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  1. Advancing Regulatory Science

VI. Modernizing Safety Testing

Table of Contents: Advancing Regulatory Science for Public Health

For more than a century, toxicology has largely relied on animal testing. Such testing, however, is costly and time consuming and does not always provide results that reliably correlate with human responses. As a result — and out of concern and respect for animals — we must develop methods for safely reducing, refining, or replacing animal testing. This requires development and validation of methods that are reliable in predicting safety and other product attributes. Advances in life sciences and engineering are ushering in the potential to dramatically change the way toxicology assessments are performed, but these new technologies have not yet been sufficiently studied or tested. Investments today can help seed a revolutionary change in toxicology and hazard assessment.

What has FDA done?

One of the cornerstones of safety assessment at the FDA is the National Center for Toxicological Research (NCTR) which is responsible for conducting FDA mission-critical, peer-reviewed, critical path (translational) research to develop a scientifically sound basis for regulatory decisions and reduce risks associated with FDA-regulated products. This research is aimed at evaluating the biological effects of potentially toxic chemicals or microorganisms; defining the complex mechanisms that govern their toxicity; understanding critical biological events in the expression of toxicity; and developing methods to improve assessment of human exposure, susceptibility, and risk.

As illustrated in the example below, each product center within the FDA is also engaged in research efforts to develop new tools and standards for evaluating safety of new drugs, biologics, or devices.

  • Novel kidney biomarkers for preclinical toxicity studies
    Unfortunately, new drug candidates often fail late in development after significant investments have already been made toward their development. It is critical to identify potential safety issues as early in the development process as possible, before human studies are performed. Some of the most common toxicity problems occur in the liver, kidney, or cardiovascular system. In recent years, FDA, working with the European Medicines Agency (EMA), has led several collaborative efforts that have brought together these agencies with academic and industrial groups in consortia, seeking to identify and qualify novel biomarkers for detecting drug-induced kidney toxicity in preclinical animal models. Recently, FDA and EMA endorsed a number of these biomarkers, originally detected and identified using microarrays. These biomarkers provide a non-invasive strategy for detecting kidney toxicity in animal models and are more sensitive and specific than traditional tests. Additionally, these markers may prove to be an effective monitoring tool for kidney toxicity in human studies. (Predictive Safety Testing Consortium http://www.c-path.org/pstc.cfm disclaimer icon)

What can FDA do with increased investment in regulatory science?

Initial regulatory science investments would be aimed at bolstering new technologies — specifically, biomarkers for better risk protection — to improve both animal and non-animal models and create bridges between them. For example, data from cell culture methods, genomics microarrays, as well as proteomics and metabolomics should be expanded and correlated with both animal testing results and experience from human clinical studies. The goal would be to replace or refine exposure experiments with predictive markers. Investments in analysis of large sets of data would provide valuable information for understanding how classes of chemicals cause toxicity. These approaches require new instrumentation, platforms, and databases, and training for FDA scientists to enable them to use and interpret data from these approaches. Collaboration with academia, industry and sister government agencies will be critical.

Another related and important area for advancing regulatory science is to increase the use of in vitro and, potentially, computer-based modeling systems for toxicology. The development of cell lines, engineered model tissues and other cell culture approaches will be critical, not only to better understand underlying mechanisms triggered in human cells following exposure but also to replace current approaches with more efficient and cost-effective toxicology studies.

The increasing deployment of new and complex technologies, such as nanotechnology, also creates the need for new approaches and methods to better evaluate, understand, and predict the potential toxicity of these materials. For all FDA regulated products, from foods to medicines, we must improve methods and models to assess and effectively communicate both risks and benefits to support sound regulatory decision-making, empower consumers and — above all — protect the public health.

Next Section: Meeting the Challenges for Regulating Tobacco

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