1. 1 CDRH Update Facilitating Medical Device Innovation and Technology Dan Schultz, MD Director, Center for Devices and Radiological Health Food and Drug Administration Sixth Annual National Forum on Biomedical Imaging in Oncology Bethesda, MD April 7, 2005

2. 2 What is a Device?

3. 3 A Computer That Helps You Hear

4. 4 Miniaturized Devices Electrical Stimulators Pacemakers

5. 5 Information-Rich Therapeutics Insulin Delivery Catheter Intravascular Glucose sensor Implantable Sc pump Personal Programming Communicator Smart Drug Delivery Devices Smart Drug Delivery Devices

6. 6 Combination Products Drug-Eluting Stents Components Stent Platform & Delivery System Carrier(s)Drug

7. 7 Intelligent Devices Stent as a Radiofrequency Identifier Preclinical Model of Self Monitoring Stent Applications: detect restenosis Measure blood pressure continuously Yogesh Gianchandani and his team at the University of Michigan

8. 8 Information Rich Therapeutics Diagnostics and Therapeutic Device Uses magnetic resonance image (MRI) guided focused ultrasound to target and destroy non-cancerous uterine fibroids Minimally Invasive Devices Image (MRI) Guided Treatment (HiFU)

9. 9 Medical Imaging Devices Digital Mammography Produces images using X-rays instead of film Image Analysis Software Aids in the detection of lung nodules

10. 10 Technology for Special Populations Left Ventricular Assist Device for Pediatric Use Stair-Climbing Wheelchair

11. 11 Technology Designed for Home Use Home Testing for HIV A Defibrillator for the Home

12. 12 Point of Care Diagnosis and Therapy Devices Enhancement of point of care testing Enhanced portability of increasingly complex laboratory analysis Example: A portable test has been approved by CBER for HIV CDRH expects other high risk technologies to follow

13. 13 Biological Medical Devices Genomics Impact on Therapeutic Products New knowledge about disease Animal models Pharmacogenomics: Identify responders Understand toxicity Clinical diagnosis Clinical treatment monitoring Personalized Medicine

14. 14 Biological Medical Devices Biotechnology Revolution Microarray Technology Providing insight into patient factors allowing for personalized medicine Amplichip Personalized Medicine

15. 15 Technology We Hope We Never Need Bioterrorism Diagnostic Testing Bioterrorism Diagnostic Testing Testing for biological warfare agents including microbes and toxic chemicals Biosensor detectors Nucleic acid amplification Challenge: Challenge: Studies using real clinical samples may not be possible so flexible regulatory and scientific alternatives are essential QuickELISA Anthrax-Pa Kit The first rapid serum antibody test for anthrax

16. 16 What are the challenges today for bringing new medical technology to market? Accelerated Pace of Technology and Innovation Complexity of New Technology Technology and Innovation

17. 17 Traditional Lateral Skull Film The Accelerating Pace of Technology and Innovation Advances in Medical Imaging

18. 18 The Accelerating Pace of Technology and Innovation Advances in Medical Imaging 41 CT slices

19. 19 The Accelerating Pace of Technology and Innovation Advances in Medical Imaging 3-D CT Imaging

20. 20 The Accelerating Pace of Technology and Innovation Advances in Medical Imaging

21. 21 Medical Device Industry Growth Dun & Bradstreet Medical Device Firm Data Number of Manufacturers by Year

22. 22 Sales Volume Growth Note: No economic adjustment to dollar value (Billions of Dollars)

23. 23 The Complexity of New Technologies Devices are getting smaller –Miniaturization, New Materials, Nanotechnology Devices are getting smarter and are providing more information –Intelligent Devices –Biotechnology Revolution –Personalized Medicine –Combination Products –Information-Rich Therapeutics

24. 24 The Complexity of New Technologies The Complexity of New Technologies Devices are becoming more convenient for the patient –Home Use –Minimally Invasive –Point of Care Diagnostics Devices are responding to heighten homeland security –Bioterrorism-Related Devices Devices are meeting the needs for special populations

25. 25 Technology and Innovation FDA Role Establish reasonable assurance of the safety and effectiveness of medical devices marketed in the U.S.

26. 26 Technology and Innovation CDRH Challenges Effectively Managing a Changing Workload –Increasing number of expedited submissions, combinations products and submissions with clinical data –New Kinds of Scientific Expertise Meeting MDUFMA Commitments –Performance goals –Third-party inspections Establishing a Premarket/Postmarket Balance –Greater degree of scrutiny

27. 27 Medical Device Program TYPE OF SUBMISSIONFY 99FY 00FY 01FY 02FY 03FY 04 Original PMA*646771495451 PMA Supplement*557546641645666635 Original IDE304311284312242226 IDE Amendment275240206252216167 IDE Supplement4,1274,3884,8114,7244,4154,312 510(k) – 10% with clinical data*4,4584,2024,2484,3204,2473,635 Original HDE121155109 HDE Supplements41016 29 Total9,8019,77510,28210,3239,8799,064 *The majority of PMAs and 510(k) applications are subject to fees. Exceptions include small business and pediatric applications. CDRH: Types and Numbers of Submissions Received

28. 28 These are the issues that we face everyday… Implementation of the Medical Device User Fee and Modernization Act of 2002… … a complex and comprehensive set of review goals, becoming more aggressive each year.

29. 29 The number of expedited submissions is growing…. The number of combination products is growing… … shortening timeframes and bringing increasingly complex scientific questions… … necessitating new kinds of technical expertise and new regulatory paradigms

30. 30 The complexity and need for clinical data is growing… Embolic protection devices Vascular anastomosis devices for CABG Image-guided bronchoscopes Barbed sutures Glaucoma shunts Daily wear contact lenses CPAP devices for apnea … requiring more in-depth review, including occasional Panel input

31. 31 Bioterrorism Emergency Measures Emergency Preparedness - Medical device emergency shortages database Bioterrorism Diagnostics and Testing - QuickELISA Anthrax-Pa Kit, the first rapid serum antibody test for anthrax ASTM F2401-04 - Standard Practice for Security Checkpoint Metal Detector Screening of Persons with Medical Devices

32. 32 Meeting Technology Innovation Challenges

33. 33 Meeting the Challenges of Technology and Innovation Strategic planning helps us achieve our goals and establish a vision for the future Meeting MDUFMA Goals Strengthening our workforce for the 21st century Enhancing our knowledge management Achieving a better pre/postmarket regulatory balance

34. 34 CDRH FY 05 Mission: CDRH promotes and protects the health of the public by ensuring the safety and effectiveness of medical devices and the safety of radiological products. Vision: Ensuring the health of the public through out the Total Product Life Cycle (TPLC) Public Health Impact Measure, assess, improve and communicate our impact on public health Magnet for Excellence Attract and retain a diverse work force to accomplish our public health mission CDRH Strategic Goals Knowledge Management Enhance use of information and communication systems to support TPLC TPLC Align CDRH programs to effectively manage the product life cycle Meet MDUFMA performance goals Strengthen our workforce for the 21 st century CDRH Priorities Enhance our knowledge management Achieve better pre/postmarket regulatory balance Public Health Promotion Assess and improve time to market for medical devices Public Health Protection Assess and improve risk management, identifying and resolving public health hazards Workforce Excellence Attract, develop and retain a highly skilled and diverse workforce to advance our public health mission Scorecar d Key Result Areas Knowledge Management Communicating with our stakeholders to meet public health challenges throughout the TPLC TPLC Effective Management in Accordance with TPLC Principles FY 05 MDUFMA performance goals Quality system for application review Review consults CoA studies Risk -based inspections MedSun and LabSun Medical device reports (MDR) Emergency Measures Priority hiring Professional development External expertise (MDFP and other initiatives) Priority Initiatives Guidance/standar ds Targeted IT initiatives Infrastructure upgrades Turbo 510(k) eConsult Communicating medical technology OIVD Model Research prioritization Radiological Health Strategy GHTF Organizational scorecards Project management plans Move to White Oak Technology Development and Innovation Patient and Consumer Protection Protecting the Homeland -- Counter Terrorism Risk-Based Management Practices Improving FDA's Business Practices Relations hip to FDA Goals Patient and Consumer Protection Empowering Consumers in Public Health Improving FDA's Business Practices

35. 35 Priority Hiring OfficeHired FY 03 FY 03Hired FY 04 FY 04 Two Year Totals Total MDUFMA Hires (#Shared)Total7557 132 (18 Shared) OC107 17 (1 Shared) 17 (1 Shared) ODE2915 44 (6 Shared) 44 (6 Shared) OCR42 6 (0 Shared) 6 (0 Shared) OIVD116 17 (0 Shared) 17 (0 Shared) OSB611 18 (1 Shared) 18 (1 Shared) OSM/OCD43 6 (0 Shared) 6 (0 Shared) OSEL1113 24 (11 Shared) 24 (11 Shared) FY 03 and FY 04 Hires (by Specialty)

36. 36 Develop training programs Provide professional and career development opportunities Science Leadership Education Program (SLEP) Basic Science Education Program (BSEP) Develop competency models ScienceManagementBusiness Professional Development

37. 37 Since its inception, MDFP has sponsored over 100 fellows in the program over 100 fellows in the programwww.fda.gov/cdrh/mdfp Premarket reviews and consults Human factors issues Human factors issues Analysis of device failure modes Analysis of device failure modes Standards and guidance development Standards and guidance development Statistical analyses Statistical analyses External Expertise Medical Device Fellowship Program (MDFP)

38. 38 Guidance Development Create a list of high priority guidances Establish performance goals Develop tracking mechanisms Engage industry stakeholders in the early stages of guidance development

39. 39 Standards Development Recognition – to have significant influence throughout the world Participation – to work with national and international committees CDRH Standards Participation 38 development organizations 238 Liaison Reps : 220 National Committees and 128 International Committees 538 Standards Activities : 365 National and 173 Other Activities Utilization Standards utilization in recent device applications - 55%

40. 40 Global Harmonization Task Force Develop guidance documents on basic regulatory practices Continue participating in GHTF study groups Study Group 1: regulatory and premarket requirements Study Group 2: postmarket vigilance Study Group 3: quality systems Study Group 4: regulatory auditing of quality systems NEW Study Group 5: Clinical Evidence Mission: Encourage the convergence of medical device regulatory practices worldwide where possible, while ensuring the safety, effectiveness, and quality of medical devices.

41. 41 Quality Systems for Application Review Focus on selected cross-cutting areas e.g., biocompatibility Use retrospective (post-decision) peer assessments Assemble quality assessment teams Continue with pilot program

42. 42 IT Initiatives Premarket Review Modernization Postmarket Medical Device Reporting (eMDR) ODE and OC Tracking Systems Electronic Registration and Listing eConsultImage2000 Turbo 510(k)

43. 43 IT Initiatives Image2000 Scan outgoing 513g and reduce backlog Decrease original PMA scanning times Scanning 510(k) in real time Electronic copies to eliminate need for scanning

44. 44 IT Initiatives Turbo 510(k) Continue pilot eSubmission with industry volunteers Develop eLoader tool for reviewers, allowing copy and paste from eSubmission into external applications Develop eReview tool, a standard 510(k) review template

45. 45 Research Prioritization Criteria For Rating Projects R egulatory need: PMA and IDE activity Scientific gaps and technical competence: leading edge products Public health impact: mortality, morbidity, quality of life FY 05 Goals Continue using prioritization model FY 04 Update 73 projects (14 programs) Approximately 90 TRC members participated Approximately 145 OSEL staff are involved 72 TRC members from CDRH, and the rest from CDER, CBER, EPA, NIST, etc.

46. 46 Critical Path Research Leverages basic science knowledge Leverages cumulative research experiences Translational Research Critical Path Research Basic Research Prototype Design or Discovery Preclinical Development FDA Filing/ Approval & Launch Preparation Clinical Development Does not compromise safety and effectiveness evaluations

47. 47 Critical Path Research Update We have reviewed and compiled all of the comments received on the public docket –Critical Path Public Docket Solicited thoughts on areas benefit from research and development of critical path evaluative tools We are nearing completion the National Critical Paths Opportunities List

48. 48 Organizational Scorecards FY 05 Goals Update Center scorecards, includes implementing Quality review Assessment metrics Develop a pilot automated scorecard tool Scorecards help manage organizational performance in CDRH strategic areas

49. 49 Project Management Plans FY 05 Goals Effectively manage long term projects and new initiatives –Project milestones –Resource requirements –Quarterly reports

50. 50 Improving Infrastructure White Oak Life Sciences building opened Dec. 2003 Shared between CDRH and CDER Considerable progress on the CDER Office building and the Award- winning Shared Use building Engineering and Physics building 100% design Expected occupancy Spring 2006

51. 51 Working Towards Meeting Performance Goals

52. 52 Scientific Review Interactive Rev Original PMA Milestones Filing Review Panel Planning Closeout Review PMA Received Panel Go/No Go Panel Meeting Filing Letter Final Decision 320 days Major Deficiency Letter ClockStops Status Letter Consults Complete 2-cycle scenario

53. 53 Original PMA Milestones Filing Review Scientific Review Panel Planning Closeout Review PMA Received Final Decision 180 days Status Letter Consults Complete Interactive Review 1-cycle scenario Panel Go/No Go Filing Letter Panel Meeting

54. 54 MDUFMA Performance Goals Performance Measured at FY 2003 Cohort Goal: None until FY 2006 FY 2004 Cohort Goal: None until FY 2006 FY 2005 Cohort Goal: None until FY 2006 3 months into FY 88.9%100.0% 6 months into FY 93.3%100.0% 9 months into FY 96.6%100.0% End of FY (12 months) 97.4%100.0% 15 months after start of FY 97.4%100.0% 18 months after start of FY 97.6% 21 months after start of FY 97.6% 24 months after start of FY 95.1% 27 months after start of FY 95.2% Remaining to close cohort 5 (of 47) 25 (of 47) TBD PMAs and Panel-track Supplements FDA Decisions within 320 Days

55. 55 Performance Measured at FY 2003 Cohort Goal: None until FY 2005 FY 2004 Cohort Goal: None until FY 2005 FY 2005 Cohort Goal: 75% 3 months into FY 100.0% 6 months into FY 100.0%100.0% 9 months into FY 100.0%84.6% End of FY (12 months) 100.0%85.0% 15 months after start of FY 86.4%84.0% 18 months after start of FY 84.0% 84.0% 21 months after start of FY 84.0% 84.0% 24 months after start of FY 84.0% 84.0% 27 months after start of FY 84.0% 84.0% Remaining to close cohort 5TBD PMAs and Panel-track Supplements First Action = Major Deficiency Letter within 150 Days MDUFMA Performance Goals

56. 56 MDUFMA Performance Goals Performance Measured at0 FY 2003 Cohort Goal: None until FY 2005 FY 2004 Cohort Goal: None until FY 2005 FY 2005 Cohort Goal: 80% 3 months into FY 87.7%86.4%100.0% 6 months into FY 86.3%89.2% 9 months into FY 89.9%92.9% End of FY (12 months) 91.9%97.3% 15 months after start of FY 93.6%97.6% 18 months after start of FY 94.1% 21 months after start of FY 94.6% 24 months after start of FY 94.1% 94.1% 27 months after start of FY 94.1% 94.1% Remaining to close cohort (of 203) (of 203) 18 (of 103) TBD 180-day Supplements FDA Decisions within 180 Days

57. 57 Performance Measured at FY 2003 Cohort Goal: None until FY 2005 FY 2004 Cohort Goal: None until FY 2005 FY 2005 Cohort Goal: 80% 3 months into FY 100.0% 6 months into FY 0.0%83.3% 9 months into FY 9.1%80.0% End of FY (12 months) 14.3%87.5% 15 months after start of FY 16.7%89.2% 18 months after start of FY 16.1% 21 months after start of FY 16.1% 24 months after start of FY 16.1% 16.1% 27 months after start of FY 16.1% 16.1% Remaining to close cohort 16 16TBD 180-day Supplements First Action = Not Approvable Letter within 120 Days MDUFMA Performance Goals

58. 58 MDUFMA Performance Goals Performance Measured at FY 2003 Cohort Goal: None until FY 2005 FY 2004 Cohort Goal: None until FY 2005 FY 2005 Cohort Goal: 75% 3 months into FY 100.0%100.0%100.0% 6 months into FY 96.1%95.6% 9 months into FY 90.7%90.7% End of FY (12 months) 87.1%89.0% 15 months after start of FY 83.7%87.3% 18 months after start of FY 79.4% 21 months after start of FY 77.3% 24 months after start of FY 76.4% 27 months after start of FY 76.0% Remaining to close cohort 25 (of 3,752) 376 (of 3,411) TBD 510(k)s SE, NSE Decisions within 90 Days

59. 59 Performance Measured at FY 2003 Cohort Goal: None until FY 2005 FY 2004 Cohort Goal: None until FY 2005 FY 2005 Cohort Goal: 70% 3 months into FY 90.0%93.5%99.6% 6 months into FY 66.2%74.4% 9 months into FY 60.2%76.0% End of FY (12 months) 59.1%78.5% 15 months after start of FY 57.9%78.4% 18 months after start of FY 57.8% 21 months after start of FY 57.9% 24 months after start of FY 57.9% 27 months after start of FY 57.9% Remaining to close cohort 25 25 376 376TBD 510(k)s First Action = Additional Information Letter within 75 Days MDUFMA Performance Goals

60. 60 Assuring Postmarket Medical Device Safety FDA under scrutiny Identifying adverse events so rare or that occur under specific conditions

61. 61 New Claims Add To Data That Put Vioxx Drug On Hot Seat New Vioxx, Celebrex Studies Show Mixed Results FDA panel votes to allow Vioxx back on market FDA Issues Public Health Advisory on Vioxx as its Manufacturer Voluntarily Withdraws the Product A Reminder That No Drug Is Risk-Free F.D.A. Panel Says Pain Relievers Should Remain on Market FDA opens hearing on safety of arthritis drugs

62. 62 Boston Scientific Stent Recall Grows to 96K Units FDA Is Reviewing Reports of Trouble With Taxus Stent Boston Scientific's Older Stents Draw Scrutiny of FDA Boston Scientific Expands Recall of Troubled Stent FDA won't expand recall of stents FDA Temperature up over Cordis Drug-coated stents may face additional FDA scrutiny FDA Advises Physicians of Adverse Events Associated with Cordis Cypher Coronary Stents

63. 63 Device GMP/QS Inspection Trends Statutory Requirement

64. 64 Links Between Process (GMP) Risks and Patient Risks are Lost Risk-based Inspections RISK Processes Inspection Risk cGMP RISK Quality Patient) Factors Patient Correlation? RISK Processes Inspection Risk RISK Quality (Patient) Factors GMPPatient Goal Goal Prioritize Actions on GMP Risks Correlating to Patient Risks

65. 65 Third Party Inspection Program Inspections of eligible manufacturers of Class II and Class III medical devices by accredited persons Inspections by accredited persons conducted in essentially the same manner as those conducted by FDA Inspections by accredited persons conducted independent of third party inspections performed under the U.S./EC Mutual Recognition Agreement (MRA)

66. 66 Third Party Inspection Program Update Implemented MDUFMA authority to accredit third parties Issued guidance Published criteria for accredited persons Selected 15 third parties to participate in the program

67. 67 Achieving Pre/Postmarket Balance

68. 68 A start, not a cure, for FDA FDA to create drug safety board Independent panel to monitor medicines once they're on market F.D.A. Moves Toward More Openness With the Public FDA to Institute Safety Board The goal is to more quickly identify problems with drugs and to issue alerts. The agency has been under growing pressure to act.

69. Building Better Reporting Systems Adverse Event Reporting System Voluntary reporting since 1973 (3%) Mandatory reporting Since 1984 - manufacturers (93%) and Importers (1%) Since 1990 - user facilities (3%) 125,000 reports/year; 1.25 million total MandatoryReporting FDA VoluntaryReporting Product Problems Clinical Problems

70. 70 Building Better Reporting Systems Medical Device Reporting (MDR) Expedite analysis of reported serious injuries Implement Phase 1 of eMDR Timely access, review and action on available and new reports FY 04 Update 57,600 reports from manufacturers, user facilities, and importers 3887 voluntary reports from health care professionals and the public 3887 voluntary reports from health care professionals and the public

71. 71 Building Better Reporting Systems MedSun and LabSun The Medical Product Surveillance Network (MedSun) is an interactive, internet-based reporting program. Continue recruitment of reporting facilities FY 04 Update: 299 facilities nationwide FY 05 Target: 350 facilities nationwide Target reports from laboratories (pathology and in vitro diagnostic tests) in the reporting hospitals (LabSun) Increase reporting from hospital laboratories

72. 72 Condition of Approval (CoA) Studies Transfer tracking and follow-up to postmarket Develop tracking system Involve epidemiology staff in PMA review Develop postmarket plan (identify products risk) Postmarket studies designed to address postmarket questions Prompt follow-up with sponsors when requirements not being met

73. 73 Condition of Approval (CoA) Studies Feedback and interaction with sponsor as CoA study progresses Public availability of study status on Agency website Panel feedback with updates, industry or CDRH Mandate postmarket study if needed

74. 74 Communicating Medical Technology As new technology emerges, it is not only our responsibility to assure its safety and effectiveness, but also to communicate its existence and usefulness to the public at large.

75. 75 Educating Healthcare Providers and Protecting Consumers through Information Safety Alerts Public Health Notifications Labeling Changes Scientific Publications FDA Patient Safety News Patient Safety Portal Recalls and Other Regulatory Actions

76. 76 Protecting Consumers through Information CDRH Disease and Product- specific Websites Diabetes Information www.fda.gov/diabetes HeartHealth Online www.fda.goc/hearthealth LASIK www.fda.gov/cdrh/lasik Whole-Body Scanning Using CT www.fda.gov/cdrh/ct Cochlear Implants www.fda.gov/cdrh/cochlear

77. 77 Educating Healthcare Providers and Consumers Communicating the existence and usefulness of new technologies One Pagers – New Device Approvals www.accessdata.fda.gov/scripts/cdrh/cfdocs/cftopi c/mda/mda-list.cfm?list+1 Utilizing the internet in various ways to promote communication and education ListServes – Breast Implants www.fda.gov/cdrh/bicl

78. 78 Providing Industry Assistance Division of Small Manufacturers, International, and Consumer Assistance Phone: 800-638-2041 or 301-443-6597 Email: DSMICA@cdrh.fda.gov Website www.fda.gov/cdrh Educational Programs GuidanceTeleconferencesLabeling Human Factors

79. 79 Facilitating Technology and Innovation Technology and Innovation Challenges Role of FDA Meeting the Challenge Accelerated Pace of Technology and Innovation Complexity of New Technology Establishing safety and effectiveness of complex technologies faster and cost-effectively Assuring postmarket medical device safety by identifying adverse events so rare or that occur under specific conditions Communicating medical device existence and usefulness to the public CDRH Strategic Planning Meeting MDUFMA Goals Strengthening our workforce for the 21st century Enhancing knowledge management Achieving pre/postmarket balance Conducting business in an open and transparent manner

80. 80