FDA Regulation of Medical Devices

Transcription

1 FDA Regulation of Medical Devices Bradley Merrill Thompson Interpharm Press, Inc. Buffalo Grove, IL

2 Dedication Acknowledgments Introduction xv xvi xvii Part I. Overview Chapter 1. The History of Medical Device Regulation 3 BEFORE FEDERAL FOOD, DRUG, AND COSMETIC ACT OF RADIATION EMITTING DEVICES 5 THE COOPER COMMITTEE AND THE 1976 AMENDMENTS 5 THE 1980s 7 GENERIC DRUG SCANDAL 8 SAFE MEDICAL DEVICES ACT OF BREAST IMPLANTS AND HEART VALVES 10 THE 1990s ENFORCEMENT AND REVIEW DELAYS 10 iii

3 iv Chapter 2. How to Find and Understand Device Law 13 SOURCES OF LAW 13 FREEDOM OF INFORMATION ACT 15 OTHER WAYS OF GETTING MEDICAL DEVICE REGULATORY INFORMATION 19 CONCLUSION 20 Chapter 3. The Rule-Making Process How to Participate 21 ADMINISTRATIVE PROCEDURES ACT 21 STRUCTURE OF THE FOOD AND DRUG ADMINISTRATION 23 CONCLUSION 24 Part II. Devices: Definition and Classification Chapter 4. The Scope of Device Regulation 29 STATUTORY DEFINITION OF A DEVICE 29 INTERPRETATIONS OF THE DEVICE DEFINITION 31 Diagnostic Devices Components and Accessories Computer Products Production Equipment Transitional Devices Combination Products Veterinary Devices Miscellaneous Devices CONCLUSION 39 Chapter 5. Device Classification and Reclassification 41 DEVICE CLASSIFICATION 41 PROBLEMS WITH THE CLASSIFICATION SCHEME 43 RECLASSIFICATION 43

4 v The Standard Reclassification Procedures Benefits and Burdens of Reclassification Experiences with Reclassification SMDA Changes Affecting Reclassification CONCLUSION 58 Part III. Premarket Controls Chapter 6. Premarket Notification 61 APPLICABILITY OF PREMARKET NOTIFICATION PROCEDURES 61 Exemptions Device Modifications Transferability Who Needs to File the 510(k) SUBSTANTIAL EQUIVALENCE 79 Intended Use Technological Features Performance Data THE 510(k) PROCESS 87 Writing a 510(k) The Notice Confidentiality FDA Review Expedited Review Communication Policy The Decision Agency and Judicial Review SPECIAL RULES 102 Product-Specific Rules Class III Devices

5 vi Kits Computer-Controlled Medical Devices CONCLUSION 104 Chapter 7. Investigational Devices 105 EXEMPTIONS FROM IDE REQUIREMENTS 105 In General IVD Device Exemption THE IDE PROCESS 113 The Players Significant and Nonsignificant Risk Devices The IDE Application Process Sponsor and Investigator Obligations Informed Consent IRB Procedures GOOD LABORATORY PRACTICE REGULATIONS 128 STUDY DESIGN 129 EMERGENCY USE 131 HUMANITARIAN DEVICE EXEMPTION 131 FEASIBILITY STUDIES 132 The Need for Feasibility Studies Feasibility Studies under the IDE Regulations The Custom Device Exemption The ASAIO Proposal The Feasibility Guidance The IND Rewrite Conclusion COMMERCIALIZATION AND PROMOTION 138 CONCLUSION 140

6 vii Chapter 8. Premarket Approval 141 SCOPE OF THE PMA PROCESS 141 THE PMA APPLICATION 142 Environmental Assessments Accessing Data in Other Files Confidentiality Foreign Data FDA REVIEW PROCESS 151 Filing Procedures for Review Panel Review Expedited Review Standard for Review The Decision Agency and Judicial Review Permanent and Temporary Suspension of PMA Postapproval Requirements Amendments, Supplements, and Reports CONCLUSION 162 Chapter 9. Product Development Protocol 163 PMA AND PDP PROCEDURES COMPARED 164 The PDP Procedure under Section 515(0 The FDA's Guideline on the PDP Procedure The PMA and PDP Compared EXPERIENCE WITH THE PDP PROCEDURE 168 BENEFITS AND PROBLEMS 169 NEEDED IMPROVEMENTS TO THE PDP PROCEDURE 170

7 viii Expanded Scope Flexibility Confidentiality CONCLUSION 175 Part IV. Postmarket Controls Chapter 10. Registration and Listing 179 REGISTRATION 179 Activities That Trigger the Registration Requirement Exemptions The Registration Process LISTING 184 Who Must List? What Devices Are Subject to the Listing Requirement? When Is Listing Required? How and Where Is the Listing Completed? What Information Is Required? Listing Updates Historical File CONCLUSION 186 Chapter 11. Good Manufacturing Practices 189 APPLICABILITY OF GMP REQUIREMENTS 189 Applicability General Exemptions Component Manufacturers Service Firms Custom Device Manufacturing Contract Manufacturer Contract Testing Laboratory Repackager or Relabeler

8 ix Imported Products Special Exemptions or Variances OVERVIEW OF THE GMP REQUIREMENTS 193 Quality Assurance System Preproduction Quality Assurance Buildings and Sanitation Equipment and Calibration Device Master Records Change Control Components Production Finished Device Evaluation Labeling Packaging Distribution Complaint and Failure Investigations Quality Assurance Audit PROPOSED CHANGES TO THE GMP REGULATIONS 214 SPECIAL RULES FOR PARTICULAR MEDICAL DEVICES 216 In Vitro Diagnostics Computerized Medical Devices CONCLUSION 218 Chapter 12. Device Labeling, Advertising, and Promotion 219 AN OVERVIEW OF THE REGULATORY SCHEME 219 LABELING REQUIREMENTS 221 EXEMPTIONS FROM LABELING REQUIREMENTS 222 Blanket Exemptions Exemptions from Requirement for Adequate Directions for Use SPECIAL CASES 224

9 x In Vitro Diagnostic Devices General Purpose Laboratory Reagents and Equipment Investigational Devices Devices Subject to Premarket Review Restricted Devices Radiation-Emitting Devices TIPS FOR WRITING LABELING 228 ADVERTISING 229 PROMOTION 229 CONCLUSION 232 Chapter 13. Device Adulteration 233 QUALITY STANDARDS 233 PERFORMANCE STANDARDS 234 Procedures for Adopting Performance Standards Voluntary Standards COLOR ADDITIVES 237 What Is Color Additive? When Do Color Additives Require Approval? How to Obtain Premarket Clearance for Color Additives CONCLUSION 239 Chapter 14. Tracking and Postmarket Surveillance 241 MEDICAL DEVICE TRACKING 241 Statutory Basis Original Proposal Reproposal Final Rule An Improvement POSTMARKET SURVEILLANCE 250 Types of Devices PMS Requirements Enforcement and Experience CONCLUSION 257

10 xi Chapter 15. Reporting Obligations 259 OVERVIEW OF REPORTING OBLIGATIONS 259 MANUFACTURING REPORTING OBLIGATIONS 261 The 1984 Regulation Changes to the MDR Regulation Current Status of the Law DISTRIBUTOR REPORTING OBLIGATIONS 265 USER FACILITY REQUIREMENTS 266 COMPLETING THE MEDWATCH FORM 269 CERTIFICATIONS 275 REPORTING CORRECTIONS AND PRODUCT REMOVALS 275 CONCLUSION 277 Chapter 16. Exporting and Importing Devices 279 FDA EXPORT REQUIREMENTS 279 Exports of Adulterated or Misbranded Devices Exports of Certain High Risk Devices Certificates of Products for Export MEDICAL DEVICE IMPORT PROCEDURES 285 General Regulatory Requirements Registration and Listing Border Procedures CONCLUSION 292 Part V. Enforcement Chapter 17. FDA Inspections 295 FDA INSPECTION PROCEDURES 295 A MANUFACTURER'S RIGHTS 296 SAMPLE INSPECTION PLAN 298 Greeter Notice of Inspection Host

11 xii Preinspection Meeting Cameras and Recorders Timing Inspection Conduct Records Samples Exit Interview and FDA 483 Establishment Inspection Report Warning Letter CONCLUSION 308 Chapter 18. FDA Enforcement 309 PROHIBITED ACTS 309 FDA DISCRETION 310 AGENCY REMEDIES 313 Civil Penalties Recalls Administrative Detention Banning Devices Notification and Repair, Replacement, or Refund Publicity Revocation of Approvals JUDICIAL ENFORCEMENT 320 Criminal Penalties Seizure and Condemnation Injunction The FDA's Choice of Remedies OTHER ENFORCEMENT ACTIVITIES 324 Other Federal Criminal Statutes Private Lawsuits States PREVENTIVE MEASURES 325 CONCLUSION 326

12 xiii Part VI. The Interplay between Device Regulation and Other Regulatory Requirements Chapter 19. State Regulation of Medical Devices 329 WHAT STATE LAWS CAN BE PREEMPTED 330 EXEMPTION FROM PREEMPTION 331 IMPACT OF PREEMPTION ON PRODUCT LIABILITY 332 CONCLUSION 334 Chapter 20. Other Federal Regulatory Schemes 335 RADIATION-EMITTING PRODUCTS 335 MEDICARE REIMBURSEMENT 339 REGULATION OF CLINICAL LABORATORIES 340 ENVIRONMENTAL REGULATION 342 CONCLUSION 344 Part VII. Conclusion Chapter 21. Future Projections 347 ENFORCEMENT 347 PREMARKET CLEARANCES 347 RULE MAKING 348 CONCLUSION 349 Appendices A. Sample Premarket Notification Letters 353 B. Instructions for Premarket Submission Cover Sheet 365 C. PMA Cover Letters 381 D. IDE Refuse to Accept Criteria 387

13 xlv E. PMA Refuse to File Criteria 393 F. Declaration of Helsinki 403 G. Engineering Change Procedure 407 H. Drafting and Approval of Labeling Procedure 421 I. Complaint Processing Procedure 427 J. MedWatch: Instructions for Completing FDA Form 3500A 439 K. Export Approval Letters 457 L CDRH Foreign Liaison Listing 463 M. Certificate for Products for Export 479 Indexes Case Law Index 489 Subject Index 491