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The new European 2017 / 745 medical devices regulation, the main points to remember
LThe European Community has adopted in 2017 two new regulations for medical devices and in vitro diagnostic medical devices that will replace the old ones adopted more than 25 years ago: 2017 / 745 Medical Device Regulation and 2017 / 746 Regulation medical devices for in vitro diagnostics.
These two regulations replace directives, a notable change because unlike the directives which had to be transposed into national law, the regulations are applicable immediately after publication and do not have to be transposed into national law.
In the remainder of this document we will focus on what are the main developments related to the 2017 / 745 rules. This document, which replaces the two 90 / 385 and 93 / 43 directives, has 178 pages compared to about sixty for the previous ones, and consists of 10 chapters and 17 annexes.
1. Key dates
The dates are particularly detailed in the article 123 of the regulation, in summary:
The date of application of the regulation is the 25 May 2017 for a date of application to the 26 May 2020.
However, the application dates related to manufacturers' obligations regarding the IUD unique device identification system are fixed for implantable devices and class III devices as of 26 May 2021. For Class IIa and IIb devices the system will apply as of 26 May 2023. For Class I devices it will apply as of 26 May 2025.
Starting from November 26 2021, manufacturers will need to register the devices in the EUDAMED database.
Certificates issued by Notified Bodies under the 90 / 385 and 93 / 42 guidelines from the 25 May 2017 will be invalidated on 25 May 2024.
From the 27 May 2025, all devices must comply with the new regulations and no device can be placed on the market from that date under the guidelines.
Starting from 27 May 2027, the coordinated evaluation procedure quantifying clinical investigations will apply to all member states
Articles: 122, 123
2. The MDCG
As part of the cooperation between the Member States, a coordination group on medical devices is set up to enable better regulation of the sector at European level.
In order to comply with the spirit of the Regulation, namely to focus on user safety, the Commission has foreseen that the appointment of notified bodies would also be analyzed by a new body - the Medical Devices Coordination Group ( GCDM) - which is also responsible for auditing notified bodies.
It contributes to the development of guidelines for the effective and harmonized application of the Regulation, in particular as regards the designation and monitoring of notified bodies, the application of the general requirements for safety and performance and the implementation of evaluation and conduct of clinical investigations by manufacturers, assessment by notified bodies and vigilance activities.
It assists the competent authorities of the Member States in their coordination activities, in particular in the areas of classification and determination of the status of devices with regard to regulation, clinical investigations, vigilance and market surveillance, including including the development and maintenance of a framework for a European market surveillance program.
It provides advice, on its own initiative or at the request of the Commission, in the examination of any matter related to the application of this Regulation.
This body is also a relay of communication between notified bodies and the Commission insofar as the GCDM will be at the center of a reporting process applicable to Class III devices.
The mission of the MDCG is to ensure market surveillance and compliance with procedures.
Articles: 104, 105, 196, 107
3. Economic operators
The Regulation defines the concept of economic operators: manufacturer, agent, importer, distributor, or a person concerned for example by sterilization or packaging, ... (Article 22).
The manufacturer is defined as "any natural or legal person who manufactures or refurbishes a device or has a device designed, manufactured or refurbished, and markets that device under his name or trademark"; actor whose responsibilities are the highest in the meaning of the 2017 / 745 regulation.
The status of the representative is defined as' any natural or legal person established in the Union who has received and accepted a written mandate from a manufacturer outside the European Union to act on his behalf for the purpose of performing specified tasks related to the obligations incumbent on the latter under this Regulation ".
The status of importers is defined in Article 2 as 'any natural or legal person established in the Union who places a device from a third country on the Union market'. The importer has the obligation to place only compliant devices on the market and to ensure that the manufacturer has completed the appropriate conformity assessment procedure before marketing them.
The distributor is defined in Article 2 as "any natural or legal person in the supply chain, other than the manufacturer or the importer, who makes a device available on the market, until the stage of its commissioning. This definition will correspond to a very large number of actors, who can go from the pharmacy to the supermarket. These actors will have obligations related to the application of the regulation such as: CE marking and declaration of conformity of the device, presence of the instructions, attribution by the manufacturer of the unique identifier, respect of storage and transport conditions, register of complaints , non-compliant products, reminders, ...
Articles: 10, 11, 13, 14, 30
4. Notified bodies
The notified body is an organization designated by a Member State of the European Union to carry out the evaluation of a product and if it can be placed on the market because it fulfills the obligations of the Regulation.
The major changes concern the strengthening of the criteria for the designation of organizations and the monitoring of these organizations. A procedure for the designation and notification of notified bodies has been put in place.
Monitoring and reassessment of the notified bodies are also planned. They include the review of the evaluation of the technical documentation and the documentation of the clinical evaluations carried out by the notified body.
Notified bodies are placed under European control for a better harmonization of practices and are now responding to enhanced specifications for competence. They are subject to new procedural requirements (unannounced visit to manufacturers, product controls).
The Commission shall also ensure that the notified bodies coordinate their activities and cooperate in a coordination group of notified bodies in the field of medical devices (including in vitro diagnostic medical devices). This group meets regularly and at least once a year.
Member States shall notify the Commission and the other Member States of the conformity assessment bodies they have designated, using the electronic notification tool of the Notified Bodies Database set up and managed by the Member States. by the Commission (NANDO)
35 Articles to 50 and Appendix VII
5. The IUD and EUDAMED system
A system of unique identification of all devices (IUD) is in place with the exception of measuring devices an identification of each device:
A manufacturer-and-device-specific IUD device identifier (IUD-ID) which provides access to the information provided in Annex VI, Part B concerning the information to be provided to the database.
An IUD "production" identifier (IUD-IP), which identifies the unit of production of the device and, if applicable, the packaged devices, as indicated in Annex VI, Part C concerning the IUD system.
This system based on international guidelines will allow traceability of the devices and thus better security or post-market surveillance as well as better control by the notified bodies.
It will also enable a better fight against counterfeiting. The use of the IUD system is also expected to improve waste procurement and disposal policies as well as inventory management by health facilities and other economic operators.
Associated with the UDI system, there is a EUDAMED database that contains all the information about medical devices received from manufacturers and notified bodies.
The Eudamed Medical Device Database is an essential tool for regulation and a priority element of the Commission for:
• strengthen market surveillance through rapid access to information on manufacturers, agents; devices and certificates, and data on vigilance;
• share information on clinical investigations;
• standardize the application of these directives.
To this end, access is granted to national competent authorities, notified bodies and economic operators.
The content of the database will be expanded later to incorporate:
• Unique Device Identifiers (UDI);
• Economic operators identified by a unique registration number;
• The accreditations and designations of the ONs and their certificates; • Extensive vigilance data, including post-market surveillance;
• Conformity assessment requests by NOs;
• Assessments of safety and clinical performance;
• Market surveillance data.
Articles: 27, 28, 29
6. Clinical evaluations
There are plans for changes in clinical assessment processes that are strengthened. Chapter VI Clinical Evaluation and Clinical Investigations describes in detail the processes to be implemented especially for Class II and III devices.
The text describes the general requirements for clinical investigations conducted to establish compliance of devices and conduct of clinical studies. It also deals with recordings and notifications of adverse events occurring during clinical investigations.
The clinical evaluation and related documentation are updated throughout the device's life cycle using the clinical data obtained by the manufacturer following the implementation of their clinical post-marketing surveillance plan (SCAC). in accordance with Annex XIV Part B and its post-marketing surveillance plan referred to in Article 84.
For Class III devices and implantable devices, the SCAC assessment report and, where applicable, the summary of the safety features and clinical performance referred to in Article 32 shall be updated at least once a year. annually by adding the data in question. Chapter VI and Annex XIV.
7. Post-market surveillance and vigilance
For each device, manufacturers design, establish, document, apply, maintain, and maintain a post-market surveillance system based on risk class and device type.
The intended post-marketing surveillance system is based on a post-marketing surveillance plan, the characteristics of which are set out in Annex III, Section 1.1.
In addition, manufacturers of Class IIa, IIb and III devices shall establish, for each device and, where appropriate, for each category or group of devices, a Periodic Safety Update Report (PSUR) summarizing the results and conclusions of analysis of post-market surveillance data collected as part of the post-market surveillance plan.
Manufacturers of devices made available on the Union market shall notify the competent authorities concerned of any serious incident concerning devices made available on the Union market, any corrective safety measures taken in respect of devices placed on the market of the Union. available on the Union market.
Targeted reports are submitted via an electronic system. Manufacturers must report on trends in incidents and side effects.
In addition, they must carry out all the necessary investigations to analyze the incidents. Competent authorities may also conduct their own investigations or studies.
The Commission shall also establish, in collaboration with the Member States, systems and processes for the active analysis of data available in the electronic system, in order to identify trends, developments or signals which, in the data, identify new risks or new sources of security concern.
7.3 Market Surveillance
Competent authorities shall monitor the characteristics and performance of compliance arrangements, taking into account the established principles of risk assessment and risk management, vigilance data and claims.
The competent authorities shall draw up annual programs for surveillance activities and devote appropriate material and human resources to carry out these activities, taking into account the European market surveillance program developed by the MDCG.
Chapter VII and Annex III
Under the aegis of the 93 / 42 / CEE directive, there were 18 rules for 56 criteria, the 2017 / 745 rule now offers 22 rules and 80 criteria.
Modifications are made to the classification system resulting in some devices having a higher risk class especially for those containing a substance that can be introduced or absorbed in or by the 21 rule body.
Four new rules are introduced, relating to:
• devices containing a nanomaterial;
• non-surgical invasive devices for administering drugs by inhalation;
• devices composed of substances or combinations
substances that are intended to be introduced into the human body through an orifice of the body or by application to the skin and which are absorbed by the human body or dispersed locally;
• therapeutic active devices with an integrated or built-in diagnostic function that largely determines the patient's management.
It is further integrated with the 11 medical device rule software classification. The software is according to its use and the associated risks in class I, IIA, IIB or III.
An 19 rule is also provided for devices incorporating nanomaterials, these devices will be following the exposure potential rated IIA, IIB or III.
Sometimes it is difficult, in some cases, to distinguish between medical devices and cosmetic products, it is also appropriate to provide in the Regulation of Cosmetics (EC) No 1223 / 2009 of the European Parliament and the Council the possibility of identifies a product through a Union-wide decision. For example: cleaning products, contact lenses, liposuction equipment, hair removal.
Article: 51 and Annex VIII
9. Quality System
Normally the Quality system is in accordance with ISO 13485 Medical Devices - Quality Management Systems - Requirements for Regulatory Purposes. This standard covers practically the same requirements as the Regulation, nevertheless there is to add some elements:
Document outlining the Regulatory Compliance Strategy, Pre-Post Commercialization UID Management Document, Clinical Investigation and Evaluation Procedures, Procedure and Document for Post-Market Surveillance and Periodic Safety Reporting (PSUR).
Designation of the Person Responsible for Regulatory Compliance (Qualified Person):
This person must demonstrate a minimum experience with, for example, a sufficient degree or professional experience in the regulatory field or quality management systems related to Article 15 medical devices.
The person responsible for regulatory affairs is responsible for:
• the control of the conformity of the devices to the quality management system;
• the drafting of the technical documentation and the EU declaration of conformity as well as their updating;
• verification of post-market surveillance obligations;
• support for notifications in the context of due diligence obligations;
• in the case of an investigation, the provision of the statement that the device in question complies with the general requirements for safety and performance regardless of the aspects of the clinical investigation.
10. Technical documentation
Annex 1 which related to the essential requirements has been renamed to general safety and performance requirements. It describes in detail all the requirements to be considered in order to control the risks when designing the product. Many elements of this appendix will be found in the technical documentation.
Annex 2 specifies the technical documentation to be put in place by the manufacturer:
• description and specifications of the device with possibly references to previous generations or similar,
• labeling information and instructions for use,
• benefit / risk analysis and risk management,
• verification and validation of the product including clinical data,
• design and manufacturing information,
• any specific information related to the product (drug substance, tissue or cell of human origin, sterility, other substances, ...)
Annex I and II
The directive is replaced by a regulation which has a direct effect as it is immediately applicable since the regulation is not transferred to national law.
The important changes in this regulation are:
• tighter inspection of devices with higher risk,
• notified bodies approved according to stricter and better controlled criteria,
• some non-medical devices such as certain cosmetic devices in this regulation,
• more transparency in the use of medical device databases to improve the traceability and use of the IUD,
• increased clinical requirements,
• worsening of post-market surveillance,
• enhanced coordination between the countries of the European Union.
Jérôme DONON – A3P
Consultant, former Group Quality Director in charge of Intercontinental at Sanofi, previously Biomedical Quality Director at Synthélabo (Porgès and ELA Médical, Synthélabo subsidiaries) after having been Director of Production of Active Implantable Medical Devices (pacemakers and cardiac defibrillators) at ELA Médical, a subsidiary of Synthelabo.
GCDM : Coordination Group of Medical Devices
IUD : Unique Identification of Devices
IUD ID : Unique Identification of Devices-Device Identification
IUD-IP : Unique Identification of Devices-Production Identification
EUDAMED : European Database on Medical Devices
ON : Notified body
SCAC : Clinical Follow-up After Marketing
NANDO : New Approach Notified and Designated Organizations
PSURs : Periodic Safety Update Report
Regulation (EU) 2017 / 745 of the European Parliament and of the 5 Board 2017 on Medical Devices, amending Directive 2001 / 83 / EC, Regulation (EC) No 178 / 2002 and Regulation (EC) No 1223 / 2009 and repealing the 90 Council Directives / 385 / EEC and 93 / 42 / EEC
Regulation (EU) 2017 / 746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98 / 79 / EC and Commission Decision 2010 / 227 / EU