Medical Device Development From Prototype to Regulatory Approval Aaron V. Kaplan, MD; Donald S. Baim, MD; John J. Smith, MD, JD; David A. Feigal, MD; Michael Simons, MD; David Jefferys, MD; Thomas J. Fogarty, MD; Richard E. Kuntz, MD, MSc; Martin B. Leon, MD T he treatment of cardiovascular disease has changed dramatically over the past 2 decades, allowing patients to live longer and better-quality lives. The introduc- tion of new therapies (both drugs and devices) has contrib- uted much to this success. Nowhere has this been more evident than in interventional cardiology, where percutaneous coronary intervention has evolved in the past 2 decades from a quirky experimental procedure to a therapeutic cornerstone for patients with coronary artery disease. In 2002, approxi- mately 800 000 percutaneous coronary intervention proce- dures were performed in the United States alone, compared with some 350 000 coronary bypass surgeries. This explosive growth has been fueled by the availability of new devices (guidewires, angioplasty balloons, stents, etc) coupled with validation by clinical data, primarily in the form of random- ized clinical trials. However, important differences have evolved in the clinical-regulatory environment between the United States and Europe that have impacted the location of clinical testing and the relative timing of commercial avail- ability. This has led to substantial differences in the speed of introduction and the extent of testing of these devices in the United States and Europe. A prime example of this difference can be seen in the introduction of the drug-coated stent that became available in European countries 1 year before its arrival in the United States. The Dartmouth Device & Drug Development Symposium was held in October 2003 with joint inventor, entrepreneur, industry, clinical, and regulatory participation, in an effort to characterize the process by which new interventional devices are currently developed and ap- proved. There was also an effort made to identify a series of “sticking-points” in the process, and to suggest some ways in which the efficiency of the process might be improved. This article will review these findings. Invention Although large medical device companies typically develop successive iterations of existing devices, most new device categories are typically developed by venture-backed start-up companies. Typically, a physician and/or engineer inventor conceives of a device solution to an unmet clinical challenge, initiates the patent process, and builds preliminary device prototypes. Preliminary bench and animal testing may be performed using the inventor’s or an acquaintance’s personal funding (angel investors). Further development typically requires engaging a team of engineers who work closely with physician advisors to bring the concept through the “design- The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Cardiology Section, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH (A.V.K., M.S.); Department of Medicine, Brigham and Women’s Hospital, Boston, Mass (D.S.B., R.E.K.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (J.J.S.); Devices Sector, Medical Devices Agency-United Kingdom (D.J.); Department of Surgery, Stanford University, Stanford, Calif (T.J.F.); and Lenox Hill Heart and Vascular Institute, New York, NY (M.B.L.). Dr Feigal is the former Director of the Center for Devices and Radiologic Health, Food and Drug Administration–USA. This article is the result in part from Sessions at the Dartmouth Drug and Device Development Symposium (3DI) held at the Woodstock Inn, Woodstock, Vt, October 30 and 31, 2003. Correspondence to Aaron V. Kaplan, MD, Section of Cardiology, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756-0001. E-mail aaron.v.kaplan@hitchcock.org (Circulation. 2004;109:3068-3072.) © 2004 American Heart Association, Inc. Circulation is available at http://www.circulationaha.org DOI: 10.1161/01.CIR.0000134695.65733.64 MINI-REVIEW: EXPERT OPINIONS 3068 by guest on February 9, 2016 http://circ.ahajournals.org/ Downloaded from