CDRH Update Facilitating Medical Device Innovation and Technology Dan

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 1

What is a Device? 2

A Computer That Helps You Hear 3

Miniaturized Devices Electrical Stimulators Pacemakers 4

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

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

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 7

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

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

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

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

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 12

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 13

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

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

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

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

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

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

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

Medical Device Industry Growth Number of Manufacturers by Year 16000 14000 12000 Ophthalmic Eletromedical X-Ray Dental Surgical Instruments Diagnostics 10000 8000 6000 4000 2000 0 1998 1999 2000 2001 2002 2003 2004 Dun & Bradstreet Medical Device Firm Data 21

Sales Volume Growth (Billions of Dollars) 350 Billions of Dollars 300 Ophthalmic 250 Electromechanical 200 X-Ray 150 Surgical 100 Instruments Dental Diagnostics 50 0 1998 2000 Year 2003 2004 Note: No economic adjustment to dollar value 22

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 23

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 24

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

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 26

Medical Device Program CDRH: Types and Numbers of Submissions Received TYPE OF SUBMISSION Original PMA* FY 99 FY 00 FY 01 FY 02 FY 03 FY 04 64 67 71 49 54 51 PMA Supplement* 557 546 641 645 666 635 Original IDE 304 311 284 312 242 226 IDE Amendment 275 240 206 252 216 167 IDE Supplement 4,127 4,388 4,811 4,724 4,415 4,312 510(k) – 10% with clinical data* 4,458 4,202 4,248 4,320 4,247 3,635 12 11 5 5 10 9 4 10 16 16 29 29 9,801 9,775 10,282 10,323 Original HDE HDE Supplements Total 9,879 9,064 * The majority of PMAs and 510(k) applications are subject to fees. Exceptions include small business and pediatric applications. 27

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. 28

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

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

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” 31

Meeting Technology Innovation Challenges 32

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 33

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 Meet MDUFMA performance goals Strengthen our workforce for the 21st century 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 FY 05 MDUFMA performance goals Quality system for application review Review consults CoA studies Risk -based inspections MedSun and LabSun Priority hiring Professional development External expertise (MDFP and other initiatives) CDRH Strategi c Goals Knowledge Management Enhance use of information and communication systems to support TPLC TPLC Align CDRH programs to effectively manage the product life cycle CDRH Prioritie s Enhance our knowledge management Achieve better pre/postmarket regulatory balance Scoreca rd 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 Priority Initiativ es Guidance/ standards Targeted IT initiatives Infrastructure upgrades Turbo 510(k) eConsult OIVD Model Research prioritization Radiological Health Strategy GHTF Organizational 34 scorecards

Priority Hiring 50 Hired Office FY 03 45 Hired FY 04 Two Year Totals Total MDUFMA Hires (#Shared) 40 35 30 25 20 Total 75 57 132 (18 Shared) OC 10 7 17 (1 Shared) ODE 29 15 44 (6 Shared) OCR 4 2 6 (0 Shared) OIVD 11 6 17 (0 Shared) OSB 6 11 18 (1 Shared) OSM/OCD 4 3 6 (0 Shared) OSEL 11 13 24 (11 Shared) 15 FY 04 10 FY 03 5 0 Medical Officers Engineers Scientists Project Managers Program Support CSOs Statistician FY 03 and FY 04 Hires (by Specialty) Attorney 35

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

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

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 38

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% 39

Global Harmonization Task Force Mission: Encourage the convergence of medical device regulatory practices worldwide where possible, while ensuring the safety, effectiveness, and quality of medical devices. 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 40

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 41

IT Initiatives Premarket Review Modernization Postmarket Medical Device Reporting (eMDR) ODE and OC Tracking Systems Electronic Registration and Listing eConsult Image2000 Turbo 510(k) 42

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 43

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 44

Research Prioritization Criteria For Rating Projects Regulatory 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. 45

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

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 47

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

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

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

Working Towards Meeting Performance Goals 51

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

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

MDUFMA Performance Goals PMAs and Panel-track Supplements FDA FDA Decisions Decisions within within 320 320 Days Days FY 2003 Cohort FY 2004 Cohort FY 2005 Cohort Goal: None until FY 2006 88.9% 93.3% 96.6% 97.4% Goal: None until FY 2006 100.0% 100.0% 100.0% 100.0% Goal: None until FY 2006 — 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) Performance Measured at 3 months into FY 6 months into FY 9 months into FY End of FY (12 months) 25 (of 47) TBD 54

MDUFMA Performance Goals PMAs and Panel-track Supplements First First Action Action “Major “Major Deficiency” Deficiency” Letter Letter within within 150 150 Days Days Performance Measured at FY 2003 Cohort FY 2004 Cohort FY 2005 Cohort Goal: None until FY 2005 Goal: None until FY 2005 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% 21 months after start of FY 84.0% 24 months after start of FY 84.0% 27 months after start of FY 84.0% Remaining to close cohort — 5 TBD 55

MDUFMA Performance Goals 180-day Supplements FDA FDA Decisions Decisions within within 180 180 Days Days FY 2003 Cohort FY 2004 Cohort Goal: None until FY 2005 Goal: None until FY 2005 3 months into FY 87.7% 86.4% 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% 27 months after start of FY 94.1% Remaining to close cohort — (of 203) Performance Measured at0 18 (of 103) FY 2005 Cohort Goal: 80% 100.0% TBD 56

MDUFMA Performance Goals 180-day Supplements First Action “Not Approvable” Letter within 120 Days FY 2003 Cohort FY 2004 Cohort Goal: None until FY 2005 Goal: None until FY 2005 3 months into FY — — 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% 27 months after start of FY 16.1% Remaining to close cohort — Performance Measured at 16 FY 2005 Cohort Goal: 80% 100.0% TBD 57

MDUFMA Performance Goals 510(k)s SE, NSE Decisions Decisions within within 90 90 Days Days FY 2003 Cohort FY 2004 Cohort Goal: None until FY 2005 100.0% 96.1% 90.7% 87.1% Goal: None until FY 2005 100.0% 95.6% 90.7% 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) Performance Measured at 3 months into FY 6 months into FY 9 months into FY End of FY (12 months) 376 (of 3,411) FY 2005 Cohort Goal: 75% 100.0% TBD 58

MDUFMA Performance Goals 510(k)s First Action “Additional Information” Information” Letter Letter within within 75 75 Days Days FY 2003 Cohort FY 2004 Cohort Performance Measured at 3 months into FY Goal: None until FY 2005 90.0% Goal: None until FY 2005 93.5% 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 25 376 FY 2005 Cohort Goal: 70% 99.6% TBD 59

Assuring Postmarket Medical Device Safety FDA under scrutiny Identifying Identifyingadverse adverseevents eventsso sorare rareor orthat thatoccur occurunder under specific specificconditions conditions 60

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

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

Device GMP/QS Inspection Trends 3500 Statutory Requirement 3000 2500 2000 Domestic Foreign 1500 1000 500 0 FY96 FY97 FY98 FY99 FY00 FY01 FY02 FY03 63

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

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) 65

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 66

Achieving Pre/Postmarket Balance 67

F.D.A. Moves Toward More Openness With the Public FDA to create drug safety board Independent panel to monitor medicines once they're on market 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. A start, not a cure, for FDA 68

Building Better Reporting Systems Adverse Event Reporting System Product Problems Mandatory Reporting FDA Voluntary Reporting Clinical Problems 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

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 70

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 71

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 72

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 73

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. 74

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 75

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 76

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 77

Providing Industry Assistance Division of Small Manufacturers, International, and Consumer Assistance Phone: 800-638-2041 or 301-443-6597 Email: [email protected] Website www.fda.gov/cdrh Educational Programs Guidance Teleconferences Labeling Human Factors 78

Facilitating Technology and Innovation Technology and Innovation Challenges Accelerated Pace of Technology and Innovation Complexity of New Technology Role of FDA 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 Meeting the Challenge 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 79

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