[Federal Register Volume 77, Number 95 (Wednesday, May 16, 2012)]
[Notices]
[Pages 28883-28886]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-11932]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2012-N-0009]
Cooperative Agreement To Support Innovation in Vaccine Clinical
Trial Design and Collaboration in Pharmacovigilance To Advance Global
Access to Safe and Effective Vaccines
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) announces its intention
to accept and consider a single source application for an award of a
cooperative agreement to the World Health Organization (WHO) in support
of collaborative efforts to advance innovative approaches to vaccine
clinical trial design and to enhance the utilization of a range of
pharmacovigilance tools as a means to further vaccine safety and
potentially facilitate more rapid introduction of new vaccines. The
goal of FDA's Center for Biologics Evaluation and Research (CBER) is to
enhance technical collaboration and cooperation between FDA, WHO, and
its Member States to facilitate strengthening regulatory capacity
globally.
DATES: Important dates are as follows:
1. The application due date is June 15, 2012.
2. The anticipated start date is September 15, 2012.
3. The expiration date is June 16, 2012.
ADDRESSES: Submit the paper application to: Vieda Hubbard, Grants
Management (HFA-500), 5630 Fishers Lane, Rockville, MD 20857, and a
copy to Leslie Haynes, Center for Biologics Evaluation and Research,
Office of the Director (HFM-30), 1401 Rockville Pike, Rockville, MD
20852-1448. For more
[[Page 28884]]
information, see section III of the SUPPLEMENTARY INFORMATION section
of this notice.
FOR FURTHER INFORMATION CONTACT:
Gopa Raychaudhuri, Office of the Director (HFM-1), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-6352,
email: gopa.raychaudhuri@fda.hhs.gov. or
Leslie Haynes, Office of the Director (HFM-30), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-3114,
email: leslie.haynes@fda.hhs.gov. or
Vieda Hubbard, Office of Acquisitions and Grants Services (HFA 500),
Food and Drug Administration, 5630 Fishers Lane, Rockville, MD 20857,
301-827-7177, email: vieda.hubbard@fda.hhs.gov.
For more information on this funding opportunity announcement (FOA)
and to obtain detailed requirements, please refer to the full FOA
located at http://www.fda.gov/BiologicsBloodVaccines/ScienceResearch/ucm297861.htm.
SUPPLEMENTARY INFORMATION:
I. Funding Opportunity Description
RFA-FD-12-022
93.103
A. Background
CBER has been a leader and active participant in the global
community to improve human health in the world's populations over many
years. A significant area of engagement for CBER is its support of
innovative science to advance vaccine development and to improve access
of the global population to safe and effective vaccines. The U.S.
Department of Health and Human Services (HHS) has invested
significantly in developing sustainable global vaccines production
capacity. Adequate regulatory oversight throughout the vaccine
development life cycle is essential in assuring the safety, purity, and
potency of vaccines and other biologicals.
WHO is the directing and coordinating authority for health within
the United Nations system. It is responsible for providing leadership
on global health matters, shaping the health research agenda, setting
norms and standards, articulating evidence-based policy options,
providing technical support to countries, and monitoring and assessing
health trends. It is the only organization with the mandate, technical
expertise, and broad reach to meet the Summary Objectives.
WHO has played a key role for over 50 years in establishing
international guidelines and standards for development and use of
vaccines and other biologicals. The assessment, licensure, regulatory
control, and surveillance of vaccines and biological medicinal products
are major challenges for national regulatory authorities confronted by
a steadily increasing number of novel products, complex quality
concerns, new regulatory issues arising from rapid technical and
technological advances, and emerging infectious diseases (e.g.,
pandemic influenza). With the globalization of markets, the volume of
vaccines and biological medicinal products crossing national borders
continues to rise, making it even more critical that regulatory
knowledge and experience be shared as appropriate to do so, and that
global monitoring to ensure product safety be harmonized to the
greatest extent possible.
WHO played a leading role in coordinating pharmacovigilance
activities and exchange of information among regulators and public
health authorities during the H1N1 pandemic. WHO has further
demonstrated its leadership in the cause of vaccine safety through its
Global Vaccine Safety Blueprint effort, a WHO initiative that focuses
on monitoring vaccine safety once a product has been licensed for use.
The Blueprint focuses on the need to monitor vaccinated populations for
the occurrence of adverse events following immunization (AEFI), and to
address vaccine safety concerns in a timely manner when they arise.
CBER has been a leader and active participant in the global
community to improve human health in the world's populations over many
years. Its international engagements have been informed by the
knowledge that protection of global public health against infectious
disease threats translates into protection of public health in the
United States. In its capacity as a Pan American Health Organization/
WHO Collaborating Center for Biological Standardization, CBER has
supported many of WHO's efforts to advance vaccine safety, including
serving on the Consultative Committee of the Global Vaccine Safety
Blueprint project, serving on the WHO Global Advisory Committee on
Vaccine Safety, and collaborating with the Uppsala Monitoring Center
(UMC), a WHO Collaborating Center that is responsible for maintaining
the global Adverse Drug Reaction database, Vigibase.
CBER seeks to support efforts to advance innovative approaches to
vaccine clinical trial designs and to enhance the utilization of a
range of pharmacovigilance tools as a means to further vaccine safety
and potentially facilitate more rapid introduction of new vaccines. The
two primary focus areas are:
1. Innovative Vaccine Clinical Trial Design
Clinical trials are performed to evaluate the safety and efficacy
of vaccines. Improving the efficiency of vaccine clinical trials in the
development process could lead to more rapid availability of new
vaccines. In the case of early phase clinical trials, new approaches
can more rapidly determine whether novel vaccine candidates are likely
to be safe and efficacious, and better approaches to optimizing
allocation of study participants between late phase clinical trials and
postmarketing safety studies could lead to more rapid access to
lifesaving vaccines, while still obtaining the data necessary to ensure
vaccine safety.
2. Vaccine Pharmacovigilance
An important regulatory tool to assure vaccines are safe and
effective is a robust pharmacovigilance system. The decision to license
a product is based on information available at the time of approval,
and the conditions for use are specified in the product label. However,
the knowledge related to the safety profile of the product can change
over time through expanded use in greater numbers of people and in
diverse populations. Rare adverse events often are not identified in
clinical trials since the numbers of subjects enrolled in the trials
are not large enough to detect low frequency signals. Thus, it is
essential to continue monitoring vaccine safety throughout the product
life cycle and to obtain and analyze any additional safety information
in ``real time.''
This project represents a collaborative effort between CBER and WHO
(and complements and builds upon other existing commitments of FDA and
HHS with WHO) to support scientific collaboration and enhance
regulatory capabilities of National Regulatory Authorities to advance
global access to safe and effective vaccines and other biologicals that
meet international standards. This project will lead to improved
technical cooperation between FDA, WHO, and its Member States.
B. Research Objectives
1. Innovative Vaccine Clinical Trial Design
In recent years there has been interest in finding innovative study
designs to speed development of promising new vaccines, particularly in
disease areas
[[Page 28885]]
where an urgent and unmet need exists. Diseases such as malaria,
tuberculosis, and human immunodeficiency virus are especially
challenging due to the widespread public health impact of these
diseases, as well as the fact that traditional vaccine development
mechanisms do not appear applicable because of the nature of the
disease pathogens and/or the natural history of the disease. Bringing
these candidate vaccines forward into larger late Phase 2 or Phase 3
clinical trials has had minimal success to date. The goals, thus, in
seeking innovative trial designs are to: (1) Minimize the number of
ineffective candidate vaccines that proceed into late Phase 2/Phase 3
trials, (2) enhance ability to identify promising candidate vaccines
early to move forward into late Phase trials, (3) obtain answers to
other scientific questions of interest (e.g. establishing correlates of
protection) more quickly, and (4) promote more efficient use of
resources. Of special interest are various types of adaptive trial
designs and other innovations in clinical study designs.
2. Improving Allocation of Safety Data Collection Throughout the
Vaccine Development Life Cycle
Achieving optimal allocation of safety data collection at each
phase of the product development life cycle requires a better
understanding of the interplay among disease morbidity and mortality,
vaccine effectiveness and safety, quality of study designs, individual
risk perception, and vaccination choice. One approach to obtain this
understanding is through mathematical simulation of the vaccine
development life cycle. Additional research in both the structure of
the mathematical models and how to decide what constitutes the
acceptable vaccine risk is needed to advance this work. Further
translation of such theoretical work into practical study designs and
pharmacovigilance activities through demonstration projects would also
be desirable.
3. Enhancing Postmarketing Surveillance of Vaccine Safety
Four types of activities are of interest:
a. Improvement of the evaluation of centralized spontaneous
reporting systems data. Efficient and rigorous analysis of spontaneous
reports of adverse events following immunization, maintained at the
UMC, through improvements in application of case definitions, data
mining algorithms, vaccine dictionaries, and development of case-based
reasoning strategies (such as text mining and natural language
processing and statistical and mathematical algorithms), and other
approaches would be considered.
b. Improvements in the interoperability of global pharmacovigilance
systems. Examples include the development and implementation of a
database that would allow tracking global distribution and use of any
vaccine (including vaccine constituents and dose information) and
enable linkages to existing global pharmacovigilance systems where
those vaccines are in use, as a basis for rapid response to vaccine
safety concerns arising in any country where a vaccine is distributed.
For countries that have electronic population-based health care data
systems, this could include improvements in data architecture (e.g. use
of electronic medical records), methods for near real-time
surveillance, and conducting definitive studies with rigorous case
definitions in an efficient manner for vaccine safety surveillance
following globally accepted standards to help create a global vaccine
safety data link.
c. Improving approaches to rigorous vaccine safety studies in low
and middle income countries (LMICs). The basic requirements for a
collaborative approach of this kind in LMICs would be: That the
methodology is simple, so it could be easily implemented and
standardized for all sites; is timely; only uses resources already
available in the local public health system; and avoids the need for
population denominators. An example of successful use of this approach
is the 2009 H1N1 influenza vaccine safety study using the self-
controlled case series methodology. Improving this approach, because of
its flexibility and applicability to countries where population
denominator information may not be available, is one direction that
could be taken.
d. Evaluating social media and mobile communication devices for
vaccine safety in LMICs. The use of social media for public health
information has received attention recently because of the success of
``Google flu trends'' (http://www.google.org/flutrends/) and
``HealthMaps'' (http://healthmap.org/en/) in identifying infectious
disease outbreaks, at least as fast as traditional methods but at lower
cost. Evaluation of methods for efficient approaches to aggregating the
highest quality information from the Internet and social media for
earlier warning of emerging safety concerns or identifying
geographically localized clusters for regulators and public health
authorities, might be beneficial. Mobile communication devices have
been successfully used for drug safety surveillance in Africa.
Evaluation of mobile devices for inexpensive alerting of central
monitoring point for AEFI might be warranted. The collation,
investigation, and analysis of such reports remains a challenge but
might be resolved by the development and deployment of artificial
intelligence systems to conduct data mining and semiautomated case-
series evaluations that would provide cogent summaries for human
review.
4. Dissemination of Successful Enhancements to the Vaccine Clinical
Trial and Pharmacovigilance Enterprise Through Seminars or Other
Training Programs
C. Eligibility Information
WHO is the directing and coordinating authority for health within
the United Nations system. It is responsible for providing leadership
on global health matters, shaping the health research agenda, setting
norms and standards, articulating evidence-based policy options,
providing technical support to countries, and monitoring and assessing
health trends. It is the only organization with the mandate, technical
expertise, and broad reach through its Member States to meet the
project goals.
II. Award Information/Funds Available
A. Award Amount
CBER anticipates providing in FY2012 up to $2 million (total costs
include direct and indirect costs) for one award subject to
availability of funds in support of this project. The possibility of 4
additional years of support up to $10 million of funding is contingent
upon successful performance and the availability of funds.
B. Length of Support
The support will be 1 year with the possibility of an additional 4
years of noncompetitive support. Continuation beyond the first year
will be based on satisfactory performance during the preceding year,
receipt of a noncompeting continuation application, and available
Federal Fiscal Year appropriations.
III. Paper Application, Registration, and Submission Information
To submit a paper application in response to this FOA, the
applicant should first review the full announcement located at http://www.fda.gov/BiologicsBloodVaccines/ScienceResearch/ucm297861.htm. (FDA
has verified the Web site addresses throughout this document, but FDA
is not responsible for any subsequent
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changes to the Web sites after this document publishes in the Federal
Register.) Persons interested in applying for a grant may obtain an
application at http://grants.nih.gov/grants/funding/phs398/phs398.html.
For all paper application submissions, the following steps are
required:
Step 1: Obtain a Dun and Bradstreet (DUNS) Number.
Step 2: Register With Central Contractor Registration.
Steps 1 and 2, in detail, can be found at http://www07.grants.gov/applicants/organization_registration.jsp. After you have followed
these steps, submit the paper application to: Vieda Hubbard, Grants
Management (HFA-500), 5630 Fishers Lane, Rockville, MD 20857, and a
copy to Leslie Haynes, Center for Biologics Evaluation and Research,
Office of the Director (HFM-30), 1401 Rockville Pike, Rockville, MD
20852-1448.
Dated: May 10, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-11932 Filed 5-15-12; 8:45 am]
BILLING CODE 4160-01-P