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Medical device regulation: landscape and trends

Complying with medical device regulation (MDR) is a critical challenge for medical device companies. This page outlines key considerations to help you plan and avoid errors in securing device approvals.

Young woman having a CAT scan

MDR throughout the product lifecycle

MDR spans the product life cycle of a medical device from discovery to distribution. Medical device companies must create and submit reports to both regulatory and notified bodies to comply with MDR. Regulatory bodies set the rules in each jurisdiction, while notified bodies evaluate and certify compliance with those rules.

Literature review – systematically searching, reviewing, and summarizing published studies, articles, reports and other data sources – is required to support MDR at each stage of a product’s existence. This includes pre-market research, development and clinical evidence, and collating and evaluating scientific and clinical data related to the post-market safety, efficacy and performance of medical devices.

Product lifecycle

Medical device product lifecycle

MDR webinars

Interested in learning more about medical device regulation from industry and regulatory experts? Watch the following webinars:

Navigating the IVDR maze: From CE certification to IVD device registration(se abre en una nueva pestaña/ventana)

  • Stefan Burde, PhD, Director, Global Focus Team IVD at TÜV SÜD

  • Gary Saner, Sr. Manager, Information Solutions, Life Sciences, Reed Tech

  • Dr. Bassil Akra, CEO and Owner of AKRA TEAM GmbH

How to pass your Clinical Evaluation Assessment Report (CEAR): Creating a pragmatic systematic literature review process to assure EU MDR approval(se abre en una nueva pestaña/ventana)

  • Jacqueline van Druten, Clinical & Regulatory Affairs Director, CLIN-r+

  • Danielle Thomas, Customer Consultant, Elsevier

  • Maria Shkrob, Life Sciences Consultant, Elsevier

Demystifying EU MDR: Navigating compliance challenges and achieving CE certification(se abre en una nueva pestaña/ventana)

  • Ben Bancroft, Medical Device Guru II, Guru Services

  • Dr. Bassil Akra, CEO and Owner of AKRA TEAM GmbH

Key reports in medical device regulation

Reports required vary depending on the requirements of different regulatory and notifying bodies, and the risk classification of the device. Broadly, reports fall into pre-market assessments and post-market surveillance categories.

Pre-market – FDA

In the US, medical device companies submit pre-market approval applications to the FDA in one of three pathways depending on the device classification, which includes IVD products:

Self-registration

Pre-market notification 510(k)

Petition for premarket approval (PMA)

Most low-risk Class I devices can be registered by the manufacturer themselves via the FDA’s website. For example, non-electric wheelchairs and handheld surgical implements.

A 510(k) clearance is authorization from the FDA to market a Class II medium-risk medical device, where similar devices already exist on the market. For example, powered wheelchairs and some pregnancy tests.

Three types of 510(k) include: • Traditional • Special • Abbreviated

This is the most demanding level required for high-risk and novel Class III products. For example, breast implants or an implantable pacemaker.

For the 510(k) and PMA pathways, manufacturers must supply extensive evidence from clinical investigations on the safety and efficacy of the device.

Pre-market – EU

Under the EU MDR, medical devices in certain risk classes must pass a pre-market authorization process known as Conformity Assessment. This determines whether all the requirements of the MDR for the device have been met to grant a CE marking that allows a device to be marketed in the EU. The Conformity Assessment covers:

  • Technical documentation: Information about the device's design, performance, labeling, instructions for use, manufacturing processes and risk management

  • General Safety and Performance Requirements (GSPRs): How the device meets GSPR requirements with appropriate evidence.

  • Clinical Evaluation Report (CER): The CER is highly important, complex and requires input from knowledge management, regulatory and clinical professionals. It is considered a “living document” that must be periodically reviewed and updated with new evidence and clinical data(se abre en una nueva pestaña/ventana)20 that becomes available. The CER contains the following elements:

    • Device description: materials used, design factors, intended purpose

    • Clinical evaluation plan: the methodology for conducting clinical evaluations and search strategy for identifying relevant data

    • Literature review: systematic and comprehensive review of published scientific literature relevant to the device, including a summary of the available evidence and any gaps or limitations

    • Clinical data: from studies conducted for the device being evaluated and from studies for a previously marketed equivalent device

    • State-of-the-art report: literature review of medical texts, clinical guidelines and peer-reviewed literature to demonstrate what is currently accepted as good practice, to prove a device is comparable to similar devices on the market and is minimal risk

    • Risk-benefit assessment: including adverse events, device failures and potential safety concerns from clinical evaluation

    • Summary of clinical evidence: meta-summary of overall clinical evidence supporting the safety and performance of the device and a conclusion on its ability to meet the intended clinical purpose

Once these reports are assembled, manufacturers must submit a Declaration of Conformity to state the device complies with the MDR stipulations. This declaration must be kept up to date and available upon request to any competent authority. For medium and high-risk devices, notified bodies independent third-party bodies nominated by EU member states assess submissions for conformity, review the documentation and conduct audits and on-site inspections before awarding the CE mark.

Reporting for In Vitro Diagnostic Regulation – EU

In the EU, IVD products are regulated separately under the EU IVDR. Companion diagnostics (CDx) are also covered under the IVDR legislation. IVDR submissions require manufacturers to submit extensive clinical evidence reports, including state-of-the-art analyses, under three headings (see fig).

Literature review is critical in two of the three. First, in establishing scientific validity, where manufacturers review academic research and scientific peer-reviewed literature from journals, conference posters, guidance or other official documents. And secondly for the clinical performance element, where peer-reviewed literature, clinical performance studies and published results of diagnostic testing must be included.

Post-market monitoring

Medical device manufacturers must conduct post-market monitoring for all their licensed medical devices. Manufacturers are required to put in place surveillance mechanisms for “reportable events” such as death, injury, other adverse effects, or a device malfunction that may pose a risk.

In recent years, regulators have taken steps to encourage active surveillance mechanisms to augment current passive surveillance methods. Passive surveillance is typically a combination of voluntary or mandatory activities, as is the case under the FDA’s post-market surveillance for medical devices; adverse events are reported to a central database or authority by device manufacturers, users or importers. Active surveillance is a proactive approach to gathering and analyzing data on potentially millions of patients in healthcare data systems; additional safety signals that may not have been identified as adverse events are detected and reported. Current passive surveillance systems employed by the FDA include:

  • Manufacturer and User Facility Device Experience (MAUDE(se abre en una nueva pestaña/ventana)21): A database that “…houses medical device reports submitted to the FDA by mandatory reporters (manufacturers, importers, device user facilities) and voluntary reporters (health care professionals, patients and consumers).” MAUDE has known limitations because its web search is limited to the past 10 years of data. Manufacturers cannot therefore rely on the database as the sole source of surveillance, or to establish rates of events, or to compare devices.

  • National Evaluation System for health Technology (NEST(se abre en una nueva pestaña/ventana)22): A collaborative database intended to “…link and synthesize data from different sources across the medical device landscape, including clinical registries, electronic health records, and medical billing claims.”

  • The Sentinel Initiative (Sentinel(se abre en una nueva pestaña/ventana)23): Led by the FDA, Sentinel complements MAUDE and NEST, and was set up to “…develop new ways to assess the safety of approved medical products including drugs, vaccines, and medical devices.”

In the EU, manufacturers are obliged to plan for passive and active surveillance to gather, record and analyze data on each of their medical devices. Member states within the EU also have individual requirements for reporting adverse events that manufacturers must be aware of. Results of surveillance are used to update the Clinical Evaluation Report and must be submitted to a shared system employed by the EU:

  • European Databank on Medical Devices (Eudamed(se abre en una nueva pestaña/ventana)24): A collaborative system that “…integrate(s) different electronic systems to collate and process information about medical devices and related companies (e.g., manufacturers),” to which manufacturers submit a Summary of Safety and Clinical Performance (SSCP).

Mandatory post-market studies and reports – FDA

Post-market reports required by the FDA fill in knowledge gaps about a device, and enable manufacturers to address safety issues that have been raised through passive and active surveillance systems. They are:

  • 522 Studies: evaluate specific aspects of, or overall device performance once a device is available on the market; often instigated when there are concerns or uncertainties about a device

  • Post-Approval Studies (PAS): gather additional data on a device's long-term safety, performance and effectiveness, and submit interim results to the FDA as studies are carried out

  • Recalls: report any action by manufacturers to recall, withdraw or correct a device

  • Annual reports: cover areas like performance and changes to labelling or manufacturing of Class III or complex devices

  • Periodic reports: address ad-hoc FDA requests for updated safety data, manufacturing changes, or results from ongoing clinical studies

In addition to the required reports from medical device companies, the FDA conducts its own reviews of the literature on medical device performance. Consequently, medical device companies will want to be proactive and perform their own reviews to mitigate the risk of recall, and identify and address any issues ahead of the FDA.

Why do regulatory submissions and applications get rejected?

Regulatory rejections or failures typically occur for two reasons:

  1. Administrative review — the device manufacturer has errors in its submission

  2. Substantive review — the weight of evidence is not deemed sufficient for approval

Substantive review might raise issues such as poor design, design faults and failure to use validated manufacturing practices. The materials used in a device’s manufacture may also be problematic. Other issues might be due to inaccurate or incomplete information. The following checklist can help you ensure a complete submission. Did you:

☑ Classify the device correctly ☑ Use up-to-date device classifications and definitions ☑ Fully assess safety performance ☑ Demonstrate no legal concerns or patent infringement ☑ Include clear labeling and instructions for use ☑ Submit all required documents, reports and evidence: - A thorough literature review - Clinical evidence on efficacy, performance and clinical benefits - State-of-the-Art requirements - Risk-benefit assessment, including a mitigation strategy

How to minimize rejections with the right literature tools and strategies

Medical device teams can significantly reduce the risk of regulatory rejection and the time associated with meeting requirements by conducting a thorough search for existing evidence in addition to having substantive product documentation. Thorough, accurate and timely use of literature reduces the burden on knowledge management, regulatory affairs and R&D professionals.

Checklist to evaluate a literature database for MDR compliance

☑ How far back does the information go? ☑ How comprehensive are the sources? ☑ Are there templates or guided search for greater efficiency, e.g., PICO search? ☑ Can you save search strings and deliver results at desired intervals? ☑ Does the database index specifically for medical devices, including: • Medical device adverse events • Medical device concepts • Global Medical Device Nomenclature (GDMN) names • Device tradenames

Medical device regulation by country

Most device manufacturers operate internationally and in multiple jurisdictions outside of the large markets in the US and the EU. They must therefore understand and comply with multiple sets of regulations simultaneously. In prioritizing markets to address, companies can acquire market sizing reports or rely on publicly available information.

Country

Governing body

Market size

USA

FDA(se abre en una nueva pestaña/ventana)

Revenue(se abre en una nueva pestaña/ventana)25 expected to show a CAGR of 5.02%, resulting in market volume of $199.10 billion by 2027. Worldwide most revenue will be generated in the United States (US $163.70 billion in 2023).

EU

EMA(se abre en una nueva pestaña/ventana)

Revenue(se abre en una nueva pestaña/ventana)26 expected to show a CAGR of 4.58%, resulting in a market volume of $162.80 billion by 2027.

UK

MHRA(se abre en una nueva pestaña/ventana)

The UK has the third largest medical(se abre en una nueva pestaña/ventana)27device market in Europe, and overall sixth largest market in medical devices worldwide.

Australia

TGA(se abre en una nueva pestaña/ventana)

Revenue(se abre en una nueva pestaña/ventana)28 in the segment in Australia is projected to reach US $6.33 billion in 2023.

Japan

PMDA(se abre en una nueva pestaña/ventana)

Considered one of the more challenging markets for foreign medical device manufacturers due to its complex registration process and language barriers.

India

CDSCO(se abre en una nueva pestaña/ventana)

Market is expected to grow(se abre en una nueva pestaña/ventana)29 over the coming years due to increased health awareness and government health initiatives. No medical device regulations existed in India prior to 2005, but authorities overhauled the medical device regulatory process in 2017 with the publication of the Medical Device Rules.

References

1 2023 MedTech Industry Benchmark Report, Greenlight Guru, 2023, pp. 10. https://www.greenlight.guru/state-of-medical-device

2 The European Union Medical Device Regulation (EU) 2017/745 (EU MDR), European Commission, 2017. https://eumdr.com/

3 Public health: Commission proposes a progressive roll-out of the new In Vitro Diagnostic Medical Devices Regulation, European Commission, 2017. https://ec.europa.eu/commission/presscorner/detail/en/IP_21_5209

4 Regulation (EU) 2023/67 of the European Parliament and of the Council of 15 March 2023, Official Journal of the European Union, 2023. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32023R0607#

5 Kosta Shatrov, Carl Rudolf Blankart, After the four-year transition period: Is the European Union's Medical Device Regulation of 2017 likely to achieve its main goals?, Health Policy, Volume 126, Issue 12, 2022, Pages 1233-1240. https://www.sciencedirect.com/science/article/pii/S016885102200255X#fig0003

6 Regulatory Trends in Medical Devices, Compliance & Risks, 2023. https://www.complianceandrisks.com/blog/regulatory-trends-in-medical-devices/

7 Mark Drlik, How Much Does it Cost to Develop a Medical Device?, Starfish Medical, 2020, Page 4. https://starfishmedical.com/assets/StarFish-Whitepaper-Cost-to-Develop-Medical-Devices-July-2020.pdf

8 510(k) Clearances, U.S. Food &Drug Administration, 2021. https://www.fda.gov/medical-devices/device-approvals-denials-and-clearances/510k-clearances

9 Maggie Fick, Medical device makers drop products as EU law sows chaos, Reuters, 2022. https://www.reuters.com/business/healthcare-pharmaceuticals/medical-device-makers-drop-products-eu-law-sows-chaos-2022-12-19/

10 Robert Fenton, How Long Does the FDA Medical Device Approval Process Take? Timeline, Qualio, 2021. https://www.qualio.com/blog/fda-medical-device-approval-process

11 Marco de Morpurgo, Nicola Landolfi, Q&A: marketing authorisation for pharmaceuticals and medical devices in European Union, Lexology, 2022. https://www.lexology.com/library/detail.aspx?g=34f0293a-0b65-4d96-a7de-9457b740c3e4

12 Medical Device Registration in Japan, THEMA, 2022. https://www.thema-med.com/en/medical-device-registration-japan/

13 Gunjan Verma, Medical Device Regulation in India, Asia Actual, 2022. https://asiaactual.com/india/medical-device-registration/

14 Medical device application processing times, Australian Government Department of Health and Aged Care, 2022. https://www.tga.gov.au/resources/resource/guidance/medical-device-application-processing-times

15 Accelerate Sustainable Capability (ASC) Pilot Study Under MDIC, U.S. Food &Drug Administration, 2021. https://www.fda.gov/medical-devices/quality-and-compliance-medical-devices/accelerate-sustainable-capability-asc-pilot-study-under-mdic

16 Dr Anja Segschneider, Medical Device Sustainability – in the EU and Germany, Johner Institute, 2022. https://www.johner-institute.com/articles/health-care/and-more/medical-device-sustainability/

17 Environmental sustainability and public health impacts, UK Medicines & Healthcare Products Regulatory Agency, 2022. https://www.gov.uk/government/consultations/consultation-on-the-future-regulation-of-medical-devices-in-the-united-kingdom/chapter-13-environmental-sustainability-and-public-health-impacts

18 Angela Daly, Medical 3D printing, intellectual property, and regulation, 3D Printing in Medicine:Second Edition, Woodhead Publishing Series in Biomaterials, 2023, pp. 385-398. https://www.sciencedirect.com/science/article/abs/pii/B9780323898317000146

19 Elijah Wreh, Cybersecurity in medical devices, Medical Device Regulation, FDA-CDRH Manufacturing, Policies and Regulation Handbook, 2023, pp. 345-368. https://www.sciencedirect.com/science/article/abs/pii/B9780323953542000141

20 Regulation (EU) 2017/745: Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC, Medical Device Coordination Group, European Commission, 2020. https://health.ec.europa.eu/system/files/2020-09/md_mdcg_2020_6_guidance_sufficient_clinical_evidence_en_0.pdf

21 MAUDE - Manufacturer and User Facility Device Experience, U.S. Food &Drug Administration. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm

22 National Evaluation System for health Technology (NEST), U.S. Food &Drug Administration, 2019. https://www.fda.gov/about-fda/cdrh-reports/national-evaluation-system-health-technology-nest

23 Sentinel Initiative. https://www.sentinelinitiative.org/

24 EUDAMED database, European Commission, 2021. https://ec.europa.eu/tools/eudamed/#/screen/home

25 Medical Devices - United States, Statista, 2021. https://www.statista.com/outlook/hmo/medical-technology/medical-devices/united-states

26 Medical Devices - Europe, Statista, 2021. https://www.statista.com/outlook/hmo/medical-technology/medical-devices/europe

27 An Overview of the UK Medical Device Industry, JONEX Global, 2022. https://www.jonexglobal.com/post/the-uk-medical-device-industry

28 Medical Devices - Australia, Statista, 2021. https://www.statista.com/outlook/hmo/medical-technology/medical-devices/australia

29 India CDSCO Medical Device Registration and Approval, EMERGO by UL, 2019. https://www.emergobyul.com/services/india-cdsco-medical-device-registration-and-approval