Transcript Document

Workings of the SNM Clinical Trials Network
Centralized IND for FLT
George Q. Mills, MD, MBA
Vice President, Medical & Regulatory Relations
Perceptive Informatics
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Discussion today includes
background information, comments and references to the
SNM Clinical Trials Network Centralized IND
Selection of [F-18] FLT: an Investigational,
non-FDA approved, PET Imaging Agent
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FDA / IOM Meeting – October 2007
Therapeutic Drug Developers Comments
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PET imaging desired for Multi-center Therapeutic Trials …but ...
numerous deficiencies with PET imaging
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 could not effectively implement PET imaging in multi-center
therapeutic clinical trials
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SNM Assessment Efforts
Multiple Discussions:
• Therapeutic Developers
• Participating PET Imaging Centers
• FDA: Pre-IND Process
Results:
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Multiple IND Design Solutions
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Regulatory
CMC
Imaging Standardization
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Solution Topics
1. Clinical Trials Network (CTN) Sites Registry
2. Selection of IND biomarker – [F-18] FLT
3. Distributed Manufacturing of PET agents – CMC
4. Imaging Standardization
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Topic 1: Clinical Trials Sites Registry
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International Registry - Investigators’ Sites
— Industry necessity & reality
— “Pick list” to match therapeutic sites
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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: Centralized IND Selection
Areas
of
Interest
Hypoxia
Apoptosis
Amyloid Receptors
Lipids
Dopaminergic Receptors
Angiogenesis
Estrogen Receptors
Selection: [F-18] FLT (Oct. 2008)
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Selection Criteria for [F-18] FLT
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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 for lung, breast,
esophageal, GI, brain, lymphoma
PRE-TX
22 days
113 days
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Topic 3: Distributed Manufacturing of PET Agents
Distributed Multicenter Manufacturing of PET Imaging
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FDA: Anticipates “single GMP product”
― PET production
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Multicenter methods of production of the
investigational PET product
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Multiple “similar” PET products by end-product
specifications
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Using the SNM Centralized IND for [F-18] FLT
 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 in IND submission
or
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CMC may be submitted through a letter of crossreference 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 4: Imaging Standardization
Solutions
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Clinical imaging with a standardized protocol
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International imaging clinical site registry – hardware/software
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Clinical trials educational programs for multicenter 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/Brain: CNS
— Cardiac
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Plans for Future Centralized IND
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FDG
FLT
FDOPA
FAZA
FMISO
Ga-68 octreotide
FES
FHDT
C-11 acetate
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Review: Solution Topics
1. Clinical Trials Network (CTN) Sites Registry
2. Selection of IND biomarker – [F-18] FLT
3. Distributed Manufacturing of PET agents – CMC
4. 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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