U.S. Food and Drug Administration
Performance Plan
2002
Improve the FDA science base to develop and/or modify research standards used for definitive risk/policy decisions.
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Integrate new genetic systems and computer-assisted toxicology (bio- informatics) in the application review process. Integrate gene chip, gene array and proteomic technologies as standards for FDA review/risk management. |
Toxicology research is moving away from using large numbers of animals with relatively few endpoints. These animal test systems are costly, time intensive and do not always mimic the human response. Because of American consumption, increasing evidence of adverse drug/chemical reactions in humans points to a need to identify and protect people at higher risk from exposure to drugs, contaminated foods, or other regulated products. In addition, toxicological research is focused on a better understanding of the biological mechanisms that cause toxic reactions. Currently, industry has been submitting drug applications with data from transgenic systems. In response, FDA scientists and reviewers are developing, evaluating and comparing in vivo and in vitro transgenic systems and computer-assisted toxicology knowledge bases.
Risk chip technology permits researchers to screen large numbers of people simultaneously for different biomarkers. This allows the identification of individuals at risk for adverse drug reactions and facilitates FDA review of individual susceptibility using profiles of agents with known toxicities and allows selection of a diverse group for clinical trials. DNA gene expression microarrays lead to better understanding of inter-species extrapolation and provide biomarkers that predict human outcomes. A less defined but more powerful technology called proteomics is also being developed. These techniques are being developed in collaboration with private industry.
Agency scientists will continue to develop/modify and apply new technologies to evaluate models as useful substitutes to determine human toxicity.
In addition, we will conduct studies using transgenic, imaging, microarray, proteomics and informatics to evaluate toxic responses in individuals and identify biomarkers that predict human outcomes.
Product/drug development is exploding due to rapid scientific advances and new technologies, such as human genome sequencing. Should FDA continue to fall behind in understanding and incorporating these technologies into its applied research and regulatory review process/policy systems, the ability of the Agency to guide industry submissions and/or review new applications will be detained along with products being delayed to patients.
In order for FDA's National Center for Toxicological Research to establish a core DNA Microarray Group to facilitate expanded research in this area, it will need:
To support goal 1, Agency researchers have developed new bioassays for use in assessing genetic damage. The National Center for Toxicological Research is actively collaborating with other FDA Centers, other agencies and academia to expand this potential. NCTR has also developed and validated a prototype computer-assisted predictive toxicology model for estrogenic compounds. The prototype predictive system has been used successfully by CFSAN and CDER to assess the estrogen-like effect of compounds. This research has been conducted in partnership with other federal agencies (NIEHS & EPA) and with industry.
To achieve goal 2, scientists have completed studies to identify markers of frequently occurring cancers in highly susceptible subpopulations. These data have been used to work with industry to develop a "risk chip" (array technology) to identify and protect large numbers of people who are highly susceptible to having adverse reactions from exposure to certain drugs, and contaminated foods. This "risk chip" has potential to be expanded to identify other biomarkers provided funds are made available.
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