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Transcript of 1 Imaging Community Critical Need #1: Standardized and Harmonized Multisite Imaging George Q. Mills,...
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Imaging Community Critical Need #1: Standardized and Harmonized Multisite Imaging
George Q. Mills, MD, MBA
Vice President, Medical & Regulatory RelationsPerceptive Informatics
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Discussion today will include comments
and references to
[F-18] FLT: an Investigational,
non-FDA approved, PET Imaging Agent
Enabling Investigational & Approved PET Imaging in Large Multicenter Clinical Trials
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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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Results:
• Multiple IND Design Solutions • Regulatory • CMC • Imaging Standardization
SNM Assessment Efforts
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Solution
Centralized Investigational PET Imaging IND: Oct. 2008
Will enable therapeutic developers’ multi-center therapeutic clinical trials
Solution: SNM Centralized IND
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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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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
Topic 1: Clinical Trials Sites - Registry
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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
Topic 2: Distributed Manufacturing of PET Agents
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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”
[F-18] FLT
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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
Drug Master File (DMF)
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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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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
Key Point
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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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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
Topic 3: Imaging Standardization
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[F-18] FLT fillable phantoms• Qualitative & Quantitative (SUV)
• VA system
— Torso: Oncology
— Head: CNS
— Cardiac
SNM Imaging Phantom Program
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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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Disclosures:
• Consultant to SNM (Society of Nuclear Medicine)
• Employee: PAREXEL/Perceptive Informatics - CRO
Thank You
George Mills, MD, MBAVice President, Medical & Regulatory Relations
Perceptive [email protected]