1. Update From FDA: Office of the Commissioner and Center for Drug Evaluation and Research Janet Woodcock, M.D. Acting Deputy Commissioner for Operations Food and Drug Administration April 7, 2005

2. Medical Imaging and The Critical Path Initiative l Central focus of critical path is developing new biomarkers and other evaluative technologies l Imaging is seen as a key technology for assessing, accelerating development and guiding use of new therapeutic options

3. Development of Imaging Technologies as Biomarkers and Surrogate Markers l Developing these data involves significant time and expense l Lack of clear commercial pathway limits enthusiasm l 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 l Similar conundrum for in vitro diagnostics

4. FDA Critical Path Initiative l FDA seeks mechanisms for qualifying such new biomarkers for regulatory use l Imaging technologies are at the forefront of our efforts l 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

5. FDA Critical Path Initiative l FDA will also begin an initiative to describe the general processes for biomarker and surrogate marker qualification for regulatory use l This effort should help clarify the pathways for development of these diagnostics

6. Critical Path Focus: Better Utilize Imaging as a Tool in Drug Development l Overall evaluation of use of imaging in drug development l Facilitating use of molecular probes and other imaging techniques in early clinical trials l Use of imaging in development of cancer treatments

7. Use of Imaging in Drug Development l FDA conducted internal survey: broad use of imaging in multiple therapeutic areas l Workshop: DIA Co-sponsored; May 5 & 6, 2005 l Hope to develop specific qualification projects in promising areas

8. Facilitating Use of Molecular Probes and other Imaging Techniques in Early Clinical Trials l Meeting on RDRC process l Master file concept for probes l Draft “Exploratory IND” Guidance l Draft guidance on laboratory production of clinical supplies

9. Exploratory IND l “Phase 0” studies – prior to traditional drug development Phase 1 trials l Microdose or low dose-limited period of administration

10. Exploratory IND (cont.) l Toxicology to support use may be similarly abbreviated l May be used for proof-of-mechanism, screening multiple compounds, microdose, imaging

11. Laboratory Production – Draft Guidance l Appropriate methods and quality control for small scale production l 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

12. Use of Imaging in Development of Cancer Treatments l Critical Path issue: Lack mechanism to rapidly incorporate new science/technology into evaluations (e.g. response) done in development trials l Measurements of tumor size as a surrogate for response l Measurement of other tumor parameters (e.g. glucose uptake) as a response surrogate l Combination measurements in composite EPs

13. Collaborations with NCI l Evaluation of use of FDG-PET in therapeutic cancer trials l Evaluation of molecular probes l Review of use of RECIST criteria in cancer trials

14. Desired Outcomes l “Gap analysis” : Current data on technology used in a particular tumor vs needed data for adoption as response measure in trials l “Trial analysis” : What trials, using what active agents, would be needed to fill in these gaps? l Mechanisms to conduct such studies

15. How to Get Such Work Accomplished l New opportunities for collaboration l Many stakeholders will have to participate: FDA, NCI, drug and biologic developers, ?payors, medical imaging industry l Hope studies can be designed to synergize with ongoing trials or with clinical care so that expense will not be prohibitive

16. Reorganizations within CDER l Creation of Office of Oncology Drug Products within CDER l Medical Imaging will be one of three Divisions l Consolidation of monoclonal antibody imaging agents & other biologics with traditional drug imaging agents l Progress ongoing – should be complete by summer

17. Reorganization: Facilitate Movement of New Science into Cancer Drug Evaluation l We believe that new imaging technologies as well as pharmacogenomics will be taken up first in cancer drug development l We hope that this will happen in a deliberate way rather than haphazardly

18. Summary l Imaging technologies are currently very important, and will become even more crucial to cancer therapeutic development l FDA, under its critical path initiative, is seeking to advance development of these imaging biomarkers in an organized fashion

19. Summary l Accomplishing this will require extensive collaboration across many stakeholders—and close attention to IP issues l NCI and FDA are collaborating in this effort