HUMAN EMBRYONIC STEM CELL RESEARCH RESOURCE INFRASTRUCTURE ENHANCEMENT AWARD

Release Date:  November 29, 2001 (see NOT-RR-03-003 and PAR-03-177)


PA NUMBER:  PAR-02-023

National Center for Research Resources
 (http://www.ncrr.nih.gov)
National Institute of Aging
 (http://www.nia.nih.gov)
National Institute of Child Health and Human Development
 (http://www.nichd.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases
 (http://www.niddk.nih.gov)
National Institute of Mental Health
 (http://www.nimh.nih.gov/)

Application receipt dates:  January 8, 2002, March 8, 2002, May 8, 2002, July 
8, 2002, and September 6, 2002.

PURPOSE

The purpose of this initiative is to increase the research resource capacity 
for basic research using human embryonic stem cells (hESC). The research 
projects proposed under this Program Announcement (PA) will address the 
expansion, testing, quality assurance, and distribution of existing cell lines 
that are in compliance with criteria for federal funding of research on 
existing hESC as described in http://grants.nih.gov/grants/guide/notice-
files/NOT-OD-02-005.html.

ELIGIBILITY REQUIREMENTS

Applicants may apply only if they have hESC listed on the NIH Human Embryonic 
Stem Cell Registry, http://escr.nih.gov. Applications may be submitted by 
domestic and foreign, for-profit and not-for-profit organizations, public and 
private, such as universities, colleges, hospitals, laboratories, units of 
State and local governments, and eligible agencies of the Federal government. 
For SBIR/STTR support, only institutions or organizations based in the United 
States or their affiliates with eligible hESC are eligible to apply. 
Racial/ethnic minority individuals, women, and persons with disabilities are 
encouraged to apply as Principal Investigators. 

MECHANISM OF SUPPORT

This PA will use both the National Institutes of Health (NIH) Resource-
Related Research Projects (R24) award mechanism and the Small Business 
Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grant 
mechanisms.  

The SBIR and STTR applications received in response to this announcement will 
be considered for both Phase I and Phase II support. This PA must be read in 
conjunction with the current Omnibus Solicitation of the Public Health Service 
for Small Business Innovation Research (SBIR) and Small Business Technology 
Transfer(STTR)Grant Applications (PHS 2001-2, or after, January, PHS 2002-2.)

The R24, SBIR and STTR mechanisms may be used to support research projects 
that will enhance the capability of resources to serve biomedical research. 
The total project period for an application submitted in response to this PA 
may not exceed 2 years. Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant. This 
PA may be reissued or additional PAs or Requests for Applications may be 
available in FY 2003 pending the availability of funds.

FUNDS AVAILABLE

It is anticipated that approximately $3 million total will be available in FY 
2002. Award of grants is contingent upon the availability of such funds for 
this purpose. It is anticipated that up to 10 grants may be awarded under this 
program in FY 2002. The specific number to be funded will depend on the merit 
and scope of the applications received.

Direct costs of awards made under the R24 mechanism are limited to $400,000 
per year for each of the planned two years of support. Grants under the SBIR 
and STTR mechanisms may reach $750,000/year. Additional solicitations may be 
available in FY 2003 pending available of funds. Funding for the second year 
will be contingent on satisfactory progress during year 1.

RESEARCH OBJECTIVES

Background

Embryonic stem cells uniquely proliferate in an undifferentiated state while 
retaining the capability to develop into the cell types derived from all three 
germ layers. Research suggests that mammalian embryonic stem cells have a 
potential for directed development that might allow for the replacement, or 
restoration, of cell and organ function.  The recent development of hESC has 
been greeted as a first step in a process that holds promise for the 
restoration of cell or organ function in man.

Substantial basic research on the characterization, mechanisms of 
differentiation, and regulation of cellular processes of hESC is essential 
before their potential in medicine can be assessed. This basic research 
requires supplies of cells that meet quality controls and behave reproducibly. 
The cells will need to be available in sufficient quantity for research and 
testing in multiple laboratories.  hESC that are acceptable for research 
purposes are listed in the NIH Human Embryonic Stem Cell Registry 
http://escr.nih.gov.  This initiative aims to enhance the availability of hESC 
for preclinical investigations. The development of quality controls to monitor 
the laboratory performance of the hESC lines is an integral part of the 
initiative.

Scope of the Activity

Costs allowed under this initiative will include:

o  Rental fees for laboratory space to support the expansion of existing 
   hECS lines in compliance with good laboratory practices (GLPs) (21 CFR 
   part 58).

o  Personnel costs for laboratory supervision, and maintenance of GLP cell 
   culture procedures. Training of new laboratory technicians is allowed       
   for the purposes of increasing skill levels to culture hECS. 

o  Equipment including those needed for the expansion, quality assurance, 
   storage, and distribution of hECS lines. Examples include: Centrifuges, 
   biocontainment hoods, fume hoods, triple gas incubators, liquid nitrogen 
   freezing and storage, -80oC freezers, water purification systems,       
   balances, steam autoclaves, standard molecular biology instruments such   
   as thermocyclers and gel electrophoresis apparatus, microscopes 
   including those equipped for fluorescent in situ hybridization studies.

o  Supplies for standard cell culture including media, plates, flasks, 
   growth factors and other nutrients, cell freezing, disposal, storage,  
   and distribution materials. 

o  Travel for the quality control certification of reagent vendors. 
   Applicants are advised to budget for travel to attend an annual 2-day  
   scientific and technical meeting in Bethesda, MD.

o  Development and support of a website that will make available 
   information concerning the availability and properties of cell lines.

Costs not allowed under this initiative:

o  Renovation, acquisition, or building of facilities.

Activities that are encouraged under this initiative include:

o  Culture of existing cells sufficient to support the distribution of 250      
   or more aliquots of 20 million cells for each supported line per year 
   for 2 years.

o  Characterization of hESC cell surface markers, DNA fingerprinting, and 
   transcriptional profiling.

o  Karyotype, telomere, and fluorescent in-situ hybridization studies of 
   cells at various passages.

o  Maintenance of frozen primary cell culture and "freeze-backs" from 
   successive passages.

o  Development of sub-lines at various passages.

o  Development of cryopreservation techniques.

o  Xenografts into experimental animals to characterize hESC cell 
   differentiation capabilities.

o  Application of vitrification techniques.

o  Quality assurance measures including studies of functionality after 
   multiple freeze/thaw cycles, and sterility testing.

o  Development of technical support materials for researchers including 
   laboratory instruction manuals and audio-visual resources.  

o  Establishment of web-based instructional materials that describe the 
   biological features of hESC.

o  Identification of optimal culture materials and conditions to maintain 
   and expand hESC. This could include the development of human feeder 
   cells and/or serum-free or serum substituted culture conditions.

o  Development of culture supplies to accompany the cells upon distribution            
   to researchers. This may be achieved via sub-contracts with commercial  
   suppliers of such materials. 

o  Training in technical skills for laboratory use of hESC.

o  Development of a plan for cost recovery for resources supplied.

Activities that are beyond the scope of this initiative and prohibited from 
support from this grant award include: 

o  Derivation of new human embryonic stem cell lines from human
   blastocysts.

o  Research and development on stem cells from animals or other human 
   sources. 

o  Research to differentiate hESC.

o  Basic research on fundamental cellular and molecular mechanisms. 

o  Animal transplantation studies with the exception of those described above.

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html must be used in 
applying for these grants.  This version of the PHS 398 is available in an 
interactive, searchable format.  For further assistance contact GrantsInfo, 
Telephone 301/435-0714, Email: GrantsInfo@nih.gov.  

The PA title and number must be typed on line 2 of the face page of the 
application form and the YES box must be marked. Submit a signed, typewritten 
original of the application, including the checklist, and three signed 
photocopies, in one package to:

Center for Scientific Review
National Institutes of Health
Two Rockledge Center, Room 1040-MSC7710
6701 Rockledge Drive
Bethesda, MD  20892-7710
(or Bethesda, MD  20817 if express mail or courier service is used)

At the time of submission, two additional copies of the application 
must be sent to the Director, Office of Review, NCRR, at the address 
listed under INQUIRIES.

The Center for Scientific Review (CSR) will not accept any application 
in response to this PA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude 
the submission of substantial revisions of an application already 
reviewed, but such applications must include an Introduction addressing 
the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness and 
responsiveness by NCRR. Applications that are incomplete or non-responsive 
will be returned to the applicant without further consideration.  

Applications that are complete and responsive to the PA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the Office of Review, NCRR in accordance with 
the review criteria stated below.  

As part of the initial merit review, all applications will receive a written 
critique, will be assigned a priority score, and receive an expedited second 
level review by the National Advisory Research Resources Council or other 
Boards or Councils as appropriate.

Review Criteria

The goals of NIH-supported research are to advance understanding of biological 
systems, improve the control of disease, and enhance health. In the written 
comments reviewers will be asked to discuss the following aspects of the 
application in order to judge the likelihood that the proposed research will 
have a substantial impact on the pursuit of these goals. The application will 
be reviewed primarily on the basis of the stated goals of the initiative:  
that is to expand the access to existing cell lines and provide high quality 
materials and information to the scientific community.

(1) Significance:  Does the proposed work enhance research resources for hESC? 

(2) Approach:  Are the plans for research resource enhancement adequately 
developed, and appropriate to the aims of the project?  Does the applicant 
acknowledge potential problem areas and consider alternative tactics?

(3) Innovation: Will the project provide improved methodologies or knowledge 
to facilitate researcher use of the cell lines?

(4) Investigator:  Are the investigator and proposed personnel sufficiently 
knowledgeable, experienced, and appropriately trained and well suited to carry 
out this work?  Is the work proposed appropriate to the experience level of 
the Principal Investigator and other researchers (if any)?

(5) Environment:  Does the scientific environment in which the work will be 
done contribute to the probability of success? Is there evidence of 
institutional support?

The reviewers will provide an administrative comment evaluating the adequacy 
and feasibility of the resource sharing plan. Recommendations regarding such 
plans are at http://www.ott.nih.gov/policy/rt_guide_final.html. This comment 
will not affect the priority score of the proposal.  NIH staff will consider 
the adequacy of the plan in determining whether to recommend an application 
for award.  The sharing plan as approved, after negotiation with the applicant 
as necessary, will become a condition of the grant award.

SBIR/STTR Review Criteria:

In addition to the above criteria applications for support under the SBIR/STTR 
programs will be assessed using the following criteria:
 
o  Does the proposed project have commercial potential to lead to a marketable
   product or process?
   
o  Are the aims original and innovative?

Phase II Applications

In addition to the above criteria, to what degree was progress toward the 
Phase I objectives met and feasibility demonstrated in providing a solid 
foundation for the proposed Phase II activity?

Phase I/Phase II Fast Track Applications

For Phase I/Phase II Fast Track applications, the following additional 
criteria will be applied:

o  Does the Phase I application specify clear, appropriate measurable goals 
   (milestones) that should be achieved prior to initiating Phase II?

o  Did the applicant submit a concise Product Development Plan that adequately 
   addresses the four areas described in Section VI, item G of this 
   solicitation?

o  To what extent was the applicant able to obtain letters of interest, 
   additional funding commitments, and/or resources from the private sector or 
   non-SBIR/STTR funding sources that would enhance the likelihood for 
   commercialization?

o  Does the project carry a high degree of commercial potential, as described 
   in the Product Development Plan?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The reasonableness of the proposed budget and duration in relation to 
   the proposed activities

o  The adequacy of the proposed protection for laboratory staff working 
   with the cells, animals or the environment, to the extent they may be   
   adversely affected by the activities proposed in the application.

AWARD CRITERIA

Applications will compete for available funds with all other recommended 
applications. Award criteria that will be used to make award decisions 
include:

o  scientific merit (as determined by peer review)and,
o  availability of funds

INQUIRIES

Inquiries concerning this PA are encouraged.  We welcome the opportunity to 
clarify any issues or respond to questions from potential applicants.

Direct inquiries regarding programmatic issues to:

Anthony Hayward, M.D., Ph.D. 
Director, Division of Clinical Research 
National Center for Research Resources
One Rockledge Centre, Room 6030
6705 Rockledge Drive, MSC 7965
Bethesda, MD  20892-7965
Telephone:  (301) 435-0790
FAX:  (301) 480-3661
Email:  haywarda@ncrr.nih.gov

Direct inquiries regarding review issues to:

Charles H. Hollingsworth, Dr.P.H.
Director, Office of Review
National Center for Research Resources
One Rockledge Centre, Room 6018
6705 Rockledge Drive, MSC 7965
Bethesda, MD  20892-7965
Telephone:  (301) 435-0806
FAX:  (301) 480-3660
Email:   charlesh@ncrr.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Mary Niemiec
Section Grants Management Officer
Office of Grants Management
National Center for Research Resources
One Rockledge Centre, Room 6086
6705 Rockledge Drive, MSC 7965
Bethesda, MD  20892-7965
Telephone:  (301) 435-0844
FAX:  (301) 480-3777
Email:  maryn@ncrr.nih.gov 


HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS led national 
activity for setting priority areas.  This Program Announcement (PA), Human 
Embryonic Stem Cell Research Resource Infrastructure Enhancement Award, is 
related to one or more of the priority areas.  Potential applicants may obtain 
a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided indicating 
that inclusion is inappropriate with respect to the health of the subjects or 
the purpose of the research. This policy results from the NIH Revitalization 
Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-
files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are 
available at 
<http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm>.
The amended policy incorporates: the use of an NIH definition of 
clinical research; updated racial and ethnic categories in compliance with the 
new OMB standards; clarification of language governing NIH-defined Phase III 
clinical trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; and 
b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines on the Inclusion of Children as Participants in 
Research Involving Human Subjects" that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html. 

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS

NIH policy requires education on the protection of human subject participants 
for all investigators submitting NIH proposals for research involving human 
subjects.  This policy announcement is found in the NIH Guide for Grants and 
Contracts Announcement dated June 5, 2000, at the following website: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  This amendment pertains to data that are (1) 
first produced in a project that is supported with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation).  Accessible under this 
amendment are research data, not trade secrets, commercial information, 
intellectual property, research resources, or other physical objects.  For 
more information about this amendment, including the definition of data, 
please see http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm

AUTHORITY AND REGULATIONS 

This program is described in the Catalog of Federal Domestic Assistance No. 
93.333 and 93.866. Awards are made under authorization of Sections 301 and 405 
of the Public Health Service Act as amended (42 USC 241 and 284) and 
administered under NIH grants policies and Federal Regulations 42 CFR 52 and 
45 CFR Parts 74 and 92.  This program is not subject to the intergovernmental 
review requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products.  In 
addition, Public law 103-227, the pro-Children Act of 1994, prohibits smoking 
in certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.

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