
[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


