Stimulating Regulatory Science

The FDA defines regulatory science as the “science of developing new tools, standards and approaches to assess the safety, efficacy, quality and performance of all FDA-regulated products.” FDA scientists have a unique vantage point from which to survey the drug development landscape. This collective regulatory knowledge can be leveraged to better understand the needs and opportunities for tools, standards and approaches in drug development. We believe advances in regulatory science are essential for the efficient development of new treatments and improved use of existing medicines.

The challenges of bringing new therapies into the clinic are many and varied. While academic funding may support novel discoveries, further progress through translational research and clinical development is resource intensive and requires rigorous, robust and reproducible data. In our view, this translational phase is often underfunded, underappreciated and underestimated. To help smooth the transition from academic discovery to regulated medicinal product, the FDA has developed various fellowships and training opportunities to give scientists in academia a better understanding of regulatory science. For drugs with breakthrough indications and for underserved populations, the FDA has established pathways and incentives to speed development, with great success; orphan drug approvals are at an all-time high.

However, failure to reproduce clinical and analytical data, and the lack of validated assays and standardized methods to collect and represent data, remain common roadblocks on the path to translation. Consistent interpretation of analytical test results requires methods that not only accurately measure the intended analytes, but do so reliably across laboratories and over time. The success and efficiency of clinical translation is also dependent on the availability of robust and meaningful biomarkers and clinical endpoints, backed by sufficient knowledge to be confident of their clinical interpretation.

Typically, the knowledge base available to any single entity is not sufficient to resolve uncertainties about the reliability or predictability of a potential translational tool. Progress in these areas necessitates multiple stakeholder partnerships. To enable such advancement, the FDA launched the Critical Path Initiative in 2004. The goal is for multiple stakeholders to share expertise and resources to aid development of better tools, standards and approaches. A good example is the Drug Development Tool Qualification Program, which promotes collective development and regulatory qualification of tools and makes them universally available. Collaborations with academic and industry experts to establish therapeutic data standards are also underway.

To complement large-scale collaborative efforts to improve drug development, FDA scientists and clinicians engage in research and communicate new knowledge, standards and methods to the drug development community through guidance documents, workshops and scientific publications. The Office of Translational Sciences (OTS) within the FDA’s Center for Drug Evaluation and Research (CDER) works to leverage the collective experience of multidisciplinary review teams to identify areas of translational research in need of additional resources – and to support them with intramural funding programs. Through these mechanisms, the FDA can provide their scientists and reviewers with the resources they need to reduce uncertainty in regulatory decision making and ultimately support the development of safe and effective medical products. For instance, OTS funds research into statistical and mathematical modeling and simulation techniques to accelerate analysis of data for exposure–response, pharmacokinetics, pharmacodynamics, pharmacogenomics, bioequivalence assessment, clinical trials, quantitative risk assessment, toxicology and product quality assessment.

It’s an ongoing journey. Extensive and thorough evaluation is required to support the evolution of novel drug development tools, standards and approaches, such as biomarkers, clinical outcome assessment instruments, data standards, and in silico models for clinical predictions. We are all learning in this space and need to understand the benefits and risks of relying on these tools to support drug development and regulatory decision-making. We need the collective knowledge of the scientific community to help set the goal posts to allow greater reliance on these methods. There also needs to be a greater appreciation by the scientific community of the role of translational research and regulatory science, the value of collaborative research, data sharing, development and utilization of standards to support data aggregation (for example, in sample repositories) for public health. To achieve that, we will continue to engage with the scientific community about regulatory science and how it supports medical product development.