Imaging Community Critical Need 1: Standardized and Harmonized Multisite Imaging

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Imaging Community Critical Need 1
Standardized and Harmonized Multisite Imaging
George Q. Mills, MD, MBA Vice President, Medical
Regulatory Relations Perceptive Informatics
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Enabling Investigational Approved PET Imaging
in Large Multicenter Clinical Trials

• Discussion today will include comments
• and references to
• F-18 FLT an Investigational,
• non-FDA approved, PET Imaging Agent

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• ISSUES
• Lack of qualified experienced imaging centers
  for large (200 sites) multi-center Phase 3
  clinical trials
• Limited supply of known/desired investigational
  PET agents
• No standardized PET imaging acquisition protocols
• No harmonized PET imaging report output
• Industry can not effectively implement PET
  imaging in large multi-center therapeutic
  clinical trials

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• SNM Assessment Efforts

• Results
• Multiple IND Design Solutions
• Regulatory
• CMC
• Imaging Standardization

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• Solution SNM Centralized IND

• Solution
• Centralized Investigational PET Imaging IND Oct.
  2008
• Will enable therapeutic developers multi-center
  therapeutic clinical trials

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• Presentation - Solution Topics
• Clinical Trials Network (CTN) Sites Registry
• Distributed Manufacturing of PET agents CMC
• Imaging Standardization
• F-18 FLT selection

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• Topic 1 Clinical Trials Sites - Registry

• International Registry - Investigators Sites
• Industry necessity reality
• Pick list to match therapeutic sites
• Registry criteria to enable industry review
  site selection
• Enrollment qualifications
• Location
• Equipment hardware software
• Personnel
• Access to investigational imaging agents
• Participation phantom program clinical trials

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• International PET imaging sites PET
  manufacturers

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• Topic 2 Distributed Manufacturing of PET Agents

• Distributed Multi-center Manufacturing of PET
  Imaging
• FDA Anticipates - single, GMP product
• PET production
• Multi-center methods of production of the
  investigational PET product
• Multiple similar PET products by end-product
  specifications

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• F-18 FLT

• Solution - Centralized IND Submission
• FDA must review CMC for all manufacturing sources
  methods
• CMC from all manufacturers supplying F-18 FLT
  to trials must be submitted directly to IND or
  through letter of cross-reference to a filed DMF
• FDA defines acceptable ranges for F-18 FLT by
  end-product specifications
• FDA accepted F-18 FLT products single IND
  GMP product

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• Drug Master File (DMF)

• DMF Efficient CMC submission tool for
  manufacturers
• Drug Manufacturers Submits Information
  Chemistry, Manufacturing and Controls (CMC) of a
  drug product or a component of a drug product to
  FDA file room to permit the FDA to review this
  information upon request only and in support of a
  specific submission

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

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• Key Point

• CMC information must be submitted in centralized
  IND
• CMC may be directly submitted to IND submission
• or
• CMC may be submitted through a letter of
  cross-reference to an existing DMF filed with FDA

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• Letter of Authorization (LOA) - Enables FDA
  review of DMF
• The DMF Holder (manufacturer) MUST submit an LOA
  (2 copies) to the DMF and route a separate copy
  to the IND Applicant
• The Applicant submits LOA in their IND
  submission the mechanism to enable review of
  the DMF by FDA
• The DMF will be reviewed ONLY when it is
  referenced in an IND submission
• In Europe, the LOA is called a Letter of Access

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• Topic 3 Imaging Standardization

• Solutions
• Clinical imaging with a standardized protocol
• hardware/software - International imaging
  clinical site registry
• Clinical trials educational programs for
  multi-center trials
• Pre-clinical imaging standardization - Phantom
  Program
• Oncology / CNS / Cardiovascular

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• SNM Imaging Phantom Program

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

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• Presentation - Solution Topics
• Clinical Trials Network (CTN) Sites Registry
• Distributed Manufacturing of PET agents CMC
• Imaging Standardization

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

• Disclosures
• Consultant to SNM (Society of Nuclear Medicine)
• Employee PAREXEL/Perceptive Informatics - CRO

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