Electrophysiology devices and the regulatory approval process within the U.S. FDA and abroad
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Almost all electrophysiology (EP) devices need to obtain premarket approval before they can be commercially sold and available for use in the community. The US Food and Drug Administration (FDA) has different paths to market approval depending on the intended use and the associated risks of the device. The European Union and Japan have device approval processes that have many similarities as well as differences to the US regulatory system. This paper describes some of the history and background of the US device approval process with an emphasis on EP devices. It provides an overview of the different regulatory pathways in the USA that are currently being utilized and contrasts them to the procedures often used in the European Union and in Japan. It also touches on the impact of the twenty-first Century Cures Act and how the balance between premarket and postmarket regulatory oversight is continually being examined and refined.
KeywordsFDA Regulation Premarket Device Approval De novo
The authors would like to thank Dr. Madoka Murakami of the Japan Pharmaceuticals and Medical Devices Agency for helpful discussions regarding the Japanese regulatory system.
Compliance with ethical standards
The authors are employees of the Food and Drug Administration.
Conflict of interest
The authors have no other conflicts of interest.
The authors have no conflicts of interest besides what is stated above (employed by FDA).
There was no Ethics Committee or IRB approval for this manuscript. There was no research involving humans or animals.
- 1.Rados C. Medical device and radiological health regulations come of age. FDA Consumer Magazine; 2006. https://www.fda.gov/downloads/AboutFDA/WhatWeDo/History/ProductRegulation/UCM593521.pdf. Accessed 17 Apr 2018.
- 2.Code of Federal Regulations Title 21 CFR 860.7. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?FR=860.7. Accessed on 18 Apr 2018.
- 3.Medical Device User Fee Amendments (MDUFA) https://www.fda.gov/ForIndustry/UserFees/MedicalDeviceUserFee/default.htm. Accessed on 14 Aug 2018.
- 4.The Product Code Classification Database. https://www.fda.gov/medical-devices/classify-your-medical-device/product-code-classification-database. Accessed on 19 Apr 2019.
- 5.FDA 510(k) premarket notification. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K161043. Accessed on 19 Apr 2019.
- 6.Atricure multifunctional linear pen 510(k) summary. https://www.accessdata.fda.gov/cdrh_docs/pdf10/K100501.pdf. Accessed on 19 Apr 2019.
- 7.Combination product definition and combination product types. https://www.fda.gov/combination-products/about-combination-products/combination-product-definition-combination-product-types last updated 18 Feb 2019. Accessed 19 Apr 2019.
- 8.IDE approval process. https://www.fda.gov/medical-devices/device-advice-investigational-device-exemption-ide/ide-approval-process. Accessed on 19 Apr 2019.
- 9.Acceptance and filing reviews for premarket approval applications (PMAs) Guidance for Industry and Food and Drug Administration Staff https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM313368.pdf. Accessed 21 Feb 2019.
- 10.Procedures for meetings of the medical devices advisory committee; Guidance for Industry and Food and Drug Administration Staff https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM440348.pdf. Last Updated 23 Mar 2018. Accessed 21 Feb 2019.
- 11.Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, et al. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation:2.3 year follow-up of the PROTECT AF (watchman left atrial appendage system for embolic protection in patients with atrial fibrillation) trial. Circulation. 2013;127(6):720–9.CrossRefGoogle Scholar
- 12.Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, et al. Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: The Prevail trial. J Am Coll Cardiol. 2014;64(1):1–12.CrossRefGoogle Scholar
- 14.ClinicalTrials.gov. Micra transcatheter pacing study. https://www.clinicaltrials.gov/ct2/results?term=NCT02004873. Accessed 19 Apr 2018.
- 15.ClinicalTrials.gov. S-ICD system IDE clinical study. https://www.clinicaltrials.gov/ct2/results?term=NCT01064076. Accessed 19 Apr 2018.
- 16.Summary of safety and effectiveness (SSED) subcutaneous implantable defibrillator. https://www.accessdata.fda.gov/cdrh_docs/pdf11/P110042b.pdf. Accessed 9 May 2018.
- 17.PMA supplements and amendments. https://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/premarketapprovalpma/ucm050467.htm#types. Accessed 30 March 2019.
- 18.Heist EK, Herre JM, Binkley PF, van Bakel AB, Porterfield JG, Porterfield LM, et al. Analysis of different device-based intrathoracic impedance vectors for detection of heart failure events (from the detect fluid early from intrathoracic impedance monitoring study). Am J Cardiol. 2014;114(8):1249–56.CrossRefGoogle Scholar
- 20.Summary of P880006/S075, P880086/S211, P910023/S279, P970013/S044, P030054/S206, P030035/S089 Ellipse and Fortify Assura ICD, Quadra Assura and Unify Assura CRT-D, Merlin PCS System Model 3330 v 14.1 Software. https://www.accessdata.fda.gov/cdrh_docs/pdf/P970013S044M.pdf. Accessed 10 Mar 2019.
- 22.Linde C, Abraham WT, Gold MR, Daubert C, REVERSE Study Group. Cardiac resynchronization therapy in asymptomatic or mildly symptomatic heart failure patients in relation to etiology: results from the REVERSE (resynchronization reVErses remodeling in systolic left vEntricular dysfunction) study. J Am Coll Cardiol. 2010;56(22):1826–31.CrossRefGoogle Scholar
- 24.Public Health Effectiveness of the FDA 510(k) Clearance process: measuring postmarket performance and other select topics: workshop report. National Academies Press (US); 2011.Google Scholar
- 25.Overview of FDA modernization Act of 1997, medical device provisions. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/overview-fda-modernization-act-1997-medical-device-provisions Last Updated 20 Aug 2018. Accessed 30 Apr 2018.
- 26.Federal Food, Drug, and Cosmetic Act (FD&C Act). https://www.fda.gov/regulatory-information/laws-enforced-fda/federal-food-drug-and-cosmetic-act-fdc-act. Last updated 29 Mar 2018. Accessed 30 Mar19.
- 27.FDA and industry actions on premarket notification (510(k)) submissions: effect on FDA review clock and goals guidance for industry and Food and Drug Administration staff https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-premarket-notification-510k-submissions-effect-fda-review-clock-and-goals Last updated 13 Feb 2018. Accessed 21Feb 2019.
- 28.Refuse to accept policy for 510(k)s guidance for industry and food and drug administration staff https://www.fda.gov/media/83888/download Issued 21 Feb 2019. Accessed on 4 Apr 2019.
- 29.Zuckerman DM, Brown P, Nissen SE. Medical device recalls and the FDA approval process. Arch Intern Med. 2011;171(11):1006–11.Google Scholar
- 31.FDA executive summary circulatory system devices panel; automated external defibrillators 515(i) Reclassification. http://www.sca-aware.org/sites/default/files/FDA_executive_summary.pdf. Accessed 13 Jun 2018.
- 32.Federal Register Volume 81, Number 74. 2016. https://www.gpo.gov/fdsys/pkg/FR-2016-04-18/html/2016-08898.htm. Accessed 13 Jun 2018.
- 33.FDA review letter of de nNovo request for classification of the ECG App. 2018. https://www.accessdata.fda.gov/cdrh_docs/pdf18/den180044.pdf. Accessed 30 Mar 2019.
- 34.De novo classification process (evaluation of automatic class III designation) guidance for industry and Food and Drug Administration staff. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/de-novo-classification-process-evaluation-automatic-class-iii-designation Last updated 14 Sept 2018. Accessed 1 May 2018.
- 36.21st Century Cures Act. Last updated 29 Mar 2018. https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/21stCenturyCuresAct/default.htm. Accessed 20 Apr 2018.
- 37.H.R.6 – 21st Century Cures Act. https://www.congress.gov/bill/114th-congress/house-bill/6. Accessed 1 May 2018.
- 40.How FDA plans to help consumers capitalize on advances in science. Gottlieb S. https://blogs.fda.gov/fdavoice/index.php/2017/07/how-fda-plans-to-help-consumers-capitalize-on-advances-in-science/ Posted 7 July 2017 by FDA Voice. Accessed on 20 Apr 2018.
- 41.Humanitarian device exemption. https://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/humanitariandeviceexemption/default.htm Last updated 27 Mar 2018. Accessed 9 May 2018.
- 42.Official Journal of the European Communities Council Directive 93/42/EEC of 14 June 1993 concerning medical devices https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:31993L0042&from=EN. Accessed Apr 19, 2019.
- 43.Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-1/dir_2001_20/dir_2001_20_en.pdf. Accessed 19 Apr 2019.
- 44.Amending the Law of the Pharmaceutical Affairs Act (in Japanese) https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000045726.html. Accessed on 18 Jul 2018.
- 46.Official Journal of the European Union Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32017R0745. Accessed on May 30 2018.
- 47.European Commission Regulatory Framework https://ec.europa.eu/growth/sectors/medical-devices/regulatory-framework_en. Accessed 30 Jun 2018.
- 48.Uchida T, Ikeno F, Ikeda K, Suzuki Y, Todaka K, Yokoi H, et al. Global cardiovascular device innovation: Japan-USA synergies: harmonization by doing (HBD) program, a consortium of regulatory agencies, medical device industry, and academic institutions. Circ J. 2013;77(7):1714–8.CrossRefGoogle Scholar
- 53.International Medical Device Regulators Forum (IMDRF) Strategic Plan 2020. http://www.imdrf.org/docs/imdrf/final/procedural/imdrf-proc-151002-strategic-plan-2020.pdf. Accessed 20 Jul 2018.
- 54.International Medical Device Regulators Forum. www.imdrf.org. Accessed on 7 July 2019.