Transcript Document

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
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Industry can not effectively implement PET imaging in large multicenter therapeutic clinical trials
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SNM Assessment Efforts
Results:
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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
1. Clinical Trials Network (CTN) Sites Registry
2. Distributed Manufacturing of PET agents – CMC
3. Imaging Standardization
4. [F-18] FLT selection
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Topic 1: Clinical Trials Sites - Registry
International Registry - Investigators’ Sites
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Industry necessity & reality
“Pick list” to match therapeutic sites
Registry criteria to enable industry review & site selection
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Enrollment & qualifications
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Location
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Equipment – hardware & software
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Personnel
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Access to investigational imaging agents
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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
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FDA – Anticipates - “single, GMP product”
―PET production
― Multi-center methods of production of the
investigational PET product
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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 Manufacturer’s 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
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I: Plant information
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II: Drug substance, drug product, intermediates and material
used in their manufacture
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III: Packaging
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IV: Excipients
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V: Other clinical, toxicology
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Key Point
CMC information must be submitted in centralized IND
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CMC may be directly submitted to IND submission
or
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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
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Clinical imaging with a standardized protocol
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hardware/software - International imaging clinical site registry
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Clinical trials educational programs for multi-center trials
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Pre-clinical imaging standardization - Phantom Program
– Oncology / CNS / Cardiovascular
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SNM Imaging Phantom Program
[F-18] FLT fillable phantoms
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Qualitative & Quantitative (SUV)
VA system
— Torso: Oncology
— Head: CNS
— Cardiac
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Presentation - Solution Topics
1. Clinical Trials Network (CTN) Sites Registry
2. Distributed Manufacturing of PET agents – CMC
3. Imaging Standardization
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Thank You
George Mills, MD, MBA
Vice President, Medical & Regulatory Relations
Perceptive Informatics
[email protected]
Disclosures:
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Consultant to SNM (Society of Nuclear Medicine)
Employee: PAREXEL/Perceptive Informatics - CRO
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