Physician modification of legally marketed medical devices: Regulatory implications under the Federal Food, Drug, and Cosmetic Act

Food and Drug Law Journal

Volumn 55, Issue 2, 2000, Pages 245-254

  Smith, John J ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEVICE; DRUG APPROVAL; DRUG LEGISLATION; DRUG MANUFACTURE; FOOD AND DRUG ADMINISTRATION; INTERVENTIONAL RADIOLOGY; LAW; MARKETING; REVIEW;

DEVICE APPROVAL; EQUIPMENT DESIGN; HUMANS; MARKETING OF HEALTH SERVICES; PHYSICIANS; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 0033939037     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (58)

1. Pub. L. No. 75-717, 52 Stat. 1040 (1938) (codified as amended 21 U.S.C. §§ 301 et seq. (1994)).
2. Pub. L. No. 87-781, 76 Stat. 780 (codified at 21 U.S.C. §§ 321, 331-332, 348, 351-353, 355, 357-360, 372, 374, 376, 381 (1994)); see also United States v. An Article of Drug . . . Bacto-Unidisk . . . , 394 U.S. 784 (1969); AMP v. Gardner, 389 F.2d 825 (2d Cir. 1968), cert. denied, 393 U.S. 825 (1968).
3. Study Group on Medical Devices, Medical Devices: A Legislative Plan. (U.S. Dept of Health, Education, and Welfare 1970).
4. Pub. L. No. 94-295, 90 Stat. 539 (codified at 15 U.S.C. § 55 (1994); 21 U.S.C. §§ 31, 331, 334, 351, 352, 358, 360, 360c-k, 374, 379, 379a, 381).
5. FDCA § 513(a)(1)(A)(ii) (21 U.S.C § 360c(a)(1)(A)(ii)).
6. Today, under FDAMA, most devices in this category are § 510(k) exempt. But even when they are subject to the 510(k) process, they are regulated by the type of medical product, though they are approved "individually." For example, a surgical instrument, class I nonexempt, must be approved via a 510(k) process, but once approved, it is subject to existing regulations for the same type of device (i.e., guidance documents, general controls, etc.). A premarket approval application (PMA) device, generally class III and representing new technology, however, is subject to general controls and a unique set of regulatory controls depending on the product itself.
7. General controls include: prohibition of adulteration (FDCA § 501), prohibition of misbranding (§ 502), banned devices (§ 516); notification, repair, and replacement or refund (§ 518); records and reports (§ 519); and restricted devices (§ 520). Unless specifically exempted by regulation, general controls contain requirements for device manufacturers or other designated persons to: 1) register their establishment with FDA; 2) list their devices with FDA; 3) comply with labeling regulations in 21 C.F.R. pts. 801, 809, or 812; 4) submit a premarket notification to FDA; and 5) design and produce devices under good manufacturing practices. See generally CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH) & FDA, PREMARKET NOTIFICATION 510(K): REGULATORY REQUIREMENTS FOR MEDICAL DEVICES (1995) [hereinafter CDRH 1]. See also Rodney R. Munsey, Trends and Events in FDA Regulation of Medical Devices Over the Last Fifty Years, 50 FOOD & DRUG L.J. 163, 166 (1995); CDRH, FDA, Device Advice (last visited Aug. 17, 1999) .
8. General controls include: prohibition of adulteration (FDCA § 501), prohibition of misbranding (§ 502), banned devices (§ 516); notification, repair, and replacement or refund (§ 518); records and reports (§ 519); and restricted devices (§ 520). Unless specifically exempted by regulation, general controls contain requirements for device manufacturers or other designated persons to: 1) register their establishment with FDA; 2) list their devices with FDA; 3) comply with labeling regulations in 21 C.F.R. pts. 801, 809, or 812; 4) submit a premarket notification to FDA; and 5) design and produce devices under good manufacturing practices. See generally CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH) & FDA, PREMARKET NOTIFICATION 510(K): REGULATORY REQUIREMENTS FOR MEDICAL DEVICES (1995) [hereinafter CDRH 1]. See also Rodney R. Munsey, Trends and Events in FDA Regulation of Medical Devices Over the Last Fifty Years, 50 FOOD & DRUG L.J. 163, 166 (1995); CDRH, FDA, Device Advice (last visited Aug. 17, 1999) .
9. Special controls may include performance standards, postmarket surveillance, patient registries, development and dissemination of guidelines, recommendations, and related devices. In the absence of any special controls established by regulation, only general controls apply to class II devices. FDCA § 513(a)(1)(B). See generally CDRH, FDA, INVESTIGATIONAL DEVICES EXEMPTIONS MANUAL (1996) [hereinafter EXEMPTIONS MANUAL].
10. Special controls may include performance standards, postmarket surveillance, patient registries, development and dissemination of guidelines, recommendations, and related devices. In the absence of any special controls established by regulation, only general controls apply to class II devices. FDCA § 513(a)(1)(B). See generally CDRH, FDA, INVESTIGATIONAL DEVICES EXEMPTIONS MANUAL (1996) [hereinafter EXEMPTIONS MANUAL].
11. These products, again, are evaluated individually under § 510(k) (if applicable), but then subject to regulations for existing products.
12. 21 U.S.C. § 360c(a)(1)(C)(ii).
13. FDCA § 510(k).
14. Richard A. Merrill, The Architecture of Government Regulation of Medical Products, 82 VA. L. REV. 1753 (1996).
15. FDCA § 515.
16. Pub. L. No. 101-629, 104 Stat. 4511 (codified at 21 U.S.C. §§ 301 note, 321, 333, 333 note, 351, 353, 360, 360c, 360c note, 360d-i, 360i note, 360j, 360j note, 3601, 360gg-hh, 360hh note, 360ii-ss, 383, 383 note; 42 U.S.C. §§ 263b-n (1994)).
17. See William F. Pritchard & Ronald F. Carey, Primer on Medical Device Regulation: U.S. Food and Drug Administration and Regulation of Medical Devices in Radiology, 205 RADIOLOGY 27, 27-36 (1997); Lee H. Monsein, Primer on Medical Device Regulation, Part I: History and Background, 205 RADIOLOGY 1, 1-9 (1997).
18. See William F. Pritchard & Ronald F. Carey, Primer on Medical Device Regulation: U.S. Food and Drug Administration and Regulation of Medical Devices in Radiology, 205 RADIOLOGY 27, 27-36 (1997); Lee H. Monsein, Primer on Medical Device Regulation, Part I: History and Background, 205 RADIOLOGY 1, 1-9 (1997).
19. Pub. L. No. 102-300, 106 Stat. 238 (codified at 21 U.S.C. §§ 301 note, 321, 331, 334, 346a, 352-353, 356-357, 360c-d, 360g-i, 360i notes, 3601, 360mm, 371-372, 372a, 376, 381; 42 U.S.C. § 262).
20. Pub. L. No. 105-115, 111 Stat. 2296 (1997), as amended 21 U.S.C. §§ 301-394 (1997).
21. See generally RADIOLOGICAL SOC'Y N. AM., THE FDA AND RADIOLOGY: IMPACT OF THE REGULATORY PROCESS ON RESEARCH, TECHNOLOGY TRANSFER, AND PATIENT CARE IN THE UNITED STATES (1996); see also S. REP. No. 105-43, at 20 (1997); see generally John E. Abele, Technology Development From the Perspective of Industry, 5 J. INVASIVE CARDIOLOGY 65 (1993).
22. See generally RADIOLOGICAL SOC'Y N. AM., THE FDA AND RADIOLOGY: IMPACT OF THE REGULATORY PROCESS ON RESEARCH, TECHNOLOGY TRANSFER, AND PATIENT CARE IN THE UNITED STATES (1996); see also S. REP. No. 105-43, at 20 (1997); see generally John E. Abele, Technology Development From the Perspective of Industry, 5 J. INVASIVE CARDIOLOGY 65 (1993).
23. See generally RADIOLOGICAL SOC'Y N. AM., THE FDA AND RADIOLOGY: IMPACT OF THE REGULATORY PROCESS ON RESEARCH, TECHNOLOGY TRANSFER, AND PATIENT CARE IN THE UNITED STATES (1996); see also S. REP. No. 105-43, at 20 (1997); see generally John E. Abele, Technology Development From the Perspective of Industry, 5 J. INVASIVE CARDIOLOGY 65 (1993).
24. Robert Temple et al., Final Report of the Committee for Clinical Review Based on a Review of Selected Medical Device Applications (FDA 1993), reprinted in SUBCOMM. ON OVERSIGHT AND INVESTIGATIONS, HOUSE COMM. ON ENERGY AND COMMERCE, 103D CONG., LESS THAN THE SUM OF ITS PARTS: REFORMS NEEDED IN THE ORGANIZATION, MANAGEMENT, AND RESOURCES OF THE FOOD AND DRUG ADMINISTRATION'S CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (1993).
25. See id.
26. See id.
27. S. REP. No. 105-43 (1997).
28. See Larry R. Pilot & Daniel R. Waldmann, Food and Drug Administration Modernization Act of 1997: Medical Device Provisions, 53 FOOD & DRUG L.J. 267 (1998).
29. FDAMA § 206.
30. The FDCA and its implementing regulations do not specify who must submit a 510(k), only the actions that parties may take that trigger its requirements. Based on these actions, FDA has noted that the following parties must submit a 510(k): 1) domestic manufacturers introducing a device into the U.S. market; 2) specification developers introducing a device into the U.S. market; 3) foreign manufacturers/exporters or U.S. representatives of foreign manufacturers/exporters introducing a device into the U.S. market, which can include distribution of imported medical devices; and 4) repackages or relabelers who make labeling changes, other than in name, or whose operations significantly affect the device. 21 C.F.R. § 807.81(a)(1999); see CDR 1, supra note 7.
31. CDRH I, supra note 27.
32. FDCA § 513(i)(1)(A)(ii).
33. FDAMA § 210.
34. Id. §§ 207, 416.
35. FDCA § 513(c).
36. See 21 C.F. R. § 807.81 (1999); CDRH & FDA, DECIDING WHEN TO SUBMIT A 510(K) FOR CHANGES TO AN EXISTING DEVICE (1997) at 1 [hereinafter CDRH II].
37. See 21 C.F. R. § 807.81 (1999); CDRH & FDA, DECIDING WHEN TO SUBMIT A 510(K) FOR CHANGES TO AN EXISTING DEVICE (1997) at 1 [hereinafter CDRH II].
38. CDRH II, supra note 31.
39. FDA Talk Paper, FDA Approves Two New Devices for Aneurysm Repair (1999).
40. T. Ohki et al., Endovascular Graft Repair of Ruptured Aortoiliac Aneurysms, 189 J. AM. C. SURGEONS 102 (1999).
41. The confusion probably results from the fact that they really are the same concept. Using a device for indication(s) outside its FDA-approved label constitutes "unapproved" or "off-label use." Modification of an approval device is at an extreme of unapproved/off-label use. Technically, modification is thus unapproved/off-label use, as the safety and effectiveness is untested. Examples of unapproved/off-label use is using an unmodified biliary stent (FDA-approved) in the peripheral vasculature. An example of modification is using an approved biliary stent as the "raw material" for building a custom, covered stent for use in iliac artery aneurysms.
42. See, e.g., United States v. Evers, 453 F. Supp. 1141 (M.D. Ala. 1978), aff'd on other grounds, 643 F.2d 1043 (5th Cir. 1981).
43. See id.; see also United States v. An Article of Device . . . Lindquist Chronosonic Ultrasound, 255 F. Supp. 374 (W.D. Ark. 1966); Schlessing v. United States, 239 F.2d 885 (9th Cir. 1956).
44. 37 Fed. Reg. 16,503 (1972).
45. See Preamble to the Final Rule Regarding New Drug, Antibiotic, and Biologic Drug Regulations, 52 Fed. Reg. 8803 (1987); Stuart L. Nightingale, Unlabeled Uses of Approved Drugs, 26 DRUG INFO. J. 141 (1992).
46. See 21 C.F.R. § 312.2(d) (1999).
47. See FDA., 1991 FDA COMPLIANCE MANUAL, No. 7292.900.
48. See Pub. L. No. 105-115, 111 Stat. at 2296.
49. See 21 U.S.C. § 396.
50. Id.
51. See Evers, 453 F. Supp. at 1141.
52. FDCA § 520(b) (21 U.S.C. § 360j(b)); 21 C.F.R. § 812.3(b).
53. EXEMPTIONS MANUAL, supra note 8.
54. See Monsein, supra note 15, at 10.
55. See Evers, 453 F. Supp. at 1141.
56. See Lindquist Chronosonic Ultrasound, 255 F. Supp. at 374.
57. See EXEMPTIONS MANUAL, supra note 8.
58. Id.