–b–(1), Major Actions). 

Section III–A–1. Major Actions Under 

the NIH Guidelines 

Experiments considered as Major 

Actions as defined in Section III–A–1-a 

under the NIH Guidelines cannot be 

initiated without submission of relevant 

information on the proposed experiment 

to the Office of Science Policy, National 

Institutes of Health, preferably by email 

to: NIHGuidelines@od.nih.gov, the 

publication of the proposal in the 

Federal Register for 15 days of 

comment, and specific approval by NIH. 

The containment conditions or 

stipulation requirements for such 

experiments will be set by NIH at the 

time of approval. Such experiments 

require Institutional Biosafety 

Committee approval before initiation. 

Specific experiments already approved 

are included in Appendix D, Major 

Actions Taken under the NIH 

Guidelines, which may be obtained from 

the Office of Science Policy, National 

Institutes of Health, preferably by 

submitting a request for this information 

to: NIHGuidelines@od.nih.gov; 

additional contact information is also 

available here and on the OSP website 

(www.osp.od.nih.gov). 

Section III–A–1-a. The deliberate 

transfer of a drug resistance trait to 

microorganisms that are not known to 

acquire the trait naturally (see Section 

V–B, Footnotes and References of 

Sections I–IV), if such acquisition could 

compromise the ability to control 

disease agents in humans, veterinary 

medicine, or agriculture, will require 

NIH Director approval. 

Consideration should be given as to 

whether the drug resistance trait to be 

used in the experiment would render 

that microorganism resistant to the 

primary drug available to and/or 

indicated for certain populations, for 

example children or pregnant women. 

At the request of an Institutional 

Biosafety Committee, NIH OSP will 


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make a determination regarding whether 

a specific experiment involving the 

deliberate transfer of a drug resistance 

trait falls under Section III–A–1-a and 

therefore requires NIH Director 

approval. An Institutional Biosafety 

Committee may also consult with NIH 

OSP regarding experiments that do not 

meet the requirements of Section III–A– 

1-a but nonetheless raise important 

public health issues. 

Section III–C currently states: 

Section III–C. Experiments that 

Require Institutional Biosafety 

Committee and Institutional Review 

Board Approvals and RAC Review (if 

applicable) Before Research Participant 

Enrollment 

Section III–C–1. Experiments 

Involving the Deliberate Transfer of 

Recombinant or Synthetic Nucleic Acid 

Molecules, or DNA or RNA Derived 

from Recombinant or Synthetic Nucleic 

Acid Molecules, into One or More 

Human Research Participants 

Human gene transfer is the deliberate 

transfer into human research 

participants of either: 

1. Recombinant nucleic acid 

molecules, or DNA or RNA derived from 

recombinant nucleic acid molecules, or 

2. Synthetic nucleic acid molecules, 

or DNA or RNA derived from synthetic 

nucleic acid molecules that meet any 

one of the following criteria: 

a. Contain more than 100 nucleotides; 

or 

b. Possess biological properties that 

enable integration into the genome (e.g., 

cis elements involved in integration); or 

c. Have the potential to replicate in a 

cell; or 

d. Can be translated or transcribed. 

No research participant shall be 

enrolled (see definition of enrollment in 

Section I–E–7) until the NIH protocol 

registration process has been completed 

(see Appendix M–I–B, Selection of 

Individual Protocols for Public RAC 

Review and Discussion). 

In its evaluation of human gene 

transfer protocols, NIH will make a 

determination, following a request from 

one or more oversight bodies involved 

in the review at an initial site(s), 

whether a proposed human gene 

transfer experiment meets the 

requirements for selecting protocols for 

public RAC review and discussion (See 

Appendix M–I–B). The process of 

public RAC review and discussion is 

intended to foster the safe and ethical 

conduct of human gene transfer 

experiments. Public review and 

discussion of a human gene transfer 

experiment (and access to relevant 

information) also serves to inform the 

public about the technical aspects of the 

proposal, the meaning and significance 

of the research, and any significant 

safety, social, and ethical implications 

of the research. 

Public RAC review and discussion of 

a human gene transfer experiment will 

be initiated in two exceptional 

circumstances: (1) Following a request 

for public RAC review from one or more 

oversight bodies involved in the review 

at an initial site(s), the NIH concurs that 

(a) the individual protocol would 

significantly benefit from RAC review 

and (b) that the submission meets one 

or more of the following NIH RAC 

review criteria: (i) The protocol uses a 

new vector, genetic material, or delivery 

methodology that represents a first-inhuman experience, thus presenting an 

unknown risk; (ii) the protocol relies on 

preclinical safety data that were 

obtained using a new preclinical model 

system of unknown and unconfirmed 

value; or (iii) the proposed vector, gene 

construct, or method of delivery is 

associated with possible toxicities that 

are not widely known and that may 

render it difficult for oversight and 

federal regulatory bodies to evaluate the 

protocol rigorously. However, if one or 

more oversight bodies involved in the 

review at an initial site(s) requests 

public RAC review, but NIH does not 

concur that (a) the individual protocol 

would significantly benefit from RAC 

review and (b) that the submission 

meets one or more of the RAC review 

criteria (listed in i, ii, or iii), then the 

NIH OSP will inform, within 10 

working days, the requesting and other 

oversight bodies involved in the review 

at an initial site(s) that public RAC 

review is not warranted. (2) The NIH 

Director, in consultation (if needed) 

with appropriate regulatory authorities, 

determines that the submission: (a) 

Meets one or more of the NIH RAC 

review criteria (listed in i, ii, or iii) and 

that public RAC review and discussion 

would provide a clear and obvious 

benefit to the scientific community or 

the public; or (b) raises significant 

scientific, societal, or ethical concerns. 

For a clinical trial site that is added 

after the completion of the NIH protocol 

registration process, no research 

participant shall be enrolled (see 

definition of enrollment in Section I–E– 

7) at the clinical trial site until IBC 

approval and IRB approval from that 

site have been obtained. Within 30 days 

of enrollment (see definition of 

enrollment in Section I–E–7) at a 

clinical trial site, the following 

documentation shall be submitted to 

NIH OSP: (1) Institutional Biosafety 

Committee approval (from the clinical 

trial site); (2) Institutional Review Board 

approval; (3) Institutional Review 

Board-approved informed consent 

document(s); and (4) NIH grant 

number(s) if applicable. 

In order to maintain public access to 

information regarding human gene 

transfer (including protocols that are not 

publicly reviewed by the RAC), the NIH 

OSP will maintain the documentation 

described in Appendices M–I through 

M–II. The information provided in 

response to Appendix M should not 

contain any confidential commercial or 

financial information or trade secrets, 

enabling all aspects of RAC review to be 

open to the public. 

Note: For specific directives concerning the 

use of retroviral vectors for gene delivery, 

consult Appendix B–V–1, Murine Retroviral 

Vectors. 

Section III–C is proposed to be 

amended as follows: 

Section III–C. Experiments Involving 

Human Gene Transfer That Require 

Institutional Biosafety Committee 

Approval Prior to Initiation 

Section III–C–1. Experiments Involving 

the Deliberate Transfer of Recombinant 

or Synthetic Nucleic Acid Molecules, or 

DNA or RNA Derived From 

Recombinant or Synthetic Nucleic Acid 

Molecules, into One or More Human 

Research Participants 

Human gene transfer is the deliberate 

transfer into human research 

participants of either: 

1. Recombinant nucleic acid 

molecules, or DNA or RNA derived from 

recombinant nucleic acid molecules, or 

2. Synthetic nucleic acid molecules, 

or DNA or RNA derived from synthetic 

nucleic acid molecules that meet any 

one of the following criteria: 

a. Contain more than 100 nucleotides; 

or 

b. Possess biological properties that 

enable integration into the genome (e.g., 

cis elements involved in integration); or 

c. Have the potential to replicate in a 

cell; or 

d. Can be translated or transcribed. 

Research cannot be initiated until 

Institutional Biosafety Committee and 

all other applicable institutional and 

regulatory authorization(s) and 

approvals have been obtained. 

An individual patient expanded 

access IND is not research subject to the 

NIH Guidelines and thus does not need 

to be submitted to an IBC, if the 

following conditions are met: (i) A PI is 

submitting an individual patient 

expanded access IND using Form FDA 

3926; (ii) the PI selects the appropriate 

box on that form to request a waiver 

under 21 CFR 56.105 of the 

requirements in 21 CFR 56.108(c); and 

(iii) the FDA concludes that such a 

waiver is appropriate. 


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Section III–D–7–b currently states: 

Section III–D–7–b. Highly Pathogenic 

Avian Influenza H5N1 strains within 

the Goose/Guangdong/96-like H5 

lineage (HPAI H5N1). Experiments 

involving influenza viruses containing a 

majority of genes and/or segments from 

a HPAI H5N1 influenza virus shall be 

conducted at BL3 enhanced 

containment, (see Appendix G–II–C–5, 

Biosafety Level 3 Enhanced for Research 

Involving Risk Group 3 Influenza 

Viruses). Experiments involving 

influenza viruses containing a minority 

of genes and/or segments from a HPAI 

H5N1 influenza virus shall be 

conducted at BL3 enhanced unless a 

risk assessment performed by the IBC 

determines that they can be conducted 

safely at biosafety level 2 and after they 

have been excluded pursuant to 9 CFR 

121.3(e). NIH OSP is available to IBCs 

to provide consultation with the RAC 

and influenza virus experts when risk 

assessments are being made to 

determine the appropriate 

biocontainment for experiments with 

influenza viruses containing a minority 

of gene/segments from HPAI H5N1. 

Such experiments may be performed at 

BL3 enhanced containment or 

containment may be lowered to 

biosafety level 2, the level of 

containment for most research with 

other influenza viruses. (USDA/APHIS 

regulations and decisions on lowering 

containment also apply). In deciding to 

lower containment, the IBC should 

consider whether, in at least two animal 

models (e.g., ferret, mouse, Syrian 

golden hamster, cotton rat, non-human 

primates), there is evidence that the 

resulting influenza virus shows reduced 

replication and virulence compared to 

the parental RG3 virus at relevant doses. 

This should be determined by 

measuring biological indices 

appropriate for the specific animal 

model (e.g., severe weight loss, elevated 

temperature, mortality or neurological 

symptoms). 

Section III–D–7–b is proposed to be 

amended as follows: 

Section III–D–7–b. Highly Pathogenic 

Avian Influenza H5N1 strains within 

the Goose/Guangdong/96-like H5 

lineage (HPAI H5N1). Experiments 

involving influenza viruses containing a 

majority of genes and/or segments from 

a HPAI H5N1 influenza virus shall be 

conducted at BL3 enhanced 

containment, (see Appendix G–II–C–5, 

Biosafety Level 3 Enhanced for Research 

Involving Risk Group 3 Influenza 

Viruses). Experiments involving 

influenza viruses containing a minority 

of genes and/or segments from a HPAI 

H5N1 influenza virus shall be 

conducted at BL3 enhanced unless a 

risk assessment performed by the IBC 

determines that they can be conducted 

safely at biosafety level 2 and after they 

have been excluded pursuant to 9 CFR 

121.3(e). NIH OSP is available to IBCs 

to provide consultation with influenza 

virus experts when risk assessments are 

being made to determine the 

appropriate biocontainment for 

experiments with influenza viruses 

containing a minority of gene/segments 

from HPAI H5N1. Such experiments 

may be performed at BL3 enhanced 

containment or containment may be 

lowered to biosafety level 2, the level of 

containment for most research with 

other influenza viruses. (USDA/APHIS 

regulations and decisions on lowering 

containment also apply). In deciding to 

lower containment, the IBC should 

consider whether, in at least two animal 

models (e.g., ferret, mouse, Syrian 

golden hamster, cotton rat, non-human 

primates), there is evidence that the 

resulting influenza virus shows reduced 

replication and virulence compared to 

the parental RG3 virus at relevant doses. 

This should be determined by 

measuring biological indices 

appropriate for the specific animal 

model (e.g., severe weight loss, elevated 

temperature, mortality or neurological 

symptoms). 

Section III–D–7–d currently states: 

Section III–D–7–d. Antiviral 

Susceptibility and Containment. The 

availability of antiviral drugs as 

preventive and therapeutic measures is 

an important safeguard for experiments 

with 1918 H1N1, HPAI H5N1, and 

human H2N2 (1957–1968). If an 

influenza virus containing genes from 

one of these viruses is resistant to both 

classes of current antiviral agents, 

adamantanes and neuraminidase 

inhibitors, higher containment may be 

required based on the risk assessment 

considering transmissibility to humans, 

virulence, pandemic potential, 

alternative antiviral agents if available, 

etc. 

Experiments with 1918 H1N1, human 

H2N2 (1957–1968) or HPAI H5N1 that 

are designed to create resistance to 

neuraminidase inhibitors or other 

effective antiviral agents (including 

investigational antiviral agents being 

developed for influenza) would be 

subject to Section III–A–1 (Major 

Actions) and require RAC review and 

NIH Director approval. As per Section I– 

A–1 of the NIH Guidelines, if the agent 

is a Select Agent, the NIH will defer to 

the appropriate federal agency (HHS or 

U.S. Department of Agriculture (USDA) 

Select Agent Divisions) on such 

experiments. 

Section III–D–7–d is proposed to be 

amended as follows: 

Section III–D–7–d. Antiviral 

Susceptibility and Containment. The 

availability of antiviral drugs as 

preventive and therapeutic measures is 

an important safeguard for experiments 

with 1918 H1N1, HPAI H5N1, and 

human H2N2 (1957–1968). If an 

influenza virus containing genes from 

one of these viruses is resistant to both 

classes of current antiviral agents, 

adamantanes and neuraminidase 

inhibitors, higher containment may be 

required based on the risk assessment 

considering transmissibility to humans, 

virulence, pandemic potential, 

alternative antiviral agents if available, 

etc. 

Experiments with 1918 H1N1, human 

H2N2 (1957–1968) or HPAI H5N1 that 

are designed to create resistance to 

neuraminidase inhibitors or other 

effective antiviral agents (including 

investigational antiviral agents being 

developed for influenza) would be 

subject to Section III–A–1 (Major 

Actions) and NIH Director approval. As 

per Section I–A–1 of the NIH 

Guidelines, if the agent is a Select 

Agent, NIH will defer to the appropriate 

Federal agency (HHS or USDA Select 

Agent Divisions) on such experiments. 

Section III–F–6 currently states: 

Section III–F–6. Those that consist 

entirely of DNA segments from different 

species that exchange DNA by known 

physiological processes, though one or 

more of the segments may be a synthetic 

equivalent. A list of such exchangers 

will be prepared and periodically 

revised by the NIH Director with advice 

of the RAC after appropriate notice and 

opportunity for public comment (see 

Section IV–C–1–b–(1)–(c), Major 

Actions). See Appendices A–I through 

A–VI, Exemptions under Section III–F– 

6—Sublists of Natural Exchangers, for a 

list of natural exchangers that are 

exempt from the NIH Guidelines. 

Section III–F–6 is proposed to be 

amended as follows: 

Section III–F–6. Those that consist 

entirely of DNA segments from different 

species that exchange DNA by known 

physiological processes, though one or 

more of the segments may be a synthetic 

equivalent. A list of such exchangers 

will be prepared and periodically 

revised by the NIH Director after 

appropriate notice and opportunity for 

public comment (see Section IV–C–1–b– 

(1)–(c), Major Actions). See Appendices 

A–I through A–VI, Exemptions under 

Section III–F–6—Sublists of Natural 

Exchangers, for a list of natural 

exchangers that are exempt from the 

NIH Guidelines. 

Section III–F–8 currently states: 

Section III–F–8. Those that do not 

present a significant risk to health or the 


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environment (see Section IV–C–1–b– 

(1)–(c), Major Actions), as determined 

by the NIH Director, with the advice of 

the RAC, and following appropriate 

notice and opportunity for public 

comment. See Appendix C, Exemptions 

under Section III–F–8 for other classes of 

experiments which are exempt from the 

NIH Guidelines. 

Section III–F–8 is proposed to be 

amended as follows: 

Section III–F–8. Those that do not 

present a significant risk to health or the 

environment (see Section IV–C–1–b– 

(1)–(c), Major Actions), as determined 

by the NIH Director, and following 

appropriate notice and opportunity for 

public comment. See Appendix C, 

Exemptions under Section III–F–8 for 

other classes of experiments which are 

exempt from the NIH Guidelines. 

Section IV–B–1–f currently states: 

Section IV–B–1–f. Ensure that when 

the institution participates in or 

sponsors recombinant or synthetic 

nucleic acid molecule research 

involving human subjects: (i) The 

Institutional Biosafety Committee has 

adequate expertise and training (using 

ad hoc consultants as deemed 

necessary), (ii) all aspects of Appendix 

M have been appropriately addressed by 

the Principal Investigator; and (iii) no 

research participant shall be enrolled 

(see definition of enrollment in Section 

I–E–7) in a human gene transfer 

experiment until the NIH protocol 

registration process has been completed 

(see Appendix M–I–B, Selection of 

Individual Protocols for Public RAC 

Review and Discussion), Institutional 

Biosafety Committee approval has been 

obtained, Institutional Review Board 

approval has been obtained, and all 

applicable regulatory authorizations 

have been obtained. Institutional 

Biosafety Committee approval must be 

obtained from the clinical trial site. 

Section IV–B–1–f is proposed to be 

amended as follows: 

Section IV–B–1–f. Ensure that when 

the institution participates in or 

sponsors recombinant or synthetic 

nucleic acid molecule research 

involving human subjects: (i) The 

Institutional Biosafety Committee has 

adequate expertise and training (using 

ad hoc consultants as deemed 

necessary), and (ii) no human gene 

transfer experiment shall be initiated 

until Institutional Biosafety Committee 

approval has been obtained, and all 

other applicable institutional and 

regulatory authorization(s) and 

approvals have been obtained. 

Institutional Biosafety Committee 

approval must be obtained from the 

clinical trial site. 

None of the other sub-sections under 

Section IV–B–1. General Information are 

proposed to be amended. 

Section IV–B–2–a–(1) currently states: 

Section IV–B–2–a–(1). The 

Institutional Biosafety Committee must 

be comprised of no fewer than five 

members so selected that they 

collectively have experience and 

expertise in recombinant or synthetic 

nucleic acid molecule technology and 

the capability to assess the safety of 

recombinant or synthetic nucleic acid 

molecule research and to identify any 

potential risk to public health or the 

environment. At least two members 

shall not be affiliated with the 

institution (apart from their membership 

on the Institutional Biosafety 

Committee) and who represent the 

interest of the surrounding community 

with respect to health and protection of 

the environment (e.g., officials of state 

or local public health or environmental 

protection agencies, members of other 

local governmental bodies, or persons 

active in medical, occupational health, 

or environmental concerns in the 

community). The Institutional Biosafety 

Committee shall include at least one 

individual with expertise in plant, plant 

pathogen, or plant pest containment 

principles when experiments utilizing 

Appendix P, Physical and Biological 

Containment for Recombinant or 

Synthetic Nucleic Acid Molecule 

Research Involving Plants, require prior 

approval by the Institutional Biosafety 

Committee. The Institutional Biosafety 

Committee shall include at least one 

scientist with expertise in animal 

containment principles when 

experiments utilizing Appendix Q, 

Physical and Biological Containment for 

Recombinant or Synthetic Nucleic Acid 

Molecule Research Involving Animals, 

require Institutional Biosafety 

Committee prior approval. When the 

institution conducts recombinant or 

synthetic nucleic acid molecule 

research at BL3, BL4, or Large Scale 

(greater than 10 liters), a Biological 

Safety Officer is mandatory and shall be 

a member of the Institutional Biosafety 

Committee (see Section IV–B–3, 

Biological Safety Officer). When the 

institution participates in or sponsors 

recombinant or synthetic nucleic acid 

molecule research involving human 

research participants, the institution 

must ensure that: (i) The Institutional 

Biosafety Committee has adequate 

expertise and training (using ad hoc 

consultants as deemed necessary); (ii) 

all aspects of Appendix M have been 

appropriately addressed by the 

Principal Investigator; (iii) no research 

participant shall be enrolled (see 

definition of enrollment in Section I–E– 

7) in a human gene transfer experiment 

until the NIH protocol registration 

process has been completed (see 

Appendix M–I–B, Selection of 

Individual Protocols for Public RAC 

Review and Discussion); and (iv) final 

IBC approval is granted only after the 

NIH protocol registration process has 

been completed (see Appendix M–I–B, 

Selection of Individual Protocols for 

Public RAC Review and Discussion). 

Institutional Biosafety Committee 

approval must be obtained from the 

clinical trial site. 

Section IV–B–2–a–(1) is proposed to 

be amended as follows: 

Section IV–B–2–a–(1). The 

Institutional Biosafety Committee must 

be comprised of no fewer than five 

members so selected that they 

collectively have experience and 

expertise in recombinant or synthetic 

nucleic acid molecule technology and 

the capability to assess the safety of 

recombinant or synthetic nucleic acid 

molecule research and to identify any 

potential risk to public health or the 

environment. At least two members 

shall not be affiliated with the 

institution (apart from their membership 

on the Institutional Biosafety 

Committee) and who represent the 

interest of the surrounding community 

with respect to health and protection of 

the environment (e.g., officials of state 

or local public health or environmental 

protection agencies, members of other 

local governmental bodies, or persons 

active in medical, occupational health, 

or environmental concerns in the 

community). The Institutional Biosafety 

Committee shall include at least one 

individual with expertise in plant, plant 

pathogen, or plant pest containment 

principles when experiments utilizing 

Appendix P, Physical and Biological 

Containment for Recombinant or 

Synthetic Nucleic Acid Molecule 

Research Involving Plants, require prior 

approval by the Institutional Biosafety 

Committee. The Institutional Biosafety 

Committee shall include at least one 

scientist with expertise in animal 

containment principles when 

experiments utilizing Appendix Q, 

Physical and Biological Containment for 

Recombinant or Synthetic Nucleic Acid 

Molecule Research Involving Animals, 

require Institutional Biosafety 

Committee prior approval. When the 

institution conducts recombinant or 

synthetic nucleic acid molecule 

research at BL3, BL4, or Large Scale 

(greater than 10 liters), a Biological 

Safety Officer is mandatory and shall be 

a member of the Institutional Biosafety 

Committee (see Section IV–B–3, 

Biological Safety Officer). When the 

institution participates in or sponsors 


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recombinant or synthetic nucleic acid 

molecule research involving human 

research participants, the institution 

must ensure that the Institutional 

Biosafety Committee has adequate 

expertise and training (using ad hoc 

consultants as deemed necessary). 

Institutional Biosafety Committee 

approval must be obtained from the 

clinical trial site. 

Section IV–B–2–b–(1) currently states: 

Section IV–B–2–b–(1). Reviewing 

recombinant or synthetic nucleic acid 

molecule research conducted at or 

sponsored by the institution for 

compliance with the NIH Guidelines as 

specified in Section III, Experiments 

Covered by the NIH Guidelines, and 

approving 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 

recombinant or synthetic nucleic acid 

molecule research; (iii) ensuring that all 

aspects of Appendix M have been 

appropriately addressed by the 

Principal Investigator; (iv) ensuring that 

no research participant is enrolled (see 

definition of enrollment in Section I–E– 

7) in a human gene transfer experiment 

until the NIH protocol registration 

process has been completed (see 

Appendix M–I–B, Selection of 

Individual Protocols for Public RAC 

Review and Discussion), Institutional 

Biosafety Committee approval (from the 

clinical trial site) has been obtained, 

Institutional Review Board approval has 

been obtained, and all applicable 

regulatory authorizations have been 

obtained; (v) for human gene transfer 

protocols selected for public RAC 

review and discussion, consideration of 

the issues raised and recommendations 

made as a result of this review and 

consideration of the Principal 

Investigator’s response to the 

recommendations; (vi) ensuring that 

final IBC approval is granted only after 

the NIH protocol registration process 

has been completed (see Appendix M– 

I–B, Selection of Individual Protocols for 

Public RAC Review and Discussion); 

and (vii) ensuring compliance with all 

surveillance, data reporting, and adverse 

event reporting requirements set forth in 

the NIH Guidelines. 

Section IV–B–2–b–(1) is proposed to 

be amended as follows: 

Section IV–B–2–b–(1). Reviewing 

recombinant or synthetic nucleic acid 

molecule research conducted at or 

sponsored by the institution for 

compliance with the NIH Guidelines as 

specified in Section III, Experiments 

Covered by the NIH Guidelines, and 

approving 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 

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 (e.g., administration, 

shedding). 

Section IV–B–2–b–(8) currently states: 

Section IV–B–2–b–(8). The 

Institutional Biosafety Committee may 

not authorize initiation of experiments 

which are not explicitly covered by the 

NIH Guidelines until NIH (with the 

advice of the RAC when required) 

establishes the containment 

requirement. 

Section IV–B–2–b–(8) is proposed to 

be amended as follows: 

Section IV–B–2–b–(8). The 

Institutional Biosafety Committee may 

not authorize initiation of experiments 

which are not explicitly covered by the 

NIH Guidelines until NIH establishes 

the containment requirement. 

None of the other sub-sections under 

Section IV–B–2. Institutional Biosafety 

Committee (IBC) are proposed to be 

amended. 

Section IV–B–6 currently states: 

Section IV–B–6. Human Gene Therapy 

Expertise 

When the institution participates in or 

sponsors recombinant or synthetic 

nucleic acid molecule research 

involving human subjects, the 

institution must ensure that: (i) The 

Institutional Biosafety Committee has 

adequate expertise and training (using 

ad hoc consultants as deemed 

necessary) and (ii) all aspects of 

Appendix M, Points to Consider in the 

Design and Submission of Protocols for 

the Transfer of Recombinant or 

Synthetic Nucleic Acid Molecules into 

One or More Human Subjects (Points to 

Consider), have been appropriately 

addressed by the Principal Investigator 

prior to its approval. 

Section IV–B–6 is proposed to be 

amended as follows: 

Section IV–B–6. Human Gene Transfer 

Expertise 

When the institution participates in or 

sponsors recombinant or synthetic 

nucleic acid molecule research 

involving human subjects, the 

institution must ensure that the 

Institutional Biosafety Committee has 

adequate expertise and training (using 

ad hoc consultants as deemed 

necessary). 

Section IV–B–7 currently states: 

Section IV–B–7. Principal Investigator 

(PI) 

On behalf of the institution, the 

Principal Investigator is responsible for 

full compliance with the NIH 

Guidelines in the conduct of 

recombinant or synthetic nucleic acid 

molecule research. A Principal 

Investigator engaged in human gene 

transfer research may delegate to 

another party, such as a corporate 

sponsor, the reporting functions set 

forth in Appendix M, with written 

notification to the NIH OSP of the 

delegation and of the name(s), address, 

telephone, and fax numbers of the 

contact. The Principal Investigator is 

responsible for ensuring that the 

reporting requirements are fulfilled and 

will be held accountable for any 

reporting lapses. 

Section IV–B–7 is proposed to be 

amended as follows: 

Section IV–B–7. Principal Investigator 

(PI) 

On behalf of the institution, the 

Principal Investigator is responsible for 

full compliance with the NIH 

Guidelines in the conduct of 

recombinant or synthetic nucleic acid 

molecule research. 

Section IV–B–7–b–(6) is proposed to 

be deleted in its entirety 

Section IV–B–7–e–(5) is proposed to 

be deleted in its entirety 

None of the other sub-sections under 

Section IV–B–7. Principal Investigator 

are proposed to be amended. 

Section IV–C currently states: 

Section IV–C. Responsibilities of the 

National Institutes of Health (NIH) 

Section IV–C–1. NIH Director 

The NIH Director is responsible for: (i) 

Establishing the NIH Guidelines, (ii) 

overseeing their implementation, and 

(iii) their final interpretation. The NIH 

Director has responsibilities under the 

NIH Guidelines that involve OSP and 

RAC. OSP’s responsibilities under the 

NIH Guidelines are administrative. 

Advice from RAC is primarily scientific, 

technical, and ethical. In certain 

circumstances, there is specific 

opportunity for public comment with 

published response prior to final action. 

Section IV–C–1-a. General 

Responsibilities 

The NIH Director is responsible for: 


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Section IV–C–1–a–(1). Promulgating 

requirements as necessary to implement 

the NIH Guidelines; 

Section IV–C–1–a–(2). Establishing 

and maintaining RAC to carry out the 

responsibilities set forth in Section IV– 

C–2, Recombinant DNA Advisory 

Committee (RAC membership is 

specified in its charter and in Section 

IV–C–2); 

Section IV–C–1–a–(3). Establishing 

and maintaining NIH OSP to carry out 

the responsibilities defined in Section 

IV–C–3, Office of Science Policy; 

Section IV–C–1–a–(4). Conducting 

and supporting training programs in 

laboratory safety for Institutional 

Biosafety Committee members, 

Biological Safety Officers and other 

institutional experts (if applicable), 

Principal Investigators, and laboratory 

staff. 

Section IV–C–1–a–(5). Establishing 

and convening Gene Therapy Policy 

Conferences as described in Appendix 

L, Gene Therapy Policy Conferences. 

Section IV–C–1–b. Specific 

Responsibilities 

In carrying out the responsibilities set 

forth in this section, the NIH Director, 

or a designee shall weigh each proposed 

action through appropriate analysis and 

consultation to determine whether it 

complies with the NIH Guidelines and 

presents no significant risk to health or 

the environment. 

Section IV–C–1–b–(1). Major Actions 

To execute Major Actions, the NIH 

Director shall seek the advice of RAC 

and provide an opportunity for public 

and federal agency comment. 

Specifically, the Notice of Meeting and 

Proposed Actions shall be published in 

the Federal Register at least 15 days 

before the RAC meeting. The NIH 

Director’s decision/recommendation (at 

his/her discretion) may be published in 

the Federal Register for 15 days of 

comment before final action is taken. 

The NIH Director’s final decision/ 

recommendation, along with responses 

to public comments, shall be published 

in the Federal Register. The RAC and 

Institutional Biosafety Committee Chairs 

shall be notified of the following 

decisions: 

Section IV–C–1–b–(1)–(a). Changing 

containment levels for types of 

experiments that are specified in the 

NIH Guidelines when a Major Action is 

involved; 

Section IV–C–1–b–(1)–(b). Assigning 

containment levels for types of 

experiments that are not explicitly 

considered in the NIH Guidelines when 

a Major Action is involved; 

Section IV–C–1–b–(1)–(c). 

Promulgating and amending a list of 

classes of recombinant or synthetic 

nucleic acid molecules to be exempt 

from the NIH Guidelines because they 

consist entirely of DNA segments from 

species that exchange DNA by known 

physiological processes or otherwise do 

not present a significant risk to health 

or the environment; 

Section IV–C–1–b–(1)–(d). Permitting 

experiments specified by Section III–A, 

Experiments that Require Institutional 

Biosafety Committee Approval, RAC 

Review, and NIH Director Approval 

Before Initiation; 

Section IV–C–1–b–(1)–(e). Certifying 

new host-vector systems with the 

exception of minor modifications of 

already certified systems (the standards 

and procedures for certification are 

described in Appendix I–II, Certification 

of Host-Vector Systems). Minor 

modifications constitute (e.g., those of 

minimal or no consequence to the 

properties relevant to containment); and 

Section IV–C–1–b–(1)–(f). Adopting 

other changes in the NIH Guidelines. 

Section IV–C–1–b–(2). Minor Actions 

NIH OSP shall carry out certain 

functions as delegated to it by the NIH 

Director (see Section IV–C–3, Office of 

Science Policy). Minor Actions (as 

determined by NIH OSP in consultation 

with the RAC Chair and one or more 

RAC members, as necessary) will be 

transmitted to RAC and Institutional 

Biosafety Committee Chairs: 

Section IV–C–1–b–(2)–(a). Changing 

containment levels for experiments that 

are specified in Section III, Experiments 

Covered by the NIH Guidelines (except 

when a Major Action is involved); 

Section IV–C–1–b–(2)–(b). Assigning 

containment levels for experiments not 

explicitly considered in the NIH 

Guidelines; 

Section IV–C–1–b–(2)–(c). Revising 

the Classification of Etiologic Agents for 

the purpose of these NIH Guidelines 

(see Section V–A, Footnotes and 

References of Sections I–IV). 

Section IV–C–1–b–(2)–(d). 

Interpreting the NIH Guidelines for 

experiments to which the NIH 

Guidelines do not specifically assign 

containment levels; 

Section IV–C–1–b–(2)–(e). Setting 

containment under Sections III–D–1–d, 

Experiments Using Risk Group 2, Risk 

Group 3, Risk Group 4, or Restricted 

Agents as Host-Vector Systems, and III– 

D–2–b, 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; 

Section IV–C–1–b–(2)–(f). Approving 

minor modifications of already certified 

host-vector systems (the standards and 

procedures for such modifications are 

described in Appendix I–II, Certification 

of Host-Vector Systems); 

Section IV–C–1–b–(2)–(g). 

Decertifying already certified hostvector systems; 

Section IV–C–1–b–(2)–(h). Adding 

new entries to the list of molecules toxic 

for vertebrates (see Appendix F, 

Containment Conditions for Cloning of 

Genes Coding for the Biosynthesis of 

Molecules Toxic for Vertebrates); and 

Section IV–C–1–b–(2)–(i). 

Determining appropriate containment 

conditions for experiments according to 

case precedents developed under 

Section IV–C–1–b–(2)–(c). 

Section IV–C is proposed to be 

amended as follows: 

Section IV–C. Responsibilities of the 

National Institutes of Health (NIH) 

Section IV–C–1. NIH Director 

The NIH Director is responsible for: (i) 

Establishing the NIH Guidelines, (ii) 

overseeing their implementation, and 

(iii) their final interpretation. The NIH 

Director has responsibilities under the 

NIH Guidelines that involve OSP. OSP’s 

responsibilities under the NIH 

Guidelines are administrative. In certain 

circumstances, there is specific 

opportunity for public comment with 

published response prior to final action. 

Section IV–C–1–a. General 

Responsibilities 

The NIH Director is responsible for: 

Section IV–C–1–a–(1). Promulgating 

requirements as necessary to implement 

the NIH Guidelines; 

Section IV–C–1–a–(2). Establishing 

and maintaining NIH OSP to carry out 

the responsibilities defined in Section 

IV–C–3, Office of Science Policy; 

Section IV–C–1–a–(3). Conducting 

and supporting training programs in 

laboratory safety for Institutional 

Biosafety Committee members, 

Biological Safety Officers and other 

institutional experts (if applicable), 

Principal Investigators, and laboratory 

staff. 

Section IV–C–1–b. Specific 

Responsibilities 

In carrying out the responsibilities set 

forth in this section, the NIH Director or 

a designee shall weigh each proposed 

action through appropriate analysis and 

consultation to determine whether it 

complies with the NIH Guidelines and 

presents no significant risk to health or 

the environment. 


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Section IV–C–1–b–(1). Major Actions 

To execute Major Actions, the NIH 

Director shall provide an opportunity 

for public and Federal agency comment. 

The NIH Director’s decision/ 

recommendation (at his/her discretion) 

may be published in the Federal 

Register for 15 days of comment before 

final action is taken. The NIH Director’s 

final decision/recommendation, along 

with responses to public comments, 

shall be published in the Federal 

Register. Institutional Biosafety 

Committee Chairs shall be notified of 

the following decisions: 

Section IV–C–1–b–(1)–(a). Changing 

containment levels for types of 

experiments that are specified in the 

NIH Guidelines when a Major Action is 

involved; 

Section IV–C–1–b–(1)–(b). Assigning 

containment levels for types of 

experiments that are not explicitly 

considered in the NIH Guidelines when 

a Major Action is involved; 

Section IV–C–1–b–(1)–(c). 

Promulgating and amending a list of 

classes of recombinant or synthetic 

nucleic acid molecules to be exempt 

from the NIH Guidelines because they 

consist entirely of DNA segments from 

species that exchange DNA by known 

physiological processes or otherwise do 

not present a significant risk to health 

or the environment; 

Section IV–C–1–b–(1)–(d). Permitting 

experiments specified by Section III–A, 

Experiments that Require Institutional 

Biosafety Committee Approval, and NIH 

Director Approval Before Initiation; 

Section IV–C–1–b–(1)–(e). Certifying 

new host-vector systems with the 

exception of minor modifications (e.g., 

those of minimal or no consequence to 

the properties relevant to containment) 

of already certified systems (the 

standards and procedures for 

certification are described in Appendix 

I–II, Certification of Host-Vector 

Systems; and 

Section IV–C–1–b–(1)–(f). Adopting 

other changes in the NIH Guidelines. 

Section IV–C–1–b–(2). Minor Actions 

NIH OSP shall carry out certain 

functions as delegated to it by the NIH 

Director (see Section IV–C–3, Office of 

Science Policy). Minor Actions will be 

transmitted to Institutional Biosafety 

Committee Chairs: 

Section IV–C–1–b–(2)–(a). Changing 

containment levels for experiments that 

are specified in Section III, Experiments 

Covered by the NIH Guidelines (except 

when a Major Action is involved); 

Section IV–C–1–b–(2)–(b). Assigning 

containment levels for experiments not 

explicitly considered in the NIH 

Guidelines; 

Section IV–C–1–b–(2)–(c). Revising 

the Classification of Etiologic Agents for 

the purpose of these NIH Guidelines 

(see Section V–A, Footnotes and 

References of Sections I–IV). 

Section IV–C–1–b–(2)–(d). 

Interpreting the NIH Guidelines for 

experiments to which the NIH 

Guidelines do not specifically assign 

containment levels; 

Section IV–C–1–b–(2)–(e). Setting 

containment under Sections III–D–1–d, 

Experiments Using Risk Group 2, Risk 

Group 3, Risk Group 4, or Restricted 

Agents as Host-Vector Systems, and III– 

D–2–b, 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; 

Section IV–C–1–b–(2)–(f). Approving 

minor modifications of already certified 

host-vector systems (the standards and 

procedures for such modifications are 

described in Appendix I–II, Certification 

of Host-Vector Systems); 

Section IV–C–1–b–(2)–(g). 

Decertifying already certified hostvector systems; 

Section IV–C–1–b–(2)–(h). Adding 

new entries to the list of molecules toxic 

for vertebrates (see Appendix F, 

Containment Conditions for Cloning of 

Genes Coding for the Biosynthesis of 

Molecules Toxic for Vertebrates); and 

Section IV–C–1–b–(2)–(i). 

Determining appropriate containment 

conditions for experiments according to 

case precedents developed under 

Section IV–C–1–b–(2)–(c). 

Section IV–C–2. Recombinant DNA 

Advisory Committee (RAC) is proposed 

to be deleted in its entirety. 

Section IV–C–3. Office of Science 

Policy (OSP) is proposed to be amended 

as follows: 

Sections IV–C–3–a through IV–C–3–f 

are proposed to be deleted in their 

entirety. Section IV–C–3–h is proposed 

to be deleted in its entirety. Section IV– 

C–3–g will be renumbered to Section 

IV–C–3–a. Section IV–C–i will be 

renumbered to Section IV–C–3–b; 

Section IV–C–3–i–(1), Section IV–C–3– 

i–(2) and Section IV–C–3–i–(3) are 

proposed to be deleted in their entirety. 

Section IV–C–3–j will be renumbered to 

Section IV–C–3–c. 

Section IV–C–3 is proposed to be 

amended as follows: 

Section IV–C–3. Office of Science Policy 

(OSP) 

OSP shall serve as a focal point for 

information on recombinant or synthetic 

nucleic acid molecule activities and 

provide advice to all within and outside 

NIH including institutions, Biological 

Safety Officers, Principal Investigators, 

Federal agencies, state and local 

governments, and institutions in the 

private sector. OSP shall carry out such 

other functions as may be delegated to 

it by the NIH Director. OSP’s 

responsibilities include (but are not 

limited to) the following: 

Section IV–C–3–a. Reviewing and 

approving experiments 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 body weight in 

organisms other than Escherichia coli 

K–12 (see Section III–B–1, Experiments 

Involving the Cloning of Toxin 

Molecules with LD50 of Less than 100 

Nanograms Per Kilogram Body Weight, 

Appendix F, Containment Conditions 

for Cloning of Genes Coding for the 

Biosynthesis of Molecules Toxic for 

Vertebrates); 

Section IV–C–3–b. Publishing in the 

Federal Register, as needed. 

Section IV–C–3–c. Reviewing and 

approving the membership of an 

institution’s Institutional Biosafety 

Committee, and where it finds the 

Institutional Biosafety Committee meets 

the requirements set forth in Section IV– 

B–2, Institutional Biosafety Committee 

(IBC), giving its approval to the 

Institutional Biosafety Committee 

membership. 

Section IV–D–5 currently states: 

Section IV–D–5. Protection of 

Proprietary Data—Voluntary 

Compliance 

Section IV–D–5–a. General 

In general, the Freedom of 

Information Act requires federal 

agencies to make their records available 

to the public upon request. However, 

this requirement does not apply to, 

among other things, ‘‘trade secrets and 

commercial or financial information 

that is obtained from a person and that 

is privileged or confidential.’’ Under 18 

U.S.C. 1905, it is a criminal offense for 

an officer or employee of the U.S. or any 

federal department or agency to publish, 

divulge, disclose, or make known ‘‘in 

any manner or to any extent not 

authorized by law any information 

coming to him in the course of his 

employment or official duties or by 

reason of any examination or 

investigation made by, or return, report 

or record made to or filed with, such 

department or agency or officer or 

employee thereof, which information 

concerns or relates to the trade secrets, 

(or) processes . . . of any person, firm, 

partnership, corporation, or 

association.’’ This provision applies to 

all employees of the federal government, 

including special Government 


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employees. Members of RAC are 

‘‘special Government employees.’’ 

Section IV–D–5 is proposed to be 

amended as follows: 

Section IV–D–5–a. General 

In general, the Freedom of 

Information Act requires federal 

agencies to make their records available 

to the public upon request. However, 

this requirement does not apply to, 

among other things, ‘‘trade secrets and 

commercial or financial information 

that is obtained from a person and that 

is privileged or confidential.’’ Under 18 

U.S.C. 1905, it is a criminal offense for 

an officer or employee of the United 

States or any federal department or 

agency to publish, divulge, disclose, or 

make known ‘‘in any manner or to any 

extent not authorized by law any 

information coming to him in the course 

of his employment or official duties or 

by reason of any examination or 

investigation made by, or return, report 

or record made to or filed with, such 

department or agency or officer or 

employee thereof, which information 

concerns or relates to the trade secrets, 

(or) processes . . . of any person, firm, 

partnership, corporation, or 

association.’’ This provision applies to 

all employees of the federal government, 

including special Government 

employees. 

None of the other sub-sections under 

Section IV are proposed to be amended. 

Section V currently states: 

Section V. Footnotes and References of 

Sections I through IV 

Section V–A. The NIH Director, with 

advice of the RAC, may revise the 

classification for the purposes of the 

NIH Guidelines (see Section IV–C–1–b– 

(2)–(e), Minor Actions). The revised list 

of organisms in each Risk Group is 

reprinted in Appendix B, Classification 

of Human Etiologic Agents on the Basis 

of Hazard. 

Section V–B. Section III, Experiments 

Covered by the NIH Guidelines, 

describes a number of places where 

judgments are to be made. In all these 

cases, the Principal Investigator shall 

make the judgment on these matters as 

part of his/her responsibility to ‘‘make 

the initial determination of the required 

levels of physical and biological 

containment in accordance with the 

NIH Guidelines’’ (see Section IV–B–7– 

c–(1)). For cases falling under Sections 

III–A through III–E, Experiments 

Covered by the NIH Guidelines, this 

judgment is to be reviewed and 

approved by the Institutional Biosafety 

Committee as part of its responsibility to 

make an ‘‘independent assessment of 

the containment levels required by the 

NIH Guidelines for the proposed 

research’’ (see Section IV–B–2–b–(1), 

Institutional Biosafety Committee). The 

Institutional Biosafety Committee may 

refer specific cases to NIH OSP as part 

of NIH OSP’s functions to ‘‘provide 

advice to all within and outside NIH’’ 

(see Section IV–C–3). NIH OSP may 

request advice from the RAC as part of 

the RAC’s responsibility for 

‘‘interpreting the NIH Guidelines for 

experiments to which the NIH 

Guidelines do not specifically assign 

containment levels’’ (see Section IV–C– 

1–b–(2)–(f), Minor Actions). 

Section V is proposed to be amended 

as follows: 

Section V–A. The NIH Director may 

revise the classification for the purposes 

of the NIH Guidelines (see Section IV– 

C–1–b–(2)–(e), Minor Actions). The 

revised list of organisms in each Risk 

Group is reprinted in Appendix B, 

Classification of Human Etiologic 

Agents on the Basis of Hazard. 

Section V–B. Section III, Experiments 

Covered by the NIH Guidelines, 

describes a number of places where 

judgments are to be made. In all these 

cases, the Principal Investigator shall 

make the judgment on these matters as 

part of his/her responsibility to ‘‘make 

the initial determination of the required 

levels of physical and biological 

containment in accordance with the 

NIH Guidelines’’ (see Section IV–B–7– 

c–(1)). For cases falling under Sections 

III–A through III–E, Experiments 

Covered by the NIH Guidelines, this 

judgment is to be reviewed and 

approved by the Institutional Biosafety 

Committee as part of its responsibility to 

make an ‘‘independent assessment of 

the containment levels required by the 

NIH Guidelines for the proposed 

research’’ (see Section IV–B–2–b–(1), 

Institutional Biosafety Committee). The 

Institutional Biosafety Committee may 

refer specific cases to NIH OSP as part 

of NIH OSP’s functions to ‘‘provide 

advice to all within and outside NIH’’ 

(see Section IV–C–3). 

Appendix A currently states: 

Appendix A. Exemptions Under Section 

III–F–6—Sublists of Natural Exchangers 

Certain specified recombinant or synthetic 

nucleic acid molecules that consist entirely 

of DNA segments from different species that 

exchange DNA by known physiological 

processes, though one or more of the 

segments may be a synthetic equivalent are 

exempt from these NIH Guidelines (see 

Section III–F–6, Exempt Experiments). 

Institutional Biosafety Committee registration 

is not required for these exempt experiments. 

A list of such exchangers will be prepared 

and periodically revised by the NIH Director 

with advice from the RAC after appropriate 

notice and opportunity for public comment 

(see Section IV–C–1-b-(1)-(c), NIH Director— 

Specific Responsibilities). For a list of natural 

exchangers that are exempt from the NIH 

Guidelines, see Appendices A–I through A– 

VI, Exemptions under Section III–F–6 

Sublists of Natural Exchangers. Section III– 

F–6, Exempt Experiments, describes 

recombinant or synthetic nucleic acid 

molecules that are: (1) Composed entirely of 

DNA segments from one or more of the 

organisms within a sublist, and (2) to be 

propagated in any of the organisms within a 

sublist (see Classification of Bergey’s Manual 

of Determinative Bacteriology; 8th edition, 

R.E. Buchanan and N.E. Gibbons, editors, 

Williams and Wilkins Company; Baltimore, 

Maryland 1984). Although these experiments 

are exempt, it is recommended that they be 

performed at the appropriate biosafety level 

for the host or recombinant/synthetic 

organism (see Biosafety in Microbiological 

and Biomedical Laboratories, 5th edition, 

2007, U.S. DHHS, Public Health Service, 

Centers for Disease Control and Prevention, 

Atlanta, Georgia, and NIH Office of Biosafety, 

Bethesda, Maryland). 

Appendix A is proposed to be 

amended as follows: 

Appendix A. Exemptions Under Section 

III–F–6—Sublists of Natural Exchangers 

Certain specified recombinant or synthetic 

nucleic acid molecules that consist entirely 

of DNA segments from different species that 

exchange DNA by known physiological 

processes, though one or more of the 

segments may be a synthetic equivalent are 

exempt from these NIH Guidelines (see 

Section III–F–6, Exempt Experiments). 

Institutional Biosafety Committee registration 

is not required for these exempt experiments. 

A list of such exchangers will be prepared 

and periodically revised by the NIH Director 

after appropriate notice and opportunity for 

public comment (see Section IV–C–1-b-(1)- 

(c), NIH Director—Specific Responsibilities. 

For a list of natural exchangers that are 

exempt from the NIH Guidelines, see 

Appendices A–I through A–VI, Exemptions 

under Section III–F–6 Sublists of Natural 

Exchangers. Section III–F–6, Exempt 

Experiments, describes recombinant or 

synthetic nucleic acid molecules that are: (1) 

Composed entirely of DNA segments from 

one or more of the organisms within a 

sublist, and (2) to be propagated in any of the 

organisms within a sublist (see Bergey’s 

Manual of Systematic Bacteriology; 2nd 

edition, Springer-Verlag; New York, NY). 

Although these experiments are exempt, it is 

recommended that they be performed at the 

appropriate biosafety level for the host or 

recombinant/synthetic organism (see 

Biosafety in Microbiological and Biomedical 

Laboratories, 5th edition, 2007, U.S. DHHS, 

Public Health Service, Centers for Disease 

Control and Prevention, Atlanta, Georgia, and 

NIH Office of Biosafety, Bethesda, Maryland). 

Appendix C–IX–A currently states: 

Appendix C–IX–A 

The NIH Director, with advice of the RAC, 

may revise the classification for the purposes 

of these NIH Guidelines (see Section IV–C– 


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1–b–(2)–(b), Minor Actions). The revised list 

of organisms in each Risk Group is located 

in Appendix B. 

Appendix C–IX–A is proposed to be 

amended as follows: 

Appendix C–IX–A 

The NIH Director may revise the 

classification for the purposes of these NIH 

Guidelines (see Section IV–C–1–b–(2)–(b), 

Minor Actions). The revised list of organisms 

in each Risk Group is located in Appendix 

B. 

None of the other sub-sections under 

Appendix C–IX. Footnotes and 

References of Appendix C are proposed 

to be amended. 

Appendix D currently states in part: 

Appendix D. Major Actions Taken 

Under the NIH Guidelines 

As noted in the subsections of Section IV– 

C–1–b–(1), the Director, NIH, may take 

certain actions with regard to the NIH 

Guidelines after the issues have been 

considered by the RAC. Some of the actions 

taken to date include the following: 

Appendix D is proposed to be 

amended as follows: 

Appendix D. Major Actions Taken 

Under the NIH Guidelines 

As noted in the subsections of Section IV– 

C–1–b–(1), the Director, NIH, may take 

certain actions with regard to the NIH 

Guidelines. (Entries up to and including D– 

118 were approved using a process that 

involved the RAC.) Some of the actions taken 

to date include the following: 

Appendix I–II currently states: 

Appendix I–II. Certification of HostVector Systems 

Appendix I–II–A. Responsibility 

Host-Vector 1 systems (other than 

Escherichia coli K–12) and Host-Vector 2 

systems may not be designated as such until 

they have been certified by the NIH Director. 

Requests for certification of host-vector 

systems may be submitted to the Office of 

Science Policy, National Institutes of Health, 

preferably by email to: NIHGuidelines@

od.nih.gov; additional contact information is 

also available here and on the OSP website 

(www.osp.od.nih.gov). Proposed host-vector 

systems will be reviewed by the RAC (see 

Section IV–C–1–b–(1)–(f), Major Actions). 

Initial review will based on the construction, 

properties, and testing of the proposed hostvector system by a subcommittee composed 

of one or more RAC members and/or ad hoc 

experts. The RAC will evaluate the 

subcommittee’s report and any other 

available information at the next scheduled 

RAC meeting. The NIH Director is 

responsible for certification of host-vector 

systems, following advice of the RAC. Minor 

modifications to existing host-vector systems 

(i.e., those that are of minimal or no 

consequence to the properties relevant to 

containment) may be certified by the NIH 

Director without prior RAC review (see 

Section IV–C–1–b–(2)–(f), Minor Actions). 

Once a host-vector system has been certified 

by the NIH Director, a notice of certification 

will be sent by NIH OSP to the applicant and 

to the Institutional Biosafety Committee 

Chairs. A list of all currently certified hostvector systems is available from the Office of 

Science Policy, National Institutes of Health, 

preferably by submitting a request for this 

information to: NIHGuidelines@od.nih.gov; 

additional contact information is also 

available here and on the OSP website 

(www.osp.od.nih.gov). The NIH Director may 

rescind the certification of a host-vector 

system (see Section IV–C–1–b–(2)–(g), Minor 

Actions). If certification is rescinded, NIH 

will instruct investigators to transfer cloned 

DNA into a different system or use the clones 

at a higher level of physical containment 

level, unless NIH determines that the already 

constructed clones incorporate adequate 

biological containment. Certification of a 

host-vector system does not extend to 

modifications of either the host or vector 

component of that system. Such modified 

systems shall be independently certified by 

the NIH Director. If modifications are minor, 

it may only be necessary for the investigator 

to submit data showing that the 

modifications have either improved or not 

impaired the major phenotypic traits on 

which the containment of the system 

depends. Substantial modifications to a 

certified host-vector system requires 

submission of complete testing data. 

Appendix I–II–B. Data To Be Submitted 

for Certification 

Appendix I–II–B–1. Host-Vector 1 

Systems Other than Escherichia coli 

K–12 

The following types of data shall be 

submitted, modified as appropriate for the 

particular system under consideration: (i) A 

description of the organism and vector; the 

strain’s natural habitat and growth 

requirements; its physiological properties, 

particularly those related to its reproduction, 

survival, and the mechanisms by which it 

exchanges genetic information; the range of 

organisms with which this organism 

normally exchanges genetic information and 

the type of information is exchanged; and 

any relevant information about its 

pathogenicity or toxicity; (ii) a description of 

the history of the particular strains and 

vectors to be used, including data on any 

mutations which render this organism less 

able to survive or transmit genetic 

information; and (iii) a general description of 

the range of experiments contemplated with 

emphasis on the need for developing such an 

Host-Vector 1 system. 

Appendix I–II–B–2. Host-Vector 2 

Systems 

Investigators planning to request HostVector 2 systems certification may obtain 

instructions from NIH OSP concerning data 

to be submitted (see Appendices I–III–N and 

O, Footnotes and References of Appendix I). 

In general, the following types of data are 

required: (i) Description of construction steps 

with indication of source, properties, and 

manner of introduction of genetic traits; (ii) 

quantitative data on the stability of genetic 

traits that contribute to the containment of 

the system; (iii) data on the survival of the 

host-vector system under non-permissive 

laboratory conditions designed to represent 

the relevant natural environment; (iv) data on 

transmissibility of the vector and/or a cloned 

DNA fragment under both permissive and 

non-permissive conditions; (v) data on all 

other properties of the system which affect 

containment and utility, including 

information on yields of phage or plasmid 

molecules, ease of DNA isolation, and ease of 

transfection or transformation; and (vi) in 

some cases, the investigator may be asked to 

submit data on survival and vector 

transmissibility from experiments in which 

the host-vector is fed to laboratory animals or 

one or more human subjects. Such in vivo 

data may be required to confirm the validity 

of predicting in vivo survival on the basis of 

in vitro experiments. Data shall be submitted 

12 weeks prior to the RAC meeting at which 

such data will be considered by the Office of 

Science Policy, National Institutes of Health, 

preferably by email to: NIHGuidelines@

od.nih.gov; additional contact information is 

also available here and on the OSP website 

(www.osp.od.nih.gov). Investigators are 

encouraged to publish their data on the 

construction, properties, and testing of 

proposed Host Vector 2 systems prior to 

consideration of the system by the RAC and 

its subcommittee. Specific instructions 

concerning the submission of data for 

proposed Escherichia coli K–12 Host-Vector 

2 system (EK2) involving either plasmids or 

bacteriophage in Escherichia coli K–12, are 

available from the Office of Science Policy, 

National Institutes of Health, preferably by 

submitting a request for this information to: 

NIHGuidelines@od.nih.gov;additional 

contact information is also available here and 

on the OSP website (www.osp.od.nih.gov). 

Appendix I–II is proposed to be 

amended as follows: 

Appendix I–II. Certification of HostVector Systems 

Appendix I–II–A. Responsibility 

Host-Vector 1 systems (other than 

Escherichia coli K–12) and Host-Vector 2 

systems may not be designated as such until 

they have been certified by the NIH Director. 

Requests for certification of host-vector 

systems may be submitted to the Office of 

Science Policy, National Institutes of Health, 

preferably by email to: NIHGuidelines@

od.nih.gov; additional contact information is 

also available here and on the OSP website 

(www.osp.od.nih.gov). Proposed host-vector 

systems will be reviewed based on the 

construction, properties, and testing of the 

proposed host-vector system by ad hoc 

experts. The NIH Director is responsible for 

certification of host-vector systems. Once a 

host-vector system has been certified by the 

NIH Director, a notice of certification will be 

sent by NIH OSP to the applicant and to the 

Institutional Biosafety Committee Chairs. A 

list of all currently certified host-vector 

systems is available from the Office of 

Science Policy, National Institutes of Health, 

preferably by submitting a request for this 

information to: NIHGuidelines@od.nih.gov; 


amozie on DSK3GDR082PROD with NOTICES1
Federal Register / Vol. 83, No. 160 / Friday, August 17, 2018 / Notices 41093 

additional contact information is also 

available here and on the OSP website 

(www.osp.od.nih.gov). The NIH Director may 

rescind the certification of a host-vector 

system (see Section IV–C–1–b–(2)–(g), Minor 

Actions). If certification is rescinded, NIH 

will instruct investigators to transfer cloned 

DNA into a different system or use the clones 

at a higher level of physical containment 

level, unless NIH determines that the already 

constructed clones incorporate adequate 

biological containment. Certification of a 

host-vector system does not extend to 

modifications of either the host or vector 

component of that system. Such modified 

systems shall be independently certified by 

the NIH Director. If modifications are minor, 

it may only be necessary for the investigator 

to submit data showing that the 

modifications have either improved or not 

impaired the major phenotypic traits on 

which the containment of the system 

depends. Substantial modifications to a 

certified host-vector system requires 

submission of complete testing data. 

Appendix I–II–B. Data To Be Submitted 

for Certification 

Appendix I–II–B–1. Host-Vector 1 

Systems Other than Escherichia coli 

K–12 

The following types of data shall be 

submitted, modified as appropriate for the 

particular system under consideration: (i) A 

description of the organism and vector; the 

strain’s natural habitat and growth 

requirements; its physiological properties, 

particularly those related to its reproduction, 

survival, and the mechanisms by which it 

exchanges genetic information; the range of 

organisms with which this organism 

normally exchanges genetic information and 

the type of information is exchanged; and 

any relevant information about its 

pathogenicity or toxicity; (ii) a description of 

the history of the particular strains and 

vectors to be used, including data on any 

mutations which render this organism less 

able to survive or transmit genetic 

information; and (iii) a general description of 

the range of experiments contemplated with 

emphasis on the need for developing such an 

Host-Vector 1 system. 

Appendix I–II–B–2. Host-Vector 2 

Systems 

Investigators planning to request HostVector 2 systems certification may obtain 

instructions from NIH OSP concerning data 

to be submitted (see Appendices I–III–N and 

O, Footnotes and References of Appendix I). 

In general, the following types of data are 

required: (i) Description of construction steps 

with indication of source, properties, and 

manner of introduction of genetic traits; (ii) 

quantitative data on the stability of genetic 

traits that contribute to the containment of 

the system; (iii) data on the survival of the 

host-vector system under non-permissive 

laboratory conditions designed to represent 

the relevant natural environment; (iv) data on 

transmissibility of the vector and/or a cloned 

DNA fragment under both permissive and 

non-permissive conditions; (v) data on all 

other properties of the system which affect 

containment and utility, including 

information on yields of phage or plasmid 

molecules, ease of DNA isolation, and ease of 

transfection or transformation; and (vi) in 

some cases, the investigator may be asked to 

submit data on survival and vector 

transmissibility from experiments in which 

the host-vector is fed to laboratory animals or 

one or more human subjects. Such in vivo 

data may be required to confirm the validity 

of predicting in vivo survival on the basis of 

in vitro experiments. Data shall be submitted 

to the Office of Science Policy, National 

Institutes of Health, preferably by email to: 

NIHGuidelines@od.nih.gov; additional 

contact information is also available here and 

on the OSP website (www.osp.od.nih.gov). 

Investigators are encouraged to publish their 

data on the construction, properties, and 

testing of proposed Host Vector 2 systems 

prior to consideration of the system by NIH. 

Specific instructions concerning the 

submission of data for proposed Escherichia 

coli K–12 Host-Vector 2 system (EK2) 

involving either plasmids or bacteriophage in 

Escherichia coli K–12, are available from the 

Office of Science Policy, National Institutes 

of Health, preferably by submitting a request 

for this information to: NIHGuidelines@

od.nih.gov; additional contact information is 

also available here and on the OSP website 

(www.osp.od.nih.gov). 

Appendix L, GENE THERAPY 

POLICY CONFERENCES (GTPCS), is 

proposed to be deleted in its entirety. 

Appendix M, Points to Consider in 

the Design and Submission of Protocols 

for the Transfer of Recombinant or 

Synthetic Nucleic Acid Molecules into 

One or More Human Research 

Participants (Points to Consider), is 

proposed to be deleted in its entirety. 

Dated: August 7, 2018. 

Lawrence A. Tabak, 

Deputy Director, National Institutes of Health. 

[FR Doc. 2018–17760 Filed 8–16–18; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Center for Scientific Review; Notice of 

Closed Meetings 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended, notice is hereby given of the 

following meetings. 

The meetings will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; PAR–17– 

144: Limited Competition: National Primate 

Research Centers (P51). 

Date: September 11–14, 2018. 

Time: 8:00 a.m. to 12:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: Hotel Vintage Portland, 422 SW 

Broadway, Portland, OR 97205. 

Contact Person: Brian H. Scott, Ph.D., 

Scientific Review Officer, National Institutes 

of Health, Center for Scientific Review, 6701 

Rockledge Drive, Bethesda, MD 20892, 301– 

827–7490, brianscott@mail.nih.gov. 

Name of Committee: Brain Disorders and 

Clinical Neuroscience Integrated Review 

Group; Pathophysiological Basis of Mental 

Disorders and Addictions Study Section. 

Date: September 13–14, 2018. 

Time: 8:00 a.m. to 5:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: Renaissance Orlando at SeaWorld, 

6677 Sea Harbor Drive, Orlando, FL 32821. 

Contact Person: Boris P. Sokolov, Ph.D., 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 5217A, 

MSC 7846, Bethesda, MD 20892, 301–408– 

9115, bsokolov@csr.nih.gov. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.306, Comparative Medicine; 

93.333, Clinical Research, 93.306, 93.333, 

93.337, 93.393–93.396, 93.837–93.844, 

93.846–93.878, 93.892, 93.893, National 

Institutes of Health, HHS) 

Dated: August 13, 2018. 

Sylvia L. Neal, 

Program Analyst, Office of Federal Advisory 

Committee Policy. 

[FR Doc. 2018–17785 Filed 8–16–18; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Draft Report on Carcinogens 

Monograph on Night Shift Work and 

Light at Night; Availability of 

Document; Request for Comments; 

Notice of Peer-Review Meeting 

AGENCY: National Institutes of Health, 

HHS. 

ACTION: Notice. 

SUMMARY: The National Toxicology 

Program (NTP) announces a meeting to 

peer review the Draft Report on 

Carcinogens Monograph on Night Shift 

Work and Light at Night. NTP has 

conducted a literature-based assessment 

to determine whether night shift work 

(e.g., working at least three hours 

between 12 a.m. and 6 a.m.) and light 

at night are cancer hazards and should 


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