1. Innovative science to improve public health1 Regulatory Science: Challenges and Opportunities William Slikker, Jr., Ph.D., ATS National Center for Toxicological Research, U.S. Food & Drug Administration The views provided in this presentation may not reflect those of the FDA

2. Innovative science to improve public health2 October 20, 2011 Dear William, The Intel International Science and Engineering Fair will be held in the “City of Champions”, Pittsburgh, Pennsylvania, from May 13 – 18, 2012. Sixteen hundred of the world’s most talented and selected high school scientists from 65 countries will earn the privilege of attending the Intel ISEF to be judged by experts in their fields, and compete for $4 million in awards. Over the years, students have consistently cited the attention and guidance of expert judges as the highlight of their Intel ISEF experience. None of this happens without you. Please consider becoming a judge for the Intel ISEF 2012. Over one thousand PhD-level judges (those with either a doctorate or six years of professional experience in a scientific field) are needed in the life, social, behavioral and physical sciences, engineering and math. Your commitment would start the evening of Tuesday, May 15, 2012, and continue through the evening of Wednesday, May 16. For information and registration, please go to https://apps.societyforscience.org/isef/judging/judapply.asp. Travel or honorarium support is not offered, but meals and training will be provided. We know that the students will make this a most memorable and enjoyable experience. It is also a chance to meet other professionals in your field from around the world. Thank you for your consideration. We look forward to welcoming you to the Intel ISEF 2012 in Pittsburgh. You can also help us by spreading the word to colleagues. Direct them to the website above or, if you want an invitation sent to someone, send their name and email to judging@societyforscience.org. Sincerely, Elizabeth Marincola President Society for Science & the Public Charles J. Vukotich, Jr., Chair, Judging, Intel ISEF Pittsburgh 2012https://apps.societyforscience.org/isef/judging/judapply.aspjudging@societyforscience.org

3. Gary Kimmel, Stephen Harris, Melissa Tassinari, Thomas Knudsen, Helen Cunny, Rochelle Tyl, Betsy Carlton, Joseph Holson, William Slikker. Birth Defects Research Article first published online: 20 JUL 2004 Volume 71, Issue 3, Volume 71, Issue 3, pages 191–192, June 2004 Volume 71, Issue 3, http://onlinelibrary.wiley.com/doi/10.1002/bdrb.20012/full DOI: 10.1002/bdrb.20012; © 2004 Wiley-Liss, Inc. Concern Over Decreased Training In Embryology And Developmental/Reproductive Toxicology Noted diminished emphasis on training in classic biology Call for pre- and post doctoral training in systems biology and whole animal research Call for collaboration between industry, government and academics to provide students with training opportunity

4. Innovative science to improve public health4 Regulatory Science: Challenges and Opportunities What is the role of Toxicology in protecting Public Health? What are the issues with product development? How is Regulatory Science changing assessment of safety and enhancing innovation? What are the educational requirements to support regulatory science? Global issues and education

5. Innovative science to improve public health5 Agarwal & Searls Nat Rev Drug Discov. 2009;8:865-878. Decreased Translation of Basic Science Investment to Products

6. What is the problem? Main reasons for drug attrition and withdrawal: Safety and efficacy related reasons of drug attrition, ADRs, drug withdrawal. What is the evidence? What is the prevalence? When does this occur? Adapted from Redfern WS et al. The Toxicologist 2010; 114 (S-1), 1081.

7. Source: DIA Daily September / October 2010 What is the problem? Impact of functional adverse effects on drug development – over a 2 months period! From Tim Hammond, PhD, AstraZeneca

8. Innovative science to improve public health8 Regulatory Science Defined as the science of developing new tools, standards and approaches to assess the safety, efficacy, quality and performance of medical products and foods

9. Innovative science to improve public health9 Regulatory Science Leadership to strengthen and support science and promote innovation at FDA Scientific excellence and professional development Recruitment and retention of outstanding scientists Mission critical applied research Collaboration and partnerships

10. Innovative science to improve public health10 NCTR - A Unique FDA Resource Established in January 1971 by Executive Order as a non-regulatory national resource owned and managed within DHHS by FDA to conduct integrated, toxicological research and foster interagency, academic, and industrial collaboration in support of risk-assessment needs related to public health.

11. Innovative science to improve public health11 NCTR Mission Conduct peer-reviewed and comprehensive toxicological research to assess safety of FDA-regulated products Develop new scientific approaches and methods to speed product development Provide multidisciplinary training in regulatory science Foster national and international collaborations with scientists from government, academia, and industry

12. Innovative science to improve public health12 Regulatory Science NCTR has engaged several next-generation regulatory science initiatives to increase the predictive capacity and cost-effectiveness of regulatory safety studies: Comprehensive whole animal studies including exposure and multiple organ system assessments, Development and evaluation of reliable technologies to improve or replace animal models, Evaluation of established, noninvasive-diagnostic clinical technologies for use in preclinical studies for hazard identification, Improving the efficiency of regulatory evaluation processes through use of bioinformatic technologies, and Exploration of new computational toxicology methods (toxicology in silico) for accurate hazard identification and development of new product leads.

13. Innovative science to improve public health13 Globalization: Impact on training needs Half of all medical devices used in this country are imported 40% of finished drugs and 80% of APIs (Active Pharmaceutical Ingredients) are imported from more than a 150 countries. Imports of APIs grew from $2.8 billion in 2000 to nearly $4.6 billion in 2007. Imports of pharmaceutical products have grown at about 13% per year for the past seven years. China has tripled its annual R&D investment over the past 15 years and will likely have the largest R&D workforce in the world by 2015. The market for contract manufacturing (outsourcing) grew to an estimated $46 billion in 2010, more than double the size of the market nine years ago. Source: Deb Autor, FDA WebView, 09/19/2011

14. Innovative science to improve public health14 NCTR Training Programs to Support Regulatory Science Postdoctoral Training Programs –Commissioner’s FDA Fellows Program –ORISE Fellows Program –FDA Staff Fellows Program NCTR STEP Program (Science Training and Exchange Professional Development Program) Visiting Scientist Program Summer Sabbatical Program Summer Undergraduate Program NCTR International Capacity Building Laboratory Training for Undergraduate International Students –University-funded studies for students from African Countries –NCTR provides an opportunity for these students to conduct hypothesis- driven research On-Site Training for Foreign Regulatory Scientists: International Science Exchange Program (ISEP) –Provides funding for Foreign Scientists to visit NCTR to learn and conduct state-of-the-art biomedical research Global Training for Global Health and Safety

15. Innovative science to improve public health15 Where Are the Jobs? By David Brooks, New York Times, Oct. 6, 2011 Innovation slowdown “The Great Stagnation” “Innovation Starvation” “False Peak” “The significant problems we face cannot be solved at the same level of thinking we were at when we created them” Einstein