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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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International PET imaging sites & PET manufacturers

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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 Informaticsgeorge.mills@perceptive.com

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