1. Center for Biologics Evaluation and Research, FDA Kathryn M. Carbone, M.D. Associate Director for Research

5. Sponsor Perspective* Drug discovery and development can run as high as $1.9 billion. “Lowering that number is the current Holy Grail of the industry.” How can the CBER help make biological product development more efficient and support more safe and effective products reaching the public? *J. Mervis, Science, Vol 309, July 29, 2005 I

6. Sponsor Perspective* “…’it’s not the number of targets validated, or the number of chemicals selected. It’s proof of concept in patients [Yamada, GSK]…[a drug] is not a success until we’ve treated a patient with it.’ [Fishman, Novartis]” “…’it’s still a crapshoot…after 30 years in this business, I haven’t met anybody who could [pick winners]’ [Ruffolo, Wyeth] But investigational products aren’t true winners until documentation of safety, efficacy and manufacturing adequate…too many drugs fail too late in the development process….costly and inefficient

7. Sponsor Perspective* “…’you can’t manage [product development] science. But it needs to be. [Ruffolo, Wyeth]” “…Knowing how to maintain a healthy [product development] pipeline…’is more or less a matter of intuition.’ [Scheller, Genentech]” Consider the value to human health of research carefully managed to target the development of the scientific tools and knowledge needed for assessment of biological product safety, efficacy and quality manufacture = Critical Path Science…

8. FDA Critical Path Research Initiative www.fda.gov/oc/initiatives/criticalpath.htm Identify, focus upon and manage research to resolve regulatory & scientific challenges to improve product development process and product availability Needed to inform policy and guidance

11. Why CBER? Unique Role vis-à-vis the Science of Biologics Product Evaluation Innovators create scientific tools that are typically applicable to their specific products and not shared with others in industry CBER research-regulators are expert in biological product development AND standard scientific disciplines..expertise not often seen in standard biomedical discovery research arenas CBER research-regulators see the successes, failures, and missed opportunities across whole classes of exciting and innovative products and want to help CBER Guidance documents that are based on science can provide a clearer, more predictable regulatory path CBER plays a convening and coordinating role for scientific needs across sponsors

12. Multitasking at the FDA: Research Supports Regulatory Mission CBER researchers fully integrated into the regulatory process (~50% average time) “Researcher-Regulator” model (unique to CBER) Review INDs and BLAs Development of Policy and Guidance Documents Meeting with Sponsors and Advisory Committees Participation in Pre-license and Biennial Inspections Evaluation of Adverse Drug Reactions and Risk Assessment Performing research relevant to product evaluation of safety, efficacy, manufacturing: Developing/evaluating scientific tools & knowledge

13. FDA Critical Path Research Initiative: CBER Leadership CBER scientists can help get better products to patients, faster through: CBER intramural research programs Working collaboratively with government, academic and industry scientists Critical Path Extramural grant programs Guidances, standards, publications, stakeholder outreach, and other creative approaches to support product development, safety/efficacy assessment and review, consistent manufacturing

14. Applicability of Research Programs to Biologics Development It’s not “basic vs. applied science”, it’s how CBER research activity is applicable to supporting biologics product approvals Hundreds of Biologics Licensing Applications and Investigational New Drug Applications directly supported by research programs (OCTGT will provide examples) Research Programs have special relevance to evaluation of Biodefense Biological and Pandemic Influenza medical products

15. Major Goals for CBER Research Program Creating efficient, high quality regulatory pathways where there are none (particularly important for OCTGT products) Applying 21 st Century science to improve efficiency and accuracy of established regulatory pathways Focus on Outcomes: Identifying and resolving specific, high priority scientific challenges in product evaluation CBER Research Program Product Safety: ~40 % Product Quality ~25 % Product Efficacy ~ 25% Other ~ 10%

16. CBER Research: Managing Regulatory Challenges Into Biological Product Successes Formal process for Internal and External Expert evaluation of proposed research plans: Priority Scientific quality Internal & External evaluation of past research achievements Internal Management reviews: Yearly cycle using Annual Research Program Reporting External Site Visits: Laboratory/Res-Reg/Office Site Visits Outcomes include: Publications, Regulatory Policy/Guidances, Invited talks, Research QA/QC

17. Managing to CBER Research Goals Guiding Research Principles for Offices and the Centers CBER Research Leadership Council to coordinate development and implementation of the Principles Priorities for accomplishments in the next 12 months identified

18. Guiding Principles The CBER research program will be highly collaborative and include laboratory, epidemiological, statistical, and clinical sciences. Its scope will encompass the scientific basis of pre-clinical and clinical studies, manufacturing, regulatory submissions, inspections, postmarketing surveillance and Guidances. The research will be of high quality, efficient, and directed and managed to provide outcomes that address scientific and regulatory challenges in product development, safety, efficacy and quality.

19. Research Leadership Council Composed of Center Scientific Leadership Tasked to innovate processes for: Ensuring stakeholder input into the research program Prioritization and goal setting Developing tools for regulatory workload assessment and evaluation of research applicability Develop Cross-cutting Research Priorities and Communication strategies, and Center-wide scientific matrix programs where appropriate

20. Examples of CBER Critical Path Investment Opportunities in Cell-Tissue-Gene Therapy Better characterization of cell therapies & links to standardized clinical/lab outcomes Appropriate toxicology approaches for complex biological products New assays, standards, biomarkers, surrogates for complex biologics safety, efficacy and quality Multipathogen and rapid detection methodologies Methods & validation of pathogen inactivation for cells, tissues and other products Improving longevity/storage of cells and tissues Enhanced clinical trial design/analysis

21. Thank you To the Advisory Committee for their time, expertise and suggestions for continuing improvement of CBER research programs