Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 9411 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Diabetes and 

Digestive and Kidney Diseases; Notice 

of Closed Meetings 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. Appendix 2), 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: National Institute of 

Diabetes and Digestive and Kidney Diseases 

Special Emphasis Panel; Urothelium and UTI 

Program Projects. 

Date: March 27, 2009. 

Time: 8:30 a.m. to 5 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: Bethesda Marriott Suites, 6711 

Democracy Boulevard, Bethesda, MD 20817. 

Contact Person: Lakshmanan Sankaran, 

PhD, Scientific Review Officer, Review 

Branch, DEA, NIDDK, National Institutes of 

Health, Room 755, 6707 Democracy 

Boulevard, Bethesda, MD 20892–5452, (301) 

594–7799, ls38z@nih.gov. 

Name of Committee: National Institute of 

Diabetes and Digestive and Kidney Diseases 

Special Emphasis Panel; Methotrexate 

Response In Treatment of UC. 

Date: April 1, 2009. 

Time: 3 p.m. to 4:30 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, Two 

Democracy Plaza, 6707 Democracy 

Boulevard, Bethesda, MD 20892, (Telephone 

Conference Call). 

Contact Person: Paul A. Rushing, PhD, 

Scientific Review Officer, Review Branch, 

DEA, NIDDK, National Institutes of Health, 

Room 747, 6707 Democracy Boulevard, 

Bethesda, MD 20892–5452, (301) 594–8895, 

rushingp@extra.niddk.nih.gov. 

Name of Committee: National Institute of 

Diabetes and Digestive and Kidney Diseases 

Special Emphasis Panel; Lifestyle 

Intervention to Treat Erectile Dysfunction 

(LITE). 

Date: April 2, 2009. 

Time: 11 a.m. to 12:30 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, Two 

Democracy Plaza, 6707 Democracy 

Boulevard, Bethesda, MD 20892, (Telephone 

Conference Call). 

Contact Person: Paul A. Rushing, PhD, 

Scientific Review Officer, Review Branch, 

DEA, NIDDK, National Institutes of Health, 

Room 747, 6707 Democracy Boulevard, 

Bethesda, MD 20892–5452, (301) 594–8895, 

rushingp@extra.niddk.nih.gov. 

Name of Committee: National Institute of 

Diabetes and Digestive and Kidney Diseases 

Special Emphasis Panel; Immunosuppression 

Withdrawal for Stable Pediatric Liver 

Transplant Recipients. 

Date: April 2, 2009. 

Time: 3 p.m. to 4:30 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, Two 

Democracy Plaza, 6707 Democracy 

Boulevard, Bethesda, MD 20892, (Telephone 

Conference Call). 

Contact Person: Paul A. Rushing, PhD, 

Scientific Review Officer, Review Branch, 

DEA, NIDDK, National Institutes of Health, 

Room 747, 6707 Democracy Boulevard, 

Bethesda, MD 20892–5452, (301) 594–8895, 

rushingp@extra.niddk.nih.gov. 

Name of Committee: National Institute of 

Diabetes and Digestive and Kidney Diseases 

Special Emphasis Panel; Ancillary Studies to 

Ongoing NIDDK Clinical Research Studies. 

Date: April 3, 2009. 

Time: 1 p.m. to 2 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, Two 

Democracy Plaza, 6707 Democracy 

Boulevard, Bethesda, MD 20892, (Telephone 

Conference Call). 

Contact Person: Barbara A Woynarowska, 

PhD, Scientific Review Officer, Review 

Branch, DEA, NIDDK, National Institutes of 

Health, Room 754, 6707 Democracy 

Boulevard, Bethesda, MD 20892–5452, (301) 

402–7172, woynarowskab@niddk.nih.gov. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.847, Diabetes, 

Endocrinology and Metabolic Research; 

93.848, Digestive Diseases and Nutrition 

Research; 93.849, Kidney Diseases, Urology 

and Hematology Research, National Institutes 

of Health, HHS) 

Dated: February 26, 2009. 

Jennifer Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. E9–4629 Filed 3–3–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Mental Health; 

Notice of Closed Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. Appendix 2), notice 

is hereby given of the following 

meeting. 

The meeting 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: National Institute of 

Mental Health Special Emphasis Panel; 

Center for AIDS Intervention Research Core 

Support. 

Date: March 27, 2009. 

Time: 11 a.m. to 2 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 

Neuroscience Center, 6001 Executive 

Boulevard, Rockville, MD 20852, (Telephone 

Conference Call). 

Contact Person: Enid Light, PhD, Scientific 

Review Officer, Division of Extramural 

Activities, National Institute of Mental 

Health, NIH, Neuroscience Center, 6001 

Executive Boulevard, Room 6132, MSC 9608, 

Bethesda, MD 20852–9608, 301–443–0322, 

elight@mail.nih.gov. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.242, Mental Health Research 

Grants; 93.281, Scientist Development 

Award, Scientist Development Award for 

Clinicians, and Research Scientist Award; 

93.282, Mental Health National Research 

Service Awards for Research Training, 

National Institutes of Health, HHS) 

Dated: February 26, 2009. 

Jennifer Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. E9–4630 Filed 3–3–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Office of Biotechnology Activities; 

Recombinant DNA Research: 

Proposed Actions Under the NIH 

Guidelines for Research Involving 

Recombinant DNA Molecules (NIH 

Guidelines) 

AGENCY: National Institutes of Health 

(NIH), PHS, DHHS. 

ACTION: Notice of consideration of a 

proposed action under the NIH 

Guidelines. 

SUMMARY: In 2006, the National Science 

Advisory Board for Biosecurity, an 

advisory committee to the Secretary of 

the Department of Health and Human 

Services, the NIH Director and all 

Federal entities that conduct/support 

life sciences research published a report 

9412 Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 

1The full document is available at http:// 

oba.od.nih.gov/biosecurity/pdf/ 

Final_NSABB_Report_on_Synthetic_Genomics.pdf. 

2The report is available from the National 

Academies Press: http://www.nap.edu/ 

catalog.php?record_id=10827#toc. 

3The full document is available at http:// 

oba.od.nih.gov/biosecurity/pdf/ 

Final_NSABB_Report_on_Synthetic_Genomics.pdf. 

entitled ‘‘Addressing Biosecurity 

Concerns Related to the Synthesis of 

Select Agents.’’ 1 The report included a 

recommendation that the United States 

Government (USG) ‘‘examine the 

language and implementation of current 

biosafety guidelines to ensure that such 

guidelines and regulations provide 

adequate guidance for working with 

synthetically derived DNA and are 

understood by all those working in areas 

addressed by the guidelines.’’ The USG 

adopted this recommendation and asked 

NIH to review the NIH Guidelines for 

Research with Recombinant DNA (NIH 

Guidelines) to evaluate whether these 

guidelines need to be revised to address 

biosafety concerns for research with 

synthetic DNA. With the advice of the 

NIH Recombinant DNA Advisory 

Committee (RAC), which is responsible 

for advising the NIH Director on all 

aspects of recombinant DNA 

technology, including revisions to the 

NIH Guidelines, the following proposed 

changes were developed. As outlined in 

more detail below, the proposed 

changes will expand the scope of the 

NIH Guidelines to specifically cover 

nucleic acid molecules made solely by 

synthetic means. The changes apply to 

basic laboratory research and clinical 

research. In addition, changes were 

made to clarify the criteria for 

determining whether an experiment to 

introduce drug resistance into a 

microorganism raises important public 

health issues such that it must be 

reviewed by the RAC and approved by 

the NIH Director. Finally, the proposed 

amendments speak to the appropriate 

level of review for recombinant or 

synthetic experiments involving more 

than half but less than two-thirds of the 

genome of certain viruses in tissue 

culture. These changes were prompted 

by an increased understanding of the 

biology of certain viruses that 

demonstrate there may be biosafety risks 

with certain viruses that contain less 

than two-thirds of the viral genome. 

DATES: The public is encouraged to 

submit written comments on this 

proposed action. Comments may be 

submitted to OBA in paper or electronic 

form at the OBA mailing, fax, and e-mail 

addresses shown below under the 

heading FOR FURTHER INFORMATION

CONTACT. All comments should be 

submitted by May 4, 2009. All written 

comments received in response to this 

notice will be available for public 

inspection in the NIH OBA office, 6705 

Rockledge Drive, Suite 750, MSC 7985, 

Bethesda, MD 20892–7985, weekdays 

between the hours of 8:30 a.m. and 5 

p.m. 

FOR FURTHER INFORMATION CONTACT: If 

you have questions, or require 

additional information about these 

proposed changes, please contact OBA 

by e-mail at oba@od.nih.gov, or 

telephone at 301–496–9838. Comments 

can be submitted to the same e-mail 

address or by fax to 301–496–9839 or 

mail to the Office of Biotechnology 

Activities, National Institutes of Health, 

6705 Rockledge Drive, Suite 750, MSC 

7985, Bethesda, Maryland 20892–7985. 

Background information may be 

obtained by contacting NIH OBA by email at oba@od.nih.gov. 

SUPPLEMENTARY INFORMATION: 

Background: Nucleic Acid (NA) 

synthesis technology, in combination 

with other rapidly evolving capabilities 

in the life sciences, such as directed 

molecular evolution and viral reverse 

genetics, has galvanized segments of the 

scientific community. It also has 

captured the attention of the general 

public and policymakers, prompting farreaching questions about the potential 

use of these techniques—including the 

synthesis of novel forms of life. These 

techniques promise to accelerate 

scientific discovery and have the 

potential to yield new therapeutics for 

disease. This same technology may lead 

to the modification of existing or the 

creation of new pathogens with 

unexpected and potentially dangerous 

characteristics. 

In 2004, the National Research 

Council (NRC) published a report that 

made an important contribution to the 

development of biosecurity policy for 

the biological sciences, ‘‘Biotechnology 

in the Age of Terrorism: Confronting the 

Dual Use Issue.’’ 2 While this report was 

not the first to recognize this problem, 

and indeed the U.S. Government (USG) 

had already initiated an examination of 

security issues in the biological 

sciences, the NRC report laid out a 

series of actions to improve biosecurity 

in life science research, one of which 

was the creation of an advisory body. 

The USG recognized the need for such 

an advisory body and formed the 

National Science Advisory Board for 

Biosecurity (NSABB) to advise the U.S. 

Government on strategies for 

minimizing the potential for misuse of 

information and technologies from life 

sciences research, taking into 

consideration both national security 

concerns and the needs of the research 

community. The NSABB, as it is 

chartered, differs somewhat from the 

panel proposed by the NRC report, but 

has aims similar to those envisioned by 

the NRC committee. 

At the NSABB’s first meeting, the 

Secretary of Health and Human Services 

tasked the NSABB with identifying 

potential biosecurity concerns raised by 

the rapidly advancing ability to 

synthesize select agents (7 CFR part 331, 

9 CFR part 121, and 42 CFR part 73) and 

other dangerous pathogens. In 2006, 

NSABB published a report entitled 

‘‘Addressing Biosecurity Concerns 

Related to the Synthesis of Select 

Agents.’’ 3 In that report the NSABB 

noted that practitioners of synthetic 

genomics or researchers using synthetic 

nucleic acids in the emerging field of 

synthetic biology are often educated in 

disciplines that do not routinely include 

formal training in biosafety, e.g., 

engineering. These researchers may be 

uncertain about when to consult an 

Institutional Biosafety Committee (IBC). 

The NSABB recommended to the 

Secretary of the Department of Health 

and Human Services that the language 

and implementation of current biosafety 

guidelines be examined to ensure that 

such guidelines and regulation provide 

adequate guidance for working with 

synthetically derived nucleic acids. This 

recommendation on the need for 

biosafety guidance was considered by 

the Executive Branch through a transFederal policy coordination process. 

The recommendation on the need for 

biosafety guidance was accepted by the 

U.S. Government with the 

understanding that implementation 

would be through modification of the 

NIH Guidelines as appropriate. The 

changes to the NIH Guidelines would 

then be cross-referenced in the Centers 

for Disease Control and Prevention/NIH 

publication entitled: Biosafety in 

Microbiological and Biomedical 

Laboratories (BMBL). 

The Recombinant DNA Advisory 

Committee (RAC) considered the 

applicability of the NIH Guidelines to 

the creation of, and experiments with 

synthetic nucleic acids (‘‘synthetic 

biology’’) and whether the NIH 

Guidelines adequately address the 

biosafety concerns that may arise from 

this research. The proposed revisions to 

the NIH Guidelines are intended to 

clarify the applicability of the NIH 

Guidelines to research with synthetic 

nucleic acids and provide principles 

and procedures for risk assessment and 

management of such research. 

While the initial NSABB 

recommendation focused on synthetic 

Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 9413 

genomics, which is the synthesis of 

nucleic acids using chemical or other 

methods that do not require traditional 

recombinant DNA techniques, it was 

recognized that this may be only be the 

first step in a research proposal. The 

synthetic nucleic acid will then likely 

be placed in cells or organisms. As it is 

articulated in the NIH Guidelines, it is 

the manipulation of the recombinant 

nucleic acids that leads to different 

biosafety concerns. As such, the focus of 

any review of synthetic genomics from 

a biosafety perspective needs to address 

the biological experiments that will be 

carried out. Therefore, with respect to 

the NIH Guidelines, the task was to 

review the biosafety considerations of 

introducing these synthetic nucleic 

acids into biological systems. 

Synthetic genomics utilizes different 

techniques than traditional recombinant 

methods of synthesis; however, the 

ultimate product may be the same. The 

biosafety considerations in most cases 

are related to the product being 

produced more than the technique used. 

In other words, the technique for 

creating sequences of nucleic acids is 

not determinative of virulence, 

transmissibility and pathogenicity of the 

product, which are key considerations 

in biosafety. There is no one to one 

correlation between increasing nucleic 

acid diversity and increasing risk of 

harm. Indeed, what has developed in 

nature involves complex and highly 

regulated sequences of nucleic acids in 

which there is often synergy between 

genes. Bringing together a number of 

genes or sequences from different 

sources may result in a nucleic acid 

sequence that is not functional in an 

organism. On the other hand, a single 

nucleic acid change which could be 

done by recombinant or synthetic means 

could lead to a significant enhancement 

in virulence. The focus of a biosafety 

analysis should be on the product with 

consideration of the source of the 

sequences. Synthetic techniques may 

result in a greater range of products than 

recombinant methods but the 

underlying challenge is the same: trying 

to understand how those disparate parts 

will act together. Ultimately a biological 

analysis of the end results will be 

required. 

Under the current risk assessment 

framework of the NIH Guidelines, the 

starting point for any risk assessment 

begins with an assessment of the parent 

organism from which the sequence is 

derived. As discussed under Section II, 

Safety Considerations, synthetic 

techniques may enable the synthesis of 

more complex chimeras containing 

sequences from a number of different 

sources. This increasing complexity 

may make the task of determining the 

parent organism more challenging. This 

is addressed in proposed language that 

will be added to the risk assessment 

section of the NIH Guidelines (see 

proposed changes to Section II–A). 

Therefore, the changes proposed 

below treat the biosafety risks of 

experiments that use recombinant and 

synthetic techniques as equivalent. 

Also, although it was recognized that 

synthetic genetic manipulation 

techniques are not necessarily a very 

recent development, the integration of 

other fields (for example, chemistry and 

engineering) may lead to rapid 

development of yet unknown products 

that may raise new biosafety risks not 

anticipated. The risk management 

framework being presented herein is 

based on the current science and that 

which appears to be feasible in the 

foreseeable future. 

The amendments will broaden the 

scope of the NIH Guidelines, which 

currently cover research involving DNA 

molecules created via recombinant 

techniques (i.e., joining of DNA 

molecules), to encompass nucleic acids 

that are synthesized chemically or by 

other means without the use of 

recombinant technology. As amended, 

the NIH Guidelines will apply to all 

nucleic acids. This is accomplished 

through changes in Section I–A, 

Purpose and Section I–B, Definition of 

Recombinant DNA Molecules. The 

required level of review will be based 

on the risk of the experiment, i.e. the 

risk to the laboratory worker, the public 

and the environment. Low risk basic 

research involving non-replicating 

synthetic nucleic acids will be exempt 

from the NIH Guidelines and from 

review at the local level. High risk basic 

and clinical studies may be subject to 

review by the RAC and the NIH. To 

effect these changes, four sections of the 

NIH Guidelines will be revised. The title 

of the document will be changed to NIH 

Guidelines for Research Involving 

Recombinant and Synthetic Nucleic 

Acid Molecules and throughout the NIH 

Guidelines the term recombinant DNA 

will be changed to recombinant and 

synthetic nucleic acids. 

In addition to broadening the scope of 

the NIH Guidelines to encompass 

synthetic nucleic acids, included are 

proposed amendments to two other 

sections of the NIH Guidelines, Section 

III–A–1 and Section III–E–1, in order to 

(1) clarify the oversight of recombinant 

experiments involving the introduction 

of drug resistance traits and (2) to 

change the level of review for 

recombinant or synthetic experiments 

involving more than half but less than 

two-thirds of the genome of certain 

viruses in tissue culture. These 

proposed amendments were 

recommended by the RAC. 

Section III–A–1 requires certain 

experiments involving the transfer of 

drug resistance traits to microorganisms 

to be reviewed by the RAC and 

approved by the NIH Director. The 

current language has raised concerns 

from IBCs and investigators seeking to 

identify those experiments that require 

this heightened review. The revisions to 

Section III–A–1 will clarify that all 

experiments involving the transfer of a 

drug resistance trait to a microorganism 

will be subject to RAC review and NIH 

Director approval if the microorganism’s 

acquisition of the trait could 

compromise public health. The changes 

will clarify that the microorganism’s 

ability to acquire the trait naturally is 

not relevant to the safety of the 

experiment, that the provisions apply 

even if the drug at issue is not 

considered the ‘‘drug of choice,’’ and 

that adverse effects on population 

subgroups need to be considered. 

Under the NIH Guidelines, approval 

for an experiment under Section III–A is 

specific to the investigator submitting 

the proposal. Recognizing that this may 

not be an efficient use of resources and 

may slow important research, a new 

provision will authorize OBA to make a 

determination that a proposed 

experiment that would fall under 

Section III–A is equivalent to an 

experiment that has been reviewed 

previously as a Major Action and 

approved by NIH Director. In such 

cases, OBA will have the authority to 

permit this research to proceed without 

going through RAC review and NIH 

Director approval if OBA determines 

that there are no substantive differences 

in experimental design and pertinent 

information has not emerged since 

submission of the initial experiment 

that would impact on the biosafety or 

public health risks for the proposed 

experiments. 

Section III–E–1 of the NIH Guidelines 

currently states that tissue culture 

experiments involving viral constructs 

that contain less than two-thirds of the 

genome of any one of the high risk 

viruses may be performed at the lowest 

containment level (Biosafety Level 1) 

and initiated upon registration with the 

local institutional biosafety committee. 

The change proposed to this section will 

increase the threshold to less than onehalf of the viral genome and require 

evidence that the resulting nucleic acid 

molecules are not capable of producing 

a replication competent virus. These 

changes are prompted by an increased 

understanding of the biology of certain 

viruses for which there may be biosafety 

9414 Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 

risks for research involving less than 

two-thirds of the viral genome. 

These recommendations were 

adopted unanimously by the RAC at its 

March 2008 meeting. Included in these 

proposed changes are targeted questions 

that were considered in developing the 

proposed revisions to the NIH 

Guidelines. NIH requests not only 

comments on the proposed changes but 

also comment on the specific issues 

raised by these questions. 

It should be noted that the NIH 

Guidelines currently apply to research 

that is conducted at or sponsored by 

institutions that receive NIH funding for 

any research involving recombinant 

DNA. Due to these proposed changes, 

the NIH Guidelines will apply to 

research that is conducted at or 

sponsored by institutions that receive 

NIH funding for any research involving 

recombinant DNA and synthetic acid 

molecules. In addition, other, non-NIH, 

U.S. Government agencies, including 

the Department of Defense, the 

Department of Veterans Affairs and 

Department of Agriculture, currently 

have policies in place stating that all 

recombinant DNA research conducted 

by or funded by these agencies must 

comply with the NIH Guidelines. While 

the NIH Guidelines may not govern all 

Government funded research, it may be 

used as a tool for the entire research 

community to understand the potential 

biosafety implications of their research. 

In reviewing the proposed changes it 

is important to understand that NIH 

Guidelines outline appropriate biosafety 

practices and containment measures for 

laboratory recombinant DNA (rDNA) 

research and govern the conduct of 

clinical trials that involve the deliberate 

transfer of rDNA, or DNA or RNA 

derived from rDNA, into human 

research participants. The focus of the 

NIH Guidelines is on the risks to 

laboratory workers, the public and the 

environment associated with rDNA 

research and if implemented, synthetic 

nucleic acid research. The NIH 

Guidelines do promote the use of 

biological containment through the 

application of highly specific biological 

barriers that may limit the infectivity, 

dissemination, or survival of 

recombinant agents outside the 

laboratory. Biological containment may, 

therefore, mitigate the consequences of 

intentional misuse of such agents but 

does not directly address biosecurity 

issues raised by deliberate exposure 

outside of a research setting. As revised, 

the NIH Guidelines will continue to 

focus on the biosafety aspects of 

research with recombinant and 

synthetic nucleic acid molecules. 

There may also be biosecurity or dual 

use research concerns with some 

research involving recombinant or 

synthetic nucleic acid molecules, but 

that is beyond the scope of the NIH 

Guidelines. Biosecurity aspects of 

research involving infectious agents are 

addressed in other venues, including for 

example, in the CDC–NIH Biosafety in 

Microbiological and Biomedical 

Laboratories, 5th Edition (Section VI, 

Principles of Laboratory Biosecurity) 

and the Select Agent Rules (42 CFR 73, 

9 CFR part 121 and 7 CFR part 131). In 

addition, the U.S.G. continues to 

address these issues. For example, the 

NSABB is developing recommendations 

for the oversight of dual use research 

and is also addressing the issue of 

personnel reliability among individuals 

working with select agents. 

Proposed Amendments to the NIH 

Guidelines 

In order to ensure that biosafety 

considerations of synthetic biology 

research are addressed appropriately, 

the NIH is proposing the following 

changes to the NIH Guidelines: 

Title of the NIH Guidelines 

The title of the document is proposed 

to be changed from the NIH Guidelines 

for Research Involving Recombinant 

DNA Molecules to the NIH Guidelines 

for Research Involving Recombinant 

and Synthetic Nucleic Acid Molecules. 

Section I. Scope of the NIH Guidelines 

In order to clarify the applicability of 

the NIH Guidelines to research 

involving synthetic nucleic acids (NA), 

the following modifications are 

proposed to Section I, Scope of the NIH 

Guidelines. 

Section 1–A. Purpose 

Section I-A (Purpose) of the NIH 

Guidelines currently states that: ‘‘the 

purpose of the NIH Guidelines is to 

specify practices for constructing and 

handling: (i) Recombinant 

deoxyribonucleic acid (DNA) molecules, 

and (ii) organisms and viruses 

containing recombinant DNA 

molecules.’’ Section I–A is proposed to 

be amended to read: ‘‘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 wholly or partially 

containing functional equivalents of 

nucleotides, or (iii) organisms and 

viruses containing such molecules.’’ 

As a result of these modifications, the 

NIH Guidelines will clearly apply to 

both recombinant and synthetically 

derived nucleic acids, including those 

that contain functional analogs of 

nucleotides (e.g. , those used in 

artificially engineered genetic systems). 

In accordance with this change in the 

scope of the NIH Guidelines the term 

‘‘recombinant DNA molecules’’ will be 

replaced with ‘‘recombinant and 

synthetic nucleic acid molecules.’’ 

Section I–B. Definition of Recombinant 

and Synthetic Nucleic Acids 

The current definition of recombinant 

DNA molecule in the NIH Guidelines 

(Section I–B) is limited because it only 

explicitly refers to DNA and requires 

that segments be joined, which may not 

need to occur in research with synthetic 

NAs. The proposed revisions to the 

definition would retain a definition of 

recombinant NA similar to the current 

one for recombinant DNA but also add 

synthetic NA created without joining of 

segments. The current definition of 

recombinant DNA in Section I–B of the 

NIH Guidelines is articulated in three 

paragraphs labeled as A, B, and C in this 

notice only. Paragraph A states: ‘‘In the 

context of the NIH Guidelines, 

recombinant DNA molecules are 

defined as either: (i) Molecules that are 

constructed outside living cells by 

joining natural or synthetic DNA 

segments to DNA molecules that can 

replicate in a living cell, or (ii) 

molecules that result from the 

replication of those described in (i) 

above.’’ Paragraph B states: ‘‘Synthetic 

DNA segments which are likely to yield 

a potentially harmful polynucleotide or 

polypeptide (e.g. , a toxin or a 

pharmacologically active agent) are 

considered as equivalent to their natural 

DNA counterpart. If the DNA segment is 

not expressed in vivo as a biologically 

active polynucleotide or polypeptide 

product it is exempt from the NIH 

Guidelines.’’ Paragraph C states: 

‘‘Genomic DNA of plants and bacteria 

that have acquired a transposable 

element, even if the latter was donated 

from a recombinant vector no longer 

present, are not subject to the NIH 

Guidelines unless the transposon itself 

contains recombinant DNA.’’ 

The following modifications are 

proposed to Section I–B. Definition of 

Recombinant DNA Molecules: 

Paragraph A is proposed to be revised 

to read: ‘‘In the context of the NIH 

Guidelines, recombinant and synthetic 

nucleic acids are defined as: (i) 

Recombinant nucleic acid molecules 

that are constructed by joining nucleic 

acid molecules and that can replicate in 

a living cell, (ii) synthetic nucleic acid 

molecules that are chemically, or by 

other means, synthesized or amplified 

nucleic acid molecules that may wholly 

or partially contain functional 

Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 9415 

equivalents of nucleotides, or (iii) 

molecules that result from the 

replication of those described in (i) or 

(ii) above.’’ 

Paragraph B will no longer be 

included in the definition. It was added 

to the NIH Guidelines in 1982 to clarify 

that then novel synthetic DNA segments 

would be considered as equivalent to 

their natural DNA counterparts with 

regards to containment conditions; 

however, it only covered synthetic DNA 

if it produced a toxin or a 

pharmacologically active agent. The 

language presented difficulty in 

interpretation because of the lack of 

definition of ‘‘toxin or a 

pharmacologically active agent.’’ 

Paragraph B is proposed to be deleted 

due to the fact that the concepts are 

sufficiently covered in the following 

portions: The new (ii) in paragraph A 

which explicitly extends the scope of 

the NIH Guidelines to cover 

recombinant and synthetic constructs, 

and Section III–F (Exempt Experiments) 

of the NIH Guidelines, which as 

discussed later, exempts those synthetic 

nucleic acid constructs that do not pose 

a significant biosafety risk. 

Paragraph C will be deleted from this 

portion and will be moved to Section 

III–F of the NIH Guidelines. This is a 

proposed reorganization of the NIH 

Guidelines so that exempt molecules 

will be described in one place. A new 

Section IIIF–7 is proposed to read: 

‘‘Genomic DNA molecules of plants and 

bacteria that have acquired a 

transposable element provided the 

transposable element does not contain 

any recombinant or synthetic DNA’’ are 

not subject to the NIH Guidelines. 

In accordance with these changes in 

the scope and definition of the NIH 

Guidelines, the term ‘‘recombinant DNA 

molecules’’ will be replaced with 

‘‘recombinant and synthetic nucleic 

molecules’’ throughout the NIH 

Guidelines. 

Section III–C–1. Experiments Involving 

the Transfer of Recombinant DNA, or 

DNA or RNA Derived From 

Recombinant DNA, Into One or More 

Human Research Participants 

In accordance with the change to the 

scope and definition of recombinant 

DNA, the definition of human gene 

transfer experiments will be amended. 

The first paragraph of Section III–C–1 

currently states: ‘‘For an experiment 

involving the deliberate transfer of 

recombinant DNA, or DNA or RNA 

derived from recombinant DNA, into 

human research participants (human 

gene transfer), no research participant 

shall be enrolled (see definition of 

enrollment in Section I–E–7) until the 

RAC review process has been completed 

(see Appendix M–I–B, RAC Review 

Requirements).’’ As amended the first 

paragraph will state: ‘‘For an experiment 

involving the deliberate transfer of 

recombinant or synthetic nucleic acids 

into human research participants 

(human gene transfer), no research 

participant shall be enrolled (see 

definition of enrollment in Section I–E– 

7) until the RAC review process has 

been completed (see Appendix M–I–B, 

RAC Review Requirements).’’ 

Section III–F. Exempt Experiments 

Additional modifications are 

proposed to augment or clarify 

experiments that are exempt from the 

NIH Guidelines, those listed in Section 

III–F. The exemptions under Section III– 

F are designed to strike a balance 

between safety and overregulation. They 

exempt certain nucleic acid molecules 

from oversight by the NIH Guidelines 

because their introduction into a 

biological system is not expected to 

have a biosafety risk that requires 

review by an IBC or the introduction of 

these nucleic molecules into biological 

systems would be akin to processes that 

already occur in nature and hence 

determining proper biosafety practices 

would be evident by the characteristics 

of naturally occurring sequence and/or 

would be covered by other guidances. Is 

there a risk that these exemptions could 

inadvertently exempt an experiment 

that is deserving of IBC review? First, it 

is important to recognize that with the 

exception of the new proposed III–F–1 

discussed below, the exemptions from 

the original NIH Guidelines have been 

preserved with minor modifications. 

While synthetic synthesis of nucleic 

acids will potentially raise new 

biosafety concerns the exemptions focus 

narrowly on a small set of products that 

should not raise biosafety concerns that 

warrant IBC review whether created by 

recombinant or synthetic means. 

To emphasize that research exempt 

from the NIH Guidelines will still have 

biosafety considerations and that other 

standards of biosafety may apply, a 

modification is proposed to the 

introductory language. Section III–F 

currently states: ‘‘The following 

recombinant DNA molecules are exempt 

from the NIH Guidelines and 

registration with the Institutional 

Biosafety Committee is not required.’’ 

This portion is proposed to read: ‘‘The 

following recombinant and/or synthetic 

nucleic acids molecules are exempt 

from the NIH Guidelines and 

registration with the Institutional 

Biosafety Committee is not required. 

However, other Federal and state 

standards of biosafety may still apply to 

such research (for example, the CDC/ 

NIH Biosafety in Microbiological and 

Biomedical Laboratories Manual).’’ 

Section III–F–1 

A new exemption under Section III– 

F–1 will exempt synthetic nucleic acids 

that cannot replicate from the NIH 

Guidelines unless they are used in 

human gene transfer (see Section III–C– 

1). This exemption is proposed so that 

the NIH Guidelines apply to synthetic 

NA research in a manner consistent 

with the current oversight of basic and 

preclinical recombinant DNA research. 

Currently oversight is limited to 

recombinant molecules that replicate or 

are derived from such molecules. The 

added section exempts basic, nonclinical research with synthetic NA that 

can not replicate or were derived from 

molecules that can replicate. The 

biosafety risks of using such constructs 

in basic and preclinical research are 

believed to be low. If a nucleic acid is 

incapable of replicating in a cell, any 

toxicity associated with that nucleic 

acid should be confined to that 

particular cell or organism and spread to 

neighboring cells or organisms should 

not occur to any appreciable degree. 

This type of risk is identical to that 

observed with chemical exposures, 

although nucleic acids are generally far 

less toxic than most chemicals. 

Members of the RAC Biosafety 

Working Group noted that one of the 

original impetuses for creating a special 

biosafety oversight for recombinant 

DNA research was the novel biosafety 

risks to the individual laboratory 

worker, the public health, and the 

environment presented by the ability of 

novel replicating nucleic acids to 

disseminate and persist within and 

outside of the laboratory. This risk of 

transmissibility is distinct from 

chemicals or other toxins, because of the 

potential for long-term persistence. 

Human gene transfer clinical trials 

should be differentiated from basic 

research. Current human gene transfer 

trials often involve non-replicating 

recombinant molecules. These are 

captured by the NIH Guidelines (see 

Section III–C–1 and Appendix M), 

because they are derived through 

recombinant technology that has steps 

involving replication (e.g., replication 

incompetent vectors, RNAi or antisense 

RNA expressed from vectors are all 

derived from replicating systems). The 

biosafety and health risks for human 

gene transfer for synthetic nonreplicating nucleic acids are not 

fundamentally different from nonreplicating recombinant vectors. 

The safety distinction between 

laboratory research and human gene 

9416 Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 

transfer is based on the difference in the 

potential health risk due to inadvertent 

lab exposure during basic or preclinical 

work and deliberate clinical gene 

transfer. The doses and routes of 

administration used in human gene 

transfer generally increase the risks. The 

risks to be considered for human gene 

transfer are not limited to the replicative 

nature of the vector but include 

transgene effects, risks of insertional 

mutagenesis, and immunological 

responses. For example, in the context 

of human gene transfer, the deliberate 

transfer of large numbers of replication 

incompetent retroviral vectors to 

hematopoietic stem cells in human 

clinical trials for X-Linked severe 

combined immunodeficiency disease 

contributed to the development of 

leukemia in some subjects starting 

several years after dosing. This is a 

unique situation in human trials that 

would not be replicated in a preclinical 

lab setting. Human gene transfer also 

raises scientific, medical, social and 

ethical considerations that warrant 

special attention and public discussion. 

The following new exemption is 

proposed to be inserted as Section III– 

F–1; the current exemptions III–F–1 

through III–F–5 are proposed to be renumbered as III–F–2 through III–F–6. 

Section III–F–6 is proposed to become 

III–F–8, because a new section III–F–7 is 

proposed to be inserted. Section III–F– 

1 is proposed to read: 

Section III–F–1: Synthetic nucleic acids 

that can not replicate, and that are not 

deliberately transferred into one or more 

human research participants (see Section 

III–C and Appendix M). 

In arriving at the conclusion that nonreplicating synthetic nucleic acids pose 

limited risks to the public or 

environment, the RAC considered 

different types of potential experiments 

involving a range of possible exposures 

(e.g., dose, route) and nucleic acids (e.g., 

positive strand RNA viruses, replication 

incompetent integrating vectors). For 

most research, the risks were considered 

sufficiently low so that little benefit was 

considered to be gained by increased 

oversight, which may hinder research. 

However, some questions remained. The 

public is encouraged to submit written 

comments on the following questions 

raised by this proposed modification to 

distinguish between laboratory and 

clinical research with replicating and 

non-replicating NA molecules. 

(1) Is there a sufficient distinction 

between the risks of basic and 

preclinical research with replicating vs. 

non-replicating synthetic molecules to 

warrant the exemption? 

(a) What are the risks with the use of 

replication incompetent integrating 

vectors in the laboratory? For example, 

preclinical research with recombinant 

lentiviral vectors is covered by the 

current NIH Guidelines because the 

vectors are generated using a step 

involving replication. At the lower 

doses typically used in laboratory 

experiments, are the risks to the 

laboratory worker of such nonreplicating, synthetic NA research 

sufficiently low as to warrant exemption 

from the NIH Guidelines? 

(2) Since the increased risk associated 

with human gene transfer is in part 

related to the administration of higher 

doses, should the exemption be limited 

to experiments involving the handling 

of low quantities or doses of NAs? What 

quantity would not be expected to pose 

a biosafety risk? 

(3) Are there examples of nonreplicating, synthetic NA research that 

should not be exempt due to greater 

potential risks (e.g., expression cassettes 

for oncogenes or toxins)? 

(4) For human gene transfer research, 

are there classes of non-replicating 

molecules that should be exempt due to 

lower potential risks (e.g., antisense 

RNA, RNAi, etc.)? If so, what criteria 

should be applied to determine such 

classes? 

Section III–F–2 

Section III–F–1 is proposed to be 

renumbered to III–F–2 and will be 

amended to clarify that replicating NAs 

that are not in cells (in addition to 

organisms and viruses) are exempt. 

Essentially, nucleic acids that are not in 

a biological system that will permit 

replication and that have not been 

modified to enable improved 

penetration of cell membranes are 

extremely unlikely to have biosafety 

risks. 

The primary risks associated with all 

nucleic acids, whether synthetic or 

natural, are the effects these can 

engender when inside an organism or 

the cellular compartment. Nucleic acids 

can alter protein expression patterns in 

cells by binding to nucleic acids and 

blocking (1) replication of DNA, (2) 

transcription of DNA into RNA and (3) 

translation of RNA into protein. 

Furthermore, binding of synthetic or 

natural DNA to cellular nucleic acids 

may result in degradation of cellular 

DNA or RNA through the activity of 

natural cellular defense mechanisms. 

Natural or synthetic DNA may have 

catalytic activity (e.g., ribozymes) that 

can cleave target sequences in nucleic 

acids. It is these effects that can 

potentially lead the cell or organism 

containing the nucleic acid to pose a 

risk to laboratory workers, the public or 

environment. 

None of the effects described above 

will occur unless the nucleic acid is 

introduced into an organism, or a cell. 

Nucleic acids, by virtue of their physical 

and chemical properties do not readily 

penetrate cell membranes. The negative 

charge of a nucleic acid molecule 

effectively prevents transfer across the 

plasma membrane of a cell unless the 

negative charges of the molecule are 

either masked or neutralized by 

addition of chemical compounds (e.g., 

cationic lipids, calcium phosphate) or 

the cell membrane is physically 

perforated (e.g., electroporation) to 

enable penetration and uptake by the 

cell. 

In practice, the current NIH 

Guidelines cover the introduction or 

modification of recombinant DNA in 

tissue culture, organisms and viruses. 

Therefore, for clarity and in recognition 

that techniques have developed to more 

readily permit introduction of nucleic 

acids into cells, the amended F–1 

speaks to cells, organisms and viruses. 

In addition, as stated above, natural 

barriers exist for entry of unmodified 

nucleic acids into cells. However, 

manipulation of molecules modified for 

improved penetration of cell membranes 

in the laboratory may have increased 

risk due to the enhanced ability to 

penetrate cell membranes and thus be 

able to replicate. Therefore, section IIIF–1 is being modified to address such 

modified nucleic acids as well. 

Specifically, Section III–F–1 is 

proposed to be renumbered as III–F–2 

and amended as follows: 

The current Section III–F–1 states: 

‘‘Those that are not in organisms or 

viruses.’’ 

Section III–F–1 will be re-numbered 

to III–F–2 and is proposed to be 

amended to: ‘‘Section III–F–2. 

Recombinant or synthetic nucleic acids 

that are not in organisms, cells or 

viruses and that have not been modified 

or manipulated (e.g., encapsulated into 

synthetic or natural vehicles) to render 

them capable of penetrating cellular 

membranes.’’ 

The proposed Sections III–F–3 

through III–F–7 retain exemptions that 

were in the original NIH Guidelines 

with minor revisions. In reviewing these 

exemptions it is important to 

understand that it is not the goal of the 

NIH Guidelines to regulate all nucleic 

acid research but rather that subset of 

research that through recombinant or 

now synthetic means results in unique 

organisms or cells that potentially 

possess characteristics not yet seen in 

nature and hence pose potential safety 

risks both to the individual as well as 

Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 9417 

the community should there be an 

inadvertent release. Specifically, the 

molecules that fall under the new 

Section III–F–3 (formerly Section III–F– 

2) are those that consist solely of the 

exact nucleic acid sequence from a 

single source that exists 

contemporaneously in nature. Those 

described in the new Sections F–4 and 

F–5 (formerly Sections F–3 and F–4) are 

nucleic acids that are being propagated 

in a host that is either the natural host 

for such nucleic acids or is a closely 

related prokaryotic or eukaryotic host. 

Again such constructs may already exist 

outside of a laboratory. Research that 

falls under F–6 (formerly Section F–5) is 

exempt because the manipulation of 

these nucleic acids in a laboratory 

setting would be equivalent to that 

which occurs in nature when certain 

organisms exchange genetic material via 

physiological processes (e.g., bacterial 

mating) outside of a laboratory setting. 

It is limited to those organisms that are 

already known to exchange DNA in 

nature. Finally, research that falls under 

the proposed Section F–7 also involves 

a natural physiological process, i.e., 

transposition. Transposons are nucleic 

acid molecules that exist in a wide 

variety of organisms from bacteria to 

humans. These molecules have the 

ability to move from one portion of an 

organism’s genome to another. This new 

Section of III–F captures what was 

previously an exemption to the 

definition in the NIH Guidelines of a 

recombinant DNA molecule. Unless a 

transposon has been modified to be a 

recombinant molecule, genomic DNA of 

either plants or bacteria that has 

acquired a transposon is not subject to 

the NIH Guidelines. This is because if 

these transposons have not been 

modified by the insertion of 

recombinant or synthetic DNA, they are 

equivalent to what is already in nature 

and the process occurs naturally outside 

of lab. 

The following changes are proposed 

for the Section III–F exemptions. 

Section III–F–3 

Section III–F–2 is proposed to be renumbered to III–F–3 and amended. In 

the current NIH Guidelines, research 

with molecules from a single DNA 

source is exempt. This would include 

molecules containing duplications or 

deletions; however, such molecules may 

present different risks than those of the 

wild type parent agents. The revised 

language is intended to clarify that 

exempt molecules must have the exact 

nucleic acid sequence from an organism 

that currently exists in nature in order 

to be exempt (e.g., because the 1918 

influenza no longer exists in nature, 

research involving the reconstructed 

virus would not qualify for this 

exemption). The exemption does not 

imply that there are no biosafety risks 

associated with such research but rather 

recognizes that the NIH Guidelines do 

not apply to wild-type strains currently 

found in nature because a risk 

assessment for such work can be made 

with reference to the biological 

characteristics of the wild-type 

organism and are covered by other NIH 

biosafety standards (for example CDC/ 

NIH Biosafety in Microbiological and 

Biomedical Laboratories Manual). 

The following modifications are 

proposed for Section III–F–2. Section 

III–F–2 is proposed to be re-numbered 

to III–F–3 and amended as follows: 

The current III–F–2 states: ‘‘Those 

that consist entirely of DNA segments 

from a single nonchromosomal or viral 

DNA source, though one or more of the 

segments may be a synthetic 

equivalent.’’ III–F–2 is proposed to be 

renumbered to III–F–3 and is proposed 

to be amended to state: ‘‘Recombinant or 

synthetic nucleic acids that consist 

solely of the exact nucleic acid sequence 

from a single source that exists 

contemporaneously in nature.’’ 

This proposed modification would 

change ‘‘single nonchromosomal or viral 

source’’ to simply ‘‘single source.’’ 

Specific comment is requested as to 

whether it is sufficiently clear that 

single source refers to ‘‘single 

chromosomal, non-chromosomal, or 

viral NA source’’ or should the language 

be specifically spelled out? 

Section III–F–4 

The current Section III–F–3 is 

proposed to be renumbered to Section 

III–F–4 and amended. Section III–F–3 

states: ‘‘Those that consist entirely of 

DNA from a prokaryotic host including 

its indigenous plasmids or viruses when 

propagated only in that host (or a 

closely related strain of the same 

species), or when transferred to another 

host by well established physiological 

means.’’ It is proposed to be amended as 

follows: ‘‘Section III–F–4. Those that 

consist entirely of nucleic acids from a 

prokaryotic host including its 

indigenous plasmids or viruses when 

propagated only in that host (or a 

closely related strain of the same 

species), or when transferred to another 

host by well established physiological 

means.’’ 

Section III–F–5 

The current Section III–F–4 is 

proposed to be renumbered to Section 

III–F–5. Section III–F–4 currently states: 

‘‘Those that consist entirely of DNA 

from a eukaryotic host including its 

chloroplasts, mitochondria, or plasmids 

(but excluding viruses) when 

propagated only in that host (or a 

closely related strain of the same 

species).’’ It is proposed to state the 

following: ‘‘Section III–F–5: Those that 

consist entirely of nucleic acids from a 

eukaryotic host including its 

chloroplasts, mitochondria, or plasmids 

(but excluding viruses) when 

propagated only in that host (or a 

closely related strain of the same 

species).’’ 

Section III–F–6 

The current Section III–F–5 is 

proposed to be renumbered to Section 

III–F–6. The current Section III–F–5 

states: ‘‘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– 

5—Sublists of Natural Exchangers, for a 

list of natural exchangers that are 

exempt from the NIH Guidelines.’’ It is 

proposed to be amended to state: 

‘‘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.’’ 

Additionally, Appendix A1–through A– 

VI will be amended to reference Section 

III–F–6 rather than III–F–5. 

Section III–F–7 

A new Section III–F–7 is proposed to 

be added. This proposed new Section 

takes an exemption that was previously 

included in the original definition 

(Section I–B) and moves it to this 

Section so that the definition of 

recombinant and nucleic acids found in 

the proposed Section I–B is solely a 

definition and does not include 

exemptions. The proposed exemption 

language has been simplified to make it 

clear that unmodified transposons used 

in research are not subject to the NIH 

9418 Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 

Guidelines even if derived from a 

recombinant or synthetic system. 

Section I–B: Genomic DNA molecules of 

plants and bacteria that have acquired a 

transposable element, even if the latter 

was donated from a recombinant vector 

no longer present, are not subject to the 

NIH Guidelines unless the transposon 

itself contains recombinant DNA. New 

Section III–F–7 is proposed to state: 

Section III–F–7. Genomic DNA molecules 

of plants and bacteria that have acquired a 

transposable element provided the 

transposable element does not contain any 

recombinant or synthetic DNA. 

Section III–F–8 

The current Section III–F–6 is 

proposed to be renumbered to Section 

III–F–8 and amended. This section 

provides a mechanism for the NIH 

Director to expand the exemptions to 

molecules not covered elsewhere in 

Section III–F. Research that falls under 

Section III–F–8 would need to have 

been reviewed and approved by the NIH 

Director following advice from the RAC 

and notice in the Federal Register to 

provide an opportunity for public 

comment. Only research that has been 

deemed to not present, following this 

extensive review process, a significant 

risk to health or the environment would 

fall under this section. 

Current Section III–F–6 states: ‘‘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, with 

the advice of the RAC, and following 

appropriate notice and opportunity for 

public comment. See Appendix C, 

Exemptions under Section III–F–6 for 

other classes of experiments which are 

exempt from the NIH Guidelines.’’ 

Section III–F–6 is proposed to be 

amended to state: ‘‘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, 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.’’ Additionally Appendix 

A1– through A–VI will be amended to 

reference Section III–F–8 rather than III– 

F–6. 

Section III–E–1. Experiments Involving 

the Formation of Recombinant DNA 

Molecules Containing No More Than 

Two-Thirds of the Genome of Any 

Eukaryotic Virus 

Experiments covered by Section III– 

E–1 can be initiated using Biosafety 

Level (BL) 1 containment 

simultaneously with Institutional 

Biosafety Committee notice. Section III– 

E–1 currently states: ‘‘Recombinant 

DNA molecules containing no more 

than two-thirds of the genome of any 

eukaryotic virus (all viruses from a 

single Family being considered identical 

[see Section V–J Footnotes and 

References of Sections I–IV ]) may be 

propagated and maintained in cells in 

tissue culture using BL1 containment. 

For such experiments, it must be 

demonstrated that the cells lack helper 

virus for the specific Families of 

defective viruses being used. If helper 

virus is present, procedures specified 

under Section III–D–3, Experiments 

Involving the Use of Infectious Animal 

or Plant DNA or RNA viruses or 

Defective Animal or Plant DNA or RNA 

viruses in the Presence of Helper Virus 

in Tissue Culture Systems, should be 

used. The DNA may contain fragments 

of the genome of viruses from more than 

one Family but each fragment shall be 

less than two-thirds of a genome.’’ 

This section applies to viral 

constructs containing less than 2⁄3 of the 

genome of any virus (with all viruses 

from a single Family being considered 

as identical). However, concerns were 

raised that this level of oversight may 

not be adequate for research with 

potential synthetic biology agents 

derived from multiple segments of NA 

from a Family of viruses. In addition, 

some wild type viruses (e.g., herpes 

viruses) may be functional with less 

than 2⁄3 of the genome present. 

Therefore, the decision was made to 

propose to change 2⁄3 to one-half of the 

genome to reflect the current 

understanding of the biology of certain 

viruses. While the use of a quantitative 

measure to define properties of 

biological organisms is imperfect, the 

more conservative standard is consistent 

with Appendix C–1 Recombinant DNA 

in Tissue Culture which exempts from 

the NIH Guidelines recombinant DNA 

molecules from Risk Groups 1 and 2 

that contain less than one-half of any 

eukaryotic viral genome. With this 

revision, experiments involving risk 

Group 3 and 4 viruses with less than 

one-half of any eukaryotic viral genome 

can be initiated at BL1 containment 

simultaneously with IBC registration 

provided evidence is also submitted 

attesting that the preparation(s) are free 

of replication competent virus, which 

may be generated through homologous 

recombination with endogenous 

proviruses or the use of a helper virus. 

If revised as proposed, an investigator 

will be permitted to initiate an 

experiment simultaneously with 

registration, since the retention of a 

quantitative standard provides such 

clear guidance. 

Section III–E–1 is proposed to be 

amended to state: ‘‘Recombinant and 

synthetic nucleic acid molecules 

containing no more than half of the 

genome of any one Risk Group 3 or 4 

eukaryotic virus (all viruses from a 

single Family being considered identical 

[see Section V–J, Footnotes and 

References of Sections I–IV ]) may be 

propagated and maintained in cells in 

tissue culture using BL1 containment 

(as defined in Appendix G) provided 

there is evidence that the resulting 

nucleic acid in these cells are not 

capable of producing a replication 

competent nucleic acid. For such 

experiments, it must be demonstrated 

that the cells lack helper virus for the 

specific Families of defective viruses 

being used. If helper virus is present, 

procedures specified under Section III– 

D–3, Experiments Involving the Use of 

Infectious Animal or Plant DNA or RNA 

viruses or Defective Animal or Plant 

DNA or RNA viruses in the Presence of 

Helper Virus in Tissue Culture Systems 

should be used. The nucleic acids may 

contain fragments of the genome of 

viruses from more than one Family but 

each fragment shall be less than one-half 

of a genome.’’ 

Section IV–A Policy 

Section IV–A concerns the roles and 

responsibilities of the local institutions 

and investigators in implementing the 

NIH Guidelines. It contains a general 

policy statement that is often evoked as 

the ‘‘spirit’’ of the NIH Guidelines 

because it acknowledges the inability of 

the document to describe specifically all 

conceivable research or emerging 

techniques; however, it remains the 

responsibility of researchers and 

institutions to adhere to ‘‘the intent of 

the NIH Guidelines as well as to their 

specifics.’’ In order to emphasize that 

the NIH Guidelines are an evolving 

document which are expected to be 

modified to address new developments 

in research or scientific techniques, the 

following modifications are proposed to 

Section IV–A (Policy). 

Section IV–A currently states: ‘‘The 

safe conduct of experiments involving 

recombinant DNA depends on the 

individual conducting such activities. 

The NIH Guidelines cannot anticipate 

every possible situation. Motivation and 

good judgment are the key essentials to 

protection of health and the 

environment. The NIH Guidelines are 

intended to assist the institution, 

Institutional Biosafety Committee, 

Biological Safety Officer, and the 

Principal Investigator in determining 

Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 9419 

safeguards that should be implemented. 

The NIH Guidelines will never be 

complete or final since all conceivable 

experiments involving recombinant 

DNA cannot be foreseen. Therefore, it is 

the responsibility of the institution and 

those associated with it to adhere to the 

intent of the NIH Guidelines as well as 

to their specifics. Each institution (and 

the Institutional Biosafety Committee 

acting on its behalf) is responsible for 

ensuring that all recombinant DNA 

research conducted at or sponsored by 

that institution is conducted in 

compliance with the NIH Guidelines. 

General recognition of institutional 

authority and responsibility properly 

establishes accountability for safe 

conduct of the research at the local 

level. The following roles and 

responsibilities constitute an 

administrative framework in which 

safety is an essential and integral part of 

research involving recombinant DNA 

molecules. Further clarifications and 

interpretations of roles and 

responsibilities will be issued by NIH as 

necessary.’’ 

Section IV–A is proposed to be 

amended to read: ‘‘The safe conduct of 

experiments involving recombinant 

DNA depends on the individual 

conducting such activities. The NIH 

Guidelines cannot anticipate every 

possible situation. Motivation and good 

judgment are the key essentials to 

protection of health and the 

environment. The NIH Guidelines are 

intended to assist the institution, 

Institutional Biosafety Committee, 

Biological Safety Officer, and the 

Principal Investigator in determining 

safeguards that should be implemented. 

The NIH Guidelines will never be 

complete or final since all experiments 

involving recombinant and/or synthetic 

nucleic acids cannot be foreseen. The 

utilization of new genetic manipulation 

techniques may enable work previously 

done by recombinant means to be 

accomplished faster, more efficiently or 

at larger scale. These techniques have 

not yet yielded organisms that present 

safety concerns that fall outside the 

current risk assessment framework used 

for recombinant DNA research. 

Nonetheless, an appropriate risk 

assessment of experiments involving 

these techniques must be conducted 

taking into account the way these 

approaches may alter the risk 

assessment. In addition, as the field 

develops, new techniques and 

applications need to be monitored and 

assessed to determine whether revisions 

to the NIH Guidelines are needed. As 

new techniques develop, the NIH 

Guidelines should be periodically 

reviewed to determine whether and how 

such research should be explicitly 

addressed. It is the responsibility of the 

institution and those associated with it 

to adhere to the intent of the NIH 

Guidelines as well as to their specifics. 

Therefore, each institution (and the 

Institutional Biosafety Committee acting 

on its behalf) is responsible for ensuring 

that all recombinant and/or synthetic 

nucleic acids research conducted at or 

sponsored by that institution is 

conducted in compliance with the NIH 

Guidelines. General recognition of 

institutional authority and 

responsibility properly establishes 

accountability for safe conduct of the 

research at the local level. The following 

roles and responsibilities constitute an 

administrative framework in which 

safety is an essential and integral part of 

research involving recombinant and/or 

synthetic nucleic acid molecules. 

Further clarifications and 

interpretations of roles and 

responsibilities will be issued by NIH as 

necessary.’’ 

Section II. Safety Considerations 

Currently, the risk assessment 

framework of the NIH Guidelines uses 

the risk group of the parent organism as 

a starting point for determining the 

necessary containment level. For 

example, genetic modifications using a 

Risk Group 3 organism (defined as 

agents that are associated with serious 

or lethal human disease for which 

preventive or therapeutic interventions 

may be available) would generally be 

carried out at BL3 but the containment 

level might be raised or lowered 

depending on the specific construct and 

the experimental manipulations. The 

RAC concluded that the current risk 

assessment framework under the NIH 

Guidelines is applicable to experiments 

with synthetic nucleic acids. However, 

additional language is proposed to 

provide further guidance for evaluating 

research utilizing the capabilities of 

synthetic biology, as use of these 

techniques may lead to the creation of 

complex organisms for which 

identification of a parent organism, the 

starting point of the existing 

recombinant DNA risk assessment, is 

more difficult. Risk assessment may also 

be complicated by the limitations in 

predicting function from sequence(s) or 

the synergistic effects from combining 

sequences from different sources in a 

novel context. 

Section II–A–3 (Comprehensive Risk 

Assessment) currently states: 

‘‘In deciding on the appropriate 

containment for an experiment, the 

initial risk assessment from Appendix 

B, Classification of Human Etiologic 

Agents on the Basis of Hazard, should 

be followed by a thorough consideration 

of the agent itself and how it is to be 

manipulated. Factors to be considered 

in determining the level of containment 

include agent factors such as: Virulence, 

pathogenicity, infectious dose, 

environmental stability, route of spread, 

communicability, operations, quantity, 

availability of vaccine or treatment, and 

gene product effects such as toxicity, 

physiological activity, and allergenicity. 

Any strain that is known to be more 

hazardous than the parent (wild-type) 

strain should be considered for handling 

at a higher containment level. Certain 

attenuated strains or strains that have 

been demonstrated to have irreversibly 

lost known virulence factors may 

qualify for a reduction of the 

containment level compared to the Risk 

Group assigned to the parent strain (see 

Section V–B, Footnotes and References 

of Sections I–IV). 

A final assessment of risk based on 

these considerations is then used to set 

the appropriate containment conditions 

for the experiment (see Section II–B, 

Containment). The containment level 

required may be equivalent to the Risk 

Group classification of the agent or it 

may be raised or lowered as a result of 

the above considerations. The 

Institutional Biosafety Committee must 

approve the risk assessment and the 

biosafety containment level for 

recombinant DNA experiments 

described in Sections III–A, 

Experiments that Require Institutional 

Biosafety Committee Approval, RAC 

Review, and NIH Director Approval 

Before Initiation; III–B, Experiments that 

Require NIH/OBA and Institutional 

Biosafety Committee Approval Before 

Initiation; III–C, Experiments that 

Require Institutional Biosafety 

Committee and Institutional Review 

Board Approvals and NIH/OBA 

Registration Before Initiation; III–D, 

Experiments that Require Institutional 

Biosafety Committee Approval Before 

Initiation. 

Careful consideration should be given 

to the types of manipulation planned for 

some higher Risk Group agents. For 

example, the RG2 dengue viruses may 

be cultured under the Biosafety Level 2 

(BL2) containment (see Section II–B); 

however, when such agents are used for 

animal inoculation or transmission 

studies, a higher containment level is 

recommended. Similarly, RG3 agents 

such as Venezuelan equine 

encephalomyelitis and yellow fever 

viruses should be handled at a higher 

containment level for animal 

inoculation and transmission 

experiments. 

9420 Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 

Individuals working with human 

immunodeficiency virus (HIV), hepatitis 

B virus (HBV) or other bloodborne 

pathogens should consult the applicable 

Occupational Safety and Health 

Administration regulation, 29 CFR 

1910.1030, and OSHA publication 3127 

(1996 revised). BL2 containment is 

recommended for activities involving all 

blood-contaminated clinical specimens, 

body fluids, and tissues from all 

humans, or from HIV- or HBV-infected 

or inoculated laboratory animals. 

Activities such as the production of 

research-laboratory scale quantities of 

HIV or other bloodborne pathogens, 

manipulating concentrated virus 

preparations, or conducting procedures 

that may produce droplets or aerosols, 

are performed in a BL2 facility using the 

additional practices and containment 

equipment recommended for BL3. 

Activities involving industrial scale 

volumes or preparations of concentrated 

HIV are conducted in a BL3 facility, or 

BL3 Large Scale if appropriate, using 

BL3 practices and containment 

equipment. 

Exotic plant pathogens and animal 

pathogens of domestic livestock and 

poultry are restricted and may require 

special laboratory design, operation and 

containment features not addressed in 

Biosafety in Microbiological and 

Biomedical Laboratories (see Section V– 

C, Footnotes and References of Sections 

I through IV). For information regarding 

the importation, possession, or use of 

these agents see Section V–G and V–H, 

Footnotes and References of Sections I 

through IV.’’ 

The first three paragraphs are 

proposed to be amended by inserting 

the following two new paragraphs 

between the current first and second 

paragraphs of Section II–A–3: 

‘‘In deciding on the appropriate 

containment for an experiment, the 

initial risk assessment from Appendix 

B, Classification of Human Etiologic 

Agents on the Basis of Hazard, should 

be followed by a thorough consideration 

of the agent itself and how it is to be 

manipulated. Factors to be considered 

in determining the level of containment 

include agent factors such as: virulence, 

pathogenicity, infectious dose, 

environmental stability, route of spread, 

communicability, operations, quantity, 

availability of vaccine or treatment, and 

gene product effects such as toxicity, 

physiological activity, and allergenicity. 

Any strain that is known to be more 

hazardous than the parent (wild-type) 

strain should be considered for handling 

at a higher containment level. Certain 

attenuated strains or strains that have 

been demonstrated to have irreversibly 

lost known virulence factors may 

qualify for a reduction of the 

containment level compared to the Risk 

Group assigned to the parent strain (see 

Section V–B, Footnotes and References 

of Sections I–IV). 

While the initial risk assessment is 

based on the identification of the Risk 

Group of the parent agent, as technology 

moves forward, it may be possible to 

develop a chimera in which the parent 

agent may not be obvious. In such cases, 

the risk assessment should involve at 

least two levels of analysis. The first 

involves a consideration of the Risk 

Groups of the source(s) of the sequences 

and the second an analysis of the 

functional attributes of these sequences 

(e.g., sequence associated with virulence 

factors, transmissibility, etc.). It may be 

prudent to first consider the highest risk 

group classification of any agent 

sequence included in the chimera. 

Other factors to be considered include 

the percentage of the genome 

contributed by each of multiple parent 

agents, and the predicted function or 

intended purpose of each contributing 

sequence. The initial assumption should 

be that all sequences will function as 

predicted in the original host context. 

The IBC must also be cognizant that 

the combination of certain sequences 

may result in an organism whose risk 

profile could be higher than that of the 

contributing organisms or sequences. 

The synergistic function of these 

sequences may be one of the key 

attributes to consider in deciding 

whether a higher containment level is 

warranted. A new biosafety risk may 

occur with a chimera formed through 

combination of sequences from a 

number of organisms or due to the 

synergistic effect of combining 

transgenes that results in a new 

phenotype. 

A final assessment of risk based on 

these considerations is then used to set 

the appropriate containment conditions 

for the experiment (see Section II–B, 

Containment). The containment level 

required may be equivalent to the Risk 

Group classification of the agent or it 

may be raised or lowered as a result of 

the above considerations. The 

Institutional Biosafety Committee must 

approve the risk assessment and the 

biosafety containment level for 

recombinant DNA experiments 

described in Sections III–A, 

Experiments that Require Institutional 

Biosafety Committee Approval, RAC 

Review, and NIH Director Approval 

Before Initiation; III–B, Experiments that 

Require NIH/OBA and Institutional 

Biosafety Committee Approval Before 

Initiation; III–C, Experiments that 

Require Institutional Biosafety 

Committee and Institutional Review 

Board Approvals and NIH/OBA 

Registration Before Initiation; III–D, 

Experiments that Require Institutional 

Biosafety Committee Approval Before 

Initiation.’’ 

Section III-A–1. Major Actions Under 

the NIH Guidelines 

In reviewing the biosafety risks for 

synthetic genomics and biology and the 

different levels of review for each 

experiment, the RAC determined that it 

is important to also evaluate the class of 

experiments that require the highest 

level of review. In doing so, it was 

determined that the language for Section 

III–A–1 of the NIH Guidelines (research 

involving the introduction of drug 

resistance) does not clearly articulate 

the types of experiments that warrant 

this heightened review. Moreover, given 

the change in the use of antibiotics and 

the public health problems raised by the 

emergence of multi-drug resistant 

bacterial strains, clearly defining those 

experiments that require heightened 

review is a public health priority. 

Section III–A–1-a currently states: 

‘‘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 use of 

the drug to control disease agents in 

humans, veterinary medicine, or 

agriculture, will be reviewed by RAC.’’ 

Section III–A–1-a is proposed to be 

amended to: ‘‘The deliberate transfer of 

a drug resistance trait to 

microorganisms, if such acquisition 

could compromise the ability to treat or 

manage disease agents in human and 

veterinary medicine, or agriculture will 

be reviewed by RAC (see Section V–B, 

Footnotes and References of Sections I– 

IV). Even if an alternative drug or drugs 

exist for the control or management of 

disease, it is important to consider how 

the research might affect the ability to 

control infection in certain groups or 

subgroups by putting them at risk of 

developing an infection by such 

microorganism for which alternative 

treatments may not be available. 

Affected groups or subgroups may 

include, but are not limited to: children, 

pregnant women, and people who are 

allergic to effective alternative 

treatments, immunocompromised or 

living in countries where the alternative 

effective treatment is not readily 

available.’’ 

The deletion of the phrase ‘‘that are 

not known to acquire the trait naturally’’ 

is proposed because the mechanism of 

acquisition should not be relevant as to 

whether these experiments pose 

potential public health risk and as such 

Federal Register / Vol. 74, No. 41 / Wednesday, March 4, 2009 / Notices 9421 

should receive a higher level of review. 

Moreover, all forms of antibiotic 

resistance occur naturally and the use of 

antibiotics creates selective pressure for 

resistant strains. The additional text 

recognizes that a drug may remain 

useful for control of a disease despite 

some percentage of the population of 

microorganisms having developed 

resistance. It is also intended to clarify 

that even if a particular drug is not 

considered the ‘‘drug of choice’’ to treat 

a disease, elimination of such a drug as 

a treatment option may still raise 

important clinical and public health 

considerations for certain 

subpopulations. 

Once a Section III–A–I–a experiment 

is reviewed by the RAC and approved 

by the NIH Director, equivalent 

experiments may not need to follow the 

same approval process to determine the 

appropriate biosafety containment level 

for the work. A new section under III– 

B (Experiments that Require NIH/OBA 

and IBC Approval before Initiation) is 

proposed to be added to allow NIH/OBA 

the discretion to review and approve 

certain experiments if NIH/OBA 

determines that an equivalent 

experiment has already been approved 

by the NIH Director and there are no 

substantial changes to the proposed 

experiment or new information that 

would raise new biosafety or public 

health issues. Under this proposal, 

Investigators will be notified by NIH/ 

OBA if such a determination has been 

made. 

The following addition is proposed to 

be added to Section III–B of the NIH 

Guidelines to allow NIH/OBA the 

discretion to review and approve certain 

experiments that have been previously 

reviewed by the RAC and approved by 

the NIH Director as a Major Action. 

‘‘Section III–B–2, Experiments that 

have been approved (under Section III– 

A–1–a) as Major Actions under the NIH 

Guidelines 

Upon receipt and review of an 

application from the investigator, NIH/ 

OBA may determine that a proposed 

experiment is equivalent to an 

experiment that has previously been 

approved by the NIH Director as a Major 

Action, including experiments approved 

prior to implementation of these 

changes. An experiment will only be 

considered equivalent if, as determined 

by NIH/OBA, there are no substantive 

differences in experimental design or 

pertinent information has not emerged 

since submission of the initial III–A–1 

experiment that would impact on the 

biosafety or public health risks for the 

proposed experiments. If such a 

determination is made by NIH/OBA, 

these experiments will not require 

review and approval under Section III– 

A.’’ 

Dated: February 26, 2009. 

Amy P. Patterson, 

Acting Director, Office of Science Policy, 

National Institutes of Health. 

[FR Doc. E9–4618 Filed 3–3–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HOMELAND 

SECURITY 

Coast Guard 

[USCG–2008–0929] 

Collection of Information Under 

Review by Office of Management and 

Budget: OMB Control Numbers: 1625– 

0040 

AGENCY: Coast Guard, DHS. 

ACTION: Thirty-day notice requesting 

comments. 

SUMMARY: In compliance with the 

Paperwork Reduction Act of 1995, this 

request for comments announces that 

the U.S. Coast Guard is forwarding an 

Information Collection Request (ICR), 

abstracted below, to the Office of 

Information and Regulatory Affairs 

(OIRA), Office of Management and 

Budget (OMB) requesting a revision of 

their approval for the following 

collection of information: 1625–0040, 

Continuous Discharge Book, 

Application, Physical Exam Report, Sea 

Service Report, Chemical Testing, Entry 

Level Physical. Our ICR describes the 

information we seek to collect from the 

public. Review and comments by OIRA 

ensure we only impose paperwork 

burdens commensurate with our 

performance of duties. 

DATES: Please submit comments on or 

before April 3, 2009. 

ADDRESSES: You may submit comments 

identified by Coast Guard docket 

number [USCG–2008–0929] to the 

Docket Management Facility (DMF) at 

the U.S. Department of Transportation 

(DOT) or to OIRA. To avoid duplication, 

please submit your comments by only 

one of the following means: 

(1) Electronic submission. (a) To Coast 

Guard docket at http:// 

www.regulation.gov. (b) To OIRA by email via: oira_submission@omb.eop.gov. 

(2) Mail or Hand delivery. (a) DMF 

(M–30), DOT, West Building Ground 

Floor, Room W12–140, 1200 New Jersey 

Avenue, SE., Washington, DC 20590– 

0001. Hand deliver between the hours of 

9 a.m. and 5 p.m., Monday through 

Friday, except Federal holidays. The 

telephone number is 202–366–9329. (b) 

To OIRA, 725 17th Street, NW., 

Washington, DC 20503, to the attention 

of the Desk Officer for the Coast Guard. 

(3) Fax. (a) To DMF, 202–493–2251. 

(b) To OIRA at 202–395–6566. To 

ensure your comments are received in 

time, mark the fax to the attention of the 

Desk Officer for the Coast Guard. 

The DMF maintains the public docket 

for this Notice. Comments and material 

received from the public, as well as 

documents mentioned in this Notice as 

being available in the docket, will 

become part of the docket and will be 

available for inspection or copying at 

room W12–140 on the West Building 

Ground Floor, 1200 New Jersey Avenue, 

SE., Washington, DC, between 9 a.m. 

and 5 p.m., Monday through Friday, 

except Federal holidays. You may also 

find the docket on the Internet at 

http://www.regulations.gov. 

A copy of the complete ICR is 

available through the docket on the 

Internet at http://www.regulations.gov. 

Additionally, copies are available from 

Commandant (CG–611), U.S. Coast 

Guard Headquarters (Attn: Mr. Arthur 

Requina), 2100 2nd Street, SW., 

Washington, DC 20593–0001. The 

telephone number is 202–475–3523. 

FOR FURTHER INFORMATION CONTACT: Mr. 

Arthur Requina, Office of Information 

Management, telephone 202–475–3523 

or fax 202–475–3929, for questions on 

these documents. Contact Ms. Renee V. 

Wright, Program Manager, Docket 

Operations, 202–366–9826, for 

questions on the docket. 

SUPPLEMENTARY INFORMATION: The Coast 

Guard invites comments on whether 

this ICR should be granted based on it 

being necessary for the proper 

performance of Departmental functions. 

In particular, the Coast Guard would 

appreciate comments addressing: (1) 

The practical utility of the collections; 

(2) the accuracy of the estimated burden 

of the collections; (3) ways to enhance 

the quality, utility, and clarity of 

information subject to the collections; 

and (4) ways to minimize the burden of 

collections on respondents, including 

the use of automated collection 

techniques or other forms of information 

technology. 

Comments to Coast Guard or OIRA 

must contain the OMB Control Number 

of the ICR. Comments to Coast Guard 

must contain the docket number of this 

request, [USCG 2008–0929]. For your 

comments to OIRA to be considered, it 

is best if they are received on or before 

April 3, 2009. 

Public participation and request for 

comments: We encourage you to 

respond to this request by submitting 

comments and related materials. We 

will post all comments received,