Investigational New Drug Applications FDA Trends and Clinical Issues

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Investigational New Drug Applications FDA
Trends and Clinical Issues
Longmont Life Science ThursdayRadisson
Conference Center May 12, 2005 Jeanne M.
Novak, Ph.D. CBR International Corp. Boulder, CO
80301 ltwww.cbrintl.comgt
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Current FDA Changes and Issues

• Reorganization of Centers and addition of
  new offices
• Congressional pressure to focus on
  facilitating pipeline of new drugs
• Agency awareness of need for expertise
• World issues and harmonization of standards
• Launch of numerous new initiatives

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Current FDA Changes and Issues Reorganization of
Centers

• Development of Office of Combination
  Products Dec 24, 2002
• Transfer of biotechnology products from
  CBER to CDER June 30, 2003
• Office Drug Evaluation VI (within Office of New
  Drugs)
• Office of Biotechnology Products (within
  Office of Pharmaceutical Science)

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Current FDA Changes and Issues Reorganization of
Centers

• Establishment of
• Office of Oncology Drug Products
• July 16, 2004
• Nation-wide search for a Director

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Clinical Development - Overview
BLA/NDA/PMA
IND
Drug Discovery
Phase 1
Phase 2
Phase 3
Development
Preclinical
GLP
GMP
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Recent FDA Initiatives

• FDAMA - 1997
• Systems-Based Inspections Feb 1, 2002
• 21 CFR Part 11 Guidance Nov 12, 2002
• Pharmaceutical cGMPs for the 21st Century
• A Risk-Based Approach Aug 21, 2002
• Process Analytical Technology Aug 2003
• Critical Path to New Medical Products Mar 04

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Recent World Initiatives

• Clinical Trials Directive
• Effective May 1, 2004 throughout the EU
• Requires that all material to be used in
  clinical trials be reviewed and certified by a
  Qualified Person (QP) to ensure manufacture
  according to cGMP.

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Current FDA Changes and Issues Focus on Pipeline
of New Products

• Congress has asked the Agency to
  evaluate current regulation of generic drugs
• Congress has taken a special interest in the
  issue of biogenerics and how to
  regulate follow-on biologics

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Critical Path to New Medical Products

• March 16, FDA released a report addressing the
  recent slowdown in innovative medical therapies
  submitted to the FDA for approval
• "Innovation/Stagnation Challenge and
  Opportunity on the Critical Path to New
  Medical Products."
• Urgent need to modernize the medical product
  development process -- the Critical Path -- to
  make product development more predictable and
  less costly.

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Critical Path to New Medical Products
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Critical Path to New Medical Products
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Critical Path to New Medical Products
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Critical Path to New Medical Products
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Critical Path to New Medical Products
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Critical Path to New Medical Products
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Critical Path to New Medical Products Impact on
Industry

• FDA will ask for industry participation in
  identifying areas of medical need
• FDA will expect industry to increase quality
  standards and efficiency to assist in filling
  the pipeline at an increased rate
• Some evidence of increasing standards seen in
  recent inspections

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Clinical Programs for New INDs

• 1. Choose Clinical Indication(s)
• 2. Draft Overall Clinical Plan(s) EARLY
• Develop Nonclinical Studies to Support
  Clinical Studies
• Consider Timelines for Parallel Program
  Efforts
• Plan for Both Success and Failure

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Clinical Programs for New INDs

• Choose Clinical Indication(s)
• - As soon as molecular activity known,
  prioritize potential target indications.
• - Prioritization should match company goals
  consider time to clinic, time to approval, cost,
  enrollment issues, target population.

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Clinical Programs for New INDs

• Draft Overall Clinical Plan(s) EARLY
• - Include the potential target indications
  and timelines
• - Include list of studies for each
  indication
• - Prepare CTO for the first two studies
  planned
• - Consider all countries in which studies
  will be run
• - Include guidelines for continuation (or
  discontinuation) of program
• - Prepare a sketch of nonclinical studies
  required

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Clinical Programs for New INDs
3. Develop Nonclinical Studies to Support
Clinical Studies - DO NOT do every
experiment! Perform Proof of Concept - Plan
for limited nonclinical PK, MIC, toxicology,
ADME programs to support initial clinical -
Get FDA feedback to insure these studies are
adequate
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Clinical Programs for New INDs

• Consider Timelines for Parallel Program Efforts
• - CMC Plan for the amount of product required
  for nonclinical and initial clinical
• - QC Develop necessary release and
  stability assays
• - QA Develop QA oversight appropriate for
  the clinical phase of development

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Clinical Programs for New INDs

• Plan for Both Success and Failure
• - Structure the early clinical trials to
  support alternate routes of administration and
  alternate indications
• - Plan for accelerated development by
  considering limitations in product
  availability site availability etc.

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Points for Clinical Study Conduct

• Establish RIGOROUS site selection criteria
• Consider IRB delays in timeline planning
• Establish routine oversight and reporting
  mechanisms (AEs SAEs enrollment stats)
• Develop clinical study documents that not only
  support the trial but support next study
• Beta test CRF format and content
• Beta test data collection methods clinical
  tests and outcome measures

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Clinical Programs for New INDs

• 1. Choose Clinical Indication(s)
• 2. Draft Overall Clinical Plan(s) EARLY
• Develop Nonclinical Studies to Support
  Clinical Studies
• Consider Timelines for Parallel Program
  Efforts
• Plan for Both Success and Failure