Update From FDA:Office of the Commissioner and Center for

Drug Evaluation and Research

Janet Woodcock, M.D.Acting Deputy Commissioner for OperationsFood and Drug AdministrationApril 7, 2005

Medical Imaging and The Critical Path Initiative

Central focus of critical path is developing new biomarkers and other evaluative technologies

Imaging is seen as a key technology for assessing, accelerating development and guiding use of new therapeutic options

Development of Imaging Technologies as Biomarkers and

Surrogate Markers

Developing these data involves significant time and expense

Lack of clear commercial pathway limits enthusiasm

However, absence of data curtails evolution of medical practice as well as medical product development: this situation is very frustrating for therapeutic developers as well as for those working on biomarkers

Similar conundrum for in vitro diagnostics

FDA Critical Path Initiative

FDA seeks mechanisms for qualifying such new biomarkers for regulatory use

Imaging technologies are at the forefront of our efforts

We believe that synergy between current drug development programs and imaging networks can be created to get this work done in a cost effective manner

FDA Critical Path Initiative

FDA will also begin an initiative to describe the general processes for biomarker and surrogate marker qualification for regulatory use

This effort should help clarify the pathways for development of these diagnostics

Critical Path Focus: Better Utilize Imaging as a Tool

in Drug Development

Overall evaluation of use of imaging in drug development

Facilitating use of molecular probes and other imaging techniques in early clinical trials

Use of imaging in development of cancer treatments

Use of Imaging in Drug Development

FDA conducted internal survey: broad use of imaging in multiple therapeutic areas

Workshop: DIA Co-sponsored; May 5 & 6, 2005

Hope to develop specific qualification projects in promising areas

Facilitating Use of Molecular Probes and other Imaging Techniques in Early

Clinical Trials

Meeting on RDRC process

Master file concept for probes

Draft “Exploratory IND” Guidance

Draft guidance on laboratory production of clinical supplies

Exploratory IND

“Phase 0” studies – prior to traditional drug development Phase 1 trials

Microdose or low dose-limited period of administration

Exploratory IND (cont.)

Toxicology to support use may be similarly abbreviated

May be used for proof-of-mechanism, screening multiple compounds, microdose, imaging

Laboratory Production – Draft Guidance

Appropriate methods and quality control for small scale production

Explain what should be filed in IND vs. records kept at site• Reflects FDA’s longstanding position – not

previously articulated• Developed in collaboration with NCI

Use of Imaging in Development of Cancer

Treatments Critical Path issue: Lack mechanism to rapidly

incorporate new science/technology into evaluations (e.g. response) done in development trials

Measurements of tumor size as a surrogate for response

Measurement of other tumor parameters (e.g. glucose uptake) as a response surrogate

Combination measurements in composite EPs

Collaborations with NCI

Evaluation of use of FDG-PET in therapeutic cancer trials

Evaluation of molecular probes

Review of use of RECIST criteria in cancer trials

Desired Outcomes

“Gap analysis” : Current data on technology used in a particular tumor vs needed data for adoption as response measure in trials

“Trial analysis” : What trials, using what active agents, would be needed to fill in these gaps?

Mechanisms to conduct such studies

How to Get Such Work Accomplished

New opportunities for collaboration Many stakeholders will have to

participate: FDA, NCI, drug and biologic developers, ?payors, medical imaging industry

Hope studies can be designed to synergize with ongoing trials or with clinical care so that expense will not be prohibitive

Reorganizations within CDER

Creation of Office of Oncology Drug Products within CDER

Medical Imaging will be one of three Divisions

Consolidation of monoclonal antibody imaging agents & other biologics with traditional drug imaging agents

Progress ongoing – should be complete by summer

Reorganization: Facilitate Movement of New Science

into Cancer Drug Evaluation

We believe that new imaging technologies as well as pharmacogenomics will be taken up first in cancer drug development

We hope that this will happen in a deliberate way rather than haphazardly

Summary

Imaging technologies are currently very important, and will become even more crucial to cancer therapeutic development

FDA, under its critical path initiative, is seeking to advance development of these imaging biomarkers in an organized fashion

Summary

Accomplishing this will require extensive collaboration across many stakeholders—and close attention to IP issues

NCI and FDA are collaborating in this effort