Understanding FDA Regulations

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the FDA regulatory landscape is in flux, especially with respect to medical devices

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Understanding FDA Regulations

  1. 1. Understanding the Regulatory Landscape.
  2. 2. Presentation Outline <ul><li>FDA Overview
  3. 3. Device Classifications / Submission Types
  4. 4. Approval / Clearance Requirements
  5. 5. Investigational Devices
  6. 6. Combination Products </li></ul>Presentation Outline
  7. 7. FDA Structure / Organization FDA Structure / Organization Center for Veterinary Devices Food and Drug Administration Center for Biologics Evaluation and Research Center for Devices and Radiological Health National Center for Toxicological Research Center for Food Safety and Applied Nutrition Center for Drug Evaluation and Research Office of Combination Products
  8. 8. CDRH Offices Office of Device Evaluation Office of In-Vitro Diagnostic Devices & Safety Office of Health & Industry Programs Office of Science & Technology Office of Compliance Office of Surveillance & Biometrics Center for Devices and Radiological Health
  9. 9. FDA Regulatory Framework <ul><li>Federal Food, Drug and Cosmetic Act (FDC Act)
  10. 10. Issued regulation classifying most types of medical devices </li></ul>
  11. 11. Entering the US Device Market <ul><li>Exempt medical devices
  12. 12. Established two primary routes for obtaining authorization to market medical devices </li></ul><ul><ul><li>510(k) premarket clearance
  13. 13. Premarket approval (PMA) </li></ul></ul><ul><li>Vast majority of nonexempt cleared via a 510(k) or approved via the PMA process </li></ul>
  14. 14. FDA Premarket Submissions Type of Submission FY02 FY03 FY04 Original PMA 49 54 51 510(k) 4,320 4,247 3,635 PMA Supplement 645 666 635 Original HDE 5 10 9 HDE Supplement 16 29 29 Original IDE 312 242 226 IDE amendment 252 216 167 IDE supplement 4,724 4,415 4,312 Total 10,323 9,879 9,064
  15. 15. FDA Medical Device User Fees   FY2008 Standard Fee (U.S. Dollars) Small Business Fee 510(k) Submission $3,404 $1,702 PMA Submission $185,000 $46,250 FDA Fees FY2008 (Oct. 1, 2007 - Sept. 30, 2008)
  16. 16. FDA Classification <ul><li>Three classes based on the levels of controls
  17. 17. Necessary to reasonably assure device safety and effectiveness </li></ul>
  18. 18. Class I Devices <ul><li>Subject to general controls </li></ul><ul><ul><li>Device listing
  19. 19. 510(k) premarket notification
  20. 20. Labeling
  21. 21. FDA quality system regulations (QSR) compliance </li></ul></ul><ul><li>Most Class I </li></ul><ul><ul><li>Exempt from 510(k) premarket notification
  22. 22. In some cases, exempt from QSR compliance, other than minimal record keeping and reporting </li></ul></ul>
  23. 23. Class II Devices <ul><li>Subject to general and special controls </li></ul><ul><ul><li>Performance standards
  24. 24. Postmarket surveillance
  25. 25. FDA guidelines </li></ul></ul><ul><li>Most Class II </li></ul><ul><ul><li>Require 510(k) submission
  26. 26. Labeling
  27. 27. QSR Compliance
  28. 28. Device Listing </li></ul></ul>
  29. 29. Class III Devices <ul><li>Subject to general and special controls </li></ul><ul><ul><li>Life sustaining
  30. 30. Life supporting
  31. 31. Implantable devices
  32. 32. New devices – not found to be substantially equivalent to legally marketed devices </li></ul></ul><ul><li>Most Class III </li></ul><ul><ul><li>Require approval of a PMA
  33. 33. Unless marketed prior to May 28, 1976 (Preamendment devices)
  34. 34. Most stringently regulated </li></ul></ul>
  35. 35. Approval / Clearance Criteria <ul><li>Before a company can market a new device, manufacturer must obtain from the FDA </li></ul><ul><ul><li>510(k) premarket clearance, or
  36. 36. premarket approval (PMA)
  37. 37. Unless the device is exempt
  38. 38. Candidate for alternate submission </li></ul></ul>
  39. 39. 510(k) Requirements <ul><li>Description of the new device </li></ul><ul><ul><li>Photographs
  40. 40. Engineering drawing </li></ul></ul><ul><li>Labeling </li></ul><ul><ul><li>Draft promotional materials </li></ul></ul><ul><li>Identification of predicate device(s)
  41. 41. Narrative and tabular comparisons
  42. 42. Predicate device’s intended use, indications
  43. 43. Technological characteristics
  44. 44. Principles of operation </li></ul><ul><li>Software documentation
  45. 45. Sterility information
  46. 46. Biocompatibility information
  47. 47. Statement or declarations of conformance to applicable standards and guidance documents
  48. 48. Summaries of any performance testing
  49. 49. Administrative requirements </li></ul><ul><ul><li>Truthfulness and accuracy statement
  50. 50. 510(k) summary
  51. 51. Payment of a user fee </li></ul></ul>
  52. 52. Some Cases to Support 510(k) <ul><li>Laboratory Testing </li></ul><ul><li>Clinical Testing </li></ul>
  53. 53. Substantial Equivalence <ul><li>A device is substantially equivalent to a legally marketed predicate device </li></ul><ul><ul><li>Both have the same intended use
  54. 54. Same technological characteristics or;
  55. 55. Different technological characteristics do not raise any new questions of safety or effectiveness and performance data that demonstrates the new device is as safe and effective as the predicate device </li><ul><li>Bench
  56. 56. Animal
  57. 57. Clinical data </li></ul></ul></ul>
  58. 58. Substantial Equivalence Analysis <ul><li>Intended use / indication for use
  59. 59. Technological characteristic
  60. 60. Clinical trials
  61. 61. Conclusions </li></ul>
  62. 62. Substantial Equivalence <ul><li>If the FDA concludes substantially equivalent </li></ul><ul><ul><li>Issue an order granting 510(k) clearance </li></ul></ul><ul><li>If the FDA concludes not substantially equivalent </li></ul><ul><ul><li>The device is a Class III, requires PMA approval
  63. 63. Unless the FDA reclassifies into Class I or II </li></ul></ul>
  64. 64. De Novo Down Classification <ul><li>FDA issues a not substantially equivalent
  65. 65. Two options </li></ul><ul><ul><li>Proceed with submission of a PMA
  66. 66. Petition the agency in writing for De Novo down classification within 30 days of receipt of the letter </li></ul></ul>
  67. 67. De Novo Down Classification <ul><li>To qualify, the device must be both “novel and low risk”
  68. 68. Novel </li></ul><ul><ul><li>Limits to not previously classified FDC Act and classified by written notice </li></ul></ul><ul><li>Low Risk </li></ul><ul><ul><li>Application to lower-risk devices the agency has found not substantially equivalent for the lack of a predicate device </li></ul></ul>
  69. 69. De Novo Requirements <ul><li>Within 30 days
  70. 70. Description of the device
  71. 71. Labeling
  72. 72. Justification for recommendation classification
  73. 73. Information to support the recommendation </li></ul><ul><ul><li>bench, animal, human clinical data </li></ul></ul><ul><li>Usually clinical data is required </li></ul>
  74. 74. De Novo Review <ul><li>FDA has 60 days to review the petition
  75. 75. If FDA classifies the device into Class I or II </li></ul><ul><ul><li>Special control guidance issues
  76. 76. Device that can be used a predicate </li></ul></ul><ul><li>If FDA determines that the device remains Class III </li></ul><ul><ul><li>PMA approval required to market </li></ul></ul>
  77. 77. PMA Requirements <ul><li>Must demonstrate safety and effectiveness of a new device, supported by valid scientific evidence
  78. 78. Convenes an advisory committee
  79. 79. Nonbinding recommendation to FDA
  80. 80. FDA inspects manufacturer’s facilities to QSR
  81. 81. FDA issues </li></ul><ul><ul><li>Approval letter, or
  82. 82. Non approvable (identifies major deficiencies) </li></ul></ul>PMA
  83. 83. PMA Requirements <ul><li>Complete description of the device
  84. 84. Complete description of the components </li></ul><ul><ul><li>Photographs
  85. 85. Engineering drawings of the device </li></ul></ul><ul><li>Detailed description of the methods, facilities and controls used to manufacture
  86. 86. Prepared labeling, advertising literature, any training material </li></ul><ul><li>Software documentation
  87. 87. Sterility information
  88. 88. Biocompatibility information
  89. 89. Extensive clinical trials
  90. 90. Animal studies
  91. 91. Bench tests
  92. 92. Published and unpublished literature
  93. 93. Bibliography of all published reports known concerning the device’s safety or effectiveness </li></ul>
  94. 94. Investigational Device Exemptions Devices that are not approved or cleared and are used in clinical trials must be labeled as Investigational Devices “IDE”
  95. 95. Investigational Device Exemptions <ul><li>The FDA may request </li></ul><ul><ul><li>Submission of animal or human clinical data to demonstrate equivalence or safety and effectiveness of a device
  96. 96. Significant risk
  97. 97. Prior approval by an Institutional Review Board (IRB)
  98. 98. Informed consent of patients
  99. 99. FDA approval of an IDE application </li></ul></ul>
  100. 100. IDE Application <ul><li>21 CFR Part 812
  101. 101. Clinical study protocol
  102. 102. A significant risk device study </li></ul><ul><ul><li>Potential for serious risk to health, safety or welfare to the subjects
  103. 103. Intended as an implant
  104. 104. Used in supporting or sustaining human life
  105. 105. Substantial importance in </li><ul><li>Diagnosing
  106. 106. Curing
  107. 107. Mitigating or treating a disease
  108. 108. Prevents impairment of human health </li></ul><li>Potential for serious risk to health, safety or welfare of a subject </li></ul></ul>
  109. 109. IDE Application <ul><li>Non significant risk (NSR) investigated device </li></ul><ul><ul><li>Requires IRB approval
  110. 110. Informed consent
  111. 111. Need not obtain FDA approval before study begins </li></ul></ul>
  112. 112. What is a Combination Product? <ul><li>Safe Medical Device Act (1990)
  113. 113. 503(g)(1) Products that constitute a combination of a drug, device or biologic </li></ul><ul><ul><li>Drug – Device
  114. 114. Device – Biologic
  115. 115. Biologic – Drug
  116. 116. Drug – Device – Biologic </li></ul></ul><ul><li>Note: Drug – Drug, or Device - Device combination not included here </li></ul>
  117. 117. What is a Combination Product? Stent Drug Stent Delivery System Polymer Slide courtesy of Nadine Ding, Guidant Corporation
  118. 118. Challenge of Combination Products CDRH CDER CBER NDA, BLA PMA, 510(K) IND, IDE Device Drug Biologic Different Frameworks Different Product Types Different FDA Reviews IND, NDA IDE, PMA, 510(k) IND, BLA CDER CDRH CBER Drug Device Biologic
  119. 119. Challenge of Combination Products Product Pre-Market Framework Approval FDA Reviewing Center Quality System Safety Reporting Device IDE PMA, 510(k) CDRH QSR MDR Drug IND NDA CDER GMP AERS Biologic IND BLA CBER / CDER GMP AERS Regulatory Complexity
  120. 120. Drug Eluting Stent System Design Slide courtesy of Nadine Ding, Guidant Corporation Drug Matrix Drug – polymer compatibility Loading capacity Release kinetics Pharmacology Polymer Chemistry Stent Tissue Mechanical scaffolding Mechanical Engineering Vascular Biology Coating integrity Vascular biology Tissue pharmacokinetics Preclinical models Vascular biology
  121. 121. Real World Examples <ul><ul><li>Drug-eluting stent CDRH
  122. 122. Drug-eluting disc (oncology) CDER
  123. 123. Contact lens/glaucoma drug CDER
  124. 124. Contact lens/glaucoma drug (new submission) CDER
  125. 125. Spinal fusion device/therapeutic protein CDRH
  126. 126. Chemo drug/monoclonal antibody CDER
  127. 127. Scaffold seeded with autologous cells CBER
  128. 128. Interferon/Ribivarin therapy CDER
  129. 129. Embolization implant device/chemo drug CDRH
  130. 130. Vertobroplasty device/analgesic CDRH </li></ul></ul>
  131. 131. Links and Resources <ul><li>FDA Center for Devices and Radiological Health (CDRH) http:// www.fda.gov/cdrh/index.html
  132. 132. FDA Office of Combination Products http:// www.fda.gov/oc/combination /
  133. 133. FDA US Agent http:// www.fda.gov/cdrh/usagent/index.html
  134. 134. FDA Establishment and Device Listing Forms http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/printforms.cfm </li></ul>
  135. 135. Thank you For additional information contact: Medical Device Launchpad 800.525.0975

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