RELEASE DATE:  September 26, 2003

PAR NUMBER:  PAR-03-177 (see addenda NOT-AI-04-012 and NOT-HL-04-102)

EXPIRATION DATE: January 12, 2005, unless reissued.

Department of Health and Human Services (DHHS)


National Institutes of Health (NIH)


National Center for Research Resources (NCRR)
National Institute on Aging (NIA)
National Institute of Child Health and Human Development (NICHD) 
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 

93.848, 93.849, 93.866.

LETTER OF INTENT RECEIPT DATES:  December 14, 2003, December 12, 2004 
APPLICATION RECEIPT DATES: January 14, 2004, January 12, 2005


o Purpose of this PAR
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Supplementary Instructions
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations


The purpose of this initiative is to enhance the availability of human 
embryonic stem cells (hESC) for research. The research projects proposed under 
this Program Announcement (PAR) will address the expansion, testing, quality 
assurance, cryopreservation and distribution of existing hESC lines that are 
in compliance with criteria for federal funding of research on existing hESC 
as described in



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  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 

Scope of the Activity

Costs allowed under this initiative will include:

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

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

o Equipment needed for the expansion, quality assurance, storage, and 
distribution of hESC and feeder lines. 

o Cell culture supplies 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. 

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 100 or 
more aliquots of two million cells for each supported line per year for three 

o Establishing the viability of existing cell cultures, performing initial 
expansion and characterization to ensure sufficient numbers of cells in 
preparation of scale-up and distribution of cells.

o Characterization of hESC by 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 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, 
extracellular matrix substrates and/or serum-free or serum substituted culture 

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

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 of 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.


This PAR 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.  As an applicant, you will be solely responsible for planning, 
directing, and executing the proposed project.

The SBIR and STTR applications received in response to this announcement will 
be considered for both Phase I and Phase II support. This PAR must be read in 
conjunction with the Omnibus Solicitation of the Public Health Service for 
Phase I SBIR Grant Applications found at and the instructions 
for Phase II Grant Applications found at

The R24, SBIR and STTR mechanisms may be used to support research projects 
that will enhance the capability of resources to serve biomedical research. 
Direct costs of awards made under the R24 mechanism are limited to $300,000 
per year for each of the planned three years of support. Grants under the SBIR 
and STTR mechanisms may reach $750,000/year.  Funding for the next year will 
be contingent on satisfactory progress during previous years of the award. The 
total project period for an application submitted in response to this PAR may 
not exceed three years. This PAR may be reissued or additional PARs or 
Requests for Applications may be available in FY 2006 pending the availability 
of funds.

You may submit (an) application(s) if your institution has any of the 
following characteristics: 
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign institutions/organizations

Special eligibility requirements for SBIR and STTR applications may be found 
at and


Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to develop 
an application for support.  Individuals from underrepresented racial and 
ethnic groups as well as individuals with disabilities are always encouraged 
to apply for NIH programs.


Applicants must have hESC lines listed on the NIH Human Embryonic Stem Cell 
Registry, For SBIR/STTR support, only institutions or 
organizations based in the United States with eligible hESC, or their 
affiliates, are eligible to apply. Racial/ethnic minority individuals, women, 
and persons with disabilities are encouraged to apply as principal 

Applicants are advised to budget for travel to attend an annual 2-day 
scientific and technical meeting in Bethesda, MD.

In addition, competing continuing (renewal) applications must give evidence at 
the time of submission that registered cell lines have been developed to a 
degree that allows for their immediate distribution. 

SBIR/STTR applicants requesting more than $500,000 in direct costs in any year 
of the proposed research must include a data sharing plan in their 
application. Details of the NIH data sharing requirements may be found at:

Each quarter, infrastructure awardees must report the number of orders for 
each approved hESC line received, together with the number of orders shipped. 
Additionally, the number and domestic/foreign status of recipients must also 
be reported. Where possible, the NIH funding status of the recipients should 
be disclosed.

Electronic copies of web-based instructional materials that describe the 
biological features of hESC and other training materials should be made 
available for posting on the NIH Stem Cell web site.


We encourage inquiries concerning this PAR and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 

o Direct your questions about scientific/research issues to:

L. Tony Beck, Ph.D. 
Program Officer, Division of Clinical Research 
National Center for Research Resources
6701 Democracy Boulevard, Room 916, MSC 4874
Bethesda, MD  20892-4874
Telephone: (301) 435-0805
FAX: (301) 480-3661

o Direct your questions about peer review issues to:

John F. Connaughton, Ph.D.
Scientific Review Administrator
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Blvd, Room 757, MSC 5452
Bethesda, MD 20892-5452
For courier services (FEDEX), use Zip Code 20817
Phone: 301-594-7797
FAX: 301-480-3505

o Direct your questions about financial or grants management matters to:

Ms. Mary Niemiec
Section Grants Management Officer
Office of Grants Management
National Center for Research Resources
6701 Democracy Boulevard, Room 1046, MSC 4874
Bethesda, MD  20892-4874Bethesda, MD  20892-4874
Telephone: (301) 435-0842
FAX:  (301) 480-3777


Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this PAR 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
The letter of intent is to be sent by the date listed at the beginning of this 
document.  The letter of intent should be sent to:

John F. Connaughton, Ph.D.
Scientific Review Administrator
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Blvd, Room 757, MSC 5452
Bethesda, MD 20892-5452
For courier services (FEDEX), use Zip Code 20817
Phone: 301-594-7797
FAX: 301-480-3505


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a Dun and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements. The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 
is available at in an 
interactive format.  For further assistance contact GrantsInfo, Telephone 
(301) 710-0267, Email:

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement must be received on or before January 14, 2004 or January 12, 
2005. SBIR/STTR applicants for Human Embryonic Stem Cell Research Resource 
Infrastructure Enhancement Awards should also use these dates.

SENDING AN APPLICATION TO THE NIH: 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
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
At the time of submission, two additional copies of the application and all 
copies of the appendix material must be sent to:

John F. Connaughton, Ph.D.
Scientific Review Administrator
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Blvd, Room 757, MSC 5452
Bethesda, MD 20892-5452
For courier services (FEDEX), use Zip Code 20817
Phone: 301-594-7797
FAX: 301-480-3505

APPLICATION PROCESSING: Applications must be received on or before January 14, 
2004 or January 12, 2005.  The CSR will not accept any application in response 
to this PAR 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 a substantial revision of 
an unfunded version of an application already reviewed, but such application 
must include an Introduction addressing the previous critique.  

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.


Applications submitted for this PAR will be assigned on the basis of 
established PHS referral guidelines. Applications that are complete will be 
evaluated for scientific and technical merit by an appropriate peer review 
group convened by the NIDDK in accordance with the review criteria stated 

As part of the initial merit review, all applications will:

o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the appropriate national advisory council 
or board


The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate each application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals.  The scientific review group 
will address and consider each of the following criteria in assigning the 
application's overall score, weighting them as appropriate for each 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority score.  
For example, an investigator may propose to carry out important work that by 
its nature is not innovative but is essential to move a field forward.

SIGNIFICANCE: Does the proposed work enhance research resources for hESC? 

APPROACH: Are the plans for hESC production, characterization and quality 
control adequately developed, and appropriate to the aims of the project?  
Does the applicant acknowledge potential problem areas and consider 
alternative tactics? Is the timeline for the proposed projects reasonable?

INNOVATION: Will the project provide improved methodologies, knowledge or 
training opportunities to facilitate researcher use of hESC lines?

INVESTIGATOR: Are the investigator and key 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)?

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Is there evidence of institutional 

ADDITIONAL REVIEW CRITERIA: Additional criteria for competing continuation 
(renewal) applications include the progress and achievements specific to this 
project since the previous competing review. The application should show that 
the previous specific aims have been accomplished and that the new goals are 
logical extensions of ongoing work. 

The reviewers will provide an administrative comment evaluating the adequacy 
and feasibility of the resource sharing plan. Recommendations regarding such 
plans are at 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 include the significance of the proposed project as 
assessed by the ability to lead to a marketable product or process. Applicants 
should refer to the SBIR/STTR review criteria at:

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

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.

subjects and protections from research risk relating to their participation in 
the proposed research will be assessed. (See criteria included in the section 
on Federal Citations, below).
to include subjects from both genders, all racial and ethnic groups (and 
subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 

be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.


Sharing Research Data

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research are expected to include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the rationale for 
not sharing research data will be assessed by the reviewers. However, 
reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score. 

BUDGET:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.


Applications submitted in response to a PAR will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities


HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.
SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $500,000 or more 
in direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible. Investigators should seek 
guidance from their institutions, on issues related to institutional policies, 
local IRB rules, as well as local, state and Federal laws and regulations, 
including the Privacy Rule. Reviewers will consider the data sharing plan but 
will not factor the plan into the determination of the scientific merit or the 
priority score.

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 "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 
a complete copy of the updated Guidelines are available at  
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 

The NIH maintains a policy 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 is available at 

requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  
You will find this policy announcement in the NIH Guide for Grants and 
Contracts Announcement, dated June 5, 2000, at

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at: and at  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s)for the hESC line(s)to be provided through these infrastructure 
awards.  Applications that do not provide this information will be returned 
without review. 

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.  Data that are (1) first produced in a 
project that is supported in whole or in part 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) may be accessed through FOIA.  
It is important for applicants to understand the basic scope of this 
amendment.  NIH has provided guidance at

Applicants may wish to place data collected under this PAR in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the application. 
In addition, applicants should think about how to structure informed consent 
statements and other human subjects procedures given the potential for wider 
use of data collected under this award.

Department of Health and Human Services (DHHS) issued final modification to 
the "Standards for Privacy of Individually Identifiable Health Information", 
the "Privacy Rule," on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified 
under the Rule as "covered entities") must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
( provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on "Am I a covered 
entity?"  Information on the impact of the HIPAA Privacy Rule on NIH processes 
involving the review, funding, and progress monitoring of grants, cooperative 
agreements, and research contracts can be found at

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.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

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 PAR is 
related to one or more of the priority areas. Potential applicants may obtain 
a copy of "Healthy People 2010" at  

AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal 
Domestic Assistance at and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards 
are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

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