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With this book, you get a really complete seminar for the new Regulations on medical devices and IVDs in the EU, ready at hand, at any time. These EU regulations create new rules for medical technology and laboratory diagnostics in Europe. Concise regulatory know-how is now required to keep or reposition medical devices and in vitro diagnostics on the European market, from syringes, contact lenses, medical device apps, pregnancy tests, nuclear magnetic resonance tomography to cancer tests, genetic diagnostics, HIV tests, hip implants, heart catheters, artificial spinal discs, stents and pacemakers. Concise regulatory training and further education of employees in companies and health care facilities is the order of the day. This also applies to biomedical and medical technology students at universities of applied sciences and biomedical universities, start-ups and spin-offs, who must make use of this know-how from the initial product idea through the further stages of product development to market access. The book provides a thorough, compact course on the new regulations, starting with perfect overview and easy navigation and going into depth where you need it: this book will make you fit and confident for the new European challenges! 344 pages; 47 col. figures; 26 tables
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Contents
Chapter 1. Overview of the New Regulatory System for Medical Devices and In Vitro Diagnostics in the EU
1.1. Transition from Directives to Regulations
1.2. The New EU Regulatory System for Medical Devices and IVDs: The Building Principles
1.2.1. New legal framework for EU product legislation
1.2.2. The New Approach Under the New Legal Framework
1.2.3. The Global Approach under the New Legal Framework
1.2.4. Plausibility Checks for Successful "European Conformity Assessments" of MD and IVD
1.2.5. ‘Special Routes’ to Market/User
1.3. Market Access Under the New Regulatory Framework: Central Concepts
1.3.1. ‘Making Available on the Market’
1.3.2. ‘Placing on the Market’
1.3.3. ‘Putting into Service’
1.3.4. ‘Manufacturer’
1.3.5. ‘Fully Refurbishing’
1.3.6. Distance Sales
1.3.7. Relabellers and Repackagers
1.4. Important Documents of the Regulatory System
1.4.1. The Main Legal Acts for MD and IVD
1.4.2. Implementing and Delegated Acts of the COM
1.4.3 Monopoly of legal interpretation of EU law
1.4.4. Non-legally binding Guidance
1.4.5. Harmonised European Standards
1.4.6. Anticipation and Monitoring of Later Changes to Legal and Interpretational Documents
1.5. Regulatory Compliance – A Short Walkthrough Along the Product Life Cycle
1.6. Transitional Provisions, Entry Into Force and Date of Application of MDR/IVDR
Chapter 2. The Scope of the Two New Regulations: Product Delineation as a MD/IVD (Qualification)
2.1 Does my product fall under the MDR?
2.2 Does my product fall under the IVDR?
2.2.1. Sources:
Chapter 3: General Obligations of Economic Operators:
3.1. Manufacturer
3.2. System&Procedure Pack Producer (SPPP)
3.3. Authorized Representative
3.4. Importer
3.5. Distributor
3.6. Person Responsible for Regulatory Compliance (PRRC)
Chapter 4. European Databank EUDAMED and its Modules; UDI-System; Identification and Traceability of MD/IVD; European Medical Device Nomenclature (EMDN)
4.1. European Database EUDAMED
4.2. UDI-System
4.3. Traceability (Identification within the supply chain)
4.4. European Medical Device Nomenclature (EMDN)
Chapter 5. General Safety and Performance Requirements for Medical Devices and IVDs
5.1 Risk Management System (RMS)
5.2. Matrix of General Safety and Performance Requirements
5.3 Important changes to the General Safety and Performance Requirements for MDs in Annex I
5.4. Preclinical Evaluation of MDs
5.5. Important changes to the General Safety and Performance Requirements for IVDs in Annex I
Chapter 6. Clinical evaluation of medical devices
Chapter 7. Performance Evaluation of In Vitro Diagnostics
Chapter 8. Clinical investigation of medical devices
Chapter 9. Performance studies of IVDs
Chapter 10. Technical Documentation (TD)
10.1. Technical documentation for MDs
10.2 Technical documentation for IVDs
Chapter 11. Classification
XI.1 Classification of Medical Devices According to MDR
XI.2 Classification of In Vitro Diagnostics According to IVDR
Chapter 12. Conformity Assessment of MDs
12.1. The Preliminary Clarifications for MDs
12.2. Checks for “Special Routes” (Outside CE-marking)
12.3. The Modular Conformity Assessment Procedure for CE Marking (Overview)
12.4. How to Find a Suitable Notified Body for my MD/MDs?
12.5. Overview: Conformity Assessment According to Annex IX-XI
12.5.1. Overview: Annex IX
12.5.2. Overview: Annex X
12.5.3. Overview Annex XI
12.6. Conformity Assessment for MDs of Classes III - I according to MDR: Art. 52
12.6.1. Class III:
12.6.2. Class IIb:
12.6.3. Class IIa:
12.6.4. Class I:
12.7. Consultation Procedures
12.8. After Successful Conformity Assessment (Classes I-III)
Chapter 13. Conformity Assessment of IVDs
13.1. Preliminary Clarifications for IVDs
13.2. Checks for “Special Routes” (Outside CE-marking)
13.3. The Modular Conformity Assessment Procedure for CE Marking (Overview)
13.4. How do I Find a Suitable Notified Body for my IVD(s)?
13.5. Overview: Conformity Assessment According to Annexes IX-XI
13.5.1. Overview: Annex IX
13.5.2. Overview: Annex X
13.5.3. Overview Annex XI
13.6. Overview: The Conformity Assessment Procedures for Classes D to A
13.6.1. IVD Conformity Assessment Class D:
13.6.2. IVD Conformity Assessment Class C:
13.6.3. IVD Conformity Assessment Class B:
13.6.4. IVD Conformity Assessment Class A:
13.7. Consultation Procedures
13.8. After Successful Conformity Assessment (Classes D - A)
Chapter 14. Surveillance After the Start of Placing on the Market, Responsibilities
Chapter 15. Post-Market Surveillance (PMS), PMS System
15.1. Sources :
15.2. Survey of PMS-System
15.3. The PMS Plan
15.4. PMS Data Analysis and Drawing Conclusions
15.5. PMS-Reporting
Chapter 16: The Vigilance System
16.1. Sources:
16.2. Survey of the Vigilance System
16.3. The Manufacturer Incident Report - MIR
16.4. The reporting obligations in the vigilance system in detail
16.4.1 Reporting of serious incidents
16.4.2. Field Safety Corrective Action (FSCA)
16.4.3. Further Variants of Vigilance Reports
16.5. Forms, Contact data for vigilance
16.5.1. Forms, Templates and help texts at the COM-homepage
16.5.2. Contact details of the competent authorities for vigilance in the EEA
16.6. Exchange of information by the competent authorities
16.6.1 EU NCARs (EU National Competent Authority Reports).
16.6.2. Single Coordinating Competent Authority and Vigilance Task Forces
16.6.3. IMDRF NCAR Exchange
16.7. Product (group)-specific guidelines on vigilance
16.8. Person responsible for regulatory compliance (PRRC)
Chapter 17. Service Part
17.1. Useful Internet addresses
17.2. List of Figures
17.3. List of Tables
17.4. List of Abbreviations
Preface
With this book, you’ll get a really complete seminar for the new Regulations of medical devices/IVDs in the EU, ready at hand, at any time.
The book will give you a quick, reliable overview of this new, often perceived as rather difficult EU regulatory environment.
You will save yourself quite a lot of money and energy of countless seminars, whether in presence or, often no less strenuous, online via Zoom or MS Teams etc.
All important aspects are thoroughly prepared. Therefore, you can go into depth with each partial seminar/chapter if required.
And when it comes to the final detail, the many target-oriented references to the new EU interpretative documents and standards will help you. You will be able to act on an equal footing with authorities, notified bodies, other economic actors or the staff of research or health institutions and always have a clear direction in front of your eyes.
Use this complete seminar for the benefit of our patients, whether you work in relevant projects, in your studies, in small or larger companies, in education, in consulting or in research and health care institutions!
In 2017, after more than four years of legal work, the European legislator presented a comprehensive revision of the legislation for medical devices and in vitro diagnostics. The aim was to create a reliable legal basis, now directly applicable EU law1, for a very dynamically growing industrial healthcare sector. This sector is characterized by rapid innovation, start-ups, spin-offs, small and medium-sized enterprises and the need for continuous training and further education, more than almost any other sector. In addition to the technical, biological and clinical sciences, regulatory know-how here plays a special role in knowledge management for development and success. In the training and further education of young people and employees, which are crucial for maintenance and further development of research and business sites, the know-how necessary for regulatory compliance must therefore not be lacking alongside the other factors! Countless failures and malinvestments are due to the lack of regulatory compliance in SMEs and start-ups (usually without their own regulatory affairs department). How many research projects have dragged a prototype across the finish line of the project without even thinking about possible market access. They have thus wasted the most valuable time or even missed the connection to the market! The new EU regulations on medical devices and IVDs prescribe a clear reorientation for the many small manufacturers, because regulatory compliance is now very explicitly part of the obligatory quality management system (QMS) with its more clearly defined life cycle processes and is to become effective across portfolios. A clear benefit of MDR and IVDR: The clear regulatory pathway under the QMS with close take-up of the crucial life-cycle processes and steps! Once mentally and organisationally incorporated, this will make the life of all manufacturers and other stakeholders much more easier.
The starting points of the new regulations were above all:
the European commitment to better anchor jointly developed global GHTF/IMDRF guidelines in the EU legal system (e.g. UDI; technical documentation; classification, conformity assessment and performance evaluation of IVDs) in order to facilitate global market access for European companies,
Desire for more legal clarity through the transfer of non-legally-binding, especially MEDDEV, guidelines content into the legal framework (especially vigilance, clinical evaluation),
Political will for increased transparency of the system for all stakeholders and the public through a new European database EUDAMED, combined with better product identification and traceability by the UDI system (Unique Device Identifier),
the political will to raise level and harmonisation of the EU conformity assessment for medical devices and IVDs and of the performance of notified bodies. Particularly in the case of implants and other high-risk products, perceived challenges to the credibility of the European system had to be tackled to assure patients are treated with well assessed, safe and effective MDs/IVDs. The so-called PIP scandal was only a bold marker; the European legislator had also identified problems with other implants and high-risk products, some of which were permitted in the EU, but had failed in other jurisdictions or concerning devices already marketed elsewhere, with no critical reassurance by EU NBs. HTA assessments, being more frequently asked now by European health care providers for reimbursement decisions, are often identifying insufficient clinical evidence provided for licensed high-risk medical devices. The health care providers wanted a more seamless transition between markets and health care systems. The legislative aims were therefore inter alia:
significant improvement
2
of clinical evaluation of medical devices and performance evaluation of IVDs; creation of a suitable clinical expert infrastructure and of specific, more clinically oriented guidelines as in the US and in the pharmaceutical sector; creation of suitable instruments to analyse and guarantee the safety, effectiveness and performance of products over longer periods of time (‘real world data’ or ‘post launch evidence generation’, e.g. as systematic evaluations of suitable implant registries, long-term studies, evaluation of biobanks, evaluation of (valid) Big Data etc., supplemented by PMS, PMCF, PMPF
3
and risk management as strong life cycle processes);
create a more homogeneous clinical research landscape in the EU on pharmaceuticals, medical devices and IVDs, especially for combination studies,
the adaptation of the sector to the EU's "New Legislative Framework (NLF)" in the regulation of products, including explicit ‘rules of the game’ for all economic operators, in particular the manufacturer. Important: the manufacturer has to follow a clearer regulatory orientation in the obligatory QMS (see
Fig. 5
and
6
and
Tab. 1
as a general orientation). (Joint) market surveillance by Competent Authorities has been improved accordingly;
Desire for better future agility of the system, e.g. in order to adequately respond to the increasing importance of companion diagnostics in personalized medicine and to medical genetic tests; as well as to the increasing importance of software in the medical devices and IVD sector, including medical device apps.
The result is a comprehensive and complex legal framework that needs to be studied carefully.
In addition to the many legal changes, there is still a crisis concerning notified bodies (NBs; "European Conformity Assessment Bodies") under the European system; while past problems of quality are now being solved, there is still a problem of quantity of available NBs, esp. for the IVDR.
Although the NB market is responding with an enormous ‘upgrade’, it is an exciting question whether sufficient and rapid renewal of the Notified Bodies, who also still have to ‘grapple’ with the new legislation and reengineer themselves, can guarantee a smooth transition into the certification world of the new regulations.
Change and rapid adaptations will therefore continue to be the proverbial constant in the coming years.
What is needed now is a reliable ‘GPS’ based on solid basic knowledge of the new regulations and clear expectations that the regulatory, interpretative and normative environment will continue to evolve in the near future. But as always: manufacturers will have to do their thing in a targeted and prudent manner. Despite the larger size of the MDR/IVDR compared to the previous Directives: There is a lot of old wine in new wineskins! Do not enter in a panic mode! This is also true for the IVDR under the conditions of the COVID-19 crisis. Prolonged transition times through the recent amendment regulation (EU) 2022/112 of IVDR should allow for a more smooth transition, after the MD sector now also in the IVD sector and will hopefully lead to the build-up of a proper network of NBs in both sectors. A lot of things will make life of manufacturers easier now:
For example, the contents of technical documentation (in Annexes II and III) are clearly defined for the first time, there are clear legal provisions for the new labelling and instructions for use; the life cycle processes (such as clinical evaluation of MD, performance evaluation of IVD, risk management, PMS, vigilance, registration obligations, regulatory requirements under the QMS) are much more precise and often derived from previous guidelines.
See the present vademecum as a compact training course designed to provide important assistance in this regard. It is intended
1. to provide a quick and reliable overview of the new regulatory system and its components and important types of documents (see esp. Fig. 1 to 7 and Tab. 2 as a roadmap and “GPS”), and
2. to elaborate on the essential components and processes of the new regulatory system along the life cycle of the products, so that the own study of the legal texts, which can never be dispensed with, may succeed all the easier, combined with the subsequent implementation in practice. It was also important here to provide a clear overview of the many interpretative documents which can provide valuable assistance, and which will be successively adapted to the regulations in the coming years.
The content of this compact regulatory course is derived from 2 main sources:
the author's experience out of many years of relevant professional activity in the Austrian Health Ministry, at EU level as a co-worker in many EU working groups of the sector (including chairmanship of the EU’s Working Group ‘Clinical Investigation and Evaluation [CIE]’), as a co-negotiator of the new regulations in Council and at the level of GHTF as one of the European representatives in Study Group 5 on Clinical Evidence, and
the lecture activities at universities of applied sciences for medical technology and biomedical engineering, seminars for actors in business and health care, lectures for medical technology clusters as well as courses for clinical investigators.
May the course provide valuable orientation and help for the education and training of biomedical and medical technology professionals, the health professions and the training and further education of employees in companies and health care facilities, as well as for research, development and consulting projects in medical technology, biomedical and clinical engineering and related areas.
Preface to the 4th edition:
The new legal framework has in the meantime been amended several times by corrigenda and by amendments of the Medical Device Regulation (MDR) and now also the In-vitro Diagnostics Regulation (IVDR), with new transition provisions and time limits, partly to accommodate for the COVID crisis.
Since the last edition of this book, also a lot of very important interpretative guidance by the EU Medical Device Coordination Group (MDCG) has accumulated and has now to be considered in the new edition.
Vienna, February 202
Legal note:
The authentic versions of the relevant legal acts, including their preambles, are those published in the Official Journal of the European Union and available in EUR-Lex. The information and views contained in this book are those of the author and do not represent the official opinion of the European Communities or of EU Member States. Despite careful processing, all information in this work is provided without guarantee; liability on the part of the author or the publisher is excluded.
It is therefore essential to study the authentic legal texts and the interpretative guidelines available; it is advisable to use (authentic) consolidated versions of the legal texts. In case of doubt, it is often advisable to consult the competent authorities or the European Commission. The legally binding interpretation of the EU legal texts is reserved to the European Court of Justice.
Should this publication contain links to third-party websites, the author accepts no liability for their contents, as he does not adopt them as his own, but merely refers to their status at the time of initial publication.
Gender:
For reasons of easier legibility, the masculine form is predominantly used for designations of persons and functions. It also applies in the female form, of course.
Acknowledgements:
My thanks go to my national, European and international colleagues in the field of medical devices for their decades of pleasant and exciting cooperation and in particular to DI Dr Martin Renhardt and Dr Reinhard Berger from the Austrian authorities, as well as to my long-standing German colleague Dr Gert Schorn, who introduced me thoroughly to the "EU system" at a young age and to whom I have enjoyed a pleasant friendship ever since.
I am also grateful for valuable input from Elisabeth Mertl for critical reading, esp. on the preclinical evaluation of MDs, Martina and Martin for critical reading of various chapters, Andreas Aichinger, Michael Ring and Prof. Gerold Labek for fruitful discussion on important practical issues.
My special thanks also go to my wife Sigrid for lecturing and for her constant efforts to achieve a reasonable work-life balance and to Felix Ecker for helping with the graphic design.
1 2 Regulations: MDR: Medical Device Regulation (EU) 2017/745 and IVDR: In vitro Diagnostic Regulation (EU) 2017/746
2 Along and beyond MEDDEV 2.7.1 rev 4
3 See list of Abbreviations!
Photo credits, image sources (cover, photos taken by W.E. with permission):
University of Applied Sciences Linz – Medical Technology, (spinal column X-ray-phantom, laboratory equipment, examination microscope); special thanks to Prof. DI Dr Martin Zauner, Msc, Dean of the Faculty of Medical Technology and Applied Social Sciences of the FH OOE and his staff; Sozialmedizinisches Zentrum Ost, Danube Hospital, Technical Directorate, (NMR, Mammography-US) Special thanks to Mr. TOAR Ing. Manfred Führer, Technical Director, and his staff.
I would like to thank Felix Ecker for the graphic composition.
Chapter 1. Overview of the New Regulatory System for Medical Devices and In Vitro Diagnostics in the EU
Let us first take a look at the transition from the current system of EU directives to the new EU regulations for medical devices and IVDs (chapter 1.1.). Then we look at the construction principles of the new regulatory system (chapter 1.2.) and finally further to its central concepts for EU internal market access (chapter 1.3.). The most important documents of the new (and partly old) regulatory system are systematically discussed (section 1.4.). We then need a short regulatory compliance walkthrough along the product life cycle, from product development, preparation for market access, conformity assessment to the obligations when keeping the product on the EU market (section 1.5.). This fundamental orientation is concluded by the transition regime from the old directives to the new regulations with relevant time frames (section 1.6.) which have been adapted recently by the EU legislators to address urgent issues of the covid-19 crisis.
1.1. Transition from Directives to Regulations
In 2017, the EU legislator transformed the previous regulatory system for medical devices, consisting of 3 EU directives and their national implementations, into a new system of 2 EU regulations. as now directly applicable EU law (see Fig. 1):
Regulation (EU) 2017/745 on medical devices (MDR)4, and
Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR)5.
Both regulations were developed in parallel and each consist of (see Fig.2+3)
Recitals
, i.e. intentions and objectives of the EU legislator which can be used as an aid to interpretation in the event of legal uncertainties,
the
Chapters and their Articles
, with the core of both legal texts, and
the
Annexes
, the binding, more technically oriented legal text, which supplement the chapters (for example Annex I on General Safety and Performance Requirements [GSPR; Annex II and III on technical documentation or Annexes IX to XI on conformity assessment modules [= modules of "European Premarket Approval"]).
The MDR/IVDR entered into force at EU level on 25 May 2017; the date of application for the MDR has been – after an amendment of the MDR - 26 May 2021 (4-year transitional period); for the IVDR, the date of application will be 26 May 2022 (5-year transitional period). For the more special transition periods and regimes, see chapter 1.6. in this book.
Fig. 1 From Directives to Regulations
Fig. 2 MDR: Structure and Content Overview
Fig. 3 IVDR: Structure and Content Overview
1.2. The New EU Regulatory System for Medical Devices and IVDs: The Building Principles
(See in particular Fig. 4) Both regulations are based on fundamental legal principles of the EU: the internal market concept and health protection (which primarily aims at safety and effectiveness, a high level of health protection, a positive clinical benefit/risk ratio according to the state of the art and minimization of risks and side effects). Both regulations follow basic regulatory principles of the internal market concept6, as is the
1.2.1. New legal framework for EU product legislation
This is about the new general legal framework for (many) EU product regulations (New Legislative Framework - NLF), which constitute the background philosophy of MDR and IVDR. NLF builds in a modernized form on important legal construction principles, which are essential for the understanding of both regulations: These are the
Fig. 4 MDR-IVDR: Building Principles and Documents - Survey
New Approach
and the
Global Approach
.
1.2.2. The New Approach Under the New Legal Framework
The New Approach is essentially about the following: The two Regulations7 define in their respective Annexes I checklist-like the General Safety and Performance Requirements (GSPR; previously called Essential Requirements - ER) of the MDs or IVDs, which, insofar as they apply to a certain MD/IVD, must be fulfilled by the products on placing on the market or on putting into service. The details to these requirements incl. eventual verification procedures and tests, or on certain processes and procedures of the regulatory system, are provided outside the legal texts by harmonized European standards, the references (titles) of which are published in the Official Journal of the EU for the respective Regulation or Directive. These harmonized standards are not binding8, but contain in their Annexes Z (ZA, ZB, …) very specific presumptions of conformity with regard to the GSPR mentioned there for an MD/IVD; i.e. if the manufacturer follows the presumptions of conformity set out in Annexes Z (ZA, ZB,...) of the standards for the fulfilment of certain GSPR, the manufacturer is entitled to a presumption of conformity in this respect from its Notified Body (NB; "European Conformity Assessment Body") or from the market surveillance authority (this presumption may be falsified under certain conditions). The manufacturer may deviate from harmonized standards but must then sufficiently justify his alternative solutions for compliance with the relevant GSPR, which usually is associated with increased work load. In the absence of harmonized European standards, current international ISO or IEC standards will often be used alternatively9. Harmonized European standards can also provide presumptions of conformity in important processes and procedures (e.g. quality management systems, clinical investigations, usability, risk management, performance studies).
The Harmonised Standards are drawn up by the European standardization bodies CEN and CENELEC (the latter for the electrotechnical sector) on the basis of standardization mandates of the EU Commission with the help of the standardization bodies of the Member States; they are jointly agreed and harmonized for certain regulations or directives after examination by the Commission. Their references (titles) are published 1-2 times a year in the Official Journal of the EU10. European standards are usually developed jointly with the global standards institutions ISO (<> CEN) and IEC (<> CENELEC); however, Appendices Z with the presumptions of conformity are only valid for the Harmonized European Standards.
Further presumptions of conformity can now be provided for certain MD/IVD groups within the framework of both regulations, especially in the clinical area and for Annex XVI products of the MDR, by Common Specifications, (CS) in the form of legal acts of the COM.
1.2.3. The Global Approach under the New Legal Framework
The global approach deals with the conformity assessment (“European Premarket Approval”) of products on the basis of modular conformity assessment procedures. These must be selected according to the class of the MD/IVD, derived upon the classification rules of Annex VIII of the MDR/IVDR. For medium and higher classes of the MD/IVD, conformity assessment is carried out by so-called Notified Bodies (NB). Notified Bodies are appointed by the Member States after their proven qualification and competence in a complex, now European supervised procedure for
specified product areas
,
specified areas of horizontal technical competence
(e.g. certain technologies (e.g. nanotechnology) or processes (e.g. molecular biological diagnostics), so-called "
horizontal competence codes
"
certain conformity assessment modules
(Annexes IX-XI or parts thereof)
11
.
The positive completion of approval modules (or certain parts12 thereof) by the manufacturer is documented by certificates (NB-certificates) from the NB (valid for a maximum of 5 years; content of NB-certificates see Annexes XII in both Regulations).
The aim of conformity assessment is the CE marking of conformity as a sign of successful EU approval (the correct CE marking is set out in Annex V of both Regulations). The CE marking not only includes proof of compliance with the requirements of MDR/IVDR but also of all EU legal acts that also apply to the product and require CE marking13 ("inclusive" CE marking). The CE marking shall be affixed visibly, legibly and indelibly to the device or its sterile packaging. Where such affixing is not possible or not warranted on account of the nature of the device, the CE marking shall be affixed to the packaging. The CE marking shall also appear in any instructions for use and on any sales packaging.
The CE marking is supplemented by the 4-digit identification number of the NB (if) involved in the conformity assessment14.
In addition, the manufacturer confirms the conformity of his medical devices/IVDs with the MDR/IVDR and the other EU legal acts applicable to his product, which also require an EU declaration of conformity in addition to the MD/IVDR, by an EU Declaration of Conformity ("inclusive" EU Declaration of Conformity) whose basic conditions are described in Art. 19/17 of the MDR/IVDR and whose minimum contents are given in Annex IV of both regulations15.
1.2.4. Plausibility Checks for Successful "European Conformity Assessments" of MD and IVD
These can be based mainly on the following elements:
Tab. 1 Plausibility Check of Successful EU Conformity Assessment for MD and IVD
1.2.5. ‘Special Routes’ to Market/User
In addition to the main route to CE marking, other access to the market/user without CE marking is possible in defined special routes, such as (humanitarian) device exemptions or interests of public health (emergency use authorizations, EUA) or patient safety or health by MS or COM16, inhouse production in/for health care facilities in the EU, clinical investigations of MDs or performance studies of IVDs, systems and procedure packs for MD, or as custom made MDs etc. (see chapters 12.2. and 13.2. of this book).
1.3. Market Access Under the New Regulatory Framework: Central Concepts
(making available on the market, placing on the market, putting into service, manufacturer, fully refurbishing)
Art. 5 of both Regulations states [underscore by author]:
Art. 5 (1): A device may be placed on the market or put into service only if it complies with this Regulation when duly supplied and properly installed, maintained and used in accordance with its intended purpose.
The Blue Guide17 of the Commission generally states:
Union harmonisation legislation applies when the product is placed on the market and to any subsequent operation which constitutes making available until it reaches the end-user.”
MDR and IVDR both target the placing on the market and the putting into service. However, it should be noted that the life cycle processes required in MDR and IVDR (e.g. risk management, PMS, vigilance, QMS, clinical evaluation of MD including PMCF, or performance evaluation of IVD including PMPF) cover the entire life cycle, i.e. also the systematic gathering of experience after the initial putting into service of the product (e.g. evaluation of an implant register; long-term studies etc.18).
Union harmonisation legislation applies to all forms of selling. A product offered in a catalogue or by means of electronic commerce has to comply with Union harmonisation legislation when the catalogue or website directs its offer to the Union market and includes an ordering and shipping system.
The Union harmonisation legislation applies to newly manufactured products but also to used and second-hand products imported from a third country when they enter the Union market
for the first time.
Consider in this context Recital (3) of MDR and IVDR: This Regulation does not seek to harmonize rules relating to the further making available on the market of medical devices [IVDR: in vitro diagnostic medical devices] after they have already been put into service (in the EU/EEA - addition by author) such as in the context of second-hand sales.
Union harmonisation legislation applies to finished products
19
.
A product which has been subject to important changes or overhauls aiming to modify its original performance, purpose or type may be considered as a new product. The person who carries out the changes becomes then the manufacturer with the corresponding obligations.”
In this context, you should also pay special attention to Art. 16 of both Regulations (see below!) concerning Relabelers and Repackagers20 and Art. 23 of the MDR and Art. 20 of the IVDR on parts and components with significant changes.
1.3.1. ‘Making Available on the Market’21 means any supply of a device, other than an investigational device[IVDR: other than a device for performance study], for distribution, consumption or use on the Union market in the course of a commercial activity, whether in return for payment or free of charge;
According to the EU Commission's Blue Guide, “a product is made available on the market when supplied for distribution, consumption or use on the Union market in the course of a commercial activity, whether in return for payment or free of charge. Such supply includes any offer for distribution, consumption or use on the Union market which could result in actual supply (e.g. an invitation to purchase, advertising campaigns).
The concept of making available refers to each individual product.
22
The central role that the concept of making available plays in Union harmonisation legislation is related to the fact that all economic operators in the supply-chain have traceability obligations and need to have an active role in ensuring that only compliant products circulate on the Union market. The concept of making available refers to each individual product, not to a type of product, and whether it was manufactured as an individual unit or in series. - The making available of a product supposes an offer or an agreement (written or verbal) between two or more legal or natural persons for the transfer of ownership, possession or any other right concerning the product in question after the stage of manufacture has taken place. The transfer does not necessarily require the physical handover of the product. This transfer can be for payment or free of charge, and it can be based on any type of legal instrument. Thus, a transfer of a product is considered to have taken place, for instance, in the circumstances of sale, loan, hire, leasing and gift. Transfer of ownership implies that the product is intended to be placed at the disposal of another legal or natural person.”
……
1.3.2. ‘Placing on the Market’23 means the first making available of a device, other than an investigational device[IVDR: other than a device for performance study], on the Union market;
The Blue Guide explains further:
Products made available on the market must comply with the applicable Union harmonisation legislation at the moment of placing on the market. This calls for a simultaneous application of various legislative acts which apply to a given product. Accordingly, the product has to be designed and manufactured in accordance with all applicable Union harmonisation legislation, as well as to undergo the conformity assessment procedures according to all applicable legislation, unless otherwise provided for
24
.
The operation is reserved either for a manufacturer or an importer, i.e. the manufacturer and the importer are the only economic operators who place products on the market. When a manufacturer or an importer supplies a product to a distributor or an end-user for the first time, the operation is always labelled in legal terms as ‘placing on the market’. Any subsequent operation, for instance, from a distributor to distributor or from a distributor to an end-user is defined as making available.
As for ‘making available’, the
concept of placing on the market refers to each individual product
25
, not to a type of product, and whether it was manufactured as an individual unit or in series.
Placing a product on the market requires an offer or an agreement (written or verbal) between two or more legal or natural persons for the transfer of ownership, possession or any other property right concerning the product in question after the stage of manufacture has taken place. This transfer could be for payment or free of charge. It does not require the physical handover of the product.
The placing on the market is the most decisive point in time concerning the application of the Union harmonised legislation. When made available on the market, products must be in compliance with the Union harmonisation legislation applicable at the time of placing on the market. Accordingly, new products manufactured in the Union and all products imported from third countries — whether new or used — must meet the provisions of the applicable Union harmonisation legislation when placed on the market, i.e. when made available for the first time on the Union market.
The making available or putting into service can only take place when the product complies with the provisions of all applicable Union harmonisation legislation at the time of its placing on the market.
Products offered for sale by online operators based in the EU are considered to have been placed on the Union market, regardless of who placed them on the market (the online operator, the importer, etc.). Products offered for sale online by sellers based outside the EU are considered to be placed on the Union market if sales are specifically targeted at EU consumers or other end-users.”
see more details concerning online operators in the Blue Guide (p.21ff);
Important: MDR and IVDR in their Articles 6 directly refer to “Distance sales”.
Finally, the Blue Guide demonstrates examples when placing on the market is not considered to take place (p.
→
).
For more information on "Placing on the market" in case of disputed questions of "whether" and "when" please refer to the Informative Document (Guidance) of the EU Commission: PLACING ON THE MARKET OF MEDICAL DEVICES26.
1.3.3. ‘Putting into Service’ means the stage at which a device, other than an investigational device[IVDR: other than a device for performance study], has been made available to the final user as being ready for use on the Union market for the first time for its intended purpose27;
Putting into service takes place at the moment of first use within the Union by the end user for the purposes for which it was intended.
This concept is also applied for MDs and IVDs.
Where the product is put into service by an employer for use by his employees, the employer is considered as the end-user.”
Important: Art. 5 (1 and 4) of both Regulations:
1. A device may be placed on the market or put into service only if it complies with this Regulation when duly supplied and properly installed, maintained and used in accordance with its intended purpose.
….
4.Devices that are manufactured and used within health institutions shall be considered as having been put into service.
With regard to in-house production in/for health institutions in the EU see specifically Art. 5 (5) of both Regulations!28
1.3.4. ‘Manufacturer’ means a natural or legal person who manufactures or fully refurbishes a device or has a device designed, manufactured or fully refurbished, and markets that device under its name or trademark29;
In both Regulations the obligations of the manufacturer are now explicitly listed in Art. 10. Furthermore Art. 16 of both Regulations state:
1. A distributor, importer or other natural or legal person shall assume the obligations incumbent on manufacturers if it does any of the following:
(a) makes available on the market a device under its name, registered trade name or registered trade mark, except in cases where a distributor or importer enters into an agreement with a manufacturer whereby the manufacturer is identified as such on the label and is responsible for meeting the requirements placed on manufacturers in this Regulation (author: means MDR or IVDR);
(b) changes the intended purpose of a device already placed on the market or put into service;
(c) modifies a device already placed on the market or put into service in such a way that compliance with the applicable requirements may be affected.
…
Relabellers and Repackagers: see section 1.3.7.
…
1.3.5. ‘Fully Refurbishing’ for the purposes of the definition of manufacturer, means the complete rebuilding of a device already placed on the market or put into service, or the making of a new device from used devices, to bring it into conformity with this Regulation, combined with the assignment of a new lifetime to the refurbished device30;
Please also have a look in this context on Art. 17 of MDR concerning single use devices and their reprocessing and the corresponding national legislations and on: Commission Implementing Regulation (EU) 2020/1207 of 19 August 2020 laying down rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards common specifications for the reprocessing of single-use devices, as well as on national legislation.
1.3.6. Distance Sales
MDR/IVDR: Art. 6 (1): A device offered by means of information society services31, to a natural or legal person established in the Union shall comply with this Regulation.
2.Without prejudice to national law regarding the exercise of the medical profession, a device that is not placed on the market but used in the context of a commercial activity, whether in return for payment or free of charge, for the provision of a diagnostic or therapeutic service offered by means of information society services32 or by other means of communication, directly or through intermediaries, to a natural or legal person established in the Union shall comply with this Regulation.
3.Upon request by a competent authority, any natural or legal person offering a device in accordance with paragraph 1 or providing a service in accordance with paragraph 2 shall make available a copy of the EU declaration of conformity of the device concerned.
4. A Member State may, on grounds of protection of public health, require a provider of information society services33, to cease its activity. On the activities of online providers, see also the Blue Guide.
1.3.7. Relabellers and Repackagers
Important considerations for Relabellers and Repackagers: (we are still on Art. 16 of both Regulations):
Art. 16.1.: see section 1.3.4. above
Art. 16.2. For the purposes of point (c) of paragraph 1, the following shall not be considered to be a modification of a device that could affect its compliance with the applicable requirements:
(a) provision, including translation, of the information supplied by the manufacturer, in accordance with Section 23 of Annex I [IVDR: Section 20 of Annex I], relating to a device already placed on the market and of further information which is necessary in order to market the device in the relevant Member State;
(b) changes to the outer packaging of a device already placed on the market, including a change of pack size, if the repackaging is necessary in order to market the device in the relevant Member State and if it is carried out in such conditions that the original condition of the device cannot be affected by it. In the case of devices placed on the market in sterile condition, it shall be presumed that the original condition of the device is adversely affected if the packaging that is necessary for maintaining the sterile condition is opened, damaged or otherwise negatively affected by the repackaging.
3. A distributor or importer that carries out any of the activities mentioned in points (a) and (b) of paragraph 2 shall indicate on the device or, where that is impracticable, on its packaging or in a document accompanying the device, the activity carried out together with its name, registered trade name or registered trade mark, registered place of business and the address at which it can be contacted, so that its location can be established. Distributors and importers shall ensure that they have in place a quality management system that includes procedures which ensure that the translation of information is accurate and up-to-date, and that the activities mentioned in points (a) and (b) of paragraph 2 are performed by a means and under conditions that preserve the original condition of the device and that the packaging of the repackaged device is not defective, of poor quality or untidy. The quality management system shall cover, inter alia, procedures ensuring that the distributor or importer is informed of any corrective action taken by the manufacturer in relation to the device in question in order to respond to safety issues or to bring it into conformity with this Regulation.
4.At least 28 days prior to making the relabelled or repackaged device available on the market, distributors or importers carrying out any of the activities mentioned in points (a) and (b) of paragraph 2 shall inform the manufacturer and the competent authority of the Member State in which they plan to make the device available of the intention to make the relabelled or repackaged device available and, upon request, shall provide the manufacturer and the competent authority with a sample or mock-up of the relabelled or repackaged device, including any translated label and instructions for use. Within the same period of 28 days, the distributor or importer shall submit to the competent authority a certificate, issued by a notified body designated for the type of devices that are subject to activities mentioned in points (a) and (b) of paragraph 2, attesting that the quality management system of the distributer or importer complies with the requirements laid down in paragraph 3.
See also: See also: MDCG 2021-26: Q&A on repackaging & relabelling activities under Article 16 of Regulation (EU) 2017/745 and Regulation (EU) 2017/746: https://ec.europa.eu/health/medical-devices-sector/new-regulations/guidance-mdcg-endorsed-documents-and-other-guidance_en
1.4. Important Documents of the Regulatory System
(see Fig. 4)
1.4.1. The Main Legal Acts for MD and IVD
Please consider here any Corrigenda and Amendments to these Regulations34:
Corrigendum of 5 May 2019 to Regulation (EU) 2017/745 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Directives 90/385/EEC and 93/42/EEC. This 1
st
Corr. of MDR brings smaller corrections for clinical investigations, clarifications and adaptations for sampling procedures of the technical documentation in the Annexes VII and IX in the course of conformity assessment, together with a clarification for the classification of accessories in Annex VIII.
Corrigendum of 27 December 2019 to Regulation (EU) 2017/745 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Directives 90/385/EEC and 93/42/EEC. This 2nd Corrigendum of MDR contains important changes to transition periods for certain Class I MDs under the MDR, see
chapt. I.6
. in this book for details. There are also further clarifications to the registration obligations and corrections to some false references.
Corrigendum of 5 May 2019 to Regulation (EU) 2017/746 on in vitro diagnostic medical devices, repealing Directive 98/79/EC and Commission decision 2010/227/EU This 1
st
Corrigendum to the IVDR contains corrections to misleading provisions for performance studies, adaptations with regard to sampling procedures for the technical documentation during conformity assessment in Annexes VII and IX.
Corrigendum of 27 December 2019 to Regulation (EU) 2017/746 on in vitro diagnostic medical devices, repealing Directive 98/79/EC and Commission decision 2010/227/EU. This 2nd Corrigendum gives corrections of some redactional errors, clarifications to registration obligations in the transition from IVD-Directive to IVDR and a clarification concerning classification acc. to Annex VIII for diagnosis of feto-maternal blood group incompatibilities.
REGULATION (EU) 2020/561 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 23 April 2020 amending Regulation (EU) 2017/745 on medical devices as regards the date of application of some of its provisions.
This amending regulation postponed the date of application of the MDR by 1 year to 26 May 2021
; it also stipulates that for certain Class I (excluding Im and Is) medical devices of Directive 93/42/EEC, for which referral to a Notified Body is now necessary under the MDR and for which an EU Declaration of Conformity was issued before 26.5.2021 under Directive 93/42/EEC and further conditions are fulfilled (see
chapter 1.6
. in this book), these may be placed on the market or put into or put into service until 26.5.2024. Furthermore, Art. 59 is amended in such a way that (emergency use) Exemptions from the Member States and the COM - in view of the COVID crisis - can already be extended under the MD Directive 93/42/EEC to the Union. Amendments from the 2nd Corr. of MDR are confirmed or clarified.
Regulation (EU) 2022/112 of the European Parliament and of the Council of 25 January 2022 amending Regulation (EU) 2017/746 as regards
transitional provisions for certain in vitro diagnostic medical devices and the deferred application of conditions for in-house devices
35
1.4.2. Implementing and Delegated Acts of the COM
Besides the two basic regulations and their Corrigenda and Amendments, we can expect a wealth of implementing legislation from COM, either as implementing acts or delegated acts based on authorisation in the regulations. This includes the future Common Specifications (CS) with specific requirements, especially for clinical aspects (clinical investigations, clinical evaluation, PMCF of specific types of MD; performance studies, performance evaluations and PMPF of specific types of IVD) of certain high-risk product types, but also of Annex XVI products.
Already issued as CS:
Commission Implementing Regulation (EU) 2020/1207 of 19 August 2020 laying down rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards
common specifications for the reprocessing of single-use devices
Commission Implementing Regulation (EU) 2021/2226 of 14 December 2021 laying down rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards
electronic instructions for use of medical devices
Commission Implementing Regulation (EU) 2021/2078 of 26 November 2021 laying down rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards the
European Database on Medical Devices (Eudamed)
Commission Implementing Regulation (EU) 2020/1207 of 19 August 2020 laying down rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards
common specifications for the reprocessing of single-use devices
Commission Implementing Regulation (EU) 2017/2185 of 23 November 2017 on the
codes for the designation of notified bodies
in medical devices under Regulation (EU) 2017/745 and in vitro diagnostic medical devices under Regulation (EU) 2017/746;
(This will be important for the search of suitable NBs, see Annex I with the codes for MDR and Annex II with the codes for IVDR; see chapters XII.4 and XIII.4 in this book)
Commission Implementing Decision (EU) 2019/1396 of 10 September 2019 laying down the rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards the
designation of expert panels in the field of medical devices
Commission Implementing Decision (EU) 2019/939 of 6 June 2019
designating issuing entities designated to operate a system for the assignment of Unique Device Identifiers (UDIs)
in the field of medical devices
(In the annex, the EU Commission has officially designated the following UDI issuing entities for an initial period of five years: (a) GS1 AISBL (b) Health
Industry Business Communications Council (HIBCC) (c) ICCBBA (d) Information Centre for proprietary medicinal products - IFA GmbH.)
COMMISSION IMPLEMENTING DECISION (EU) 2020/437 of 24 March 2020 concerning harmonised standards for medical devices in support of Council Directive 93/42/EEC;
COMMISSION IMPLEMENTING DECISION (EU) 2019/1396 of 10 September 2019 laying down detailed rules for the implementation of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards the
designation of expert panels for medical devices
.
COMMISSION IMPLEMENTING DECISION (EU) 2021/1182
of 16 July 2021 on the harmonised standards for medical devices drafted in support of Regulation (EU) 2017/745 of the European Parliament and of the Council36
COMMISSION IMPLEMENTING DECISION (EU) 2021/1195 of 19 July 2021 on the harmonised standards for in vitro diagnostic medical devices drafted in support of Regulation (EU) 2017/746 of the European Parliament and of the Council37
Please also note that the following implementing legislation of the COM for the Medical Devices Directive is, until further notice, to be considered implementing legislation under the MDR:
COMMISSION REGULATION (EU) No. 722/2012 of 8 August 2012
2012 concerning particular requirements as regards the requirements laid down in Council Directives 90/385/EEC and 93/42/EEC with respect to active implantable medical devices and medical devices manufactured utilising tissues of animal origin.
[Protection against TSEs (transmissible spongiform encephalopathies, like BSE, scrapie, CJD and vCJD]
Further implementation legislation will follow; the prioritization can be anticipated on the basis of the the rolling plan of the COM38 and the roadmap on the CAMD homepage39; within the framework of regulatory compliance, these must be tracked under the QMS as well as any Amendments and Corrigenda of the underlying MDR and IVDR.
1.4.3 Monopoly of legal interpretation of EU law
The (legally binding) monopoly on interpretation of EU law is the responsibility of the European Court of Justice and Judgements and Decisions of the ECJ40 must also be carefully pursued.
1.4.4. Non-legally binding Guidance
Due to the strong heterogeneity of the product area, a dense, non-legally binding set of guidelines (guidance) is being and has been developed for the medical device/IVD sector.
MDCG (Medical Device Coordination Group) is now the originator of most of the guidance (MDCG-documents) for the new Regulations41; there may also be still guidance from the COM or the CAMD.
1.4.4.1. MDCG guidance42
currently centres on these issues for the MDR/IVDR:
