The SNM Centralized IND

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The SNM Centralized IND Clinical Trials
Network Enabling Implementation
Investigational Approved PET Imaging in Large
Multicenter Clinical Trials
George Q. Mills, MD, MBA September 9, 2009
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Therapeutic Drug Developers Comments

• PET imaging desired for Multicenter Therapeutic
  Trials
• butnumerous deficiencies
• Lack of
• Limited supply of investigational PET agents
• Standardized PET imaging acquisition protocols
• Harmonized PET imaging report output
• Qualified experienced imaging centers
  large (200 sites) multicenter clinical trials
• Industry could not effectively implement PET
  imaging in multicenter therapeutic clinical
  trials

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• SNM Assessment Efforts
• Therapeutic Developers
• Participating PET Imaging Centers
• FDA Pre-IND Process
• Results - Design solutions
• Centralized Investigational PET Imaging IND
• to Enable Therapeutic Developers Multicenter
  Therapeutic Clinical Trials
• Distributed Manufacturing
• Investigational PET imaging Agents

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• SNM Centralized IND
• Demonstration Project - Future development INDs
• F-18 FLT first choice available broad
  potential
• Regulatory
• CMC
• Imaging Standardization

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Clinical Trials Sites Network - Registry

• Investigator international site registry
• Forming Pick List - therapeutic developers
  
• Enrollment qualifications
• Location
• Geography
• Patient population access
• Equipment hardware software
• Personnel
• Access to investigational imaging agents
• Participation phantom program clinical
  trials

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• World wide interest - imagers manufacturers

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• Regulatory multicenter IND manufacturing
• Multicenter INDs - Single source
  investigational product
• CMC Investigational F-18 FLT sources
• Multiple production sites multiple methods
• Distributed manufacturing multiple
  end-product specs
• SNM Centralized IND F-18 FLT
  FDA CMC
  review of all sources acceptable ranges for
  end-product specifications

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Review through submission to IND file directly or
through Drug Master File (DMF) a submission
tool of efficiency for manufacturers

• Information concerning the Chemistry,
  Manufacturing and Controls (CMC) of a drug
  product or a component of a drug product to
  permit the FDA to review this information upon
  request in support of a submission

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Types of DMFs

• Five Types
• I Plant information
• II Drug substance, drug product, intermediates
  and material used in their manufacture
• III Packaging
• IV Excipients
• V Other clinical, tox

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Who must file a DMF?

• CMC information must be available for IND review
  
• CMC must be in an IND submission or in a DMF
• There is no legal or regulatory requirement to
  file a DMF (submission by Holder,ref by
  applicant or authorized party)
• Applicant submits a Letter of Authorization (LOA)
  from the Holder with their IND submission

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Letter of Authorization (LOA) Enabling review
of DMF

• The DMF will be reviewed ONLY when it is
  referenced in a submission or another DMF
  (initially receives an administrative review)
• The Holder MUST submit an LOA (2 copies) to the
  DMF and send a copy to the Applicant
• The Applicant submits LOA in their submission
  the mechanism to trigger review of the DMF by FDA
• In Europe, the LOA is called a Letter of Access

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DMF Advantages

• Maintains proprietary information/trade secrets
  (e.g. manufacturing procedure) belonging to the
  Holder, from being revealed to the Applicant
  while permitting review by FDA
• Permit review of information referenced by a
  number of applicants will be used to support
  submissions from many sponsors
• Time efficient cost effective

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• Imaging standardization
• Pre-clinical Imaging Standardization - Imaging
  Phantom Program
• Oncology CNS - Cardiovascular
• Clinical imaging - Standardized protocol
• International imaging clinical site registry (217
  sites) documentation of equipment demonstrated
  capabilities
• Clinical Trials Educational programs
  Multicenter Trials

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SNM Imaging Phantom Program

• F-18 fillable phantoms
• Qualitative Quantitative (SUV)
• VA system
• Torso Oncology ?
• Head CNS
• Cardiac

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Selection - F-18 FLT

• Investigational PET imaging biomarker
• Literature reports of potential for
  demonstrating tumor proliferation
• Potential as a surrogate marker for evaluating
  investigational oncology therapeutics as well as
  existing therapeutics
• Broadly applicable to lung, breast, esophageal,
  GI, brain, lymphoma

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• Topics
• Overview Key Elements Centralized IND
• Clinical Trials Network
• Resources
• Sites Registry
• Phantom Program
• Education Training Program
• F-18 FLT selection

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Thank you
George Mills, MD, MBA Vice President, Medical
Regulatory Relations Perceptive
Informatics george.mills_at_perceptive.com
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