Marketing Approval for Medical Devices in European Union

 

D. Bhavyasri, K. Manikandan, R. Kamaraj*

Department of Pharmaceutical Regulatory Affairs, SRM Institute of Science and Technology,

SRM College of Pharmacy, Kattankulathur-603203 Dist – Kancheepuram, India

 

ABSTRACT:

The demand of medical devices has risen globally, especially in Europe. The devices regulated in Europe must ensure the safety and effectiveness of these products. There are various principles to approve the medical devices in the European market. The biggest companies are in Germany (27%), UK (11%), Italy, Switzerland, Spain and France (16%). The Europe has very good gobal impact in medical device marketing. The classification is based upon risk management, the medium and high risk requires the conformity assessment (CE marking) done by Notified bodies. There are four levels of classification of devices. Various EU directives that has impact on medical devices. International medical device regulatory forum (IMDRF), is followed by regulatory department of countries like Austrila, Brazil, Canada, China, EU, Japan, the United States, and WHO. The approved medical devices in European market must ensure the best protection of patient health. The development timelines for Noval drug and chemical entity take much longer time compared to medical devices. There are about 500,000 life supporting machines in which 20,000 are of generic group. Various rules on clinical evaluation and clinical investigation help in strengthening the regulatory system in Europe. To explore in marketing level premarket testing and postmarked vigilance is required.

 

 

 

 

 

I. INTRODUCTION:

It started in the year 1990, regulation related to medical device was announced by the European Union (EU) Medical Device Directives to maintain safety and performance of medical device. For a manufacturer in the European market of medical device required for relevant directives have to meet and CE mark is applied. CE marking on the product permits to be legally placed in the market with in EFTA & European Union (EU) single market (30 countries). A new ordinance was issued by the European parliament for medical devices (MDR) and in-vitro diagnostics (IVDR) on May 5, 2017. The charge of harmonizing & regulating requirements of medical devices is conducted by the European Commission is collaborated with the Member State’s Health Authorities. Medical engineering is employed to save many lives suffering from various diseased conditions.

 

The purpose of harmonization is to combine different national requirements into one law in the EU. Medical technologies help us in diagnosing, monitoring and caring for every single patient. There are more than 500,000 medical technologies currently available and registered. The European medical technology industries have 575,000 people employees in 25,000 medical technology industries. The regulation and harmonizing requirements of the medical devices task is undertaken by the European Commission in close association with the Member State’s Authorities. This process mainly includes active implantable, non-implantable and in vitro diagnostic medical devices. Some of the example for medical devices sutures, dental filling materials, blood bags, bone cements¹.

 

 

Fig 1. Development of New European Medical device Regulations.

 

II. REGULATORY DIRECTIVES:

The medical device is administered in EEA- European Economic Area (EEA=EU+EFTA, totally 30 member states) by 3 New Approach Directives.

i. 90/385 EEC, Active implantable medical devices.

ii. 93/42 EEC, Medical devices.

iii. 98/79 EC, IVD devices^{2, 3}.

 

III.  SCOPE:

 

Fig 2. Changes in the regulatory environment

 

It is important to maintain physical health and safety protection for EU citizens, by following the effective and efficient rules on medical devices. The European economy, Germany has the highest figure of people engaged in the medical engineering sector. The latest progress in science and innovation to bring the safe device in the market. To make more dependable and more advanced devices for future challenges, we necessitate adopting the final rules for important changes to the current arrangement. The new EU regulations have to be strengthened to defend the safety of all medical devices implies:

·      To maintain high degree of wellness and safety & protection of EU citizens by utilizing their products.

·      The loose and fair business deal of the products from the beginning to end in EU.

·      EU legislation is modified to the significant technical and scientific progress appearing in this sector over the last 20 years⁴.

 

IV. DEFINITION:

1.      Medical devices:

“Any instrument, apparatus, appliance, software, material or other article, whether used solely or in combination, including the software intended by its maker to be used specifically for diagnostic and remedial purpose and required for its proper application, destined by the manufacturer to be used for human beings for purpose of

·      Diagnosis, prevention, monitoring, treatment or alleviation of disease,

·      Diagnosis, monitoring, treatment, alleviation of compensation for an injury or impairment,

·      Investigation, replacement or modification of the shape of a physiological process,

·      Control of conception⁵.

 

V. APPLICABILITY OF MEDICAL DEVICES REGULATIONS:

1. MDR (Medical Device Regulations) For:

·      15 Member states:

Austria (became a member in 1995), Belgium (Founder Member in 1957), Denmark (1973), Finland (1995), France (FM 1957), Germany (FM 1957), Greece (1981), Ireland (1973), Italy (FM 1957),  Luxemburg (FM 1957), the Netherlands (FM 1957), Portugal (1986), Spain (1986), Sweden (1995) and United Kingdom (Great Britain) (1973).

 

·      10 New Member States (after May 1, 2004):

Czech Republic (2004), Cyprus (2004), Estonia (2004), Hungary (2004), Latvia (2004), Lithuania (2004), Malta (2004), Poland (2004), Slovakia (2004) and Slovenia (2004).

 

·      2 New Member States (after January 1, 2007):

Rumania (1995) & Bulgaria (1995).

 

·      Candidate States:

Turkey (applied for membership in 1987)^{5, 6}.

 

VI. THE ROLE OF BSI (British Standards Institution) IN MARKET ACCESS IN EUROPE:

BSI recruit over 130 medical device experts with experience in product lifecycle, including research and development, fabrication, and quality assurance. BSI will benefit from exceptional product and regulatory expertise, it ensures cost effective documentation that stands up to scrutiny and supports your long term goals by following few tips. The range of BSI is to ensure with Notified body to the Medical Device Directives. To market the medical device in Europe CE marking (Conformity European) is a legal necessity. More than 100 years, BSI expertise has provided the guarantee of safety and quality to the manufacturers in and over 150 countries⁷.

 

1.    Premarketing notification requirements:

A.   CE Marking:

 

 

Fig 3: The CE conformity marking

 

In the Europe regulations, the medical devices classified into Class I, Class IIa, Class IIb, and Class III based on degree of peril. The device with higher risk must come after the strictest conformity assessment, in lodge to receive “Conformite Europeene” (CE) mark. CE mark is a mandatory valid requirement for most machinery, electric and electronic products, many other merchandise sold or put into service in Europe. All medical devices intend to sell and use in EU required CE mark in front getting in the EU marketplace. The timelines for gaining approval differs from each category of devices, complexity of design and risk to the user to use of the gimmick. After being approved for marketing Class I device’s validity is undetermined and for Class II and III devices validity is for 3 years.

 

The procedure for market authorization in medical devices, there are 3 levels of governmental involvement:

·      No attachment for (Class I devices), apart from notification to the national competent Authority.

·      Indirect attachment by supervision of the Notified Body that has direct participation (Class Is/Im, IIa/IIb, and III).

·      Direct, but partial, involvement of Competent Authority. This exclusion applies for products containing a drug, substance, products utilizing animal tissue under the Directive (722/2012/EC) in some countries additional national measures have been carried out^7,8.

 

B.   Key dates:

·      May 2018 – Declaration MDR

·      May 2021 – Date of applicability

·      May 2025 – Prolonged validity of MDD Certificates

·      May 2026 – Last putting into service of devices under the MDD

 

There are two ways to get the CE mark for medical devices. Ace is to be validated by notifying body's certificates from them. Some other method is named “Declaration of Conformity”, which firms can declare their products are safe with appropriate labelling and manufacturing data. All the same, the second method only works for medical devices with low danger. In the examples with higher risk, the validation certifications by notifying bodies is obligatory⁹.

 

C.     Notified bodies:

The Notified body is an individualistic certification scheme that is “notified” by European Member State Competent Authority to order the product or federation conforms to the significant necessity for CE marking. Expert government agencies for medical devices are usually the particular Member States’ Ministry of Health, or an agency within the Ministry of Health. EU consists of various divisions of the European Commission and is answerable for Directive’s proper execution. Each state (member state) owns their own competent authority in control of market surveillance and appointing and examining the independent Conformity Assessment Bodies.

 

The designated conformity assessment bodies are listed out by the European Commission, this operation known as “notification” therefore the name “Notified Body”. The notified body is effectively accountable for pre-market evaluation of medical devices. They manage all facets of rating from the fabrication operation to post- marketing surveillance.

 

Producers are answerable to examine that their products come across EU safety, wellness, and environmental protection needed, and also conformity assessment, works up the expert file, issue the EU declaration of compliance, and attach the CE marking to the merchandise. No medical device can be placed on the market within Europe without CE marks in one of the three medical devices. The CE mark is also applicable in the countries of the “European Economic Area”¹⁰.

 

2.      How to get CE marking for medical device?:

The current European CE approval process shows the following steps:

 

1.      To regulate the device: Medical Device Directive (93/42/EEC), In Vitro Diagnostic Devices Directive (98/79/EC) or Active Implantable Medical Devices Directive (90/385/EEC).

2.      To certify various classification of device.

3.      To perform Quality Management System, if applicable. Majority of them use ISO 13485 to meet their necessity.

4.      To maintain a CE marking Technical File or Design Dossier, and audited from Notified body.

5.      To appoint the Authorized Representative (EC Rep) located in Europe.

6.      Notified body audit the quality system and technical file or design dossier.

7.      Register the device with Competent Authorities if necessary.

8.      Finally to determine the Declaration of Conformity (DoC) ¹¹.

 

 

Fig 4: CE making Flowchart

 

3.     Timeline for approval of Medical devices:

·      Class I    – Approval is not Required

·      Class IIa  – 1 to 3 months

·      Class IIb  – 3 to 6 months

·      Class III   –  6 to 9 months

 

 

VII. POST MARKET CLINICAL FOLLOWUP STUDIES IN MEDICAL DEVICES:

This study is resulted in accordance to CE marking of the device with its approved labelling. PMCF studies show a long term performance or safety of medical devices. Eudamed (European Databank on Medical devices) is used for Post Market Clinical Follow-up studies. The design, execution, and necessity for documentation of PMCF study have to meet the need applicable to clinical investigation. PMCF results in corrective or preventive actions, for example, like improve in the labelling/instruction for use, changes and improve to manufacturing processes, changes to device design or public health notification. Altogether it provides clinical evidence for the clinical evaluation process. For implantable and Class III devices, manufactures must list a “summary of safety and clinical performance” that will validated by Notified Body and made publicaly available. Manufacturers must review their system against the new MDR/IVDR, implement all new requirements, and train their staff ^{12, 13}.

 

VIII. CONCLUSION:

The changes from the history of directive in medical devices, new innovations must bring protection to human life. In which Regulatory system for medical devices play a vital part in bringing the latest innovative technology to market. The timeline, procedures must be maintained for each classification of devices while marketing. CE marking not only ensures the quality of product but also safe and effectiveness of medical devices. Key players of CE marking process are Authorised representative, Notified bodies, Competent authorities. In order to maintain regulatory pathway premarket assessment and postmarked vigilance is required to market he devices.

 

IX. CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

X. ACKNOWLEDGEMENT:

Authors want to acknowledge the management of SRM college of pharmacy, SRM institute of science and technology for valuable support.

 

XI. REFERENCE:

1.     Bikash Chatterjee,Preparing for the new European medical device regulations, Pharmatech Associates, 2017.

2.     Christa Alenstter. “EU and member state medical devices regulation”, International Journal of Technology Assessment in Health Care, 01/2003.

3.     European Commission. Classification of medical devices (MEDDEV 2.4/1 Rev. 9). June 2010.

4.     European Council. Directive 93/42/EEC concerning medical devices. June 14, 199.

5.     Heneghan C, Thompson M, Billingsley M, Medical-device recalls in the UK and the device-regulation  process: retrospective review of safety notices and alerts. BMJ open 2011.

6.     European Commission. Medical devices: guidance MEDDEVs. June 10, 2011.

7.     CE marking: the fast route to compliance in the European Union. Hertfordshire, United Kingdom, BSI.

8.     Schreyogg J, Baumler M, Busee R. Balancing adoption and affordability of medical devices in Europe. Health Policy 2009;92:218-224.

9.     Teysseyre, Patricia. “European Union: Medical Device Regulatory System”, Hamdbook of Medical Device Regulatory Affairs in Asia, 2013.

10.   Global Medical Device Nomenclature (GMDN) Agency, 2010.

11.   CE marking: the fast route to compliance in the European Union. Hertfordshire, United Kingdom, BSI  (http;/www/bsigroup.com/upload/product%20Services/About%20CE%20marking/CE Brochure) 2010 pdf.

12.   European Commission. Medical devices: Council of the European Union. Council Directive 2007/47/EC. September 21, 2007.

13.   Commission decision 2010/227/EU of 19 April 2010 on the European Databank on medical devices (EUDAMED). 2010 http://eurdlex.europaeu/LexUriServ.do?uri=OJ:L2010:1020045:0048:EU:PDF,last accessed 2-1-2015.

 

 

 

 

 

 

Accepted on 16.06.2018        © RJPT All right reserved

Research J. Pharm. and Tech 2019; 12(1): 391-395.