SUBJECT: Response to the OVRR Office Site Visit Review
Team Comments
On May 19, 2006 a
team of independent external reviewers conducted a review of the Office of
Vaccines Research and Review (OVRR), Center for Biologics Evaluation and
Research (CBER) research program. The
committee provided a global review of the research program management and
organization of the OVRR, and made recommendations that could strengthen
scientific programs within the Office. OVRR
responses to committee comments are provided below:
1. Comment on the
contributions of OVRR research to the scientific mission of CBER and the FDA
and to biological product regulation.
“OVRR could benefit from the development of a more comprehensive
strategic plan to address its broad missions more effectively. Such a plan would enumerate, prioritize, and
coordinate common thematic areas such as immunogenicity, safety, and assay
development across multiple offices/laboratories. The strategic plan would also anticipate
subject areas which would likely be of particular importance to OVRR (e.g.,
pandemic influenza). Decisions regarding
recruitment, resource allocation, and research expansion could then be based on
the strategic plan. “
OVRR RESPONSE: OVRR participates in CBER and FDA strategic
planning. Table 1 details the goals of
the FDA Strategic Action Plan. Each of
the goals is linked to important objectives of the Department of Health and
Human Services. CBER and OVRR have
applied these goals and objectives to enhance consumer access to safe and
effective biologics, including vaccines.
Each of the four major goals of the FDA Strategic Action Plan published
in 2007 contains objectives related to strengthening scientific activities and
aligning programs with the regulatory mission of the agency. An important continuing objective of the
Center and Office is to “strengthen the
scientific foundation of FDA’s regulatory mission” (Objective 1.1 of the
FDA Strategic Action Plan, Table 1). The
National Vaccine Plan is currently being updated by the Department of Health
& Human Services to address critical national requirements through 5- and
10-year goals. These strategic planning
documents will help shape the future scientific activities of the Office.
In FY 2007 OVRR established a new research management system
(see Figure 1. The OVRR Research
Management Process) that incorporated recommendations from the Office Site
Visit Review Committee, CBER’s Research Leadership Council, senior OVRR
leadership, and others to support priority setting, the development of research
programs relevant to the OVRR regulatory mission and programmatic
decision-making. A key deliverable of
this process is the OVRR Research Plan, which is updated annually. Integrated research plans for the Office were
prepared for FY 2007 and FY 2008. The newly
created OVRR Scientific Management Committee provides guidance and oversight
over the research planning process, identifies Office research priorities, supports
a transparent process for decision-making, establishes processes for evaluating
research progress, and makes recommendations concerning the allocation of
limited Office resources. For FY 2009 research
priorities, long term goals and specific aims will be established by evaluating
the OVRR regulatory workload, receiving input from external groups (such as the
National Institutes of Health, FDA and Industry Vaccine Roundtable,
international organizations (e.g. WHO, EMEA, etc), and other stakeholders), recommendations
from senior OVRR and CBER leadership, evaluation of strategic infrastructural
needs, identification of future technology needs, and appraisal of domestic and
global public health requirements.
In FY 2007 four major research priorities were established
based upon the regulatory workload, high impact issues, Critical Path
challenges, pre- and post-licensure issues and emerging public health
issues. The priorities identified
include:
I. Improve or develop new methods that enhance
the safety of vaccines and related products
II. Improve or
develop new methods that enhance the effectiveness of vaccines and related
products
III. Facilitate the
development of new biological products for high-priority public health
threats, including emerging diseases
and BT agents
IV. Develop and
evaluate novel scientific technologies and standards to improve biological
product regulatory pathways, availability and quality of vaccines and related
products
Long term and short term research specific aims linked to
Office priorities are identified within individual investigator research
plans. Research plans are developed and
reviewed through comprehensive interactions between principal investigators and
their laboratory chiefs. Division
Directors and Laboratory Chiefs evaluate proposed research efforts against
available resources. Fiscal and
personnel resource targets are established by the Office Director using input
from his staff and CBER Office of Management.
When possible, thematic program areas that encompass related
research efforts are being established. Since
FY 2007 cross-divisional influenza projects have been consolidated into a
single program that addresses scientific priorities related to the development
and regulation of seasonal and pandemic influenza vaccines. Similar programs that focus upon cell substrates,
allergenics, and biodefense projects externally funded by the National
Institutes of Health have been established.
The specific aims and scientific objectives of these programs have been
integrated into OVRR strategic planning.
Additional programs will be organized and aligned with OVRR priority
goals based upon shared research objectives for the FY 2009 research program.
2. Comment on ways to
improve visibility of the OVVR research programs and on its integration into
the biologics regulation process.
“One
approach for increasing the visibility of research efforts at OVRR would be to
seek FDA representation on scientific advisory committees of major
collaborative groups/centers for relevant research. An example of such in the HIV vaccine field is
the committee which advises the Vaccine
Research Center
at NIH, the NIAID-sponsored
Center for HIV AIDS
Vaccine Immunology (CHAVI), and the HIV Vaccine Trials Network (HVTN). Such advisory representation should entail
research interaction, rather than being restricted to regulatory issues.”
OVRR RESPONSE: OVRR scientific personnel regularly
participate as expert and technical advisors on national and international panels
and research review committees for the World Health Organization, Pan American
Health Organization, National Institutes of Health, the Defense Advanced
Research Projects Agency, the Centers for Disease Control and Prevention, and
the American Academy of Microbiology. While the technical advice of the staff is
frequently sought, their participation on committees related to regulated
products must be limited to avoid regulatory conflicts of interest. OVRR scientific staffs are open to
collaborations and other interactions through a variety of professional
organizations. A representative list of
advisory committees and other groups that included OVRR scientists is presented
in Table 2.
3. Recommend
opportunities for research expansion, redirection and new
collaboration/leveraging.
“It is unclear how much work is done with academic
institutions, particularly clinical investigators. Making additional linkages
with such potential collaborators is likely to be useful and productive.”
OVRR RESPONSE: Collaborations with academic scientists
are managed at the investigator level and reviewed by OVRR senior management. Currently, OVRR scientists participate in
hundreds of academic collaborations.
Significant leveraging and collaborative projects are reported in annual
progress reports. OVRR scientists participate
regularly in domestic and international scientific organizations. OVRR
scientists are recognized experts in selected products areas related to the
development and regulation of vaccines and allergenic products. See Table 3 for
a list of academic research collaborations in FY 2007/2008.
4. Identify research
management strategies for anticipating future biological products and related
research programs.
“OVRR appears to lack a well developed strategic plan that overlays all
the separate lab programs. This plan
needs to be cross cutting and integrative of expertise and resources in
individual labs and use these components to address critical components of the
FDA's vaccine mission such as a better understanding of vaccine immunity and
safety.”
OVRR RESPONSE: Integrated cross-divisional research
plans were prepared in FY 2007 and FY 2008. A new research management process
was established for the Office in 2007 that supports priority setting, the
development of research programs relevant to the OVRR regulatory mission and
programmatic decision-making.
“[T]he career pathway
in OVRR should be structured to make it more appealing to new members and what
components of these very large issues need to be developed to help the
individual programs move forward.”
OVRR RESPONSE: OVRR supports a comprehensive career
management process within CBER and the FDA.
The CBER Research Scientist Peer Review Committee provides oversight for
scientist advancement within the Center.
The recruitment, retention, and development of an accomplished
scientific research staff are critical for achieving CBER’s and OVRR’s
mission. In support of CBER’s regulatory
mission, each CBER research scientist fills a mixed duty position combining
both research and regulatory activities. This position is by using two Office
of Personnel Management (OPM) position classification guides: the research
segment is evaluated using the four factor Research Grade Evaluation Guide
(RGEG) and the regulatory segment using the nine factor, Factor Evaluation
System (FES) Guide. Scientific staff are
recommended for peer review and promotion through their respective Laboratory
Chiefs and Division Directors. Figure 2
presents a summary of the OVRR scientist career path.
For appropriate and consistent evaluation of scientists
performing the combination of both review and laboratory activities, CBER
established the Promotion and Conversion Evaluation (PCE) Committee. The PCE Committee is charged to evaluate the
scientific qualifications and contributions of:
(1) Research-regulator scientists considered for promotion to GS-13 and
above; (2) Service Fellows considered for conversion to a permanent
research-regulator position at GS-13 and above; (3) Permanent Staff Scientists
considered for reassignment as permanent Senior Investigator positions; (4)
Outside candidates considered for employment as permanent Staff
Scientists/Senior Investigators at GS-13 and above; and (5) Mandatory four year
cyclical review of Research-regulator scientists (GS-13 to GS-15). The PCE Committee will also review such
candidates from other FDA Centers as requested by that Center’s leadership.
Laboratory Chiefs and Division Directors are responsible for
mentoring the scientific staff within their organizations. Mentoring is an important performance element
in annual supervisor Performance Management Plans. A CBER-sponsored mentoring program pairs
staff with more senior employees and recognizes excellence in this area through
an annual award sponsored by the Center Director.
“[A]n active seminar
program would be useful to maintain awareness of activities not covered by
internal programs and should seek out speakers from company labs as well as
from academic/government labs.”
OVRR RESPONSE: Active weekly seminars are conducted in
the Division of Viral Products and Division of Bacterial, Allergenic and
Parasitic Products. Internal and
external speakers are invited to provide progress reports on important research
and technology advances. Office and
Divisional operating funds have been dedicated to support presentations by
outside speakers. All OVRR employees are
invited to participate in work-in-progress or other presentations. In some cases, seminars are broadcast through
the FDA intranet to reach office-based review scientists. See Table 4 for a list of representative
seminars sponsored by our product divisions.
“Prior
to filing an IND, it would be appropriate in some cases to present to CBER
staff an overview of a technology and how it applies to an upcoming development
program that will come under CBER scrutiny.”
OVRR RESPONSE: Technology reviews are regularly
performed in the context of division work-in-progress seminars. Additionally, many
laboratories conduct regular journal meetings that provide overviews of
important technology breakthroughs. Product-related presentations can be
conducted during the review of specific manufacturer submissions. CMC and product reviewers provide expert
knowledge and technical expertise during the review of sponsor submissions.
5. Provide recommendations
for attracting, developing and retaining high quality science and medical
experts for OVRR.
“Concern was expressed
over the possibility that the leadership in OVRR is aging and not being
replenished by younger people. … An
overall strategic plan needs to come from senior leadership but it needs input
and buy-in from below and needs to be implemented with the understanding that
the current structure seems fragile so that one must be careful not to destroy
things in the process of improving them.”
OVRR RESPONSE: OVRR has a robust program to attract
fellows into our scientific programs.
Post graduate scientific staff can be trained either through the CBER Service
Fellow Program or through the ORISE/IRTA Contract Fellowship Training Program. OVRR currently has approximately 39 Staff Fellows/Visiting
Associates and 82 ORISE/IRTA fellows.
Staff Fellows participate in a structured program that can lead to
permanent federal service appointments. ORISE/IRTA
fellows are contractor personnel that can complete for federal positions as
they become available. Peer review of
staff fellow scientific and regulatory performance provides OVRR with the
highest quality scientific staff. See
Table 5 for a distribution of post graduate fellows by OVRR division.
“One way to attract
new talent to OVRR is to implement a system of reward for successful research,
either financially or in terms of providing more lab space or research funding,
or promotion.”
OVRR RESPONSE: Scientific staffs are recognized currently
for their scientific achievements through two systems of reward. Offices
nominate high performing laboratory staff (and other disciplines) for special
recognition by the CBER Center Director.
Senior and junior scientific and technical staff can be recognized in
individual categories. Award nominations
are reviewed and ranked by a central committee representing diverse
disciplines. Separately, federal
employees are evaluated within a structured award system tied to annual
performance evaluations. “Fully Successful”
and “Exceptional” evaluations may result in incremental salary increases and
annual bonuses. ORISE/IRTA personnel are
recommended for annual salary adjustments based upon performance but can not
receive performance bonuses due to federal contracting regulations. The distributions of laboratory space and
other opportunities are restricted by available resources. Division Directors are responsible for
assessing the resource needs of individual laboratories within their areas. OVRR is considering establishing a small
innovative research grant program using internal Office funds in order to
reward and encourage the development of new research opportunities and enhance
the development of emerging scientific leaders in the Office.
“Research conduct within
CBER is similar to the operation of an academic institution; therefore, it is
not unreasonable to look for additional ways to follow that model more closely.
Dr. Carbone mentioned creation of core
facilities, which reduce the overhead and need for duplication of costly items
of equipment. It may therefore be useful
to obtain more information from medical schools on the operation of a
combination of research and service activities. For example, an academic
institution may have an excellent faculty development program that provides
assistance to junior faculty on a wide range of subjects from availability of
childcare in the community to creation of a teaching and research portfolio to
grant and manuscript writing.”
OVRR RESPONSE: The OVRR scientific staff is represented
on the CBER Biomedical Research Coordinating Committee (BRCC). The CBER BRCC serves as a forum for
discussion of issues pertaining to research
activities. Topics may include, but are not limited to, standards of research
conduct and ethics, common equipment, Good Laboratory Practice accreditation,
mentoring, and policies on service contracts for maintenance of costly research
equipment. The CBER BRCC is responsible for creating an environment for better
research communication within the Center.
The CBER Research Central intranet also provides opportunities to
identify common scientific interests and collaborations. The BRCC facilitates the activities of special
scientific interest groups at CBER, such as genomic, immunology, and scientific
computing. Inter-Center interest groups
are sponsored at the agency level. BRCC meeting
topics may include standards of research conduct and ethics, common equipment,
Good Laboratory Practice accreditation, mentoring, and policies on service contracts
for maintenance of costly research equipment, management of the animal or core
facilities, mentoring and training, research support, establishment and
maintenance of an up-to-date web-based database of skills and specialties
available at CBER, and opportunities for external funding.
In a related activity, CBER supports a Career
Development & Mentoring Program.
Junior scientific staff may work with more senior personnel who guide
them in their career development. Mentees have the opportunity to increase
knowledge of the organizational dynamics that can affect careers; network with
other Center and Agency employees and leaders; identify or refine career goals
based on a realistic self-assessment; develop knowledge, skills, and abilities
focused at supporting career goals; and develop a plan for achieving career
goals based on an understanding of organizational needs.
In addition to the above OVRR supports the training
and professional development of postdoctoral fellows and other staff. Laboratories and divisions provide
operational funds for staff training and travel. Recently, CBER established a training fund
that can be used by all civilian FTE staff for professional development. OVRR set aside additional funding in FY 2008
(up to $ 48,000) to support training opportunities for research and review
staff. Depending upon the availability
of funds, our goal is to give scientists the opportunity to attend one
professional society meeting per year.
Fellows can also present their work at the annual National Institutes of
Health (NIH) Research Festival, in seminar series of the various campus
scientific Interest Groups, and in journal clubs and work-in-progress series at
CBER. The following opportunities are
also available to our postdoctoral fellows:
·
CBER training courses
that include communication skills, scientific and technical writing, scientific
writing for publication, making high-quality presentations, teamwork, managing
time and priorities in the CBER environment, and negotiation skills.
·
NIH training courses
in scientific speaking, scientific writing, interview skills, and grant
preparation.
·
Courses in the Foundation
for Advanced Education in the Sciences (FAES) graduate school in a variety of
subject areas.
·
Representation at the
NIH Fellows Committee (FelCon), which aims to enhance training opportunities
and sponsors many training courses and seminars that FDA and NIH postdoctoral
fellows are eligible to attend.
·
Participation in an
annual scientific job fair held as part of the NIH Research Festival
·
Yearly NIH workshops
on such subjects as résumé preparation and diverse career options (e.g.,
teaching, patent office, drug development, academia).
·
Childcare resources
·
FDA Employee
Assistance Program
·
FDA TRANSHARE Program
(transportation incentive program)
·
Parklawn Health Clinic
(selected health services)
Conclusions:
“The Committee
believes research within OVRR to be of high quality and acknowledges the
numerous scientific accomplishments of the research staff. There is, however, clearly a pressing need
for improved funding support and recruitment strategies to recruit talented
young scientists in order to maintain the high quality of research, as well as
to improve the public’s image of OVRR and the research that it performs. The
committee wishes to convey its strong concern that without the addition of
substantial and sustained new financial support for the OVRR research
enterprise, OVRR runs a serious risk of not being able to accomplish its
multiple missions. In addition, CBER and
OVRR, within the limits inherent in the fact that the FDA is a government
institution, could consider following models that have been established by
academic institutions. All of these
issues could be addressed by the development of a clear strategic plan that
incorporates the preceding recommendations and aims at producing a program that
is cross-disciplinary between the OVRR divisions and laboratories.”
OVRR RESPONSE: OVRR appreciates the support and
recommendations of the Office Site Visit Review Team. While internal resources for the program has
been austere, the future for OVRR scientific activities is bright as evidenced
by the ability of our scientists to win support from competitive internal and
external sources of funding. The FDA
Science Board and others have recognized the value of the intramural program to
address critical scientific needs of the agency. Our scientific activities will continue to
support the critical pathway to safe and effective vaccines and biologics need
to protect the domestic and global public health.
Table 2. OVRR Participation on
Advisory Groups and Committees
ATCC Standards Development Working Group on Standardization
of in vitro Assays to Determine Anthrax Toxin Activities
CDC Advisory Committee for the Elimination of Tuberculosis
DHHS Biotechnology Engagement Program, Peer Review Panels
Gates Foundation for Medical Research, Scientific Advisory
Panels
International Association of Biologicals (IABs) Human
Vaccines Scientific Committee
International Panel for the Nomenclature of Hepatitis C
Intragovernmental Select Agents and Toxins Technical
Advisory Committee
National
Academy of Science Panel
for International Grant
National Vaccine Program Office Award, Peer Review Panel
NIAID Biodefence Study section: Animal Models for Radiation
Injury, Protection, and Therapy
NIAID/NIH Animal Models for Hepatitis C Virus Infection,
Peer Review Panels
NIAID/NIH Leadership for HIV/AIDS Clinical Trials Networks,
RFP Review Panel
NIAID/NIH special emphasis panel, Opportunistic Infections
and Malignancies in AIDS
NIAID/NIH Viral Hepatitis, Peer Review Panels
NIAID/NIH, AIDS Special Emphasis Panel: HIV Vaccine Design
and Development Teams
NIAID/NIH, AIDS Special Emphasis Panel: HIV Vaccine Program
Project Grants
NIAID/NIH, AIDS Special Emphasis Panel: HIV Vaccine Research
& Design
NIAID/NIH, AIDS Special Emphasis Panel: Innovation Grant
Program for approaches in HIV vaccine Research
NIAID/NIH, AIDS Special Emphasis Panel: Integrated
Preclinical AIDS Vaccine development program
NIAID/NIH, HIV/AIDS Vaccine, Peer Review Panels
Parenteral Drug Association Mycoplasma Task Force
Scientific Advisory Board, ATCC Expert Panel on the
Development of Standards for Biodefense
Scientific Advisory Board, Middle Atlantic
Regional Center
of Excellence for Biodefense and
Emerging Infectious Disease Research
Scientific Advisory Panel, International Vaccine Institute, Seoul, Korea
U.S.
Military HIV Research Program, External Review Panel
Weapons of Mass Destruction Medical Counter Measures Product
Tools Development Working Group
Wellcome Trust Programme Project, Peer Review Panels
WHO Expert Panel on Hepatitis A Vaccines
Table 3. OVRR Academic Collaborations
Akashi Hospital/Kyoto Medical School
Albert
Einstein College
of Medicine
Colorado
State University
Drexel
University
Eidgenössische Technische Hochschule (ETH), Zurich
Georgetown
University
Harvard
University
Hunter College, New
York
Institute of Poliomyelitis and Viral Encephalitides, Moscow
Johns
Hopkins University
London
School of Tropical
Medicine and Hygiene
LSU Eye Center, New Orleans, LA
Ludwig Institute for Cancer Research
Mayo Clinic
Monash University,
Australia
Ohio
State University
Pennsylvania
State University
Purdue
University
Queens University, Belfast,
UK
Rockefeller
University
Roswell Park Memorial Institute
S. Kimmel
Cancer Center
Saint Jude Children’s Research Hospital
Saitama
University
Southern Research Inst., Frederick, MD
Southern Research Institute, Birmingham, AL
Stanford
Medical Center
State Research Center
of Virology and Biotechnology,
Russia
Stockholm
University
Stony Brook
University Medical
Center
UMDNJ-New
Jersey Medical
School
Uniformed Service
University of Health
Sciences
University
of Michigan
University
of Vienna
University
of Ottawa
University
of Alabama
University of California Davis
University of California, Santa
Barbara
University of California, San
Francisco
University
of Cincinnati
University
of Florida
University
of Illinois
University of Iowa
Medical School
University of Kansas
Medical Center
University of Maryland
Medical School
University
of Maryland, Baltimore
University of Maryland, College
Park
University
of Minnesota
University of
Napoli, Italy
University
of New Mexico
University of North Carolina-Chapel Hill
University of
Oxford, United Kingdom.
University
of Rochester
University of Sassari, Sassari,
Italy
University of Texas at Austin
University of Texas at Tyler
University of Texas, Galveston
University
of Victoria
University of Virginia, Charlottesville
University
of Colorado
University of
Edmonton, Canada
VU Medical Center, Amsterdam,
Netherlands
Wright State University,
Dayton, OH
