NATIONAL GENE VECTOR LABORATORIES

Release Date:  December 1, 2000
 
RFA:  RR-01-001

National Center for Research Resources
 (http://www.ncrr.nih.gov/)
National Cancer Institute
 (http://www.nci.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases
 (http://www.niddk.nih.gov/)
National Institute of Arthritis and Musculoskeletal and Skin Diseases
 (http://www.nih.gov/niams/)
National Institute of Neurological Diseases and Stroke
 (http://www.ninds.nih.gov/)


Letter of Intent Receipt Date:  January  11, 2001
Application Receipt Date:       February 22, 2001

PURPOSE

The National Gene Vector Laboratories (NGVL) were established in 1995 
to produce clinical grade vectors for human gene transfer protocols. 
The purpose of this Request for Applications (RFA) is to continue the 
support of the NGVL to produce and distribute such vectors and to 
perform related toxicology studies for Phase I and II human clinical 
gene transfer protocols.

For purposes of this solicitation, the term “vector” is used in the 
broadest sense to refer to any vehicle designed to deliver genetic 
material into human somatic cells for therapeutic purposes.

The National Center for Research Resources (NCRR), together with the 
National Cancer Institute (NCI), National Institute of Diabetes and 
Digestive and Kidney Diseases (NIDDK), the National Institute of 
Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the 
National Institute of Neurological Diseases and Stroke (NINDS) as co-
sponsors, invite applications to join as participants in the National 
Gene Vector Laboratories.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic not-for-profit organizations, 
both public and private, such as universities, colleges, hospitals, 
laboratories, units of state and local governments, and eligible 
agencies of the Federal government.  Foreign institutions are not 
eligible to receive awards under this solicitation.  Individual members 
of racial and/or ethnic minority groups, women, and persons with 
disabilities are encouraged to apply.  National Institutes of Health 
(NIH) policies and requirements that govern the research grant programs 
will apply.

MECHANISM OF SUPPORT

The administrative and funding instrument to be used for this program 
will be the cooperative agreement (U42), assistance mechanism rather 
than an acquisition mechanism, in which substantial NIH scientific 
and/or programmatic involvement with the awardees is anticipated during 
performance of the activity.  Under a cooperative agreement, the NIH 
supports and/or stimulates the recipients’ activities by working in 
partnership with the awardee, without assuming the direction of, prime 
responsibility for, or dominance in the activity.  Rather, such 
responsibilities reside with the awardees for the project as a whole, 
although specific tasks and activities are shared among the awardees 
and the NIH Institutes and Centers (ICs). Details of the 
responsibilities, relationships, and governance of a study funded under 
a cooperative agreement are discussed later in this document under the 
section entitled “Terms and Conditions of the Award.”  

The anticipated award date is September 2001.  The total project period 
for an application submitted in response to this RFA may not exceed 
five years. Although this RFA is currently anticipated to be a one-time 
solicitation, if it is determined that there is a sufficient, 
continuing need, NCRR will invite competitive new and/or competitive 
continuation cooperative agreement applications for review in accord 
with the procedures described in REVIEW CONSIDERATIONS.  

FUNDS AVAILABLE

NCRR plans to commit approximately $2 million in total costs in FY 2001 
to support three to six awards in response to this RFA.  These awards 
are to support the research infrastructure for generating both specific 
human gene vectors and relevant toxicology data.  In addition, 
categorical ICs whose missions are addressed by a specific protocol can 
elect to support vector production and toxicology studies for that 
protocol.

Support for awards pursuant to this RFA will be contingent upon the 
quality and number of applications received and the availability of 
funds for this purpose. Furthermore, because the nature and scope of 
the activities proposed in response to this RFA will vary, it is 
anticipated that the size of individual awards will also vary.

RESEARCH OBJECTIVES

Background

Advances in the fields of molecular biology and genetics have led to 
the identification and characterization of many genes and their 
products.  As a consequence, over 400  gene transfer clinical protocols 
have been initiated in the United States during the past decade.   
Specific gene transfer studies have addressed single gene disorders 
such as cystic fibrosis, severe combined immune deficiencies, 
hemoglobinopathies, hemophilia, and hyperlipidemia; multifactorial 
disorders such as cancer and heart disease; and infectious diseases 
such as acquired immunodeficiency syndrome (AIDS).  
While the promise of gene transfer was viewed as great, the technical 
requirements and the expense of vector development, production, and 
safety testing limited the capacity of clinical investigators to 
proceed with implementation of many protocols.  Frequently, 
investigators had neither the ability to generate clinical grade vector 
in sufficient quantity nor the financial resources or time required to 
obtain the needed vector from commercial manufacturers.  The 
unavailability of vector constituted a barrier to progress in the field 
of gene transfer.

In response to these needs, the NGVL was established as a cooperative 
national effort to produce and distribute vectors for human gene 
transfer studies. The availability of the resources provided by these 
facilities lowered the cost barrier posed to investigators for the 
production of vectors and generated vectors for rare disorders for 
which there was little commercial interest. 

The NGVL Coordinating Center was also established in 1995 and is 
located at the Indiana University.  It is responsible for organizing 
the meetings of the NGVL Review Committee and Steering Committee, 
receiving investigator requests for NGVL services, oversight of 
compliance with the NGVL Policy and Procedures document 
(http://www.iupui.edu/~iucc/ngvl), maintenance of the Toxicology Master 
File, post-distribution monitoring and other administrative issues.  
Indiana University is also the site of an existing NGVL Production 
Facility that generates retroviral vector.

However, additional research on development and production of such 
vectors is still needed and many protocols still lack an adequate 
supply of clinical-grade vector.

Unexpected or serious adverse events (SAEs) represent a potential 
danger in any clinical trial.  To minimize the likelihood or 
seriousness of such events occurring during clinical research, 
toxicology studies are frequently required by the FDA before a trial is 
initiated.  However, many grants do not provide support for such 
studies.  In addition, toxicology data that are generated are usually 
considered to be proprietary and held within a Drug Master File, 
unavailable to other investigators.  Consequently, toxicology studies 
are often repeated at great cost to both the research community and 
funding entities.  

Objectives and Scope

The objective of this RFA is to expand this national infrastructure by 
inviting applicants to become part of the NGVL network.  Awardees will 
then be designated either as Production Facilities to construct, 
produce and distribute vectors for Phase I and II human gene transfer 
protocols or as Toxicology Centers to generate and share toxicology 
data relevant to particular gene vectors for such protocols.
  
Through this cooperative agreement, the awardees will develop methods 
to produce vectors requested by clinical investigators and will assist 
in refining those protocols.  In addition, some awardees will perform 
toxicology studies for NGVL-approved applications.  

Quantities of clinical grade vectors, suitable for toxicology studies 
and sufficient for approved human gene transfer protocols will be made 
at the Production Facilities and distributed to investigators whose 
protocols have been approved by the NGVL Steering Committees and 
participating ICs.  Highest priority for vector production will be 
given to projects that have peer-reviewed grant support.  

Applicants seeking designation as an NGVL Production Facility must have 
the necessary expertise, have produced vector for human clinical trials 
and have established procedures and facilities that meet FDA criteria 
for current Good Manufacturing Practices (cGMP).  They must identify 
the vector(s), which may include retrovirus, adenovirus, adeno-
associated virus, herpesvirus, lentivirus, non-viral vectors or other 
types of vector that would be produced at their facility, and how they 
would incorporate new technologies in the future. Applicants should 
describe not only their capability to produce vectors for more than one 
protocol simultaneously, but also their maximum production capacity, 
storage, safety, quality oversight and record keeping procedures.  

Applicants seeking designation as Toxicology Centers within the NGVL 
network should document their ability to perform toxicology studies on 
vectors for NGVL-approved protocols.  The resultant information from 
these studies will be maintained within NGVL databases and made 
accessible to the scientific community.  These applicants should 
provide detailed information on their expertise, prior experience and 
facilities to conduct such animal and in vitro studies in support of 
human clinical trials as well as existing safety oversight and record 
keeping procedures.  Animal facilities must be described fully and be 
in compliance with local, State and Federal requirements.  Informatics 
and statistical infrastructure, procedures for transfer of data into 
the NGVL Toxicology Master File, quality control and quality assurance 
should also be addressed.  

Respondents to this RFA must indicate if they are applying for an award 
as either a vector Production Facility or a vector Toxicology Center or 
both.  If an institution wishes to be designated as both a vector 
Production Facility and Toxicology Center, two separate applications 
must be submitted.  Each would then be reviewed on its own merits.

SPECIAL REQUIREMENTS

These cooperative agreements (U42s) will require cooperation among the 
NCRR Program Coordinator, the participating IC Program Officers, and 
the Directors of the NGVL vector Production Facilities and Toxicology 
Centers to maximize their effectiveness.  A number of issues need to be 
addressed in their applications to promote the development of 
collaboration among the award recipients. These are discussed below.

Terms and Conditions of Award

The following terms and conditions will be incorporated into the award 
statement and provided to the Director of the NGVL facility as well as 
the institutional official at the time of award.  These special Terms 
of Award are in addition to, and not in lieu of, otherwise applicable 
OMB administrative guidelines, HHS Grant Administration Regulations at 
45 CFR Parts 74 and 92, and other HHS, PHS, and NIH Grant 
Administration policy statements.

The administrative and funding instrument used for this program is a 
cooperative agreement (U42).  As described previously, the dominant 
role and prime responsibility for the activity resides with the 
awardee(s) for the project as a whole, although specific tasks and 
activities in carrying out the project(s) will be shared among the 
awardees, the NCRR Program Coordinator and the participating IC Program 
Officers. 

1. Awardee Rights and Responsibilities

Separate awards will be made to establish vector Production Facilities 
and Toxicology Centers.  

Production Facilities will be responsible for generating clinical grade 
vectors, performing appropriate safety testing, maintaining quality 
control and assurance, storing and distributing vector and operating 
according to cGMP guidelines appropriate for Phase I and II studies.

Toxicology Centers will be responsible for conducting animal and in 
vitro toxicology studies that the FDA determines are needed before a 
particular clinical gene transfer trial can begin.  They will obtain, 
collate, analyze and store the data generated.  The data will be 
transmitted in the appropriate format both to the investigator for 
subsequent transmission to the FDA and to the NGVL Coordinating Center 
for inclusion in the Toxicology Master File.

Each NGVL awardee will designate a Director and Associate Director for 
that NGVL facility.  They will then plan and design the details of the 
project including appropriate methods for defining and operating the 
facility and retaining the primary responsibility for its performance.  
Each NGVL facility Director must agree to participate with the NCRR 
Program Coordinator and the IC Program Officers as a member of the NGVL 
Steering Committee to provide oversight according to the NGVL Policy 
and Procedures document. Each Director, in cooperation with the other 
Steering Committee members, will be responsible for developing the 
details of the operating policies of the NGVL, including definition of 
objectives and approaches, planning, implementation, and interaction 
with other Directors, and assurance of scientific integrity.  

The Coordinating Center Director will not only chair both the Steering 
Committee and Review Committee meetings but also be responsible for 
administration, meeting preparations, meeting agendas, writing and 
distributing minutes, and provide written critiques to applicants who 
request vector production or toxicology data of the decisions made by 
the NGVL. The Director of the Coordinating Center will not cast a vote 
on applications submitted to the Review Committee.

The Coordinating Center Director and each NGVL Facility Director must 
present a progress report at each meeting for incorporation into the 
minutes.  The Steering Committee will meet at least semi-annually.

2. I/C Staff Responsibilities

One representative from the NCRR will be designated to serve as the 
NGVL Program Coordinator of the cooperative agreement.  The NGVL 
Program Coordinator and one Program Officer from each co-sponsoring IC 
will serve on the Steering Committee in order to bring that 
individual’s unique perspective on a given categorical disease for 
which the individual oversees genetic research.  In consultation with 
the NGVL Directors, these individuals may convene workshops or sponsor 
seminars on advances in gene transfer accomplished through NIH support.  
The IC Program Officers will participate in all Steering Committee 
meetings and assist in developing operating policies, quality control 
procedures, and policies that require cooperative action.  However, 
while the NGVL Program Coordinator and participating IC Program 
Officers may attend Steering Committee meetings, their cumulative votes 
will never exceed 40 percent.  

The NGVL Program Coordinator and IC Program Officers may attend the 
Review Committee meetings but will not vote or express opinions that 
may influence the voting of the Review Committee members.  

The NGVL Program Coordinator will assist in coordinating the activities 
of the NGVL facilities and the exchange of information.  The role of 
the NGVL Program Coordinator and IC Program Officers, as detailed 
throughout these terms of cooperation, is to assist and facilitate, but 
not to direct activities of the NGVL.  They will act as liaisons to the 
NIH and as information resources, bringing together groups with 
characterized vectors and groups with the requisite resources and 
expertise to implement high quality clinical gene transfer research.  

3. Collaborative Responsibilities

NGVL Steering Committee

The Steering Committee coordinates and facilitates the activities 
supported by these cooperative agreements.

Each member of the Steering Committee will have one vote and decisions 
will be made on the basis of a simple majority.  The total percentage 
of NIH representatives will not exceed 40 percent of the membership.  

The members of the Steering Committee will establish the functions of 
the Steering Committee, its method of operation, quality control 
assurance, and cooperation among the NGVL Directors, the NIH 
representatives, and recipients of the vectors and toxicology data 
generated by the facilities.  The Steering Committee will also make 
provisions for an arbitration panel as described below.  Criteria for 
accession and discontinuance of use of the facility will also be 
delineated.  The Steering Committee will then reach a consensus on 
these issues and update the existing NGVL Policy and Procedures 
document. The Steering Committee will meet semi-annually at which time 
members will discuss these and other functional issues.

The NGVL Steering Committee will appoint outside experts to review 
investigators’ requests for vector and toxicology support.  Rules 
governing the selection and tenure of the members of that NGVL Review 
Committee will be also be established by the Steering Committee.  The 
Directors and Associate Directors of the NGVL facilities may not attend 
meetings of the Review Committee.   They may neither participate in the 
discussions nor vote nor seek to influence the decisions of the Review 
Committee.  The Director of the NGVL Coordinating Center will chair 
both the Steering Committee and Review Committee meetings.

NGVL Review Committee 

The Review Committee will meet semi-annually to consider applications 
from investigators that request production of vector or toxicology 
studies relevant to their protocols.  This Committee will review the 
quality of the pre-clinical data, qualifications of the applicant and 
his/her institution, ethical issues, clinical protocol, consent 
documents and other issues outlined in the NGVL Policy and Procedures 
document.    

Arbitration

Any disagreement that may arise between an awardee and the ICs on 
scientific or programmatic matters may be brought to arbitration.  A 
panel of external consultants will be created, and convened as needed, 
to resolve any irreconcilable differences of opinion related to such 
matters.  The panel will include one member selected by the NGVL 
Facility Directors, one member selected by the ICs, and a third member 
chosen by the other two members of the arbitration panel.  These 
special arbitration procedures in no way affect an awardee's right to 
appeal an adverse determination in accordance with PHS regulations at 
42 CFR part 50, subpart D and HHS regulations at 45 CFR part 16.  
Applicants should anticipate probable areas of conflict and put forward 
an arbitration plan in their applications.

LETTERS OF INTENT

Prospective applicants are asked to submit a letter of intent that 
includes a descriptive title of the proposed application, the name, 
address, and telephone number of the Principal Investigator, the 
identities of other key personnel and participating institutions, and 
the number and title of the RFA to which the application will respond.  
Although a letter of intent is neither required nor binding, and does 
not enter into the review of a subsequent application, its contents 
allow NCRR staff to estimate the potential review workload and plan the 
review.

The letter of intent is to be faxed, E-mailed, or mailed to John Meyer, 
Ph.D. at the address listed under INQUIRIES by January 11, 2001.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used 
in applying for the cooperative agreement described in this RFA.  These 
forms are available at most institutional offices of sponsored research 
and from the Division of Extramural Outreach and Information Resources, 
National Institutes of Health, Two Rockledge Centre, 6701 Rockledge 
Drive, MSC 7910, Bethesda, Maryland 20892-7910, telephone 301-435-0714, 
email: GrantsInfo@nih.gov.  Application forms are also available on the 
Internet at: 
http://grants.nih.gov/grants/funding/phs398/forms_toc.html. 

Special Application Requirements

The general instructions for format, budget issues, etc., in the 
application packet should be followed except for the following.  The 
Research Plan may not exceed 100 pages, and must address the issues 
listed below as well as points discussed in the Review Criteria section 
of this RFA.  The budget pages of the application must address points 
raised below.

Applicants to this RFA should consider the points below as examples of 
relevant information to include in the application.  These are examples 
only and should not be construed as being required or limiting. 
Applicants are encouraged to address these and/or other points 
pertinent to the objectives of the RFA.

1. Resources

Those responding to this RFA may apply for designation as either a 
vector Production Facility or a Toxicology Center or both.

A detailed description of the vector Production Facility and its 
compliance with current Good Manufacturing Practice as defined by the 
Food and Drug Administration (FDA) should be included. Documentation 
must be provided of the maximum number of vectors that may be produced 
and maintained simultaneously and per year. Access to computer 
facilities should be documented.

A detailed description of the facilities available to carry out 
toxicology studies in compliance with Good Laboratory Practices as 
defined by the FDA should be included. Access to animal and virology 
facilities as well as any necessary computer facilities should be 
documented.

Compliance with Federal regulations for protection of human subjects 
and animals must be documented. In addition, as a condition of award, 
an awardee must be site visited and receive a favorable assessment by 
an outside panel of individuals qualified to review facilities and 
protocols with regard to cGMP and human subjects and animal protection 
issues relevant to this RFA before any vector can be produced or 
toxicology studies are initiated for NGVL-approved applications.

For current FDA guidance related to facilities for human gene transfer, 
contact:

Division of Establishment Licensing
1401 Rockville Pike, HFM-205
Rockville, MD  20852-1448
Telephone:  (301) 594-2049

For information about Good Manufacturing Practices refer to Title 21 of 
the Code of Federal Regulations (CFR), sections 210-211 and 610.  
Information about Good Laboratory Practices is listed in CFR Title 21, 
section 58.

Pertinent portions of the CFR can be ordered from:

The Government Printing Office
Superintendent of Documents
Washington, DC  20402
Telephone:  (202) 783-3238

2. Scientific Expertise and Experience in Vector Production and 
Toxicology

Documentation of experience in vector production and expertise in 
virology and molecular genetics should be provided.  An understanding 
of important trends in gene transfer research and plans for 
incorporation of new technologies in the future should also be 
documented.

Documentation should also be provided regarding which vectors will be 
produced along with detailed descriptions of production methodologies.  
Experience in producing clinical grade vectors for prior human gene 
transfer protocols should be detailed, accompanied by the type(s) and 
quantities of vector generated, the titers obtained, and the 
corresponding times required attain them.  Prior experience and future 
plans to establish and maintain master cell banks and producer cell 
lines should be included.

Experience with, knowledge of, and ability to adhere to, FDA guidelines 
for quality control and safety testing for microbial contamination, 
endogenous and replication-competent viruses, and other contaminants of 
vectors at all stages of development and maintenance, including post 
distribution monitoring, should be documented.  Indicate whether safety 
tests required will be performed within or contracted outside of the 
proposed NGVL facility.

Methods of certification of supernatants and final products should be 
described and outside sources of safety testing should be identified.

Respondents applying for support as a Toxicology Center should provide 
information on all animal models that are available.  Information on 
all resources and expertise in pathology and pharmacology should be 
provided, accompanied by a listing of toxicology studies performed over 
the previous 5 years in support of Investigational New Drug (IND) 
applications.  The list may include toxicology studies for gene 
transfer and non-gene transfer INDs.

Since human somatic cell gene transfer involves the administration of 
materials of biological products, it is regulated by the Center for 
Biologics Evaluation and Research (CBER), FDA.  IND applications are 
filed concerning clinical use of such products.  Respondents to this 
RFA should convey their familiarity with such requirements for 
clinical, pre-clinical and animal studies.

CBER has prepared documents relevant to this RFA that include:

o “Points to Consider in Human Somatic Cell Therapy” (1991)  

o “Points to Consider in the Production and Testing of New Drugs and 
Biologicals Produced by Recombinant DNA Technology” (1985) 

o “Points to Consider in the Characterization of Cell Lines Used to 
Produce Biologicals” (1987) 

o “Points to Consider in the Manufacture and Testing of Monoclonal 
Antibody Products for Human Use” (1987) 

o “Points to Consider in the Collection, Processing, and Testing of Ex-
Vivo Activated Mononuclear Leukocytes for Administration to Humans” 
(1989)

Copies of Points to Consider documents are available from:

The Division of Congressional and Public Affairs
CBER
HFM-12
1401 Rockville Pike, Suite 200 N
Rockville, MD  20852-1448
Telephone:  (301) 594-0830

CBER staff members are also available to respond to questions at (301) 
594-0830.

3. Collaborative Abilities

The NGVL must function as a collaborative effort among the awardees, 
the Coordinating Center, the NCRR Program Coordinator, the IC Program 
Officers and the clinical investigators.

Applicants should propose detailed plans for how they will participate 
in the Steering Committee and other aspects of this cooperative 
resource.  The issues of conflicts of interest should be discussed.  
Suggested requirements for access to, and termination of use of, the 
facilities should also be discussed.  Issues of intellectual property 
and authorship of and plans for publications should be addressed.  
Applicants are encouraged to review the current NGVL Policy and 
Procedures document available at http://www.iupui.edu/~iucc/ngvl.

Methods should be proposed for establishing inventories of vectors, 
procedures for maintaining and distributing products, tracking of the 
status of clinical studies and material transfer agreements.

Rules for access to the NGVL resources should be proposed and the 
relationship between users and investigators proposing studies defined.

4. Adherence to Terms of Cooperation

Because the Terms of Cooperation discussed above will be included in 
all awards issued as a result of the RFA, it is critical that each 
applicant include specific plans on interacting with the other awardees 
and NIH representatives involved in this cooperative agreement, 
especially with regard to the sharing of laboratory and clinical 
resources, policies and expertise.  The applicant’s experience in other 
multi-center efforts should be described.

BUDGET AND RELATED ISSUES

In order to fully achieve the goal of this initiative, up to four 
vector Production Facilities and two Toxicology Centers are proposed 
for support. The award will provide up to $500,000 per year in total 
costs to support the infrastructure of an individual facility.   
Categorical ICs will provide additional funding to support the 
production of specific vectors and related toxicology studies.

Applicants should complete the budget information as directed in the 
PHS 398 application form.

Budgets for personnel and infrastructure operation must be outlined 
with the additional, specific costs of producing and distributing a 
representative vector or generating and sharing toxicology studies 
being itemized separately.  Production Facility applicants should 
provide a sample budget that includes costs to produce master and 
producer cell banks and safety testing.  Toxicology Centers should 
provide sample budgets for each of small animal, large animal and non-
human primate studies.

The Director of each NGVL Production Facility or Toxicology Center will 
be a member of the Steering Committee that will meet semi-annually.  
Travel funds for Steering Committee and other approved meetings will be 
provided by the NGVL Coordinating Center.

During the course of the project period, it is anticipated that 
technologies will improve and the proposed protocols may change.  
Accordingly, it is expected that the awardees will adjust their 
methodologies to accommodate such changes.  Workshops to review new 
developments in the field may be organized under the auspices of the 
NGVL. 

Applications should present five budget periods of 12 months each that 
provide adequate budget justification for all applicable direct and F&A 
costs.  An estimate of personnel efforts and corresponding costs, 
including the principal investigators and other staff must be included.  

APPLICATIONS NOT CONFORMING TO THESE GUIDELINES WILL BE CONSIDERED 
UNRESPONSIVE TO THIS RFA AND WILL BE RETURNED WITHOUT FURTHER REVIEW

The RFA label available in the PHS 398 (rev. 4/98) application form 
must be affixed to the bottom of the face page of the application.  
Type the RFA number on the label.  Failure to use this label could 
result in delayed processing of the application such that it may not 
reach the review committee in time for review.  Line 1 should indicate 
whether the application is for an award as a Production Facility or as 
a Toxicology Center.  In addition, the RFA title and number must be 
typed on line 2 of the face page of the application form.  

Submit a signed, typewritten original of the application, including the 
Checklist, and two signed photocopies, in one package to:

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

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

Applications must be received by February 22, 2001.  If an application 
is received after this date it will be returned to the applicant 
without review.

The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA 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 that 
addresses the issues raised in the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the 
Center for Scientific Review and for responsiveness by NCRR.  
Applications that are incomplete or non-responsive will be returned to 
the applicant without further consideration.  Applications must adhere 
to the page limitations and Special Application Requirements noted 
under the section APPLICATION PROCEDURES above to be considered 
responsive.  

Applications that are complete and responsive to the RFA 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 and may undergo a 
process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under 
review, will be discussed, assigned a priority score, and receive a 
second level review by the National Advisory Research Resources 
Council.

Review Criteria

The goals of NIH-supported research are to advance understanding of 
biological systems, improve the control of disease, and enhance the 
health of humankind.  The scientific and technical merits of the 
proposed activities and the organizational plans for participating in 
the NGVL and the extent to which they address the overall goals and 
objectives of the RFA will be reviewed.  Reviewers will be asked to 
provide written comments on:

o Qualifications and experience of the applicant and staff in producing 
clinical grade gene vectors or generating toxicology data for these 
vectors.

o Scientific plans, methods, and analyses.  Are they adequately 
developed, well integrated, and appropriate to production of clinical 
grade vector and/or performance of relevant toxicology studies?  Does 
the applicant acknowledge potential problem areas and consider 
alternative tactics?

o Experience in organizing and participating in collaborative efforts 
in relevant arenas such as vector production, clinical trials and 
toxicology studies.

o Capability to produce vectors of appropriate type and quantity 
within a reasonable time frame and at a reasonable cost.  Is the 
proposed budget justified?

o Plans for effective and synergistic cooperation and coordination 
among awardees, the NGVL Coordinating Center, the Steering Committee, 
the NGVL Program Coordinator, the IC Program Officers and the 
investigators who request NGVL resources. 

o Organizational attributes of the Production Facility or Toxicology 
Center.  

o Availability and quality of facilities and resources required for 
this effort, noting that this award does not provide support for 
construction or renovation of facilities.

o Scientific environment in which the work would be done.  Would it 
contribute to the probability of success?  Are there unique features 
present?  

o Experience in addressing issues inherent in cGMP, Good Laboratory 
Practice, Good Clinical Practice and protection of human subjects.

o Qualifications of the applicant and staff in providing statistical 
and data management laboratory database designs, data collection and 
database security.

o Evidence of institutional support. 

o Experience in implementing appropriate material transfer agreements.

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 plans to include, recruit and retain both genders, 
minorities and their subgroups, and children as appropriate for the 
scientific goals of the research.

o The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the 
project proposed in the application.  

Schedule

Letter of Intent Receipt Date:  January 11, 2001
Application Receipt Date:       February 22, 2001
Peer Review Date:               May-June, 2001
Council Review:                 September 13-14, 2001
Anticipated Award Date:         September 2001

AWARD CRITERIA

The earliest anticipated date of award is September 1, 2001.  Awards 
will be based primarily on the scientific merit, vector production 
capability and/or ability to perform required toxicology studies, 
programmatic priorities and availability of funds.  Some consideration 
may also be given to geographic diversity.  The award will be subject 
to administrative review by NCRR and the Participating ICs upon receipt 
of each annual non-competitive renewal application.

Termination or Modification

NCRR reserves the right to terminate or modify each NGVL award in the 
event of (a) failure to develop, implement or maintain functionality, 
(b) substantial shortfall in efficiency, data reporting, quality 
control, or other such major breach in either vector production or 
generation of appropriate toxicology data, (c) substantive changes in 
an agreed-upon protocol with which the ICs cannot concur, (d) ethical 
issues, (e) lack of compliance with cGMP guidelines, (f) significant 
non-compliance with other relevant Federal guidelines, or (g) failure 
to provide the FDA relevant vector information or data on behalf of an 
investigator.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Richard Knazek, M.D. 
Medical Officer
Clinical Research Area
National Center for Research Resources
One Rockledge Centre, Room 6030
6705 Rockledge Drive, MSC 7965
Bethesda, MD  20892-7965
Telephone: (301) 435-0792
FAX: (301) 480-3661
Email: richardk@ncrr.nih.gov

Direct inquiries regarding review issues to:

John Meyer, Ph.D.
Deputy 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:  meyerj@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 

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.

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 RFA is 
related to all 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 
biomedical and behavioral research projects involving human subjects, 
unless a clear and compelling rationale and justification are 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 research involving human subjects should 
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities 
as Subjects in Clinical Research," published in the NIH Guide for 
Grants and Contracts on August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: 
The revisions relate to NIH defined Phase III clinical trials and 
require: a) all applications or proposals and/or protocols to 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) all investigators to report accrual, 
and to conduct and report 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 NIH, unless there are clear and compelling 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.

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance 
No. 93.333.  Awards are made under authorization of the Public Health 
Service Act, Titles III and IV, Sections 301, 479, and 480, as amended, 
Public Laws 78-410 and 99-158, 42 U.S.C. 241, 287, and 287a, as 
amended, and administered under NIH grants policies and Federal 
Regulations 42 CFR 52 and 45 CRF Part 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 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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