Center for Biologics Evaluation and Research

STRATEGIC PLAN FOR 

REGULATORY SCIENCE AND RESEARCH 

2012-2016 

 

May 2012 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Biologics Evaluation and Research
CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

 Opening Statement from the Center Director

The Food and Drug Administration’s (FDA) Center for Biologics Evaluation and 

Research (CBER) plays a leading role in the development of therapies that will 

become the standard of care in the 21st Century, both in the United States and 

around the world. These emerging therapies include a wide variety of biologic 

products, such as those for gene replacement and tissue regeneration. In addition, 

novel strategies and approaches may be employed for developing new vaccines. 

CBER plays a significant role in maintaining a safe and adequate supply of blood and 

blood products. 

To meet these challenges, CBER’s regulatory science and research program must 

provide the environment to facilitate the development of new biological products and 

evaluate them for safety and effectiveness. Biological products may have great 

complexity and diversity of structure and function; are vulnerable to contamination; 

are inherently difficult to manufacture; and have the potential for long-term adverse 

effects of treatment. These challenges require that CBER’s regulatory science and 

research program supports CBER reviewer decisions so that they may be at the 

forefront of the underlying research fields that drive the development of these 

biologic products and the evolving technology designed to evaluate them. 

The development of the CBER Strategic Plan for Regulatory Science and Research is 

based on the CBER mission and Strategic Plan1. The CBER Strategic Plan for 

Regulatory Science and Research also supports FDA’s Strategic Plan for Regulatory 

Science and ongoing FDA research initiatives (Refer to Appendix A for additional 

details.) 

The CBER Strategic Plan for Regulatory Science and Research provides an overview 

of CBER’s regulatory environment addressing the challenges of regulating biologics, 

the researcher-reviewer model used in CBER, and a description of the CBER’s 

Research Management program. This information will provide an explanation and 

context for understanding CBER’s research strategic goals, objectives, and 

strategies. 

The CBER Strategic Plan for Regulatory Science and Research details the types of 

research programs needed to address the challenging regulatory issues CBER will 

face in the next several years. The plan also describes the technology and 

infrastructure required to meet those needs and the steps we will take to put those 

resources to use efficiently and effectively. 

Karen Midthun, MD 

Director, Center for Biologics Evaluation and Research 

 

1 The CBER Strategic Plan may be accessed by the CBER Internet link 

(http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsan

dTobacco/CBER/UCM266867.pdf) 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

Table of Contents 

Opening Statement from the Center Director ..................................................... 2 

CBER Mission................................................................................................. 4

CBER Strategic Goals....................................................................................................................4 

CBER Regulatory Environment.......................................................................................... 4

CBER STRATEGIC PLAN FOR REGULATORY SCIENCE AND RESEARCH .................... 9 

CBER Vision for Regulatory Science and Research ............................................... 9 

Regulatory Science and Research Priorities ........................................................ 9 

Regulatory Science and Research Strategic Goals ..............................................10 

I. Increase the nation’s preparedness to address threats as a result of terrorism 

and pandemic influenza and emerging infectious diseases. ...........................10 

A. Rapid Pathogen Detection ....................................................................10 

B. Preparedness for Pandemic Influenza ....................................................11 

C. Preparedness for Biological, Chemical or Radiologic Acts of Terrorism.........11 

II. Improve global public health through international collaboration including 

research and information sharing. .............................................................13 

III.Enhance the ability of advanced science and technology to facilitate 

development of safe and effective biological products. .................................13 

A. Evaluate and implement novel methods and technology ...........................14 

B. Facilitate development of safe, effective, and innovative products for 

regenerative medicine and to treat chronic diseases such as cancer,and rare 

diseases................................................................................................14 

IV.Ensure the safety of biological products. ....................................................17 

V. Enhance research excellence and accountability ..........................................18 

A. Establish an infrastructure that supports high-quality state-of-the-art 

scientific investigations............................................................................18 

B. Training and leveraging resources .........................................................20 

C. Evaluation of research programs to ensure quality, productivity, and FDA 

mission relevance ...................................................................................20 

Appendix A – CBER’s Support of FDA Research Initiatives ...................................22 

Appendix B – CBER Organization .....................................................................24 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

CBER Mission

To ensure the safety, purity, and potency, of biological products including vaccines, 

blood and blood products, and cells, tissues, and gene therapies for the prevention, 

diagnosis, and treatment of human diseases, conditions, or injury. Through our 

mission, we also help to defend the public against the threats of emerging infectious 

diseases and bioterrorism. 

In fulfilling our mission as a Center in the U.S. Food and Drug Administration, we 

apply the following principles with the highest ethical standards and integrity: 

 Develop, maintain, and support a high-quality and diverse workforce 

 Ensure compliance with laws and regulations through review, education, 

surveillance, and enforcement 

 Conduct research as an essential element of science-based decision-making 

CBER Strategic Goals2

CBER’s Strategic Plan has six strategic goals covering four programmatic and two 

supporting areas. These goals are the following: 

1. Increase the nation’s preparedness to address threats as a result of terrorism, 

pandemic influenza and emerging infectious diseases 

2. Improve global public health through international collaboration including 

research and information sharing 

3. Enhance the ability of advances in science and technology to facilitate 

development of safe and effective biological products 

4. Ensure the safety of biological products 

5. Advance regulatory science and research 

6. Manage for organizational excellence and accountability

CBER Regulatory Environment 

The challenge of regulating a diverse and complex group of biologic products is 

addressed with the CBER researcher-reviewer model. The CBER Research 

Management Program ensures that the contributions based upon individual expertise 

facilitated by use of the researcher-reviewer model meet CBER’s objectives and 

support FDA’s Advancing Regulatory Science Initiative. 

1. Challenges of Regulating Biologics 

CBER regulates a wide variety of complex biologic products (Figure 1) that differ 

significantly from chemically synthesized drugs. These products include blood, blood 

components and blood products, test kits used to screen blood and tissues for 

infectious agents, vaccines, allergenic products, tissues, and cutting-edge medical 

products such as cell and gene therapies. These products address critical public 

 

2 Four of CBER’s Strategic Goals are the same as long-term objectives contained in the FDA 

Strategic Priorities (2011 – 2015) under the FDA’s strategic goal entitled, “Promote Public 

Health by Advancing the Safety and Effectiveness of Medical Products – Advance Biologics 

Safety and Effectiveness.” See page 2 for the Internet link for accessing the CBER Strategic 

Plan. 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

health needs, such as prevention of childhood mortality and morbidity from 

infectious disease through licensure of safe and effective vaccines; life-saving 

treatments that require blood, blood components, and blood products; novel ways of 

treating chronic diseases, including metabolic disorders, cancer, diabetes, and 

neurologic disorders; and enabling wound healing and other types of tissue 

regeneration. 

Figure 1.  CBER regulates diverse and complex products.

 

 

 Therapies 

 

 

 

 

Cell & Gene Whole Blood, Blood 

Components, Blood 

Products 

Vaccines: Preventive & 

Therapeutic Xenotransplantation

Tissues 

Selected Devices

Allergenic Extracts

CBER-regulated products pose four significant regulatory challenges that reflect both 

the rapid pace of biomedical research and the nature of the products the center 

regulates: 

 Complexity and diversity: Biologics are complex and diverse, and often 

incorporate new scientific knowledge. CBER reviewers must have an in-depth 

understanding of the technology used to prepare them, and when feasible, 

knowledge of the mechanism of action 

 Vulnerability to contamination: Biologic source materials used to 

manufacture products (e.g., mammalian cell lines) and the source of the 

product itself (e.g., blood from human donors) are particularly vulnerable to 

contamination with infectious agents 

 Processing difficulties: Biologics cannot withstand common purification and 

decontamination methods, and thus require rigorous control of the source 

materials, manufacturing processes, and sensitive and specific safety, 

potency, and purity testing 

 Long-term adverse effects of treatment: Some biological products, for 

example certain infused cells or integrating viral vectors, have the potential to 

persist long-term in the body. Some types of adverse events, which might 

include cancer, may take years to occur, and understanding how to monitor 

and clinically respond to such adverse events poses unique challenges 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

To address these challenges, CBER scientists and reviewers have expertise in testing 

and evaluating the risks associated with different source materials. They also must 

proactively develop standards, reference materials, and validated methods for 

testing safety, potency, and purity. CBER also conducts risk-benefit analyses of 

products and establishes careful surveillance for adverse events that might be 

caused by biological products. 

2. CBER Researcher-Reviewer Model Supports Development of Safe and 

 Effective Products 

CBER researchers working at the frontier of biomedical innovation and discovery 

contribute critical knowledge and expertise that supports the center's mission. This 

also gives the center expertise in the new technologies and classes of biologicals 

being developed by industry. 

CBER makes efficient use of limited resources in addressing high priority scientific 

questions of regulatory importance by relying on both full-time reviewers and 

researcher-reviewers. The latter are scientists who have both regulatory 

responsibilities and conduct mission-related research. This combination of regulatory 

and research expertise enables CBER to play critical roles in: 

 Identifying and solving problems affecting development of new product 

classes 

 Characterizing and developing appropriate models for predictive pre-clinical 

testing of biological products under development, many of which are complex 

and novel 

 Developing testing methods, reference materials, or other tools, to evaluate 

product safety and efficacy 

 Identifying and implementing efficient new technologies for testing the safety 

and quality of currently licensed products 

 Identifying actual or potential safety or efficacy problems with a new 

biological product that might not be obvious to the manufacturer 

 Sharing new knowledge by making presentations at public conferences and 

publishing research results in peer-reviewed scientific journals, thus 

facilitating development of products 

3. CBER Research Management Program 

CBER coordinates its regulatory science and research efforts through Associate 

Directors for Research (ADRs) who work both in the Office of the Center Director and 

within each office that has a research component. The offices that have a research 

component are the Office of Vaccines Research and Review, the Office of Blood 

Research and Review, the Office of Cellular, Tissue and Gene Therapies, the Office of 

Biostatistics and Epidemiology, and the Office of Compliance and Biologics Quality. 

Appendix B provides an overview of CBER’s organizational structure. The ADR at the 

center level develops center-wide policies and procedures to ensure that regulatory 

science and research programs of CBER are aligned with its regulatory mission. The 

office ADRs work closely with the center ADR to identify areas for development or 

improvement of policy and to implement these policies and procedures. 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

The Center Director and ADR administer a research management strategy that 

supports the overall goals of the regulatory science and research programs in order 

to ensure that research is relevant to our regulatory mission, is aligned with stated 

priorities, and represents productive, high quality science. Our research 

management strategy is supported by four “pillars” (Figure 3): 

1) Strategic planning and priority setting 

2) Appropriate allocation of resources 

3) Researcher-Reviewer model 

4) Internal and external evaluation to ensure quality, productivity, and 

 regulatory and public health relevance 

 

 Figure 2. Four Pillars Supporting CBER’s Regulatory Science 

Strategic Planning and Priority Setting 

Each office uses a variety of sources to inform its strategic planning and prioritysetting, including consideration of specific products under development but not yet 

submitted by the sponsor (horizon scanning). Typical sources include regulatory 

portfolio reviews; input from full-time review staff, researcher-reviewers, and office 

management; informal information gathering at scientific meetings; and formal 

external input from advisory committees, site visits, and workshops. Each office 

ADR synthesizes the input into specific research priorities, with broad research 

priorities at the center level reflecting office-specific priorities. Office ADRs also 

provide an annual research program report to the center ADR that includes a 

summary of the office’s regulatory portfolio (current and anticipated products), 

strategic planning for research programs, research priorities, and a summary of key 

scientific accomplishments from the prior year. 

Appropriate Allocation of Resources 

 

Office ADRs work with their respective office and division directors annually to 

evaluate all research programs within their office for regulatory relevance, 

productivity, and quality. To facilitate this review, CBER implemented an online 

reporting system requiring an annual progress report from each CBER researcher7
CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

reviewer that includes plans for the coming year. This evaluation informs the 

division and office directors during their annual allocation of research resources. 

Office ADRs develop a budget proposal for each scientific program for the coming 

year based on the regulatory relevance, productivity, and quality. Following review 

and approval by office and division directors, the ADRs submit their reports to the 

center ADR. The center ADR and director review and approve the research program 

reports and proposed budgets to ensure consistency and fairness and to inform 

center-wide strategic planning for the research program. 

Researcher-Reviewer Model 

The use of researcher-reviewers enables CBER to maintain investigator-initiated 

research with input and oversight from CBER management. These researcherreviewers also perform the same review activities as full-time review scientists, and 

thus are often the first to understand how to use their research skills and knowledge 

to address regulatory challenges and, when necessary, to respond in a timely 

manner to public health crises through laboratory investigations. The researcherreviewer model enables CBER to rapidly focus limited research resources onto highpriority issues. 

Internal and External Evaluation 

CBER ensures accountability to its stakeholders through a combination of internal 

annual and cyclic evaluations, external scientific peer reviews, and input from a 

variety of external sources. Internal reviews include 1) annual management review 

of all research programs for relevance to priorities, quality, productivity, and 

feasibility; and 2) internal peer review of all researcher-reviewers at GS-13 or higher 

grade levels. 

CBER also reviews its support to FDA research initiatives to ensure that research 

planning is incorporating these commitments and progress is being reported. CBER 

supports four FDA research initiatives: Critical Path, Advancing Regulatory Science, 

Nanotechnology Regulatory Science, and Medical Countermeasures. Appendix A 

provides a description of the FDA research initiatives and the CBER support provided. 

External reviews include site visits for each laboratory unit every four years by an 

external panel of expert scientists working in the same scientific fields as the 

scientists under peer review, as well as periodic programmatic reviews through 

relevant advisory committees. For example, each product office has undergone 

programmatic reviews by an FDA advisory committee in the past five years, and in 

2012-13, the center is scheduled for programmatic review of our research by the 

FDA Science Board. 

With the direction set forth in the CBER Regulatory Science and Research Strategic 

Plan, CBER’s regulatory science research program will be strengthened and enhanced 

to provide an important tool for supporting the science-based regulatory decisions 

and policy-making that facilitate the licensure of safe and effective products. Thus, 

this cross-cutting CBER Strategic Plan for Regulatory Science and Research plan 

provides a road map to implement FDA and CBER’s commitment to advancing 

regulatory science and research. See the graphic below to show the role of 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

regulatory science and research in the development of biologics products 

development. 

Using Science and Regulation to 

Advance Product Development

Regulatory Regulatory 

Public Health Public Health Challenge Challenge

Novel Product Novel Product

Regulatory Regulatory 

Science: Science:

Discovery

Regulatory Regulatory New Tools

Policy/Decision Policy/Decision

Licensed Licensed 

Product Product

Improved Improved 

Data –

Benefit/Risk Benefit/Risk

+

Figure 3. Using Science and Regulation to Advance Product Development. 

CBER STRATEGIC PLAN FOR REGULATORY SCIENCE AND 

RESEARCH 

The center ADR developed the strategic plan under the direction of the Center 

Director. The purpose of the plan is to explain the vision and provide the long term 

strategic goals, objectives, and strategies for implementation for regulatory science 

and research over the next four years. 

CBER Vision for Regulatory Science and Research 

CBER‘s scientific research will be proactive, anticipating regulatory and public health 

issues while being responsive to emerging public health and regulatory issues. 

Therefore, our research will be collaborative, of highest quality and relevance, and 

integral to the center’s regulatory mission and public health portfolio. The research 

program will provide CBER with appropriate scientific expertise, tools, and data to 

support science-based decision-making and policy development. 

Regulatory Science and Research Priorities 

The aim of our scientific research is to ensure the safety, efficacy, and availability of 

biological products and to ensure the development of appropriate regulatory 

pathways. The specific priorities will be discussed under each strategic goal. 

The Regulatory Science and Research Strategic Goals are based on the CBER 

strategic goals. Included in this strategic plan is a cross-cutting goal focused on 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

research excellence and accountability. For each strategic goal, the plan summarizes 

how we will direct regulatory science and research priorities to specific areas. Each 

area includes a general description of activity, strategies for implementation, and an 

outcome statement. 

The five strategic goals for regulatory science and research are to: 

1. Increase the nation’s preparedness to address threats as a result of terrorism 

 and pandemic influenza and emerging infectious diseases 

2. Improve global public health through international collaboration including 

 research and information sharing 

3. Enhance the ability of advanced science and technology to facilitate development 

 of safe and effective biological products

4. Ensure the safety of biological products 

5. Enhance research excellence and accountability 

Regulatory Science and Research Strategic Goals 

 

I. Increase the nation’s preparedness to address threats as a result of 

terrorism and pandemic influenza and emerging infectious diseases. 

CBER regulatory science and research priorities will focus on developing a 

comprehensive approach to rapid pathogen detection, enhancing preparedness for 

seasonal and influenza vaccines, and facilitating licensure of medical 

countermeasures for treating or preventing diseases due to bioterrorist attacks. 

A. Rapid Pathogen Detection 

The threat posed by transmissible infectious microorganisms in biological products 

has led to the establishment of a variety of safety measures: donors of blood and 

tissues must be tested for pathogens and deferred if necessary; biologic products 

must be tested for bacteria and fungi during manufacture whenever feasible; and 

vaccines, cell and gene therapies, and the cell substrates used to manufacture 

these products must be tested for a wide variety of infectious agents that are not 

amendable to methods for inactivating or removing them during manufacture. 

Furthermore, newly emerging infectious agents could also threaten the safety of 

blood and tissues due to the spread of disease vectors (e.g., dengue), travel and 

immigration (e.g., malaria), terrorism (e.g., anthrax), or previously rare or 

unknown agents. 

Strategies for Implementation 

CBER will support a proactive, comprehensive approach to pathogen 

detection and reduction, responding to new and emerging safety threats 

by: 

 Working collaboratively within the center and with sister agencies in DHHS to 

identify, assess, monitor and prioritize emerging threats 

 Creating a scientific team to facilitate development and availability of 

reagents, samples and methods for developing, validating, and deploying 

screening tests for emerging priority pathogens through public-private 

collaboration 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

 Assessing and encouraging development of new technologies that enable 

rapid, sensitive, specific, high throughput, cost-effective screening of blood, 

tissues and their donors, and other biologics for known, emerging and 

unknown pathogens, including monitoring and testing during manufacturing 

 Developing and evaluating methods for broad pathogen detection 

 Assessing, developing, and improving new methods to inactivate pathogens 

without impairing product function 

 Improving microbial safety of human tissue products by developing and 

evaluating better processing conditions, pathogen inactivation, and/or 

pathogen detection 

Outcome: 

CBER will enhance the safety of blood and tissue supplies through improved 

methods and implementation procedures for detecting or inactivating pathogens. 

B. Preparedness for Pandemic Influenza 

CBER ensures the safety, quality, and potency of both seasonal and pandemic 

influenza vaccines. 

Strategies for Implementation 

CBER will prepare for pandemic influenza while enhancing yearly review 

for seasonal influenza vaccines by: 

 Developing and evaluating improved tools and methods to enhance safety, 

effectiveness, quality, and potency testing of influenza vaccines, including 

faster methods to develop reference reagents and to perform tests for 

potency and sterility to allow for more rapid response in pandemics 

 Identifying and implementing new approaches to reliably generate seed 

stocks that replicate more efficiently, thus speeding vaccine manufacture 

 Developing and evaluating preclinical methods to screen novel adjuvants for 

adverse effects prior to clinical trials, thus increasing the availability of highly 

effective vaccines during a pandemic 

 Evaluating the safety of new production methods for influenza vaccines, such 

as use of mammalian cell substrates 

Outcome:

CBER will achieve more rapid preparation, testing, and deployment of seasonal and 

pandemic influenza vaccines that are safe, potent, and effective. 

C. Preparedness for Biological, Chemical or Radiologic Acts of Terrorism 

CBER focuses on vaccines and therapeutics to prevent or treat diseases caused by 

bioterrorism agents and on regenerative medicine products for the treatment of 

victims of chemical or radiological terrorist attacks. 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

1. Bioterrorism Agents 

The inability to conduct human efficacy studies because such studies are not ethical 

or feasible means that the development of most vaccines and therapeutics for 

bioterrorism agents will be based on nonclinical data, where possible.3

Strategies for Implementation 

CBER will facilitate use of the Animal Rule to support licensure of products 

for treating or preventing bioterrorist attacks by: 

 Developing and evaluating nonclinical models to study pathogenesis and 

identify relevant correlates of immunity 

 Creating methods and models to study potential toxic effects of vaccine 

antigens, adjuvants, and other components of vaccines 

 Determining biomarkers of pathogenicity and developing new methods to 

evaluate and ensure the safety of live vaccines 

 Studying mechanisms of vaccine-related adverse events, ways to mitigate 

them, and biomarkers of predisposition to adverse events 

 Creating methods to evaluate and improve immunogenicity, potency, and 

efficacy of vaccines 

 Studying innate and adaptive immunity against viral and bacterial diseases, 

and mechanisms of immunopathology (including allergy), and developing new 

approaches to inducing protective immunity 

Outcome:

CBER will contribute to development and availability of new methods and models to 

assess medical countermeasures for treating or preventing bioterrorist attacks. 

2. Chemical or Radiological Agents 

CBER regulates products used to treat persons injured by chemical or radiological 

acts of terrorism. These products include cell-based therapies for wound repair, 

tissue regeneration, and reconstitution of bone marrow. 

Strategies for Implementation 

CBER will prepare to evaluate novel regenerative medicine products for 

treating victims of chemical or radiological terrorist attacks by: 

 Improving the safety and efficacy of stem cell-based products and 

combination and tissue engineering medical products by using systems 

biology, modern methods of cell characterization (e.g., genomics, epigenetic 

analysis, proteomics, cell surface phenotypic analysis, and measures of in 

vitro function), and assessment and development of animal models to identify 

biomarkers for appropriate cell differentiation state and function, localization, 

and controlled proliferation.

 

3 For more on requirements for licensure under these conditions see “The Animal 

Rule”: New Drug and Biological Drug Products; Evidence Needed to Demonstrate 

Effectiveness of New Drugs When Human Efficacy Studies Are Not Ethical or 

Feasible; Final Rule, 5/31/2002.

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

Outcome:

CBER will increase the availability of safe and effective medical countermeasures to 

prevent or treat conditions caused by biological, chemical or radiologic terrorist 

attacks. 

II. Improve global public health through international collaboration including 

research and information sharing. 

CBER regulatory science and research priorities will focus on working with 

international partners and developing countries in vaccines related projects and 

overseeing the screening of the blood supply for infectious agents in an effort to 

reduce the spread of global infectious disease. 

Strategies for Implementation 

CBER research will address public health and regulatory problems of 

global significance by: 

 Developing and evaluating pre-clinical models to study pathogenesis and 

protective immunity and to identify correlates of immunity that facilitate 

development of vaccines for the developing world (e.g., TB, malaria, yellow 

fever, dengue) 

 Implementing international collaborations for surveillance of new forms of HIV 

that evade blood screening assays by evaluating HIV strains in Africa and 

elsewhere around the world 

 Developing panels, reagents, and methods to detect emerging threats to the 

blood supply (e.g., babesia, malaria, dengue virus, and chikungunya virus) 

 Collaborating with the World Health Organization, government agencies or 

private foundations to support and enhance our research into under-funded 

global health diseases 

 Transferring FDA advances to the public domain to improve efficacy and 

safety of vaccines and blood and blood products that promote global public 

health 

Outcome: 

CBER will improve the availability of safe and effective medical products to address 

global public health problems. 

III. Enhance the ability of advanced science and technology to facilitate 

development of safe and effective biological products. 

CBER regulatory science and research priorities will focus on improving CBER 

scientists need to keep pace with, evaluate, and implement when applicable, 

innovative technologies to improve test methods for both currently licensed 

products and those under development. The aim is to identify ways that advanced 

science and technology can enhance safety, quality, potency, or availability of 

CBER-regulated biological products. 

In addition, CBER must maintain and enhance its scientific expertise, 

infrastructure, and internal processes in order to efficiently regulate innovative 

products now being developed to treat chronic diseases such as cancer,and rare 

disorders. This preparation will also be key to CBER’s ability to perform in-house 

research that addresses potential scientific challenges to product development due 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

to lack of such critical tools as appropriate test methods, preclinical models, and 

clinical biomarkers. 

A. Evaluate and implement novel methods and technology 

CBER will evaluate and implement novel methods to improve reliability, sensitivity, 

and specificity of assays for product development and lot release. 

Strategies for Implementation: 

CBER will evaluate and implement novel methods based on recent 

technologic developments that will enhance product safety or quality by: 

 Developing highly sensitive, rapid methods to test the sterility of biological 

products 

 Evaluating the utility of novel scientific technologies such as NMR, genomics, 

and epigenomics for product characterization, leading to improved 

consistency and reliability of manufacturing processes for complex biological 

products under development or already licensed 

 Evaluating and developing methods for characterizing recombinant proteins to 

improve consistency, safety, and quality and facilitate licensure of biosimilars 

 Evaluating the safety and efficacy of nanomaterials used in medical products 

 Performing statistical research to support development and evaluation of new 

bioassays and tests 

Outcome: 

CBER will achieve timely application of novel methods and technology to improve 

product safety, quality, and availability. 

B. Facilitate development of safe, effective, and innovative products for 

regenerative medicine and to treat chronic diseases such as cancer,and 

rare diseases 

CBER will facilitate development of innovative products for unmet medical needs, 

such as regenerative medicine as well as novel treatments of cancer and chronic 

and rare diseases, by: 

 Developing improved tools for clinical trial design and analysis 

 Implementing multi-disciplinary research to improve our understanding of 

how to regulate cell-based therapies such as stem cell-derived products and 

tissue engineered medical products 

 Performing research into nonclinical models and methods to assess safety and 

potency of products for therapy of cancer and rare diseases

1. Clinical Trial Design and Analysis Facilitating New Product Development 

CBER will help bring innovative products to the market more quickly and efficiently 

by using and developing statistical methods for clinical trial design and analysis, 

including simulation modeling, Bayesian and adaptive designs, and other analytic 

approaches to improve evaluation of product safety and efficacy. 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

Strategies for Implementation: 

CBER will implement the use of novel approaches to clinical trial design 

and analysis by: 

 Developing mathematical and statistical models to design and simulate the 

processes and factors comprising a clinical trial 

 Improving collaborative and training opportunities for staff in adaptive/flexible 

design and Bayesian statistical methods to facilitate appropriate use of these 

tools during clinical development of innovative therapies 

Outcome: 

CBER will advance innovative products to the marketplace more quickly, efficiently, 

and economically. 

2. Innovative Products Relying on Living Cells 

Regenerative medicine is an emerging multi-disciplinary field whose products hold 

great potential for treating or curing genetic disorders, neurological conditions, 

diabetes, arthritis, cancer and other diseases, by repairing damaged tissues and 

ultimately, producing artificial organs for transplantation. 

 

A key strategy in this field is the use of human stem cells to produce cells that 

have the specific structure and function needed to treat disease, replace failed 

organs and tissues, or restore their function. CBER must learn how to assess the 

risks of these novel technologies and identify product characteristics that can 

predict safety and efficacy in quality-control tests. These characteristics will be 

critical for predicting if a specific stem-cell-derived product will perform the desired 

function, or alternatively migrate to an incorrect location, form a tumor, or have 

unstable function or structural features after implantation. Assessing these 

characteristics is complicated by the lack of relevant and predictive in vitro and 

animal models. 

CBER also regulates tissue-engineered medical products (TEMPs), which often are 

combination products comprised of two or more regulated components (i.e., 

biologic/device, biologic/drug, biologic/device/drug). As a result, the components 

of a combination product may have been developed with disparate manufacturing 

techniques and controls that CBER must take into account during the regulatory 

process. Furthermore, interactions among components during product maturation 

in vitro or in vivo (e.g. cell-scaffold constructs) and the potential for changes in 

product quality during clinical use (e.g., advanced cell delivery systems) introduce 

additional regulatory concerns. CBER seeks to characterize parameters that predict 

product safety and efficacy but that are not excessively burdensome, in order to 

facilitate development of safe and effective TEMPs. 

Strategies for Implementation 

CBER will facilitate development of safe and effective cellular therapeutics 

for treating human disease and: 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

 Identifying critical in vitro and in vivo markers of product safety, quality, and 

potency, especially characteristics of cell therapy products that are 

measurable in vitro and correlate with in vivo outcomes 

 Developing animal models to evaluate stem-cell-derived and other cell 

therapies and tissue-engineered products, and using state-of-the-art imaging 

techniques to observe cell fate, migration, and function, in animal models 

 Enhancing expertise in stem cell biology, differentiation pathways, impact of 

interactions between living cells and materials, and various forms of 

encapsulation likely to be used in tissue engineered products 

 Developing Cross-Agency efforts to address the challenges posed by novel 

combination products for regenerative medicine.

Outcome: 

CBER will achieve more rapid development of safe and effective therapies for 

regenerative medicine, chronic diseases such as cancer, and rare disorders, based 

on living cells, including stem cell-derived and tissue engineered medical products. 

3. Innovative Products for Treating Cancer, including Cell and Gene 

Therapy, Tumor Vaccines, and Immunotherapy 

CBER has regulatory oversight of novel cancer treatments, such as cell and gene 

therapies, and tumor vaccines and other immunotherapy products. Although some 

products are in phase 3 clinical trials (last phase of investigational testing prior to 

submitting biologics license application), nearing license application, or already 

licensed, many fail during phase 3 trials. In addition, some products have been 

associated with unforeseen adverse events, lack of activity, or inconsistent product 

performance, despite satisfying current lot release and preclinical testing 

requirements. CBER regulators and industry need new test methods and 

biomarkers that can predict safety and effective clinical performance and thus help 

avoid the loss of time and money caused by late stage product failures. 

Strategies for Implementation: 

CBER will facilitate development of novel therapeutic approaches to treat 

cancer by: 

 Supporting virology, molecular biology, tumor biology, and immunology 

studies of the safety and efficacy of gene transfer and tumor vaccines 

 Developing and analyzing animal models for their reliability and sensitivity in 

detecting potential adverse events associated with gene transfer, tumor 

vaccines and immunotherapy products 

 Developing and analyzing animal models for cancer to assess safety and 

efficacy of tumor therapies 

Outcome: 

CBER will contribute to more timely availability of innovative, safe, and effective 

therapies for cancer patients. 

4. Novel therapies for rare diseases. 

In the United States, approximately 1 of every 5,000 individuals has a "rare 

disease," that is, a disease that affects less than 200,000 individuals (e.g., 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

hemophilia, cystic fibrosis, and many even rarer conditions, including some forms 

of blindness or immune deficiency). Many treatments are only palliative and not 

curative. Therefore, there is a need for improved treatments that cure rare 

inherited diseases, such as by recombinant proteins or gene therapy. 

Strategies for Implementation: 

CBER will facilitate development of novel therapies for rare diseases by: 

 Developing and evaluating improved preclinical models to assess safety and 

efficacy of recombinant protein and gene therapies 

 Developing and assessing new ways to transfer genes that improve safety 

and efficacy of gene therapy 

 Evaluating and developing new ways to improve recombinant protein 

characterization to improve product quality and facilitate licensure of 

biosimilars

 Outcome: 

CBER will make safe and effective novel therapies for rare diseases more readily 

available. 

IV. Ensure the safety of biological products. 

CBER regulatory science and research priorities will focus on developing improved 

surveillance of adverse events that may be caused by investigational products that 

may occur very infrequently during clinical trials, when relatively few individuals 

are treated with them. 

Therefore, it is critical to conduct surveillance for possible adverse events after 

the product comes to market, when significantly more people are exposed, and if 

possible, to identify individual risk factors that predispose individuals to specific 

adverse events. In the future, personalized medicine may help ensure patients 

receive the correct product at the correct dose, and avoid products which would be 

particularly risky for them, thus improving risk-benefit ratio of treatments.

Strategies for Implementation 

CBER will enhance its ability to detect low frequency adverse events 

associated with licensed products by: 

 Partnering with government agencies and private organizations to access 

large healthcare datasets that enable more rapid and sensitive detection and 

study of adverse events caused by biologics (e.g., through initiatives such as 

the Post-licensure Rapid Immunization Safety Monitoring (PRISM) program 

and the Blood Safety Continuous Active-surveillance Network (BloodSCAN) 

under the FDA's Mini-Sentinel initiative. 

 Developing and implementing methods to monitor and analyze a broad range 

of potential biologics-related adverse events 

 Developing and assessing methods for safety signal detection and developing 

protocols and thresholds for confirmatory studies 

 Conducting quantitative risk assessments and risk-benefit assessments to 

assess the impact of external events and influences on the safety and/or 

availability of biologics (e.g., the impact of pandemic influenza on blood 

supply) 

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CBER Strategic Plan for Regulatory Science and Research 

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 Enhancing in-house human genomics expertise and partnering with other 

government agencies to facilitate evaluation of regulatory genomics data for 

regulatory decision-making 

 Partnering with government and private sectors in pre- and post-approval 

studies to obtain and analyze human genomic data to determine the 

significance of genetic associations with specific adverse events to obtain a 

better understanding of the etiology of adverse effects from biologic products 

to facilitate the development of personalized medicine 

Outcome: 

CBER may improve the safety of biological products by using faster and more 

sensitive methods for adverse event surveillance and support the adoption of 

personalized medicine. 

V. Enhance research excellence and accountability 

CBER regulatory science and research priorities will focus on enhancing its 

regulatory science and research priorities by improving its laboratories, scientific 

computing capabilities, and scientific skill sets. We will also provide additional 

human resource capabilities. As part of this effort we will strengthen our evaluation 

processes and evaluate CBER regulatory science and research programs 

periodically for regulatory and public health relevance, productivity, and quality. 

A. Establish an infrastructure that supports high-quality state-of-the-art 

scientific investigations. 

Consolidating laboratory and office staff at the White Oak campus will enable CBER 

scientists to work in a state-of-the-art research facility that supports current and 

future research programs. This facility will include computer-intensive scientific 

technologies that are critical for addressing important regulatory and public health 

issues. Indeed, recent developments in high performance hardware and software 

have made unprecedented computer resources available to CBER researchers, 

which the center will use for: molecular modeling (e.g., vaccine safety studies), 

microarray and genomics (e.g., improved characterization of cell therapies, 

vaccines and blood products), proteomics and metabolomics (e.g., improved 

vaccine characterization and blood product safety), systems biology (e.g., 

improved characterization of cells and increased tissue safety), post-marketing 

surveillance of large databases (e.g., monitoring the safety of biologics through 

their life cycle), simulation and Monte Carlo modeling (e.g., safety decision 

analysis support), clinical trials and Bayesian analyses (e.g., making marketed 

biologics safer). 

Strategies for Implementation: 

CBER will design the laboratory building at the White Oak campus with 

expanded capacity in the vivarium, the biotechnology core facility, BSL-3 

dedicated suites, NMR suite, and storage areas by: 

 Expanding imaging capacity (7.0 Tesla small animal magnetic resonance 

imaging (MRI), digital X-ray, In vivo Imaging System (IVIS), ultrasound, and 

transmission electron microscope) for sophisticated studies of products, 

allowing in-life measurements and improved preclinical assessment of 

biologics 

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CBER Strategic Plan for Regulatory Science and Research 

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 Supplementing core facility with additional technologic capabilities to support 

high throughput sequencing (“next generation”), flow cytometry (sterile 

sorting and multi-colorimetric flow cytometric analysis), and high resolution 

confocal microscopy (for living and fixed cells, tissues, and whole animals) 

 Establishing ten Biological Safety Level (BSL)-3 suites to enable work with at 

least 12 infectious agents, accommodating 36 principal investigators; capacity 

for animal holding rooms and capability for sterile sorting and live cell 

imaging of infected cells by state-of-the-art flow cytometry and confocal 

microscopy within BSL-3 suites 

 Providing a suite to support nuclear magnetic resonance equipment (NMR), 

with plans to replace current NMRs with models having larger magnets as 

they become available and are needed for studies requiring improved 

molecular resolution.

CBER will oversee execution of the design of the new laboratory by: 

 Monitoring the construction phase of the laboratory building 

 Providing scientific equipment by transfer from the previous buildings, 

procurement when replacement is necessary, and installation of scientific 

equipment by qualified personnel 

 Resourcing and planning for optimal maintenance and operation of the new 

facility and scientific equipment

CBER will meet the ongoing and future scientific and computing resource 

needs of our research programs by developing collaborative approaches to 

facilitate: 

 Seeking outside funding from private foundations or government agencies 

with shared goals 

 Protecting intellectual property arising from discoveries within CBER 

laboratories 

 Implementing CRADAs, Research Collaboration Agreements, and Material 

Transfer Agreements that facilitate scientific collaborations with scientists in 

other FDA Centers, NIH, other government agencies, international 

organizations, academia, or private industry, thus leveraging our scientific 

expertise and resources 

 Identifying and utilizing high performance computing resources, as proposed 

in the CBER high performance computing strategic road map 

 Developing improved and secure data storage and network access and 

bandwidth 

 Improving FDA processes for procuring and accessing scientific computing 

software & hardware 

 Improving availability of application engineering expertise and support for 

advanced computing 

 Leveraging use of and access to high performance computing resources 

among other FDA centers and NIH 

Outcome: 

CBER will make available state-of-the-art laboratory facilities and scientific 

computing resources to support the ability of CBER scientists to evaluate and use 

novel technologies in assessing innovative medical products, and solve regulatory 

issues with an impact on the development of complex biological products. 

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CBER Strategic Plan for Regulatory Science and Research 

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B. Training and leveraging resources 

CBER must maintain, update, and enhance the scientific expertise of staff in order 

to address novel regulatory issues through scientific research. Therefore, the 

center must provide resources to ensure that the scientific staff can evaluate and 

use state-of-the-art technology and remain current in their scientific knowledge. 

CBER will achieve this by combining training opportunities and support for 

collaborative science. 

Strategies for Implementation: 

CBER will provide training opportunities that include: 

 Attendance at relevant scientific meetings and specific technical or scientific 

courses to update expertise or skills 

 Providing CBER training courses to support and strengthen core skills for 

scientific research (e.g., grant application and manuscript writing) 

 Supporting short sabbaticals to collaborating laboratories for training in new 

technologies or methods that will enhance the center's own research program 

CBER will leverage resources and human capital opportunities to solve 

regulatory issues with an impact on development of complex biological 

products by: 

 Identifying and applying funding from private foundations or government 

agencies with shared goals 

 Protecting intellectual property arising from discoveries made in CBER 

laboratories 

 Implementing CRADAs, Research Collaboration Agreements, and Material 

Transfer Agreements that facilitate scientific collaborations with scientists in 

other FDA Centers, NIH, other government agencies, international 

organizations, academia, or private industry, thus leveraging our scientific 

expertise and resources 

 Using fellowship programs (e.g., ORISE, Service and Commissioner's 

Fellowship Programs, NCI-DA Inter-Agency Oncology Task Force) to attract 

talented scientists with skills and knowledge needed at CBER and provide 

them scientific training

Outcome: 

CBER will recruit and retain scientific staff with up-to-date skills and knowledge 

that enables them to perform research that utilizes innovative science and 

technology.

C. Evaluation of research programs to ensure quality, productivity, and 

FDA mission relevance 

CBER will strengthen its evaluation processes by ensuring CBER regulatory science 

and research programs are evaluated periodically for regulatory and public health 

relevance, productivity, and quality. 

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CBER Strategic Plan for Regulatory Science and Research 

FY 2012 - 2016 

Strategies for Implementation: 

CBER will support and perform research relevant to public health and 

regulatory priorities in an efficient and scientifically rigorous manner; we 

will continue to implement the following research management strategies: 

 Ensuring the most relevant regulatory problems are addressed by cosponsoring and participating in workshops, participating in advisory 

committee meetings, attending relevant scientific and regulatory meetings, 

and engaging outside experts to review our scientific programs on a regular 

basis 

 Engaging in internal discussions to identify emerging scientific and regulatory 

issues that can be effectively addressed by CBER’s research and use those 

discussions as the basis of office- and center-wide research priorities 

 Using peer review and managerial oversight to allocate resources to highly 

qualified, productive principal investigators doing rigorous science relevant to 

stated priorities 

 Using internal peer review to evaluate scientific relevance, quality, and 

productivity every four years, or when a scientist is deemed ready for 

conversion to a permanent position or promotion 

 Using formal external scientific peer review of principal investigators through 

site visits every four years to evaluate the public health and regulatory 

impact, quality, and productivity of their scientific programs 

 Using annual reporting via an online database of scientific accomplishments, 

future plans, publications of peer-reviewed scientific articles, relevant 

guidance documents, and other relevant output to annually evaluate the 

outcomes of CBER research programs 

 Allocating research resources to scientific programs that address CBER’s longterm objectives, stated regulatory science and research priorities, and 

represent high quality well-designed, productive science, based on the abovementioned management strategies

Outcome: 

CBER will perform high-quality, productive research that addresses critical 

regulatory and public health scientific problems and that supports regulatory 

decision-making and policy development. 

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CBER Strategic Plan for Regulatory Science and Research 

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Appendix A – CBER’s Support of FDA Research Initiatives 

FDA’s Advancing Regulatory Science Initiative 

In August, 2011, FDA issued a Strategic Plan, “Advancing Regulatory Science at 

FDA” (available at 

http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm267719.h

tm ). This cross-cutting strategic plan provides a guide to implement FDA’s 

commitment to advancing regulatory science and innovation made in the FDA’s 

Strategic Priorities documents issued in April 2011. The FDA Strategic Priorities 

document defines “Regulatory Science” as the science of developing new tools, 

standards and approaches to assess the safety, efficacy, quality and performance of 

FDA-regulated products. 

The Strategic Plan identifies eight priority areas for regulatory science that would 

support FDA’s public health and regulatory mission: 

1) Modernize toxicology to enhance product safety 

2) Stimulate innovation in clinical evaluations and personalized medicine to 

improve product development and patient outcomes 

3) Support new approaches to improve product manufacturing and quality 

4) Ensure FDA readiness to evaluate innovative emerging technologies 

5) Harness diverse data through information sciences to improve health 

outcomes 

6) Implement a new prevention-focused food safety system to protect public 

health 

7) Facilitate development of medical countermeasures to protect against threats 

to U.S. and global health and security 

8) Strengthen social and behavioral science to help consumers and professionals 

make informed decisions about regulated products 

Building on commitments in the FDA’s Strategic Plan and in CBER’s Strategic Plan, 

CBER has developed a Strategic Plan for Regulatory Science and Research that 

outlines its goals, objectives and strategies for supporting the priority areas (except 

for the food safety-related area) of regulatory science supporting the health of the 

American public and global public health. 

In addition, this plan supports FDA-wide initiatives that have a regulatory science 

component built into them. These initiatives are: 1) Nanotechnology Regulatory 

Science Initiative; and 2) Medical Countermeasures Initiative. A brief description 

and CBER’s contributions to each of these initiatives are provided. 

Regulatory Science and Innovation (formerly Critical Path Initiative)

FDA launched Critical Path Initiative (CPI) in 2006 to overcome product development 

roadblocks using existing and newly created scientific knowledge, new methodology 

and tools, and nonclinical models. The goals of CPI include: 

1) Improving drug evaluation tools 

2) Streamlining clinical trials 

3) Harnessing the power of bioinformatics 

4) Advancing manufacturing technologies using 21st Century science 

5) Developing innovative solutions to urgent public health needs 

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CBER Strategic Plan for Regulatory Science and Research 

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The CPI was later expanded in scope to include all FDA-regulated products. The 

Office of the Chief Scientists (OCS) administers the CPI through its Office of 

Regulatory Science and Innovation. This organization provides central coordination 

for the CPI; leads certain FDA-wide CPI projects, and supports CPI projects in the 

centers with funding, staffing, and/or project management. 

FDA’s Nanotechnology Regulatory Science Initiative 

The FDA Nanotechnology program includes support in regulatory science intended to 

achieve three objectives: 

1) Increased training for FDA staff to support review activities of FDA-regulated 

products that contain engineered nanomaterials or use nanotechnology for 

the manufacturing process 

2) Creation of two core laboratories that provide equipment and methodologies 

to allow FDA scientists to further their research to support development of 

safe and effective FDA-regulated products 

3) Establishment of a competitive FDA-wide grants program, called Collaborative 

Opportunities for Research Excellence in Science. (Details about these three 

areas and the implementation plan for the FDA’s Nanotechnology Regulatory 

Science Initiative are available at 

http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/ucm273

325.htm) 

CBER participates in the Nanotechnology Regulatory Science Initiative by serving on 

the Nanotechnology Task Force, a cross-FDA body that oversees this initiative, and 

through targeted research relevant to CBER-regulated nanotechnology products. 

FDA’s Medical Countermeasures Initiative 

The FDA’s Medical Countermeasures initiative (or MCMi) was developed in order to 

facilitate development of novel medical countermeasures used in response to natural 

or man-made public health disasters. The MCMi is a critical component to the 

Nation’s preparedness efforts. Natural public health disasters include a novel strain 

of influenza that could cause a pandemic or other emerging infectious diseases. 

Man-made disasters arising from potential terrorist attacks include bioterrorist, 

chemical, burn, blast, or nuclear attacks. The MCMi has three pillars: 

1) Enhancing the regulatory review process for the highest priority medical 

countermeasures and related technologies 

2) Advancing regulatory science for medical countermeasure development 

3) Optimizing our regulatory and legal framework 

CBER will continue to use its scientific resources to address regulatory science needs 

to support development of MCMs, including those related to preparedness for 

pandemic influenza, emerging infectious disease, and bioterrorist threat agents. 

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CBER Strategic Plan for Regulatory Science and Research 

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24

Appendix B – CBER Organization