MEDICAL DEVICE R&D - International Regulatory Aspects
- Tristan GICQUEL
- Feb 13, 2024
- 6 min read
INTRODUCTION
"I invite you to explore the primary challenges and opportunities in research and development (R&D) within the medical device sector.
This analysis delves into the regulatory nuances and complexities of technological development, comparing approaches in key regions such as Europe, the United Kingdom, the United States, and Canada, and highlights regulatory strategies tailored to medical devices for rare diseases".
1. OVERVIEW OF R&D DEVELOPMENT FOR MEDICAL DEVICES
1.1. THE IMPORTANCE OF R&D IN MEDICAL DEVICES
The development of medical devices (MD) is marked by challenges, both technically and regulatory. Innovators must not only prove that their products are safe and effective but also navigate through a complex and constantly evolving regulatory landscape. Therefore, close collaboration between engineers, researchers, healthcare professionals, and regulatory advisors is essential to overcome these obstacles and succeed in bringing innovative medical devices to market.
1.2. PHASES OF R&D
R&D of medical devices typically unfolds in several distinct phases, each crucial to the success of the final product:
Preliminary design and development
This initial phase includes the product conceptualization, feasibility studies, and the precise definition of technical specifications. This is the moment where ideas are explored and evaluated in terms of technical viability and commercial potential.
Prototype development
Promising concepts are turned into tangible prototypes. These prototypes undergo rigorous laboratory testing to assess their functionality, safety, and performance.
Preclinical trials
Before testing the device on human beings, preclinical trials are conducted to examine its safety and efficacy. These tests may include in vitro studies, computer simulations, and studies on animal models.
Clinical trials
is crucial step aims to evaluate the device under real conditions of use on patientThs. Clinical trials are essential for obtaining the data necessary for regulatory approval of the device.
Authorization and marketing
Once clinical trials are successful, the device can be submitted to regulatory authorities for market authorization. This step requires comprehensive documentation demonstrating the device's safety and efficacy.
Vigilance
Globally, it is generally mandatory to maintain continuous regulatory surveillance to ensure the safety of devices on the market, even after they have been commercialized.
2. THE REGULATORY FRAMEWORK FOR MEDICAL DEVICES
For the success of R&D in medical devices, it is crucial to understand the regulatory frameworks specific to different regions of the world, including Europe (as well as the national specificity of certain key countries), the United Kingdom, the United States, and Canada. This chapter aims to shed light on the diverse regulatory paths and highlight the particularities of each region.
2.1. EUROPE AND EUROPEAN COUNTRIES - General regulatory aspects:
Europe, with its new Medical Devices Regulation (MDR)[1], [2], has recently overhauled its regulatory approach, aiming to strengthen market surveillance and increase transparency for end-users.
This regulation introduces stricter requirements for clinical evaluation and post-market surveillance, placing a strong emphasis on patient safety [1], [2]. Meanwhile, the European Medicines Agency (EMA)[3] plays a crucial role in the evaluation and surveillance of medicines, though its impact on medical devices is more indirect.
Specificity
Introduction of the Medical Devices Regulation (MDR) aiming to enhance harmonization of surveillance and transparency in R&D at the European level. [1], [2].
The EMA plays an indirect but crucial role, especially for combination devices, these hybrids where technology meets pharmacology, undergo a rigorous dual evaluation to ensure they meet European safety and efficacy standards. [3].
A two-tier system with European harmonization and national specifics like the European harmonization through CE marking [4] but national specifics for clinical trials and vigilance. This structure ensures maximum protection while respecting the particularities of each Member State.
Classification of Medical Devices and control
In Europe, medical devices are classified according to the Medical Devices Regulation (MDR) into four main categories based on the risk they present: Class I (low risk), Class IIa and IIb (medium risk), and Class III (high risk) [5]. This classification influences the regulatory requirements applicable, with Class I devices subject to fewer controls than those of Classes IIa, IIb, and III, which require a more thorough conformity assessment before market placement [1], [5].
Additionally, each medical device is monitored and traced through the Unique Device Identification (UDI) system [6] aimed at facilitating the tracking of devices throughout their lifecycle, from manufacture to clinical use, thus allowing rapid response in case of recall and improving incident management significantly enhancing patient safety [6].
Approval and Pre-marketing
All European countries require CE Marking for the marketing of MDs [4], [7]. It is a demanding authorization process for devices of class II to IV, including the evaluation of safety, efficacy, and quality. It ensures a standard of quality and safety for free trade across Europe. Notified bodies play a central role in this certification [4], [7].
Clinical Trial Authorization
Although the approval process for clinical trials is guided by European regulations [1], it is administered at the national level where each country has its own specific system of procedures for the approval of clinical trials, often involving national health authorities and local ethics committees [8], [9], [10], [11], [12].
Market Authorization
The necessity of CE marking to market MDs in the EU, facilitating once obtained, free movement in all Member States [1], [4], [7]. Mention of Switzerland which, while recognizing the CE marking, may require additional steps, such as registration with Swissmedic, (the Swiss regulatory authority)[12], [13].
Existence of Regulatory Processes to Accelerate R&D in Rare Diseases
Although there is no specific regulatory process in the MDR to accelerate the development of medical devices for rare diseases (as is the case with EMA for pharmaceuticals), the European framework allows for some flexibility. Initiatives aimed at encouraging innovation can benefit from adapted procedures, such as simplified conformity assessments or increased support for devices addressing an unmet medical need, including those for rare diseases.
Table 1 : EUROPE AND EUROPEAN COUNTRIES - General regulatory aspects.
2.2. UNITED KINGDOM (MHRA) - General regulatory aspects:
With Brexit, the United Kingdom has taken a decisive turn, establishing its own regulatory framework for medical devices through the "Medicines and Healthcare products Regulatory Agency" (MHRA) [15], [16].
This new beginning promises to harmonize patient safety principles while promoting national innovation. The specifics introduced by the MHRA reflect a commitment to support research and development, navigating between the legacies of the European Union and a renewed British vision [15], [16].
Classification of Medical Devices and control
The classification in the United Kingdom follows a system similar to the EU pre-Brexit, managed by the MHRA, with four categories based on the level of risk [19].
Approval and Pre-marketing
Manufacturers must register their devices with the MHRA and demonstrate compliance with British standards for quality, safety, and performance, including the adoption of the UKCA marking [18].
Clinical Trial Authorization
Clinical trials require rigorous MHRA approval, emphasizing patient safety and data integrity [20].
Post-market Surveillance
The MHRA imposes increased post-market vigilance to ensure the ongoing safety of devices, with systems for rapid incident management [21].
Existence of Regulatory Processes to Accelerate R&D in Rare Diseases
Although no specific process currently exists, the United Kingdom, through the MHRA, recognizes the importance of accelerating the development of medical devices for rare diseases. While specific information on regulatory processes dedicated to rare diseases is not explicitly mentioned, the post-Brexit British framework is designed to be agile, potentially allowing acceleration pathways for innovation in this critical area.
Table 2 : UNITED KINGDOM (MHRA) - General regulatory aspects
2.3. UNITED STATES (FDA) - General regulatory aspects:
In the United States, the Food and Drug Administration (FDA) guides medical devices to market [22]. Classified into three categories based on risk [23], Class I devices are subject to fewer constraints (510(k) notification) [23], [24], while Class III devices, essential for life support, undergo rigorous evaluation, including pre-market approval (PMA) [23], [25].
The clinical trial pathway is meticulously monitored by the FDA, starting with an Investigational Device Exemption (IDE) application [26], [27]. This step is crucial, providing necessary safety and efficacy data.
With its dual-path approval processes (510(k) and PMA), the FDA asserts its commitment to safety while fostering innovation. This strict regulatory and scientific framework ensures that medical devices introduced to the market are safe and effective, with the FDA overseeing each step, from design to post-market surveillance, setting a high standard for market access while also promoting innovation within the industry.
Specificity
Guides R&D of medical devices to market with a risk-based classification[23].
Classification of Medical Devices and control
Devices are classified into three risk levels (I to III), with increased control for higher-risk devices (Class III) [23].
Existence of Regulatory Processes to Accelerate R&D in Rare Diseases
Breakthrough Devices Program: Aims to facilitate and expedite the development and regulatory review of devices offering more effective treatment or diagnosis for serious conditions. Eligible devices benefit from increased interaction with the FDA, priority evaluation, and expedited review [30].
Humanitarian Use Device (HUD) Designation: Encourages the development of devices for diseases affecting fewer than 200,000 people in the United States, offering support in development, reduced fees, and tax credits[31].
Humanitarian Device Exemption (HDE): For devices intended to treat or diagnose a disease affecting fewer than 8,000 people per year in the United States. Devices with HDE must prove their safety and that the benefits justify the risks, without the need to demonstrate proof of effectiveness[32].
Table 3 : UNITED STATES (FDA) - General Regulatory Aspects.
2.4. CANADA (HEALTH CANADA) - General regulatory aspects:
Canada is distinguished by its rigorous and innovative approach in the regulation of medical devices, overseen by Health Canada[33]. What makes it unique is its meticulous review process, notably through obtaining a Medical Device License (MDL) [34], which places a strong emphasis on quality and safety. This framework ensures that each medical device marketed meets high standards, thus guaranteeing efficacy and safety for users.
Innovation is at the heart of the Canadian system, with accelerated access pathways for technologies deemed essential, reflecting a perfect balance between scientific rigor and accessibility. This robust framework aims not only to protect public health but also to encourage innovation in the healthcare sector.
Specificity
Rigorous and innovative approach, focus on quality and safety through the Medical Device License (MDL)[34].
Approval and Pre-marketing
Classes I to IV. Requires demonstration of safety, efficacy, and quality, including details on design, manufacturing, and clinical trial outcomes[36]. Health Canada must approve these devices before they are marketed.
Additionally, a Medical Device Establishment License (MDEL) is also mandatory for manufacturers, importers, or distributors of Class II to IV devices, certifying compliance with Good Manufacturing Practices (GMP)[37].
Market Authorization
The Medical Device License (MDL): Required for the marketing of Class II to IV devices, this authorization is issued by Health Canada after a rigorous evaluation[34].
Post-market Surveillance
Includes mandatory reporting of serious incidents through Health Canada's reporting program and may require additional post-market studies to assess the ongoing performance of the device in the market[39].
Existence of Regulatory Processes to Accelerate R&D in Rare Diseases
Special Access Program: Canada offers a Special Access Program, which allows the use of unapproved medical devices in the country for situations where existing treatments have failed, are not available, or are nonexistent. This program is particularly useful for medical devices intended for the treatment of rare diseases, offering an accelerated pathway to meet the urgent needs of patients[40].
Table 4 : CANADA (HEALTH CANADA) - General regulatory aspects
3. SUMMARY TABLE OF INTERNATIONAL MEDICAL DEVICE R&D
Table 5 : INTERNATIONAL MEDICAL DEVICE R&D - General Regulatory Aspects
HOPING THIS BRIEF SUMMARY HELPS YOU IN YOUR FUTURE PROJECTS IN R&D FOR MEDICAL DEVICES !
If you need help with your regulatory R&D for medical devices, feel free to contact me at contact@orphanquantum.com
See you soon,
Tristan.
*If I find more resources, I will add them to this list.
** Please let me know if you are aware of other rare disease resources that I may have missed and that could be relevant to include in this list.
SOURCES
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