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

1. Understanding the Regulatory Landscape.

3. Device Classifications / Submission Types

4. Approval / Clearance Requirements

5. Investigational Devices

6. Combination Products Presentation Outline

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. 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

10. Issued regulation classifying most types of medical devices

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. 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)

17. Necessary to reasonably assure device safety and effectiveness

19. 510(k) premarket notification

20. Labeling

22. In some cases, exempt from QSR compliance, other than minimal record keeping and reporting

24. Postmarket surveillance

26. Labeling

27. QSR Compliance

28. Device Listing

30. Life supporting

31. Implantable devices

33. Unless marketed prior to May 28, 1976 (Preamendment devices)

34. Most stringently regulated

36. premarket approval (PMA)

37. Unless the device is exempt

38. Candidate for alternate submission

41. Narrative and tabular comparisons

42. Predicate device’s intended use, indications

43. Technological characteristics

45. Sterility information

46. Biocompatibility information

47. Statement or declarations of conformance to applicable standards and guidance documents

48. Summaries of any performance testing

50. 510(k) summary

51. Payment of a user fee

54. Same technological characteristics or;

56. Animal

57. Clinical data

59. Technological characteristic

60. Clinical trials

61. Conclusions

63. Unless the FDA reclassifies into Class I or II

66. Petition the agency in writing for De Novo down classification within 30 days of receipt of the letter

70. Description of the device

71. Labeling

72. Justification for recommendation classification

78. Convenes an advisory committee

79. Nonbinding recommendation to FDA

80. FDA inspects manufacturer’s facilities to QSR

82. Non approvable (identifies major deficiencies) PMA

87. Sterility information

88. Biocompatibility information

89. Extensive clinical trials

90. Animal studies

91. Bench tests

92. Published and unpublished literature

93. Bibliography of all published reports known concerning the device’s safety or effectiveness

94. Investigational Device Exemptions Devices that are not approved or cleared and are used in clinical trials must be labeled as Investigational Devices “IDE”

96. Significant risk

97. Prior approval by an Institutional Review Board (IRB)

98. Informed consent of patients

99. FDA approval of an IDE application

101. Clinical study protocol

103. Intended as an implant

104. Used in supporting or sustaining human life

106. Curing

107. Mitigating or treating a disease

110. Informed consent

111. Need not obtain FDA approval before study begins

114. Device – Biologic

115. Biologic – Drug

117. What is a Combination Product? Stent Drug Stent Delivery System Polymer Slide courtesy of Nadine Ding, Guidant Corporation

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. 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. 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

122. Drug-eluting disc (oncology) CDER

123. Contact lens/glaucoma drug CDER

124. Contact lens/glaucoma drug (new submission) CDER

125. Spinal fusion device/therapeutic protein CDRH

126. Chemo drug/monoclonal antibody CDER

127. Scaffold seeded with autologous cells CBER

128. Interferon/Ribivarin therapy CDER

129. Embolization implant device/chemo drug CDRH

130. Vertobroplasty device/analgesic CDRH

132. FDA Office of Combination Products http:// www.fda.gov/oc/combination /

133. FDA US Agent http:// www.fda.gov/cdrh/usagent/index.html

134. FDA Establishment and Device Listing Forms http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/printforms.cfm

135. Thank you For additional information contact: Medical Device Launchpad 800.525.0975