Regulation and Clinical Investigation of Medical Device in the European Union

Manita; Aakash       Deep; Vikram; Avtar   C.   Rana; Prabodh    C.   Sharma

doi:10.2174/2213476X06666190821095407

Abstract

Background: Medical devices are the machine, tool, instrument, apparatus, implant, calibrator in vitro, software, the similar or related object intended for use by the manufacturer alone or in combination becoming increasingly important in the healthcare sector as these are used to diagnosis, control, prevention or treatment of an illness. Safety of the world population is the highest priority in order to launch new medical devices for the treatment and diagnostic of several diseases. New innovation in industries and regulations work together to provide devices for different world market and to improve quality and safety of exiting devices in the market. The main key for devices is to classify the determination of actual regulatory pathway which ensures the safety standards and other regulatory requirements in a specific country. We perform clinical trials for medical device which are quite different from the clinical trials performed for drug analysis. For any high-risk devices, the new EU law states that the manufacturer has to prepare a complete summary for their evidence. The clinical trials regulation provides more transparency on clinical trials data. Complete transparency is required for the maximum possibility of informed decisions in order to use new medical devices.

Objective: The current manuscript will provide the information regarding the regulatory framework for the approval of medical devices and clinical investigation of medical device in European Union and comparison of approval process of medical device in USA, EU and India. The aim of this paper is to provide an overview of the most suitable and emerging requirements that manufacturers need for introducing their medical devices in the market in compliance with the MDR regulations.

Conclusion: The proposal for a modified regulation of medical devices aims to ensure more robust clinical data in support of the CE marking applications of the medical device. The clinical investigation requirements will be mandatory, and there will be an obligation to demonstrate the clinical benefits of the device and provide a rigorous equivalence test if the assessment is based on comparison devices. The new European legislation should require the premarket demonstration of clinical efficacy and safety, using a randomized controlled trial if possible, and a transparent clinical review, preferably centralized.

Keywords: Medical device, medical device regulation, clinical investigations of medical devices, postmarketing clinical follow-up, healthcare, calibrator.

« Previous Next »

Graphical Abstract

[1] 
Rathinamoorthy R, Rajendran S.  Regulatory bodies
and their roles associated with medical devices and
wound dressings. Advanced Textiles for Wound Care.
Wood head Publishing 2019; pp. 423-61.
[http://dx.doi.org/10.1016/B978-0-08-102192-7.00015-1] 
[2] 
Maak TG, Wylie JD. Medical device regulation: A comparison of the United States and the European Union. J Am Acad Orthop Surg  2016; 24(8): 537-43.
[http://dx.doi.org/10.5435/JAAOS-D-15-00403] [PMID:  27195383] 
[3] 
 Ec.europa.eu. 2019. [cited: 22 December 2018];
Available at: https://ec.europa.eu/docsroom/docu-ments/13053/attachments/1/translations/en/renditions/native
[4] 
Ramakrishna S, Tian L, Wang C, Liao S, Teo W.  Clinical testing of a new medical device. 1st Ed. Sawston:
Woodhead Publishing 2015; pp. 1-256.
[5] 
Van Drongelen A, Hessels J, Geertsma R.  Comparison
of market authorization systems of medical devices
in USA and Europe. 2015. Available from: https://www.rijksoverheid.nl/binaries/rijksoverheid/documenten/rapporten/2015/01/01/comparison-of-market-authorization-systems-of-medical-devices-in-usa-and-europe/comparison-of-market-authorization-systems-of-medical-devices-in-usa-and-europe.pdf
[6] 
 European Union. 2019. Countries - European Union -
European Commission. [cited: 25 December 2018];
Available from: https://europa.eu/european-union/about-eu/countries_en
[7] 
 Medical device regulation and ISO quality standard.
2019. What is a Medical Device? (official definition
for EU, USA, China, Brazil). [cited: 26 December
2018]; Available from: https://easymedicaldevice. com/medical-device-definition/
[8] 
 EUPATI. European Patients Academy. [cited: 29 December
2018]. Available from:https://www.eupati. eu/glossary/medical-device/
[9] 
Rohilla A, Deep A, Khurana G, Yadav M, Marwaha RK, Sharma PC. Regulatory success and challenges for medical devices in United States and European Union. Appl Clin Res Clin Trials Regul Aff  2018; 5(3): 181-99.
[http://dx.doi.org/10.2174/2213476X05666180709154549] 
[10] 
French-Mowat E, Burnett J. How are medical devices regulated in the European Union? J roy Soc Med  2012; 105(1): 22-8.
[http://dx.doi.org/10.1258/jrsm.2012.120036] 
[11] 
 Emergo. 2019. Global Medical Device Consulting.
[cited: 31 December 2018]. Available from: https://www.emergobyul.com/res-ources/worldwide/global-regulatory-comparison-tool
[12] 
 Internal Market, Industry, Entrepreneurship and
SMEs - European Commission. 2019. Medical devices - Internal Market, Industry, Entrepreneurship
and SMEs - European Commission. [cited: 2 March
2019] Available from: https://ec.europa.eu/growth/single-market/european-standards/harmonised-standards/medical-devices_en
[13] 
Fiedler BA, Ferguson M.  Overview of medical device
clinical trials. Managing medical devices within a
regulatory framework. 2017; pp. 17-32.
[http://dx.doi.org/10.1016/B978-0-12-804179-6.00002-2] 
[14] 
 Meddeviceonline.com. 2019. 8 Key changes to understand
in the new European MDR and IVDR.
[cited: 02 January 2019]. Available from: https://www.meddeviceonline.com/doc/key-changes-to-understand-in-the-new-european-mdr-and-ivdr-0001
[15] 
 Benesch D. 2019. The new European Medical Device
Regulation (MDR). [cited: 16 February 2019].
Available from: http://blog.profil.com/blog/the-new-european-medical-device-regulation
[16] 
Wagner MV, Schanze T. Challenges of medical device regulation for small and medium sized enterprises. Curr Dir Biomed Eng  2018; 4(1): 653-6.
[http://dx.doi.org/10.1515/cdbme-2018-0157] 
[17] 
 Enhesa.com. 2019. EU Directive vs EU regulation:
What's the difference? | Enhesa. [Accessed 1 February
2019]. Available from: https://www.enhesa.com/blog/eu-directive-vs-eu-regulation-whats-difference
[18] 
 Intertek.com. 2019. The EU Medical Devices Regulation
(MDR 2017/745). [Accessed 2 March 2019].
Available from: http://www.intertek.com/auditing/medical/mdr-2017-745/
[19] 
 Internal Market, Industry, Entrepreneurship and
SMEs - European Commission. 2019. New regulations
- internal market, industry, entrepreneurship and
SMEs - European Commission. [Accessed: 2 March
2019]. Available from: http://ec.europa.eu/growth/sectors/medical-devices/new-regulations_en
[20] 
Process I, Wizemann T, Process I, and Wizemann T.  2019. The Global Framework for Regulation of
Medical Devices. [cited: 2 Februray 2019]. Available
from: https://www.ncbi.nlm.nih.gov/books/NBK209785/
[21] 
 Internal Market, Industry, Entrepreneurship and
SMEs - European Commission. 2019. Notified bodies
- Internal Market, Industry, Entrepreneurship and
SMEs - European Commission. [Accessed: 5 January
2019]. Available from: https://ec.europa.eu/growth/single-market/goods/building-blocks/notified-bodies_ en.
[22] 
Ganesh GN, Nishanthini B, Vidhya LT. Medical device regulation in US, Europe, China and India. Inter J Drug Reg Aff  2017; 5(2): 17-25.
[http://dx.doi.org/10.22270/ijdra.v5i2.198] 
[23] 
Gupta SK. Medical device regulations: A current perspective. J Young Pharm  2016; 8(1): 6-11.
[24] 
Parvizi N, Woods K. Regulation of medicines and medical devices: Contrasts and similarities. Clin Med (Lond)  2014; 14(1): 6-12.
[http://dx.doi.org/10.7861/clinmedicine.14-1-6] [PMID:  24532735] 
[25] 
 BobGeorge, D. 2019. Registration of medical devices.
PubMed Central (PMC). [Accessed: 9 January 2019].
Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146078/
[26] 
 Emergo. 2019. Europe CE marking regulatory process
for medical devices. 2019. [cited: 11 January
2019]. Available from:https://www.emergobyul.com/resources/europe-process-chart
[27] 
Hamburg MA, Sharfstein JM. The FDA as a public health agency. N Engl J Med  2009; 360(24): 2493-5.
[http://dx.doi.org/10.1056/NEJMp0903764] [PMID:  19470577] 
[28] 
Liotta LA, Petricoin EF III. Regulatory approval pathways for molecular diagnostic technology. Methods Mol Biol  2012; 823: 409-20.
[http://dx.doi.org/10.1007/978-1-60327-216-2_27] [PMID:  22081361] 
[29] 
Sethi R, Popli H, Sethi S. Medical devices regulation in United States of America, European Union and India: A Comparative Study. Pharm Regul Aff  2017; 6(179): 2.
[http://dx.doi.org/10.4172/2167-7689.1000179] 
[30] 
 Danish Medicines Agency. 2019. Guidance on application.
[cited: 12 January 2019]. Available from: https://laegemiddelstyrelsen.dk/en/devices/legislation-and-guidance/guidance/guidance-on-application-for-the-authorisation-for-clinical-investigation-of-medical-devices/#3.%20Afpr%C3%B8vningsplan
[31] 
 Eur-lex.europa.eu. 2019. EUR-Lex - 52003DC0386 -
EN. [cited: 19 January 2019].
Available from: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:52003DC0386:EN: HTML.
[32] 
 Abhi.org.uk. 2019. Clinical investigations of medical
devices. [cited: 21 January 2019].
Available from: https://www.abhi.org.uk/what-we-do/influencing-regulation/clinical-investigations/
[33] 
 Clinical-evaluation.com. 2019. Clinical trial for a
medical device in Europe. [cited: 27 January 2019].
Available from: http://www.clinical-evaluation.com/web/00-wcms/index.php?article_id=35&clang=1
[34] 
Bianco S, Nunziata A, Pozzoli G. Clinical investigations on medical devices, after the new European regulation (2017/745). Clin Trial Pract Open J  2017; 1(1): 10-4.
[35] 
 Serious Adverse Event (SAE) reporting, State Institute
for Drug Control. [cited 27 January 2019].
Available from: http://www.sukl.eu/medical-devices/serious-adverse-event-sae-reporting
[36] 
 EUPATI. European Patients Academy: Clinical trial
approval in Europe. 2019. [cited: 28 January 2019]. Available from: https://www.eupati.eu/clinical-development-and-trials/clinical-trial-approval-in-europe/
[37] 
 Ec.europa.eu. 2019. [cited: 29 January 2019].
Available from: https://ec.europa.eu/docsroom/docu-ments/10336/attachments/1/translations/en/renditions/native
[38] 
 Abhi.org.uk. 2019. Clinical investigations of medical
devices. [cited: 30 January 2019].
Available from: https://www.abhi.org.uk/what-we-do/supporting-regulation/clinical-investigations/
[39] 
 Danish Medicines Agency. 2019. Guidance on application.
[cited: 31 January 2019]. Available from: https://laegemiddelstyrelsen.dk/en/devices/legislation-and-guidance/guidance/guidance-on-application-for-the-authorisation-for-clinical-investigation-of-medical-devices/#3.%20Afpr%C3%B8vningsplan
[40] 
 Danish Medicines Agency. 2019. Regulatory requirements.
[cited: 1 February 2019].
Available from: https://laegemiddelstyrelsendk/en/
devices/clinical-investigations/regulatory-requirements/
[41] 
 Emergo. 2019. Post-Market Clinical Follow-up
(PMCF) studies in Europe. [cited: 01 February 2019].
Available from: https://www.emergobyul.com/resources/post-market-clinical-follow-pmcf-studies-europe
[42] 
 Clinical-evaluation.com. 2019. Post-Market Studies.
[cited: 2 February 2019].
Available from: http://www.clinical-evaluation.com/web/00-wcms/index.php?article_id=36&clang=1
[43] 
 Assets.publishing.service.gov.uk. 2019. [cited: 5 February
2019]. Available from: https://assets.publishing. service.gov.uk/government/uploads/system/uploads/attachment_data/file/741719/Guidance_for_mfrs_on_clinical_trials_September_2018.pdf
[44] 
 Arnold & Porter. 2019. New European MEDDEV
guidance on stand-alone software | publications and
presentations | Arnold & Porter. [cited: 6 Febraury
2019] Available from: https://www.arnoldporter.com/en/perspectives/publications/2016/07/new-european-meddev-guidance
[45] 
 Guidance - Internal market, industry, entrepreneurship
and SMEs - European Commission. Internal
Market, Industry, Entrepreneurship and SMEs -
European Commission. 2019. [cited 7 February
2019]. Available from: http://ec.europa.eu/gro-wth/sectors/medical-devices/current-directives/guidance_en
[46] 
 Qarad.com. 2019. MEDDEV - qarad. [cited: 8 February
2019]. Available from: https://www.qarad.com/library/guidance-documents
[47] 
 ProClinical. 2019. The top 10 medical device companies
(2018) | ProClinical Recruitment blogs. [cited: 9
Febraury 2019]. Available from: https://www. proclinical.com/blogs/2018-5/the-top-10-medical-device-companies-2018
[48] 
 Posts, V. 2019. Top-10 Medical devices companies
2018 - IgeaHub. IgeaHub. [cited: 11 February 2019].
Available from: https://www.igeahub.com/2018/08/03/top-10-medical-devices-companies-2018/
[49] 
 Medical Product Outsourcing. 2019. Top 10 Challenges
of the New MDR. [cited: 12 February 2019].
Available from: https://www.mpo-mag.com/contents/view_online-exclusives/2017-06-22/top-10-challeng-es-of-the-new-mdr

Rights & Permissions Print Cite

Article Metrics

41

4

DOI https://dx.doi.org/10.2174/2213476X06666190821095407	Print ISSN 2213-476X
Publisher Name Bentham Science Publisher	Online ISSN 2213-4778

Applied Clinical Research, Clinical Trials and Regulatory Affairs

Regulation and Clinical Investigation of Medical Device in the European Union

Abstract Play Pause

Graphical Abstract

Related Journals

Abstract