fda’s “critical path” initiative presentation to fda science board janet woodcock, m.d. acting...
TRANSCRIPT
FDA’s “Critical Path” InitiativePresentation to
FDA Science Board
Janet Woodcock, M.D.
Acting Deputy Commissioner
for Operations
The Challenge
Multiple serious diseases afflict our population and require better treatments: autism, addictive disorders, Alzheimer’s disease, AIDS, bipolar disorders, cancer, cystic fibrosis, heart diseases, diabetes, morbid obesity, multiple sclerosis, muscular dystrophy, rheumatoid arthritis, osteoarthritis, systemic lupus,
schizophrenia, stroke, and many more
Prevention
Prevention of diseases is an equally important goal
Primary prevention: certain cancers, AIDS, heart disease
Early detection and intervention: diabetes, cancers, obesity, Alzheimer’s disease
The Societal Challenge
Urgency of need – timely development Aging of population Mounting burden of illness Benefits of prevention vs. secondary
intervention
High degree of certainty related to performance Providing access & affordability
Optimism Based onNew Biomedical Discoveries
Sequencing of the human genome Genomic and proteomic technologies Systems biology Advances in medical imaging Nanotechnology advances Tissue engineering Drug discovery: combinatorial chemistry and
automated microscale screening
Ten Year Investment Trends
Doubling over 5 years of NIH funding
Pharmaceutical R&D investment increasing at the same rate
Major investments in biotechnology
A Matching Acceleration of Product Development Has Been Expected
10-Year Trends in Device Premarket Applications
In Addition, Medical Product Development Costs are Escalating Rapidly
Costs of bringing a successful drug to market estimated between $0.8 – 1.7B
Higher failure rate of candidates in clinical development
What’s the Diagnosis?
Investment & progress in basic biomedical science has for surpassed investment and progress in the medical product development process
The development process – the critical path to patients – becoming a serious bottleneck to delivery of new products
We are using the evaluation tools and infrastructure of the last century to develop this century’s advances
Rx
Utilize new scientific knowledge to improve the medical product development process
Develop robust applied research program into critical path scientific areas, to lead to generalized knowledge
Strengthen academic bases for critical path disciplines
Intensify FDA involvement in critical path research and standards development
The Critical Path for Medical Product Development
Three Dimensions of the Critical Path
Assessment of Safety – how to predict if a potential product will be harmful?
Proof of Efficacy -- how to determine if a potential product will have medical benefit?
Industrialization – how to manufacture a product at commercial scale with consistently high quality?
Working in Three Dimensions on the Critical Path
Critical Path Science Base
The science necessary to evaluate and predict safety and efficacy, and to enable manufacture is different from the science that generates the new idea for a drug, biologic, or device.
In general, NIH and academia do not perform research in this area
CP research is complementary to basic and translational research, but results in the creation of new tools for the product development process.
Research Support for Product Development
Evaluative Tools
In early stages, developers use scientific tools to select candidates that are predicted to have a high probability of safety and effectiveness
Laboratory tests, computer models and animal studies are used to make these predictions
Evaluative tools
In the later stages of development, human testing is used to confirm earlier predictions
Early human safety and efficacy testing is not extensive enough for confirmation, but preliminary estimates are made using biomarkers
What is a Predictive Safety Tool?
Genomic expression system evaluating compound impact on liver cell function
Predictive Safety Tool?
Reference standards and Test System for Gene Therapy Vector Potency
Predictive Efficacy Tool?
Computer model for outcomes of incremental device modifications
Predictive Efficacy Tool?
Quantitative biomarker that can be used both in Animal & early Human Trials to indicate effect and guide Dose & Regimen Decisions
Confirmatory Safety Tool
Standardized Acceptable Trial Design to Definitively Assess a Safety risk (hepatotoxicity, QTc prolongation, etc.)
Confirmatory Safety Tool
Available clinical trial network to rapidly and efficiently answer specific safety queries using a large simple trial format
Confirmatory Efficacy Tool
FDA guidance document on use of a specific technology as an accepted surrogate marker within a specific clinical trial framework
Confirmatory Efficacy Tool
Consortium – based trial frameworks to allow manufacturers to pool resources to answer specific efficacy question pertaining to a class of devices or drugs
Confirmatory Efficacy Tool
Standardized case report forms
Data collection and data format standards for clinical trials
FDA’s Critical Path Initiative
A serious attempt to bring attention and focus to the need for targeted scientific efforts to modernize the techniques and methods used to evaluate the safety, efficacy and quality of medical products as they move from product selection and design to mass manufacture.
FDA Initiative Goals
Get more innovative products to patients.
Achieve robust product development pathways that are efficient and predictable.
Develop new toolkits that bring scientific advances into the product development process.
Perform research on tools that remove specific identified obstacles in product development.
Why FDA? Unique Role of the Agency vis-à-vis the Critical Path
FDA scientists are involved in review during product development--they see the successes, failures, and missed opportunities
FDA guidance documents are known to foster innovation and improve chances of success.
Convening and coordinating role for new biomarker and clinical method development
Biomarker Questions or Surrogate Marker
How to accumulate existing “data” into “Knowledge”, (or, even better) into generalizable “principles”?
Who is responsible for doing this? Cross-series and study analysis Evaluation of the primary data Identification of gaps Conduct of research to close gaps
How would the “Knowledge” be then incorporated into an evaluation protocol or tool?
Example: Biomarker or Surrogate Marker Development
Marker developed by academic or industrial scientists as part of research project
After publication of method, used in more laboratories
Begins to be adopted by academic clinicians (home brew)
Example: Biomarker or Surrogate Marker
Widespread clinical use: series describing correlations with outcomes (not in trials) reported
Use in trials – summary data reported
Calls for use as biomarker or surrogate markers for evaluation of new technologies
Access to New Medical Technology: Part of FDA Mission
“....The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.”
Initial Steps
“Innovation/Stagnation” Report, announced by Commissioner McClellan and Deputy Commissioner Dr. Crawford on March 16
Today’s Presentation to FDA Science Board
Extensive discussions with stakeholders: patient groups, industry, academia, government scientists
The Path Forward
Identify/prioritize the most severe development problems and areas that provide the greatest opportunity -- solicit input from wide variety of sources.
Construct a national Critical Path Opportunities List and publicize it.
Re-focus internal activities and research.
Seek community concurs on additional steps
Conclusions
FDA’s Critical Path Report raises serious concerns about the ability of the current development process to get innovations to patients rapidly and efficiently
Preliminary discussions with key experts in industry and academia are validating this analysis of the development problem
Conclusions
FDA is continuing this dialog with a wide range of stakeholders—to reach agreement on the problem scope and definition
We are also working on defining specific opportunities for overcoming these hurdles—the opportunities list should provide examples of concrete, deliverable steps that could be accomplished