FDA

1
FDAs Critical Path InitiativePresentation to
FDA Science Board

• Janet Woodcock, M.D.
• Acting Deputy Commissioner
• for Operations

2
The Challenge

• Multiple serious diseases afflict our population
  and require better treatments autism, addictive
  disorders, Alzheimers 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

3
Prevention

• Prevention of diseases is an equally important
  goal
• Primary prevention certain cancers, AIDS, heart
  disease
• Early detection and intervention diabetes,
  cancers, obesity, Alzheimers disease

4
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

5
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

6
Ten Year Investment Trends

• Doubling over 5 years of NIH funding
• Pharmaceutical RD investment increasing at the
  same rate
• Major investments in biotechnology

7
(No Transcript)
8
A Matching Acceleration of Product Development
Has Been Expected
9
(No Transcript)
10
10-Year Trends in Device Premarket Applications
11
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

12
Whats 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 centurys advances

13
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

14
The Critical Path for Medical Product Development
15
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?

16
Working in Three Dimensions on the Critical Path
17
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.

18
Research Support for Product Development
19
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

20
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

21
What is a Predictive Safety Tool?

• Genomic expression system evaluating compound
  impact on liver cell function

22
Predictive Safety Tool?

• Reference standards and Test System for Gene
  Therapy Vector Potency

23
Predictive Efficacy Tool?

• Computer model for outcomes of incremental device
  modifications

24
Predictive Efficacy Tool?

• Quantitative biomarker that can be used both in
  Animal early Human Trials to indicate effect
  and guide Dose Regimen Decisions

25
Confirmatory Safety Tool

• Standardized Acceptable Trial Design to
  Definitively Assess a Safety risk
  (hepatotoxicity, QTc prolongation, etc.)

26
Confirmatory Safety Tool

• Available clinical trial network to rapidly and
  efficiently answer specific safety queries using
  a large simple trial format

27
Confirmatory Efficacy Tool

• FDA guidance document on use of a specific
  technology as an accepted surrogate marker within
  a specific clinical trial framework

28
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

29
Confirmatory Efficacy Tool

• Standardized case report forms
• Data collection and data format standards for
  clinical trials

30
FDAs 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.

31
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.

32
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

33
(No Transcript)
34
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?

35
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)

36
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

37
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.

38
Initial Steps

• Innovation/Stagnation Report, announced by
  Commissioner McClellan and Deputy Commissioner
  Dr. Crawford on March 16
• Todays Presentation to FDA Science Board
• Extensive discussions with stakeholders patient
  groups, industry, academia, government scientists

39
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

40
Conclusions

• FDAs 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

41
Conclusions

• FDA is continuing this dialog with a wide range
  of stakeholdersto reach agreement on the problem
  scope and definition
• We are also working on defining specific
  opportunities for overcoming these hurdlesthe
  opportunities list should provide examples of
  concrete, deliverable steps that could be
  accomplished

42
(No Transcript)