In FY 2005, the Agency will continue to collaborate with other government agencies, industry, and academia to accomplish the applied research needed to perform our mission. FDA-regulated products play an essential role in the health and everyday lives of Americans. But the industries that make these products can't remain healthy themselves unless they continue to innovate. Continued improvement in Americans' health and longevity also depends on the success of industry innovation to bring better products to market, managing risk and cost.
When developing a new technology, companies often grapple with technical uncertainties in making the new technology perform effectively, or regulatory uncertainty, for example, if the new technology raises new safety questions. Companies may also face market uncertainties related to public perception of product risk, or other factors that affect the likelihood of commercial success-- and continued investment in a new technology-- even when it holds scientific promise. These development hurdles are on the "critical path" to realizing the benefits of investments in basic research in science and medicine, but addressing these obstacles is not part of the role, or a core expertise, of basic research. As the lead arbiter of product safety and effectiveness -- and market readiness -- FDA has a unique role and expertise in the applied research needed to bridge the gap between basic discovery and commercial reality.
The need for FDA involvement and leadership in targeted, applied research has never been greater. Today, the incredible biomedical discoveries of the last decade, fueled by research investment over the last 30 years, promise even more significant progress in the decades to come, perhaps even the prospect of widespread preventive and curative interventions. For this to happen, research findings must be transformed into actual products ready to be used in the clinic. But an ever-widening gap is developing between basic science knowledge and application in clinical practice. Currently, the flow of innovative pharmaceuticals into the market is slowed worldwide; vaccine development has been seriously inhibited over the last decade; medical device manufacturers find that the clinical trial process cannot keep pace with technological evolution. Breakthrough research concepts are getting bogged down in development because serious technical hurdles are not being addressed; new development tools are needed.
FDA research is focused on developing these kinds of tools, including statistical models to enable more reliable and cost-efficient product development, reference assays and methods for safer and cheaper manufacturing, and physical reference standards to speed development of new medical devices. In addition to producing these essential tools, FDA research fosters continued product/technology expertise within the agency, critical to our effectiveness in early consultations with product innovators seeking agency advice on new study designs and troubleshooting problems in novel product manufacturing.
Recent examples of FDA critical path research that has resulted in major public health impact include:
FDA research contributes to a strong science base that improves and maintains the safety and effectiveness of regulated products by ensuring quality, safety and performance. Applied studies serve the needs of the Agency's regulatory mission. These studies include setting standards for activities ranging from laboratory techniques to determine if a drug, device, or biologic are is safe and effective and surveillance for unexpected threats to the public health from foods and medical products to regulatory enforcement. The following briefly explains the planned research, demonstration and evaluation activities for FDA in FY 2005.
The FDA participates in the DHHS Research Coordination Council (RCC) Workgroups, which brings together representatives from each of the HHS agencies to discuss research, demonstration, and evaluation activities throughout the Department. The goal of the Workgroups is to define RD&E goals and approaches at each HHS agency; ensure they match the President's and the Secretary's priorities; determine unplanned redundancies; and, foster appropriate collaborations within HHS (and the broader Federal sector, where appropriate).
FDA research falls into six research priorities, five of which are Secretarial priorities. Orphan Products Development is FDA's only Agency-specific research priority. FDA's research increases for FY 2005 are within Food Defense, Patient Safety, Quality, and Reducing Medical Errors, and Generic Drugs. These support the Secretarial Research Initiatives of "Ensuring our Homeland is Prepared to Respond to Health Emergencies" and "Realizing the Possibilities of 21st Century Health Care", respectively.
FDA’s programs are directed to facilitate the safe and effective use of organ transplantation through the characterization of organ transplantation quality, purity, safety and efficacy. Specific programs include work to explore novel strategies for repair, regeneration, or replacement of tissues damaged or lost due to trauma or other pathology and the use of stem cells products to repair damaged tissue (bone marrow). Expertise in cell biology, molecular biology, genomics, and proteomics are included in the characterization of cell-based products produced outside the patient. Other programs study the transplantation immune responses, as sponsors are developing a variety of strategies utilizing drugs, biologics, hamatopoietic cell transplantation to avoid organ rejection and to induce acceptance of transplanted tissues and organs.
In addition to the research on transplantation, the Agency also has programs related to the evaluation of artificial organs and organ assists. These projects include the evaluation of prosthetic heart valves, ventricular assists, stents, and bypass pumps. Other projects include new intra-ocular lens implants, retinal implants, cochlear and middle ear implants. Much of this research focuses on test method development that examines specific device attributes.
The concern for the safety and efficacy of drugs, biologicals, and devices directs the focus of FDA’s research programs. This focus on safety and efficacy has a direct impact on programs to identify patient responses to these products. Specific programs include: 1) development and validation of methods and biomarkers to detect drug induced tissue injury and elucidation of underlying mechanisms; 2) assessment of factors that contribute to variability in pediatric Pharmacokinetics and/or pharmacodynamic studies, age-dependent metabolic changes, developing mathematical models predict drug transfer from mother's blood milk estimate exposure breastfed infants; 3) development, improvement, standardization diagnostic tests for transmissible infectious agents products; 4) measurement potency predicting adverse reactions blood-based 5) potency, purity, safety prophylactic therapeutic vaccines anti-allergenic therapies; 6) evaluation counterfeit products product contaminants a rapid reliable manner; 7) management the risk vaccine neutotoxicity through development of preclinical safety tests and postmarketing studies for virus vaccines; 8) use of genomics to identify early signs of renal or hepatic failure; 9) development of improved methods for evaluation of drug-eluting stents and interventional cardiology devices; and, 10) development of performance assessment methodology for state-of-the-art diagnostic imaging system.
In the food defense area, the programs involve intramural, extramural, and consortium (industry and/or academia) programs in the development of analytical detection methods and the characterization of the agents in food including animal feeds. The work includes the validation and performance evaluation of existing rapid screening tests for priority agents on high-priority foods, with the ultimate goal of having field-deployable technologies that meet performance and validation standards. This work also involves the development of confirmation and "fingerprinting" approaches for the select agents in food. In addition, the work includes the characterization of the abilities of non-traditional bacterial pathogens to survive and grow in FDA-regulated foods during processing.
The FDA research on vaccines and biological products includes for smallpox and anthrax the development, evaluation, and licensure of new-generation smallpox vaccines, new assays to measure vaccinia-specific immune responses and vaccine potency for smallpox, evaluation of components of Bacillus anthracis for treatment of patients suffering from anthrax toxin, and development of improved vaccines for anthrax. For other agents, the research includes evaluation of an effective and safe vaccine product for prevention of plague; detecting and identifying outline toxin, measuring its potency and treating its effects; and developing correlates of immune protection for clinical studies using animal models for tularemia vaccines. There are also programs ongoing to develop live cell systems for detection and identification of toxic agents in low concentrations for medical diagnosis.
While the above are FDA's primary focus on bioterrorism, there is an Interagency Agreement with the Federal Aviation Administration for the development of test methods and drafting of voluntary standards for testing medical devices for electromagnetic emissions for fields emitted from security screening systems.
FDA’s food safety and security research approach is threefold, involving an intramural program, extramural and consortia with industry/or academia ( e.g., National Center for Food Safety and Technology). The intramural effort focuses on microbiology and chemistry (including radiation). In microbiology, several projects involve examining existing clinical or environmental rapid detection methods for certain agents of concern to determine how well such methods perform when using high priority foods determined from classified threat assessments. These methods are being evaluated and augmented for food security. Where no previous methods existed in foods, new methods are being developed with intramural projects and competitively funded grants and cooperative agreements. Food security detection methods will be incorporated into CDC's Lab Response Network and the Food Emergency Response Network (FERN). FDA has also developed a Microbial Forensics Research Program, which uses a cladistic framework for the strain differentiation of foodborne pathogens. FDA is collaborating with the FBI, CIA, Department of Homeland Security, and the Department of Defense on developing this technology for precise identification of foodborne agents of bioterrorism. The National Center for Food Safety and Technology has initiated prevention/mitigation projects concerning the characteristics (growth, survival) of microbial threat agents in high priority foods and the thermal inactivation kinetics of these agents.
Since the President's and the Secretary's RD&E priorities for food safety and food defense are represented under the DHHS Research Coordination Council (RCC) Priority, Ensuring Our Homeland is Prepared to Respond to Health Emergencies, FDA's Center for Food Safety and Applied Nutrition (CFSAN) activities clearly matched the themes and sub-themes of this priority. The RCC Workgroups brought together representatives from each of the HHS agencies over FY 2003 to discuss the RD&E activities of each agency. The goal of these was to define RD&E goals and approaches at each HHS agency, ensure they are aligned with the President's and the Secretary's priorities, determine unplanned redundancies, and foster appropriate collaborations within HHS (and the broader Federal sector, where appropriate) to inform the HHS RCC and, in turn, the FY 2004 and 2005 budget development process. The ultimate goal of the RCC is to direct HHS resources where they are most needed and to complete the associated activity in a timely, cost-effective, and informative manner.
With the heightened concern about the potential use of foods as a vehicle for the dissemination of chemical, microbiological, and radiological agents, there has been a concerted effort during the past two years to (1) enhance the detection capabilities of laboratories, including the development and validation of methods suitable for use with foods, and (2) to assure the availability of adequate medical countermeasures. These endeavors have been and will continue to be priority areas for the vast majority of the FDA's limited intramural and extramural research programs. However, the nation's food defense programs are now moving into the next phase, wherein the ability to respond rapidly is being integrated with the development of strategies for preventing or deterring the use of foods as a vehicle for terror. There is a critical need for proactive steps, wherein validated technologies that can actively reduce food defense risks are integrated into the manufacture, distribution, and marketing of foods. Likewise, the nation needs to be prepared with technologies that can verifiably assist the food industry in recovery if a terrorism event involving foods were to occur. For example, there is a need for validation methods for decontaminating food processing facilities and, possibly, the remediation or disposal of large quantities of food products. Successful implementation of this component of an integrated food defense program is dependent on the availability of key scientific information and its application via technologies that can be applied practically to both the domestic and imported food industries.
The strategy/agenda for food defense research in FY2004/2005 is the acquisition of scientific information and technological advances that are needed to develop effective "shields" to attacks on the security of the nation's food supply. As such, the research will focus on three broad areas:
For food safety, FDA's programs have microbiology contaminant, chemical contaminant, biotechnology/allergenicity, seafood, dietary supplement, animal drug residues, color additives, and market studies components. For the microbiology component, the determination of microbiological risk and its mitigation drives the research program. Included is work in the detection, characterization, and behavior microbial genetics, molecular virology, and the molecular nature of the human pathogens in the food supply combined with the characterization of the foodborne microbial pathogens in food. All this information is vital to our ability to develop risk assessment models for pathogens such as Escherichia coli 0157:H7, Listeria monocytogenes, and Clostridium botulinum as intervention strategies to reduce the hazards and public health risk. This work includes intramural and extramural programs and collaborations with the Illinois Institute for Technology, food industry members, and the Joint Institute for Food Safety and Applied Nutrition (JIFSAN).
While the above program relates to the occurrence of selected pathogens in food, there is also a component to the microbiology issues related to the emergence of antibiotic resistant pathogens in food following the feeding of antibiotics to food producing animals. The Agency conducts studies to improve our understanding of how resistance develops, disseminates, and persists in the animal production environment. These studies include intramural and outside collaborations. In addition, the Agency has a collaborative program with CDC and nine public health laboratories involved in the National Antimicrobial Resistance Monitoring System (NARMS) to develop surveillance data on pathogens found in various foods.
For chemical contaminants, biotechnology/allergenicity, seafood, animal drug residues, dietary supplements, and color additives the programs are focused on the development of detection methods. Examples of analysis included for methods detection include pesticides, mycotoxin, dioxins, antibiotics in animal derived food, food allergens and Dry9C protein, bacterial and viral pathogens and toxins in seafood, botanicals, soy isoflavones, trans fatty acids, and confirmation analysis for colors. These programs involve intramural and extramural efforts and collaborations with the Illinois Institute for Technology, the JIFSAN, and the University of Mississippi's National Center for Natural Products Research.
The market studies component of this work involves estimating the changes in consumer and producer behavior in response to agency regulations and policies. In addition, the relationship between risk assessment and economic analysis is also explored. The Health and Diet Survey collects information on consumer knowledge, awareness, attitudes, and behaviors related to diet and health issues.
FDA conducts research in health disparities through the identification of genetic polymorphisms; conducting epidemiological studies for post market surveillance of chemical toxicants found in foods, drugs, cosmetics, and medical devices; human exposure biomonitoring; the extrapolation of the results of animal surveys to humans; and the development and validation of DNA Microarray Technology for human diagnostics. FDA needs to apply the latest techniques in genomic research to the regulatory process, to determine the potency of suspected mutagens and carcinogens. FDA conducts fundamental research aimed at defining the pathways from initial DNA damage to mutation, by developing, validating, and implementing reliable and sensitive mutation detection methodologies to assess genetic risk for FDA regulatory purposes.
Scientific evidence of the importance of sex differences throughout the lifespan is prevalent. FDA will conduct research on how these sex differences influence product safety and effectiveness by funding research aimed at understanding the genomics and proteomics of sex differences. The results of these studies will serve as a basis for developing efficient risk management programs. Current research designed to fill the gap in information regarding use of therapeutic agents for counterterrorism in women and the elderly will be translated into information for consumers. FDA will continue to develop a system to track information such as the inclusion of women in clinical trials and the analysis of clinical data by sex, age, and ethnicity. This data will be analyzed and used for the development of policy and standards for data collection, clinical trial design, and the dissemination of information regarding the risks associated with the use of medical products.
Experimental and focus group studies will use mail-intercept and Internet methods to investigate qualified health claims for conventional foods and dietary supplements, the Emord-petitioned health claims for dietary supplements, and the proposed footnote that will accompany the trans fat declaration on the Nutrition Facts Panel. Focus groups will also investigate allergen labeling wording and formats and evaluate a variety of symbols and formats designed to provide consumers with "weight of evidence" information for qualified health claims.
Influenza is an easily communicated virus with many variants that may or may not be susceptible to immune responses generated to other strains. In the case of expected spread of a very novel strain of influenza virus, it would be valuable to develop influenza immunization strategies that confer immunity against entire categories of influenza virus strains. Agency research programs are exploring these immunization strategies designed to optimize broad cross-protection. The goal is to further improve the ability to protect against viral infection without having to know in advance what virus strain is circulating.
The Agency has an ongoing program to prevent the spread of transmissible Bovine Spongiform Encephalopathies (BSE) in cattle. Current programs focus on the development of improved detection methods and validation of rapid tests for detecting prohibited material in animal feed. Currently, there are no methods that will discriminate between the prohibited and exempt materials.
Scientific evidence of the importance of gender differences in disease and illness throughout the lifespan is prevalent. However, there is a lack of evidence that explains the impact of these differences on disease prevention, and the impact of sex differences on the safety and efficacy of medical products used to prevent, diagnose and treat disease. FDA programs will increase the understanding of gender differences in health and disease prevention and response to medical interventions. The results of such studies will improve prevention, diagnosis, and treatment of disease in women and men. The Agency is continuing development of a system to track demographic information such as the inclusion of women in clinical trials and the analysis of clinical data by sex, age, and ethnicity. The clinical trial data will be analyzed and used for the development of policy and standards for data collection, clinical trial design, and the dissemination of information regarding the risks associated with the use of medical products.
Disease specific programs include those in cancer, HIV/AIDS, and cardiovascular disease. The cancer research is focused on determining the variability in metabolic phenotype and genotype in women with respect to their recurrence of breast cancer following high-dose radiation and chemotherapy and assessing the toxicities and carcinogenic risk associated with specific chemicals and gene-nutrient interactions, and the introduction of new techniques to assess toxicities and carcinogenic risk. In the Agency's work on HIV/AIDS, the focus is on the evaluation and acceptance of vaccines. For cardiovascular disease, this is a component of the Agency's women's health program that is focused on prevention, diagnosis, and treatment.
FDA scientists perform fundamental research to develop and validate quantitative biomarkers of neurotoxicity, which are then used for the comprehensive evaluation of neuroactive chemicals of concern to FDA regulatory centers. The FDA research program includes the availability of facilities for rodent and non-human primate research that help reduce the risk of extrapolating data across species whenever possible. Collaborative behavioral studies are being conducted in partnership with the Arkansas Children's Hospital.
The goal of the Orphan Products Development (OPD) Grant Program is to encourage clinical development of products for use in treatment of rare diseases or conditions, affecting fewer than 200,000 persons in the United States. The products studied may be drugs, biologics, medical devices, or medical foods. Grant applications are solicited through a Request for Applications published annually in the Federal Register.
The OPD grant program is FDA’s only agency specific research priority, which corresponds with the Research Coordination Council Research Themes and Priority Research Areas on several fronts. First, with regard to the specific research themes, the OPD grant program allows for research in a variety of areas including disabilities, healthy development of youth, mental health, organ transplantation, infant mortality, infectious diseases, and cancer. Secondly, research supported by the OPD grant program falls within the following priority areas: Protecting and Empowering Specific Populations, Realizing the Possibilities of 21st Century Health Care, Understanding Health Differences and Disparities—Closing the Gaps, and Preventing Disease, Illness, and Injury. These activities support FDA's mission to promote and protect the public health by helping safe and effective products reach the market in a timely way.
During the DHHS RCC process, FDA and other HHS agencies reviewed research projects in eleven areas. Agencies were made aware of unique differences in projects, complementary areas were compared, and confirmation that no duplication exists. The working group discussions highlight gaps to be filled and elicit suggestions for collaborations between groups for eliminating these gaps through future research efforts. Compiling research templates by the RCC providing an opportunity for scientists and administrators to easily review ongoing research for collaborative opportunities, share lessons learned, and exchange the latest scientific information. At FDA, we have already identified several examples of research that have led to for further intra-agency collaboration, including:
Although there are many opportunities for collaboration identified through the DHHS RCC process, scientific studies take time to develop, plan and coordinate across the scientific community, therefore, at this time we cannot demonstrate or report further collaboration with other DHHS Agencies. This also reflects the uniqueness of the FDA research program focused on the application of the latest technologies to FDA regulated products.
Currently, FDA participates in the DHHS RCC as well as other research coordinating groups including:
FDA will continue to be an active participant in RCC meetings and research reporting, as well as continuing the Agency's participation in other research coordinating groups throughout HHS to better utilize opportunities for coordination of RD&E projects.
| FOOD AND DRUG ADMINISTRATION |
|
|---|---|
| Research Theme |
FY 2005 Request |
| I. Realizing the Possibilities of 21st Century Health Care |
21,048 |
| II. Ensuring our Homeland is Prepared to Respond to Health Emergencies |
74,347 |
| III. Understanding Health Differences and Disparities---Closing the Gaps |
13,048 |
| IV. Preventing Disease, Illness, and Injury |
17,848 |
| V. Protecting and Empowering Specific Populations |
8,349 |
| VI. Agency Specific Priorities |
16,006 |
| A. Orphan Products Development 2/ |
|
| BA |
|
|
TOTAL AGENCY RESEARCH FUNDING |
150,646 |
1/ FDA reviews and makes decisions regarding new products that are the result of cutting-edge science. These decisions must be credible, not only with our peers, but also with the general public. Not only does our applied research help us obtain this credibility but it also has the side benefits of providing useful insights for product developers as to how they can solve important technical problems, and helping to make sure that the Agency has adequate expertise to make appropriate decisions and develop regulatory policies in areas of increasingly complex science.
2/ Orphan Products Development includes Orphan Products grants and related Administrative costs.