Transcript Document
The SNM Centralized IND & Clinical Trials Network Enabling Implementation Investigational & Approved PET Imaging in Large Multicenter Clinical Trials George Q. Mills, MD, MBA September 9, 2009 Therapeutic Drug Developers Comments PET imaging desired for Multicenter Therapeutic Trials …but…numerous deficiencies… Lack of… 1. 2. 3. 4. Limited supply of investigational PET agents Standardized PET imaging acquisition protocols Harmonized PET imaging report output Qualified & experienced imaging centers large (200+ sites) multicenter clinical trials Industry could not effectively implement PET imaging in multicenter therapeutic clinical trials Page ‹#› SNM – Assessment Efforts Therapeutic Developers Participating PET Imaging Centers FDA – Pre-IND Process Results - Design solutions Centralized Investigational PET Imaging IND to Enable Therapeutic Developers’ Multicenter Therapeutic Clinical Trials Distributed Manufacturing Investigational PET imaging Agents Page ‹#› SNM Centralized IND – Demonstration Project - Future development INDs – F-18 FLT – first choice – available – broad potential 1. Regulatory 2. CMC 3. Imaging Standardization Page ‹#› Clinical Trials Sites Network - Registry Investigator international site registry Forming “Pick List” - therapeutic developers Enrollment & qualifications Location • Geography • Patient population access Equipment – hardware & software Personnel Access to investigational imaging agents Participation – phantom program – clinical trials Page ‹#› World wide interest - imagers & manufacturers Page ‹#› Regulatory – multicenter IND manufacturing Multicenter INDs - “Single source” – investigational product CMC – Investigational F-18 FLT sources • Multiple production sites & multiple methods • “Distributed manufacturing” = multiple end-product specs • SNM Centralized IND F-18 FLT FDA CMC review of all sources – acceptable ranges for endproduct specifications Page ‹#› Review through submission to IND file directly or through Drug Master File (DMF) “a submission tool of efficiency for manufacturers” • Information concerning the Chemistry, Manufacturing and Controls (CMC) of a drug product or a component of a drug product to permit the FDA to review this information upon request in support of a submission Page ‹#› Types of DMFs Five Types • I: Plant information • II: Drug substance, drug product, intermediates and material used in their manufacture • III: Packaging • IV: Excipients • V: Other clinical, tox Page ‹#› Who must file a DMF? CMC information must be available for IND review: CMC must be in an IND submission or in a DMF – There is no legal or regulatory requirement to file a DMF (submission by Holder,…ref by applicant or authorized party) – Applicant submits a Letter of Authorization (LOA) from the Holder with their IND Page ‹#› Letter of Authorization (LOA) – Enabling review of DMF • The DMF will be reviewed ONLY when it is referenced in a submission or another DMF (initially receives an administrative review) • The Holder MUST submit an LOA (2 copies) to the DMF and send a copy to the Applicant • The Applicant submits LOA in their submission… the mechanism to trigger review of the DMF by FDA Page ‹#› DMF Advantages • Maintains proprietary information/trade secrets (e.g. manufacturing procedure) belonging to the Holder, from being revealed to the Applicant while permitting review by FDA • Permit review of information referenced by a number of applicants & will be used to support submissions from many sponsors • Time efficient – cost effective Page ‹#› Imaging standardization 1. Pre-clinical Imaging Standardization - Imaging Phantom Program Oncology – CNS - Cardiovascular 2. Clinical imaging - Standardized protocol 3. International imaging clinical site registry (217 sites) documentation of equipment & demonstrated capabilities 4. Clinical Trials Educational programs – Multicenter Trials Page ‹#› SNM Imaging Phantom Program F-18 fillable phantoms – Qualitative & Quantitative (SUV) – VA system • Torso – Oncology • Head – CNS • Cardiac Page ‹#› Selection - F-18 FLT • Investigational PET imaging biomarker • Literature reports of “potential” for demonstrating tumor proliferation PRE-TX • Potential as a surrogate marker for evaluating investigational oncology therapeutics as well as existing therapeutics 22 days • Broadly applicable to lung, breast, esophageal, GI, brain, lymphoma 113 days Page ‹#› Topics • Overview – Key Elements – Centralized IND • Clinical Trials Network – Resources – Sites Registry – Phantom Program – Education & Training Program • F-18 FLT selection Page ‹#› Thank you George Mills, MD, MBA Vice President, Medical & Regulatory Relations Perceptive Informatics [email protected] Page ‹#› Page ‹#› Page ‹#›