The US vs. the EU: A look at the pre- and post-market regulation of medical devices with Medtronic's pacemaker devices as a case study.
By Brooke Struyk
Abstract:
The term "medical devices" is usually used very broadly when referring to a type of technology that helps patients with their health. There are challenges with the categorization of medical devices that might impact their approval process and their availability on the market for patients and providers to use. A slower and more diligent approval process might delay the population's access to lifesaving and life-sustaining technologies. A quicker and more streamlined approval process might increase the risks associated with medical technology use. Residents of the United States (US) often rely on agencies such as the FDA to offer its stamp of approval for medical devices for such devices to be considered safe and secure. Yet, medical device recalls still happen in the US, which indicates possible inefficiencies within the FDA's regulatory processes. Could inefficiencies in the FDA's medical device approval and regulation processes be causing harm and/or preventing positive outcomes by imposing high barriers to entry for medical device approval? To address this question, this blogpost uses a comparative approach to review the US and the European Union (EU) medical device approval and regulation processes using the case study of the Medrtonic's pacemaker devices. Most pacemakers are made in Europe and sold in the US. These devices not only have to pass the EU's medical device regulations but also must pass the FDA's regulations. This blog post focuses on the premarket and post-market regulatory processes for Medrtonic's pacemaker devices.
Premarket approval of medical devices
FDA approval is one of the most important steps for medical device companies to get their device onto the US market. The FDA heavily relies on its extensive premarket process to ensure that every device on the market is safe for consumers. This process is split into two different groups: the 501K pathway and the general approval pathway (PMA).[1]The general premarket approval process (PMA) requires clinical data, panel reviews, nonclinical studies, and quality inspections by the FDA personnel,[2] as well as a high application fee (approximately $370,000).[3] It might take multiple years for a medical device to be approved by the FDA via the PMA pathway. The 501K pathway is a simplified FDA approval pathway for medical devices with slight adjustments. For this pathway to be an option, there must be a similar device on the market that has already been previously approved. This pathway has fewer barriers to approval since the application fee is less expensive (approximately $12,000), clinical data is not required, the manufacturers are not inspected, and there can be some gaps in the safety information.
The European Union (EU) uses a system of medical device approval based on the FDA via an entity called the European Medicines Agency (EMA). The EMA system's main goal is to generalize the approval process for all countries in the union. EMA was created to improve the overall process of medical device approval because many countries in the EU did not have established qualified standards. For a number of years now, the EU has been working on perfecting its system, but there are still many flaws regarding its premarket process. There are three steps to the EU's premarket process: approval, submission of clinical data, and accountability.[4] The premarket process for the EU is manufacturer-focused regarding accountability. This means that the manufacturer is required to have a unique device identifier system to be used for the post-market surveillance of the device in case of any future issues. Another premarket surveillance regulation is that the final approval decision is up to the Conformité Européenne (CE), not EMA.[5] CE is a marking of medical devices, among other products, that identifies their conformity with safety, performance and quality standards as well as regulatory requirements for products sold within the European Economic Area (EEA). This means that EMA is focused on evaluating clinical data and safety information, while approval of the device comes from the CE.
The classification of devices appears to be similar in the US and in the EU with three classes of medical devices.[6] Class I devices include low-risk medical devices such as elastic bandages and tongue depressors. Class II devices include moderate-risk devices such as powered wheelchairs, pregnancy tests, and blood pressure cuffs. Class III devices include high-risk devices that were "designed to maintain health and sustain life" and are "important in preventing impairment of human health and pose a potential risk of illness or injury if the device fails."[7] Such devices include insulin pumps, deep-brain stimulators, and artificial pacemakers. The classification of medical devices is important as it allows the FDA and the CE to standardize and regulate medical devices.
Post-market surveillance of medical devices
Post-market surveillance involves monitoring the device's real-world performance. While the FDA places significant emphasis on premarket evaluations for medical devices, it's important to acknowledge that recalls still happen, and FDA approval does not eliminate all risks associated with medical device use. This holds especially true considering the diverse range of individuals who use medical devices and may be affected by them differently. There are three classes of recalled devices based on the "health hazard presented" as classified by the FDA. [8] Class I is the most serious type of recall. It indicates there is a significant risk associated with the use of the medical device that can cause irreversible harm, injury, or even death. Class II recall indicates that the medical device may cause temporary or medically reversible adverse health outcomes. Class III recall is the least serious type of recall. It indicates that there are likely no adverse health consequences caused by the recalled medical device. These classes help the FDA determine how dangerous the device is for others, especially if it malfunctions, and the level at which the device should be classified.[9] The recalling entity typically works with the FDA to conduct the recall, communicate about it, and remove or correct the affected devices to ensure user safety.[10]
The FDA establishes certain post-market requirements for medical device manufacturers and distributors. These include medical device tracking systems (manufacturing, production, and distribution) as well as reporting requirements of "device malfunctions, serious injuries or deaths."[11] Additionally, post-market requirements include "nonbinding recommendations" under Section 522 of the Federal Food, Drug, and Cosmetic Act guidance for the FDA and corporations (issued on October 7, 2022), providing authority to the FDA to require post-market surveillance of certain class II or class III devices.[12] This means that post-market surveillance is conducted only if and when the FDA identifies a potential issue with a medical device (class II or class III) and a review team determines that post-market surveillance is warranted.[13] Therefore, post-market surveillance is not a default requirement for all medical devices in the US.
Post-market surveillance involves data collection and analysis regarding a medical device on the market to assess its safety and effectiveness in use. It is important for improved public health and user safety. The EU post-market surveillance places more regulatory requirements on all parties involved. In May 2011, the European Commission formally established the European Databank on Medical Devices, also known as Eudamed.[14] Since then, improvements have been made to meet technical demands, enhance completeness, transparency, and data quality.[15] It is now utilizing Eudamed2 as the main databank "to strengthen market surveillance and transparency in the field of medical devices."[16]Eudamed2 is a web-based portal, not accessible to the public, which allows for the exchange of information between "national competent authorities and the Commission."[17] Eudamed2m is an obligatory databank, which means it is required for all medical devices surveilled in the EU.
Medtronic pacemakers in the United States versus the EU.
Currently, the leading pacemaker company in both the EU and the US is Medtronic.[18] Medtronic is an American medical device company based in Minnesota and Ireland that sells its products globally. In both the EU and the US, pacemakers like Azure, an app-connected pacemaker, Advisa MRI, a safe-to-use MRI pacemaker, and Adapta, a physiologic pacemaker, were all approved in both the Netherlands and the US, making Medtronic's pacemaker devices an appropriate device to review as a case study.[19]
When comparing Medtronic recalls from the EU and the US, there is a noticeable difference. The Cobalt XT, Cobalt, ICDs, and CRT-Ds were recalled by Medtronic due to a reduced shock during high-voltage therapy. This recall was classified as a Class I device recall by the FDA, meaning that this device's issue could lead to significant injury or potential death. The notice of recall that was issued by Medtronic was put out on June 3, 2022.[20] The FDA recalled the device on June 22, 2022; however, on July 15, 2022, an article came out about how Medtronic was warning the EU to recall their devices.[21] This would mean that it would take the European Union at least another month after the FDA to recall the dangerous devices. This fact is interesting, considering that the EU's system is very focused on post-market issues rather than just premarket.
In April 2015, the CE approved and authorized the sale of the Micra Transcatheter Pacing System.[22] Almost an entire year later, the FDA approved the same system on April 6, 2016.[23] This specific case shows the long premarket approval process from the FDA due to the originality of this device on the market. This also demonstrates that the EU's specific premarket approval process works to make device approval faster. However, when looking at the Micra AV, an even smaller pacemaker put on the market in 2019, the FDA approved the device on January 15, 2020, after sitting in the approval process for less than three months.[24] The CE finally approved the device six months later, on June 15, 2020.[25] This may be of interest as it contradicts the previous statement regarding the FDA and the EU's approval process.
Conclusion
This blog post shows that both the US and the EU are concerned with patient safety, but the regulatory mechanisms of premarket approval and post-market surveillance differ. The increased requirements within the EU regarding post-market surveillance set the EU system apart from the one in the US. The EU system prioritizes medical device approval efficiency for faster access to such devices by those who need them. Since the EU's Eudamed2 databank is continuously improving, the EU medical device market is likely to be more efficient at premarket approvals and post-market surveillance. The FDA has room for improvement in terms of effective post-market surveillance.
Medtronic's pacemaker case study underscores the importance of understanding and navigating these regulatory variations to ensure the continuous improvement of medical devices' safety and efficacy. It also demonstrates that inefficiencies with medical device approval and regulation processes are present within the EU and the US regulatory frameworks. Regulators must be cognizant of potential harms due to medical device use as well as potential harms if a particular medical device is delayed due to regulatory roadblocks. There needs to be a balanced approach to medical device approval and regulation, which considers the risks of disease and risks associated with medical technologies. A complete assurance of safety might not be possible as there are always risks associated with the complexity of human bodies and with the unpredictability of technologies and systems.
The process of approval and surveillance of medical devices in the US and the EU is complex and shaped by distinct regulatory frameworks. Nations must balance different regulatory requirements, patients' safety, and corporate interests. This blogpost reveals the need for more research on the subject and a more comprehensive analysis of multiple case studies addressing medical device regulation. Case studies, in particular, can be useful to evaluate how premarket approval and post-market surveillance regulation play out in life. Further research is also necessary to evaluate how these regulations impact not only the availability of medical devices but also their accessibility to different populations within society. Different regulatory standards for medical devices impact not only the individual users, medical providers or corporations, health insurance providers, manufacturers, and distributors of medical devices but also populations at large and their health outcomes, both positive and negative.
[1] C. W. K. M.E. Milam, "The current status and future of FDA-approved artificial intelligence tools in chest radiology in the United States," vol. 78, no. 2, 2022. [Online]. Available: https://www.sciencedirect.com/science/article/abs/pii/S0009926022005141.
[2] FDA. “PMA Review Process,” 2021. Accessed 12/08/23. https://www.fda.gov/medical-devices/premarket-approval-pma/pma-review-process.
[3] M. M. O. Aashka Shah, Joseph M. Maurice, "Review of approvals and recalls of US specific medical devices in general and plastic surgery," 2023. [Online]. Available: https://www.sciencedirect.com/science/article/pii/S2666262023000049.
[4] D. M. E. Donawa, "European Device Regulatory Revolution: A Personal View," 2020. [Online]. Available: https://www.donawa.com/wp-content/uploads/2019/06/donawa_personal_view_jun2010.pdf.
[5] A. G. Fraser, "Implementing the new European Regulations on medical devices—clinical responsibilities for evidence-based practice: a report from the Regulatory Affairs Committee of the European Society of Cardiology," European Heart Journal, vol. 41, no. 27, 2020. [Online]. Available: https://academic.oup.com/eurheartj/article/41/27/2589/5849536.
[6] M. M. O. Aashka Shah, Joseph M. Maurice, "Review of approvals and recalls of US specific medical devices in general and plastic surgery," 2023. [Online]. Available: https://www.sciencedirect.com/science/article/pii/S2666262023000049.
[7] Brantly, Nataliya D. “Homefront to Battlefield: Why the U.S. Military Should Care About Biomedical Cybersecurity.” The Cyber Defense Review 6, no. 2 (2021): 93–110. https://www.jstor.org/stable/27021378.
[8] FDA. “Recalls, Corrections and Removals (Devices),” 2020. Accessed 12.11.23. https://www.fda.gov/medical-devices/postmarket-requirements-devices/recalls-corrections-and-removals-devices.
[9] M. M. O. Aashka Shah, Joseph M. Maurice, "Review of approvals and recalls of US specific medical devices in general and plastic surgery," 2023. [Online]. Available: https://www.sciencedirect.com/science/article/pii/S2666262023000049.
[10] FDA. “Recalls, Corrections and Removals (Devices),” 2020. Accessed 12.11.23. https://www.fda.gov/medical-devices/postmarket-requirements-devices/recalls-corrections-and-removals-devices.
[11] FDA. “Postmarket Requirements (Devices),” 2018. Accessed 12.11.23. https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/postmarket-requirements-devices.
[12] FDA. “Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act. Guidance for Industry and Food and Drug Administration Staff.” 2022. Accessed 12.11.23. https://www.fda.gov/media/81015/download.
[13] FDA. “Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act. Guidance for Industry and Food and Drug Administration Staff.” 2022. Accessed 12.11.23. https://www.fda.gov/media/81015/download.
[14] D. M. E. Donawa, "European Device Regulatory Revolution: A Personal View," 2020. [Online]. Available: https://www.donawa.com/wp-content/uploads/2019/06/donawa_personal_view_jun2010.pdf.
[15] European Commission. “Evaluation of the “EUropean DAtabank on MEdical Devices,” 2012. https://health.ec.europa.eu/system/files/2020-09/md_eudamed-evaluation_en_0.pdf.
[16] European Commission. “Market surveillance and vigilance.” 2023. Accessed 12.11.23. https://health.ec.europa.eu/medical-devices-sector/directives/market-surveillance-and-vigilance_en.
[17] European Commission. “Market surveillance and vigilance.” 2023. Accessed 12.11.23. https://health.ec.europa.eu/medical-devices-sector/directives/market-surveillance-and-vigilance_en.
[18] E. Matrick, "Pacemakers: Top Brands per Segment in the US," 2022. [Online]. Available: https://idataresearch.com/pacemakers-top-brands-per-segment-in-the-u-s/#:~:text=In%20terms%20of%20the%20most,'%2020%20and%20Q4'%2020.
[19] Medtronic Europe. "Our Pacemakers." 2019. Available: https://europe.medtronic.com/xd-en/your-health/treatments-therapies/pacemakers/our.html.
Medtronic USA. "Our Pacemakers." 2023. Available: https://www.medtronic.com/us-en/patients/treatments-therapies/pacemakers/our.html.
[20] FDA, "Medtronic Recalls Cobalt XT, Cobalt and Crome ICDs and CRT-Ds for Risk that Devices May Issue a Short Circuit Alert and Deliver Reduced Energy Shock During High Voltage Therapy." [Online]. Available: https://www.fda.gov/medical-devices/medical-device-recalls/medtronic-recalls-cobalt-xt-cobalt-and-crome-icds-and-crt-ds-risk-devices-may-issue-short-circuit.
[21] R. Zipp, "Medtronic warns European healthcare providers of safety problem in defibrillators," 2022. [Online]. Available: https://www.medtechdive.com/news/medtronic-warns-european-providers-safety-problem-defibril/627371/.
[22] Medtronic, "Medtronic Micra™ AV Receives CE Mark," 2020. [Online]. Available: https://news.medtronic.com/2020-06-15-Medtronic-Micra-TM-AV-Receives-CE-Mark.
[23] FDA, "Premarket Approval (PMA)." [Online]. Available: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=p150033.
[24] FDA, "FDA: Premarket Approval (PMA)". [Online]. Available: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P150033S061.
[25] Medtronic, "Medtronic Micra™ AV Receives CE Mark," 2020. [Online]. Available: https://news.medtronic.com/2020-06-15-Medtronic-Micra-TM-AV-Receives-CE-Mark.