Center for Biologics Evaluation and Research,

FDA

Kathryn M. Carbone, M.D.Associate Director for Research

Vision for CBER

INNOVATIVE TECHNOLOGY ADVANCING PUBLIC HEALTH

Protect and improve public and individual health in the US and, where feasible, globally

Facilitate the development, approval and access to safe and effective products and promising new technologies

Strengthen CBER as a preeminentregulatory organization for biologics

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

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

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…= Critical Path Science…

FDA Critical Path Research Initiativewww.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

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

Multitasking at the FDA: Multitasking at the FDA: Research Supports Regulatory Research Supports Regulatory MissionMission

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

FDA Critical Path ResearchInitiative: 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

Applicability of Research Applicability of Research Programs to Biologics Programs to Biologics

DevelopmentDevelopment

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

Major Goals for CBER Research Program

Creating efficient, high quality regulatory pathways where there are none (particularly important for OCTGT products)

Applying 21st 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%

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

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

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.

Research Leadership Council

Composed of Center Scientific LeadershipTasked to innovate processes for:

Ensuring stakeholder input into the research program

Prioritization and goal settingDeveloping 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

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

Thank you To the Advisory Committee for

their time, expertise and suggestions for continuing improvement of CBER research programs