AXENDIA  Bringing Medical Devices to the Market Bringing Medical Devices to the Market Paths and Pitfalls By Daniel R. Matlis and David J. Lennard February 21 st, 2007

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Agenda Business Issues Facing The Device Industry FDA Requirements For Medical Devices Medical Device Submission Vehicles Same Or Novel? Design Changes: Knowing When To Stop Discussion

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, About the Speakers David J. Lennard 30 years experience in Life-Sciences 25 years with Johnson & Johnson Worked in project management, manufacturing, product/process development, clinical research, medical device reporting, product liability, regulatory affairs and quality assurance and compliance Holds two U.S. Patents Daniel R. Matlis 16 Years Experience in Life-Sciences Involved in projects spanning R&D, Manufacturing, Regulatory Compliance, Business Development Sales, Marketing and Information Technology. Governance, Risk Management and Compliance Computer System and Software Compliance

AXENDIA  Business Issues Facing the Device Industry

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Business Issues Market Factors Reimbursement Intellectual Property Manufacturing Factors Import / Export Laws 40% of approved device firms manufacture abroad Sales, Marketing and Licensing Better to be first than Best Know your buyer Know your competition Regulatory Factors Device Development Studies conducted world-wide Post Marketing Vigilance is a world-wide network Application formats are becoming harmonized Inspectional Methods are converging

AXENDIA  FDA Requirements for Medical Devices

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, FDA’s Role in Technology and Innovation Technology and Innovation Challenges Role of FDAMeeting 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

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Regulatory Process Differences DrugsBiologicsDevices FDA CenterCDERCBERCDRH R&DDiscoverIdentifyDesign Primary mode of effect ChemicalMetabolic Mechanical or Electrical Biological issues PharmacokineticTo xicity Systemic Toxicity Systemic & Local Biocompatibility Local Good Manufacturing Practice cGMP 21 CFR Part 210, 211 cGMP 21 CFR Part 211 QSR 21 CFR 820 Manufacturing Process Batch (Solid Dose, creams, ointments, injectable) Batch (Injectable) Batch (Simple) Serialized (Complex) Adverse Event Reporting Adverse Event Reporting System (AERS) Medical Device Reporting (MDR)

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Patchwork of Regulatory Requirements Food and Drug Administration Safety Effectiveness Clinical utility Hospital and Clinical Laboratory FDA Health Care Financing Administration (HCFA) Clinical Laboratory Improvement Amendments (CLIA) Mammography Quality Standards Act (MQSA) Other Authorities Federal Communications Commission (wireless, telemetry) Nuclear Regulatory Commission (Nuclear radiation) Rinse and Repeat for every country you plan to market in

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, The Basic Regulatory Requirements Manufacturers of medical devices distributed in the U.S. must comply with: Premarket Notification 510(k), unless exempt, or Premarket Approval (PMA), Establishment registration on form FDA-2891 Medical Device Listing on form FDA-2892 Quality System Regulation (QSR) Labeling Requirements Medical Device Reporting (MDR)

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Pre-Approval 510(k) Submission Components Medical Device User Fee Cover Sheet CDRH Premarket Review Submission Cover Sheet (voluntary) 510(k) Cover Letter Executive Summary Indications for Use Statement 510(k) Summary or 510(k) Statement Truthful and Accuracy Statement Class III Summary and Certification (if Applicable) Financial Certification or Disclosure Statement Device Description Substantial Equivalence Labeling Sterilization and Shelf Life Biocompatibility Software (if Applicable) Electromagnetic Compatibility and Electrical Safety (if Applicable) Performance Testing

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Post-Approval Quality System Regulation 21 CFR Part 820 Regulates methods used in & facilities and controls used for: Designing Purchasing Manufacturing Packaging Labeling Storing Installing Servicing Manufacturing facilities undergo FDA inspections to assure compliance with the QSR

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Risk-based Inspections RISK  Processes Inspection Risk QSR RISK  Quality (Patient) Factors Patient Safety No Correlation RISK  Processes Inspection Risk RISK  Quality (Patient) Factors QSR High Correlation Risk Based Inspection Approach Traditional Inspection Approach Patient Safety

AXENDIA  Medical Device Submission Vehicles

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, No Guarantees Even if you do all the right things, there are no guarantees FDA is “people” Target submission to facilitate review Focus your energies on meeting requirements, not working around them

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Who Decides Device Classification? FDA established classifications for approximately 1,700 different generic types of devices and grouped them into 16 medical specialties referred to as panels Anesthesiology 870 Cardiovascular 862 Clinical Chemistry and Clinical Toxicology 872 Dental 874 Ear, Nose, and Throat 876 Gastroenterology and Urology 878 General and Plastic Surgery 880 General Hospital and Personal Use 864 Hematology and Pathology 866 Immunology and Microbiology 882 Neurology 884 Obstetrical and Gynecological 886 Ophthalmic 888 Orthopedic 890 Physical Medicine 892 Radiology

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Class I: less stringent classification 47% of medical devices fall under this category Subject to general controls Premarket Notification 510(k), unless exempt 74% of the Class I devices are exempt from the premarket notification process Establishment registration Device Registration & Listing Quality System (QS) regulation (Good Manufacturing Practices –GMP’s) Labeling requirements Misbranding

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Class I Device Root canal post Dental floss Tongue depressor Surgeons glove

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Class II: Need to meet performance standards 43% of medical devices fall under this category In addition to general controls Class II require: post-market surveillance

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Class II Devices Oxygen mask Powered wheelchair Skull clamp Ultrasonic imager

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Class III Devices 10% of medical devices fall under this category Class III are those devices for which there is not enough information to show that general controls and performance standards would ensure their safety and effectiveness these include: devices implanted in the body life supporting or sustaining devices

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Class III Devices Intraocular lens Heart valve Infant radiant warmer Ventricular bypass device Blood cell separator Pacemaker

AXENDIA  Same or Novel

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Same or Novel The 510(k) paradox Proving Equivalency Different but not too different If you goal is to run a business Let the pendulum swing to approvable Then iterate for improvements Systems Approach to bringing device to market Involve all the key stake holder from the beginning

AXENDIA  Dealing with Design Changes Knowing when to Stop

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Knowing When to Stop Drawing the line in the sand Don’t wait for perfect! Safe and effective Be strict on setting release date goals

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Key Points Be familiar with the 510(k) regulations Check for CDRH Guidance Documents: Administrative Device Specific General Scientific Concerns Software EMC Material Safety Submission Checklists Consider FDA-recognized consensus standards

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, 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 Don’t look for Shortcuts

AXENDIA   Copyright 2007 by Axendia, Inc.Prepared for UCKIZ, February 21st, Discussion Contact Information David J. Lennard phone:(215) Daniel R. Matlis phone:(215) website: Journal: