FDAs Critical Path to Medical Product Development Through Collaboration

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FDAs Critical Path to Medical Product
Development Through Collaboration

• Wendy R. Sanhai, Ph.D.
• Senior Scientific Advisor
• Office of the Commissioner, FDA
• NIH/CTSA June 6, 2007

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Outline

• FDAs Mission
• What is the Critical Path Initiative (CPI)
• Why should CPI be important to you
• Mechanisms of collaboration with FDA
• Case studies of collaborations with FDA under CPI

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FDAs Mission Statement

• The FDA is responsible for protecting the
  public health by assuring the safety, efficacy,
  and security of human and veterinary drugs,
  biological products, medical devices, our
  nations food supply, cosmetics, and products
  that emit radiation.
• 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.

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The Genesis(March 2004)
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Problem High Risk Cost of Product Development
Fewer new Medical Products
Trends in RD Spending vs. New Drug Biologic
Applications

• Despite advances in basic science/
• research, success rate of product
• development has NOT improved
• Lower chance of success
• New compounds entering Phase I
• development today have 8 chance
• of reaching market, vs. 14 chance
• 15 years ago
• Phase III failure rate now reported
• to be 50 vs. 20 in Phase III,
• 10 years ago

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Stagnation
PrototypeDesign orDiscovery
FDA Filing/ Approval Launch
BasicResearch
PreclinicalDevelopment
Clinical Development
MarketApplication
Approval
CRITICAL PATH
Why is the CPI important to you?
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Act II(March 2006)
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Priorities Under CPI Ripe for Collaboration

• Better Evaluation Tools (33) Biomarkers,
  Molecular Assays (IVD, prognostic, assessment)
• Streamlining Clinical Trials (12)
• Harnessing Bioinformatics (8)
• Moving Manufacturing into 21st Century (13)
• Developing Products to Address Urgent Public
  Health Needs (5)
• Specific At-Risk Populations Pediatrics (5)

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Basic Steps in Developing PPPs with FDA (not
comprehensive! not consecutive!)
Start with the Public Health Need,
SCIENCE! Identify Priorities for multiple
stakeholders (done 76!)
Identify gaps/avoid duplication e.g.
biomarkers Hold expert workshop, Identify
partners etc.

• Leverage resources/expertise
• Identify partners define roles/responsibilities
• Co-develop proposals, budgets, timelines etc.
• Implement joint POC projects
• Share data in public domain as quickly as
  appropriate

Some Benefits PRIVATE PARTNERS Know-how,
Predictive Tools Input in Project
Selection ACADEMIA Best Practices, Publications,
Patents, Additional Grants FDA Guidances,
Standard-setting, Evaluative Tools, Clinical
Data Patients faster, safer and cheaper medical
products!!!!
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LEVERAGING MECHANISMS (some tools)

• http//www.fda.gov/oc/leveraging/handbook.html
• CDA Confidentiality Disclosure Agreement
• MOU Memorandum of Understanding
• CRADA Coorporative Research and Development
  Agreement
• CO-SPONSORSHIP AGREEMENT
• MTA Material Transfer Agreement
• CONTRACT
• GRANT
• IAG Interagency Agreement
• COOPERATIVE AGREEMENT
• LICENSE/S (for FDA inventions or if subject
  inventions result from collaboration/s)
• GIFT FUND AUTHORITY (usually never an option)

KEY THESE ARE MEANS TO AN END! NO MORE TIME
THAN NECESSARY
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Categories of PPPs under CPI

• FDA and Academic Partnerships
• FDA and Private Industry Partnerships
• FDA and other entities (other government,
  non-profit etc.)
• FDA and NIH Partnerships

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Opportunities on the Path
Predictive Safety Testing Consortium
OBQI, Exp IND, Nano
CSRC, Warfarin project
FDG/PET in NHL
Genetic basis of adverse events
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COLLABORATION MODEL
NIH
CMS
FDA
INDUSTRY
Mortara/Academic
ACADEMIA
PT. GROUPS
DCRI
PUBLIC-PRIVATE CONSORTIUM
PROEFSSIONAL ORGANIZATIONS
PPP STEERING COMMITTEES WORKING GROUPS
NON-PROFIT STATE, OTHER

• IDENTIFY MUTUAL PRORITIES
• POOL RESOURCES/EXPERTISE
• DEFINE ROLES/RESPONSIBILITIES
• GAP ANALYSES (WHATS KNOWN?)
• CO-DEVELOP PROPOSALS
• BUDGETS
• TIMELINES
• RFPs

IMPLEMENT PROJETCS
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Drugs Pulled from the Market Due to Cardiac
Safety Issues

• Rofecoxib Oct 2004
• Cisapride Jul 2000
• Grepafloxacin Nov 1999
• Astemizole Jun 1999
• Sertindole Dec 1998
• Terfenadine Feb 1998

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Critical Path to Accelerate Therapies C-PATH
Institute

• Mission
• To perform services and conduct educational
  research programs in support of the FDAs CPI
• To serve as neutral ground in establishing
  affiliations with academia, industry and others
  to accelerate the development of medical products
• To work with stakeholders to develop and
  implement applied research and educational
  programs aligned with the CPI

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C-Path/Utah/FDACollaborative Cardiovascular
Drug Safety and Biomarker Research Program

• C-Path has established a collaboration with
  scientists at the University of Utah,
  Intermountain Healthcare and LDS Hospital
• To evaluate tools that will accelerate the safe
  development of new drugs and diagnostics for
  cardiovascular disease
• FDA, per Congressional mandate, to execute a
  co-operative agreement with C-Path/Utah first
  project identified under this program

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WarfarinImpact of Genetics

• Gene Variants (35 of patients) retrospective
• Lower final dose
• Longer time to stabilize dose
• Greater risk of bleeding
• Can a prospective study demonstrate
• 1. Greater efficacy Strokes?
• 2. Less toxicity Bleeding?

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Results

• The results of these analyses will be presented
  to the FDA in regular meetings/reports
• Monograph or white paper written jointly by
  C-Path and University of Utah/Intermountain
  Health Care
• This information will become incorporated into
  drug labeling, Guidance documents (FDA)
• Widely disseminated to inform medical
  practice/public

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Predictive Safety Testing Consortium
Toxicogenomics

• Most major pharmaceutical companies have
  developed animal genomic markers to evaluate
  organ toxicity
• Not generally available since proprietary
• Predictive Safety Testing Consortium with
  C-Path Institute
• Companies will contribute assays and validate
  each others assays in animal studies
• FDA participation essential

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Predictive Safety Testing Consortium Payoff?

• Identify genomic tests that are better or earlier
  predictors of organ toxicity (liver, kidney,
  heart, muscle, etc.)
• Help screen compounds before human testing a
  proven approach
• Develop better international testing algorithms
• Identify responders!!
• Improve drug safety!!

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Overview of OBQI Context and Framework for
Activities
DHHS Public Domain
NCIs 2015 Goal, FDAs Critical Path Initiative
Interagency Oncology Task Force (IOTF)
Oncology Biomarker Qualification Initiative (OBQI)
Identification of Mutual Priorities Under the
FDAs Critical Path, NCIs 2015 Goal and CMS
Mission
Co-Development of Concepts Papers and
Justification for Scientific Projects
Joint NCI/FDA/CMS Intramural
Collaborations
Public Private Partnerships (multiple partner
framework)
Public/Private Domain
MULTIPLE DEMONSTRATION/POC PROJECTS (via multiple
mechanisms)
Cancer Imaging
Mol Assays/ Targeted Therapies
Data mining
Clinical Trials
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Molecular Assays/Targeted TherapiesCollaboration

• Goal Develop tests to identify tumors with a
  high
• probability of response to a give
  drug
• Completed
• Federal Alliance (FDA/NCI/CMSMOU)
• ID low-hanging fruitlist of potential targets
• Develop concept paper and seek feedback (first
  step done)
• ID neutral ground and capable third party
  (C-Path)
• Needed
• ID partners (private, academic)
• Develop POC/demonstration project/s and framework
  for collaboration
• Execute necessary agreements
• Implement projects, monitor, reportsuccesses
  (failures)

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FDA Guidance Development 101

• The Agencys interpretation or policy on a
  regulatory issue
• Represents the Agencys current thinking
• Not binding
• Generally prepared by FDA staff for applicants,
  sponsors and public
• Generally includes information on
• Design
• Production
• Labeling
• Promotion and Inspection and Enforcement Policies
• Manufacturing, and Processing
• Testing of Regulated Products

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Some Elements of Business Model

• Pooling IP, resources, expertise
• Share Data Proprietary, Pre-clinical, clinical,
  pre-competitive?
• Models Sematech, PQRI, SNP Consortium, others
• Contracts/Agreements with timelines,
  deliverables, specific terms and conditions?
  (Licenses non-exclusive commercial,
  research-use?)
• Implement POC project/s
• Develop Research/predictive tools, know-how
• Likely employ multiple mechanisms

Data/Deliverables FDA Guidances
NIH/CMS Decisions
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FDA Has a Unique Role Scientists Involved in
Review Throughout Development--see successes,
failures, missed opportunities
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Thank You!

• Wendy.Sanhai_at_oc.fda.gov
• Phone [phone]