European Medical Device Regulation: Collaboration To Drive Innovation
MEDTECH REGULATIONS UPDATEEuropean Medical Device Regulation:Collaboration to Drive Innovationby Monica Tocchi, MD, PhDABSTRACTEurope, the second largest global medtech market, is enduring a major overhaul as two brand new regulations formedical devices and in-vitro diagnostics will soon replace previous legislation. By May 26, 2020, more complex ruleswill impact the daily work of manufacturers, health professionals as well as the public, creating new opportunitiesfor collaboration to drive innovation. Complying with the new Medical Device Regulation seems overwhelming andmany don’t know where to start. This paper discusses the key changes and best practices for a successful transitionto the new legislative framework.THE ACTORSIn the new European Medical Devices Regulation (MDR)745/2017 [1], Economic Operators are defined as “amanufacturer, authorized representative, importer ordistributor”, lumped together under the acronym of MAID.Health Institution means an “organization with the primarypurpose of the care or treatment of patients or the promotionof public health”. In addition, User means “any healthcareprofessional or lay person who uses a device”, while a LayPerson is “an individual who does not have formal educationin a relevant field of healthcare or medical discipline; in vitrouse, software, material or other similar or related articleintended for human beings, for one or more of the specificmedical purpose(s).”For all stakeholders, it is imperative to get ready for theregulatory framework as soon as possible. MDR is complexlegislation and manufacturers and economic operators needto analyze various factors that impact their practice. Updatesand new obligations span every aspect of the medical devicelifecycle, from development and clinical evaluation to marketaccess, surveillance and vigilance. Indeed, economicoperators and health institutions in Europe are expected tocomply with the applicable requirements of the MDR by theapplication date of May 26, 2020.A proactive approach is needed to understand therequirements applicable to different devices and entities toavoid setbacks in healthcare delivery and business liability.The new MDR intent is to reinforce the scrutiny of notifiedbodies and supervision of competent authorities, whilstalso introducing provisions as to transparency, complianceand traceability throughout the supply chain for medicaldevices (Figure 1). Today, supply chain qualification andcollaboration is a game-changing differentiator.Figure 1. Supply chain and cooperation of economic operators(MAID) under the MDRCreating open lines of communication, establishingprograms for engagement and regulatory training are keyelements to the MDR transition. This paper discussesthe importance of mastering the MDR requirements andpresents Meditrial’s regulatory compliance approach for asuccessful transition.Dr. Monica TocchiFounder and Chief Medical Officer, MeditrialDr. Tocchi is a cardiologist and regulatory expertinvolved in writing standards on clinical trials (ISO14155), cardiac valve replacement and repair (ISO5840; ISO 5910), cardiac occluders (ISO 22679) .1 White Paper January 2020Meditrial is a trusted international consulting firm,Authorized Representative and certified provider ofeffective medical and regulatory trainings.Meditrial is recognized as a leading CRO and digitalhealth provider for medtech trials and applicationsfor US approval and European CE marking.Meditrial www.meditrial.net
THE MEDTECH MARKETPerhaps no other sector of life sciences encounters asmuch transformation and opportunity as the medicaldevice industry. Rapid growth is a result of technologicaladvancements combined with the rising burden of populationaging and chronic diseases. Based on the comprehensivestudy conducted by Fortune Business Insights, the globalmedical devices market size in 2018 was valued at 425.5billion and is expected to reach 612.7 billion by 2025. [2]Europe is the second largest medtech market after the US,with estimated value of 115 billion in 2017, representing27% of the world market. [3] New regulatory requirements,fierce competition, and rapidly emerging technologies arecreating new challenges for those operating in the sector.In particular, the stricter MDR requirements are drivingup costs and increasing the risk of costly compliancefailures. Startups and small companies experiencedifficulty navigating the complex approval processes. Also,established companies are exposed to third-party risk relatedto new obligations extended to suppliers and subcontractors.Industry therefore is facing the need to assess the impact ofchanges and prepare an action plan, defining the strategyfor implementing appropriate upgrades, integrating newtechnologies and processes which are necessary to enabletimely and effective compliance. Companies also need toensure they have the right internal competencies requiredby the new MDR.KEY CHANGESThe new MDR comprises 10 Chapters (Table 1) whichinclude a total of 123 articles; and 17 Annexes (Table 2).Compared to the previous Medical Device Directive, theMDR promotes a shift to a life-cycle approach, and bringsEurope closer than ever before to the US regulatoryframework [3].ABBREVIATIONS AND RNSSCPUDIClinical Evaluation ReportDevice IdentifierIn vitro Diagnostic Device RegulationGeneral Safety and Performance RequirementsMedical Devices RegulationMedical Device DirectiveNotified BodyProduct IdentifierPost Market Clinical Follow-UpPerson Responsible for Regulatory ComplianceManufacturer, Autohrized Representative,Importer, Distributor (Economic Operators)Single Identification Number (for clinical trials)Safety and Performance RequirementSingle Identification Number(for Economic Operators)Summary of Safety and Clinical PerformanceUnique Device IdentifiersEUDAMEDThe philosophy of the MDR is based on a central repositoryof information to lay the foundation for collaboration,transparency and interaction of all parties, namely thenew European databank for medical devices and in vitrodiagnostic devices (Figure 2) [4]. The EUDAMED databankhas been in existence for many years but was onlyaccessible by the European Commission and the NationalCompetent Authorities (NCAs).With the MDR, EUDAMED-2 expands to contain moreextensive data and allow access to many more groupsincluding the European Commission, NCAs, NotifiedBodies, MAID, Sponsors and the public.Figure 2. Functioning of EUDAMED-2, European Databank according to the MDR and IVDR2 White Paper January 2020Meditrial www.meditrial.net
EUROPEAN MDR : COLLABORATION FOR INNOVATIONEUDAMED-2 will allow economic operators to register theirorganization and devices, upload relevant documentation,apply for clinical investigations and performance studies,and upload post-market surveillance documentation. Itis forecast that 70,000 organizations will register, withan estimate of more than 300,000 users. The EuropeanCommission has recently set up a new webpage to shareinformation on EUDAMED implementation [4]. Economicoperators should regularly check this page to keep updatedand be ready to o plan an appropriate data upload andtransfer strategy.Unique Device IdentificationThe new Regulations introduce a system of unique deviceidentifiers (UDIs) to facilitate the traceability of devices,significantly enhancing the effectiveness of the post-marketsafety-related activities and allowing better monitoringby competent authorities. The UDI system should alsoimprove purchasing, and waste disposal policies, and stockmanagement by health institutions and other economicoperators.Devices will be allocated a device identifier (DI) andproduction series or batches will be identified with aproduction identifier (PI). The basic UDI-DI must also bereferenced in the declaration of conformity.In the US, FDArules require medical device labelers to submit data to theGlobal Unique Device Identification Database (GUDID) forthe highest-risk medical devices.Although the US and European authorities are aiming fora globally harmonized and pursue a consistent approachbased on the use of standardized nomenclature, variationsstill exist. MedTech Europe released a document thathighlights the differences between the US UDI and EU UDIsystem requirements [5].Table 1. MDR CHAPTERSCHAPTER ICHAPTER IICHAPTER IIICHAPTER IVCHAPTER VCHAPTER VICHAPTER VIICHAPTER VIIICHAPTER IXCHAPTER XScope and definitionsMaking available on the market andputting into service of devices, obligationsof economic operators, reprocessing, CEmarking, free movementIdentification and traceability of devices,registration of devices and of economicoperators, summary of safety and clinicalperformance, European database onmedical devicesNotified BodiesClassification and conformity assessmentClinical evaluation and clinicalinvestigationsPost-market surveillance, vigilance andmarket surveillanceCooperation between member states,medical device coordination group, expertlaboratories, expert panels and deviceregistersConfidentiality, data protection, fundingand penaltiesFinal provisionsCompliance requirementsThe MDR integrates requirements on authorizedrepresentation, clinical evaluation, vigilance, and postmarket clinical follow-up. Details on new obligations to bemet by manufacturers can be found in MDR Article 10.As an example, the terminology of the MDR has changed.There are no more “essential requirements” as per MDD;under MDR, these are now safety and performancerequirements (SPR).The compliance of all marketed devices with the SPRpresented in MDR Annex I has to be reassessed, withreference to current standards and state of the art. Alongwith these are increased requirements for clinical data.Previously a literature review and reliance on data of similardevices may have been sufficient, but some companies willnow need data from clinical studies. In fact, equivalenceis now more rigorously interpreted and only applicable ina limited number of cases. The qualification requirementsfor auditing and criteria for notified body (NB) reviewshave increased, emphasizing clinical data and clinicalevaluations. The UK competent authority has created aninteractive introductory guide to the MDR and IVDR, thatcan be consulted for additional information [5].COMPLIANCE CHAMPIONSOne of the first steps for compliance, is to have a designatedperson responsible for regulatory compliance (PRRC).This person must have a relevant degree or sufficient workexperience to understand and meet the requirements ofthe standard. In addition, the PRCC must also designatedby outsourced suppliers: importers and distributors aredeeply affected by the new regulation, leading to the needto address respective responsibilities regarding verificationof compliance, cooperation in complaint handling and fieldTable 2. MDR ANNEXESIIIIIIIVVVIVIIVIIIIXXXIXIIXIIIXIVXVXVIXVII3 White Paper January 2020General safety and performance requirements.Technical documentation.Technical documentation on post market surveillance.EU declaration of conformity.CE marking of conformity.Information to be submitted upon the registration ofdevices and economic operators in accordance withArticles 29 par 4 and 31, core data elements to beprovided to the UDI database, the UDI system.Requirements to be met by notified bodiesClassification rules.Conformity assessment on a quality managementsystem and on assessment of technicaldocumentationConformity assessment based on type- examination.Conformity assessment based on product conformityverification.Certificates issued by a notified body.Procedure for custom-made devices.Clinical evaluation and post- market clinical follow-up.Clinical investigations.List of groups of products without an intendedmedical purpose referred to in Article 1 par 2.Correlation table.Meditrial www.meditrial.net
safety corrective actions and cooperating with manufacturersand Competent Authorities in device traceability.A small company may not have a properly experienced andqualified regulatory person on-staff. Given the shortage ofexpert resources, it is urgent for any company to identify theright resources to fulfill this critical role, and ensure the rightqualifications of the champion for each of the key suppliersor economic operators.IMPACT ON MANUFACTURERSAs under the current regulatory regime, manufacturers ofmedical devices take prime responsibility for getting a CEmark certification for the European market. Now, companiesneed to manage the necessary upgrades to get newproducts CE- marked or old products re-certified under thenew Regulation.Conformity assessment procedures are more complex,and equivalence with other devices will be more rigorouslyinterpreted, reducing reliance on evidence from the marketand leading to the need for more clinical investigations.Clinical data and Clinical Evaluation Report (CER) will faceheavy scrutiny and require recurring updates. Manufacturersmust also fulfill increased post-market surveillancerequirements, perform Post-Market Clinical Follow-up(PMCF) studies when required to address residual risks,and deliver Period Safety Update Reports (Class IIa devicesand above).IMPORTERS, DISTRIBUTORS ANDAUTHORIZED REPRESENTATIVESManufacturers outside the EU market should have acontract with an authorized representative inside the EU,whereas designating an importer or distributor is optional.The Regulations clarify the respective responsibilities ofthese economic operators (Figure 1), that are now for thefirst time involved in the evaluation of compliance and areexposed to direct liability for product nonconformities.The Regulations also clarify the distinction between vigilanceand post-market surveillance, pointing to the involvementof the entire supply chain. Reporting serious incidents andconducting safety-related corrective actions requires directand efficient cooperation between healthcare professionals,health institutions, manufacturers, economic operators andnational competent authorities for medical devices.Selection of the Authorized Representative is a fundamentalchoice for non-EU companies, but it can also be a valuableoption for small and medium-size European companies whoseek support and advice for compliance. An AuthorizedRepresentative firm with expertise in regulatory affairscan facilitate fulfilling many of the MDR obligations, suchas registration in Eudamed, assistance with FSCA andincident reporting, and compliance support. Under theMDR, the Authorized representative will take on more riskand liability, as the firm will be held jointly and severallyliable for defective medical devices. As such, Manufacturerscan expect that their representative will monitor compliancemore thoroughly.4 White Paper January 2020HEALTHCARE PROFESSIONALS ANDHEALTH INSTITUTIONSHealthcare professionals need to be aware that theRegulations are more stringent than the previous Directives.During the transition from Directives to Regulations and fora few years afterward (until 2025), some products certifiedunder the Directives and products certified under the newRegulations will coexist on the market. Both will have equalstatus under the law, and no discrimination in public tendersmay take place.The Regulations require manufacturers to implement postmarket surveillance follow-up plans. This could lead to theneed for health institutions to provide more informationabout their experience with their medical devices. Healthinstitutions could prepare for this by thinking about convenientways to gather information about their experience withmedical devices.In addition, with each implantable device, the manufacturerwill have to deliver implant card-carrying-appropriateinformation. This card, including the patient’s identity, shallbe supplied to each patient fitted with an implant. Healthinstitutions shall allow rapid access to the informationcontained on the implant card to any patient fitted with adevice, unless the type of implant is exempt from thisobligation (currently this includes for example staples anddental hardware).Finally, if a health institution itself is sponsoring orthe healthcare professional is taking part in a clinicalinvestigation or a performance study, the institution needsto be aware of enhanced MDR obligations.TIMELINESMDR will take effect on May 26, 2020. Exclusion to thedeadline of May 2020 is the implementation of UDI (UniqueDevice Identification), for classes IIa and IIb – May 26th,2023 and classes I and III – May 26th, 2026.The EUDAMED launch is expected to be delayed byabout 2 years, i.e. May 2022 [4]. As such, Member Statesare discussing temporary solutions to be adopted for theapplication of the related Article 123 paragraph d, untilEUDAMED becomes operational. However, the MDR dateof application is not affected by the EUDAMED delay, andmanufacturers are expected to comply with the preparationand exchange of all required reports using the existingsystems as far as possible.For clinical investigations new requirements, the applicationdate is May 2020, although the MDR coordinated assessmentprocedure which allows the centralized approval of amultinational clinical trial by a single coordinating MemberState, will only be implemented from May 26, 2017.QUALITY SYSTEM UPGRADEEven when a manufacturer has products on the Europeanmarket, and CE certificates have been renewed to enablecontinued commercialization under the “old” regulation,the manufacturer must to evaluate the impact of theMeditrial www.meditrial.net
EUROPEAN MDR : COLLABORATION FOR INNOVATIONMDR and update the quality system, to meet the newrequirements by May 2020. All audits after this date will beto the MDR standard. As such, companies must conducta quality system assessment and identify areas impactedby the changes. Importantly, the upgrade requires thatinterconnections are created among all quality documents,records, product information, and risk management. In otherwords, the documentation and quality records and products’documentation need to be a seamless system of data andinformation.New or updated procedures are essential to comply with theextensive MDR requirements. Consultation with regulatoryexperts is more important than ever to figure out whatapplies to each company and how devices will be impacted.It is up to manufacturers to know the timelines and what todo to ensure products are compliant with MDR.Some distributors and importers may never have had aquality system before. Under this regulation, every importeror distributor and the authorized representative will needto develop one. The manufacturer, therefore, need to beproactive, ensuring and documenting that suppliers areaware of the new regulations and are compliant.CONCLUSIONThe EU MDR deeply impacts economic operators and healthinstitutions alike, creating the need to adopt a structuredcross-functional approach in order to change together andadjust to the new scenario. The level of time and effort neededfor defining the strategy and planning the implementation ofthe new regulations is not to be underestimated. Expandedcollaborations and broader partnerships are vital in thishighly competitive and specialized industry to drive medtechinnovation in Europe in the age of the MDR.As industry seeks access to global markets and harmonizedrequirements are still a future goal, a winning strategy relieson the ability of organizations to build robust internationalalliances and guarantee effective stakeholder supervisionbased on high staff competence and strong projectmanagement capabilities. Especially for small and mid-sizedcompanies, the balance between in-house capabilities andoutsourced support, as well as the implementation of moderndigital software to aid R&D and quality management, areparamount for market success.TIPS TO GET READYIf you are involved with the MDR transition strategy, gapassessments, or simply getting up to speed quickly onthe MDR requirements, start by learning the regulationfirsthand by identifying suitable training for key people inyour organization. The knowledge gained will allow you toasses the impact on your organization and the appropriatenext steps to meet the new requirements for all membersof the supply chain, health institutions and healthcareprofessionals.Rely on regulatory experts, who have assisted multiplemedical device companies with QA/RA compliance, toaddress all of your questions and help you organize aspecific transition strategy for your company based on your5 White Paper January 2020product range, certification cycle, and markets you serve.Gain the competence needed to interact effectively withyour Notified Body. Expert consulting groups may provide aheadstart and accelerate your transition, reducing businessrisk and enabling success.For example, Meditrial, a trusted consulting company andEuropean representative. offers clear and effective trainingcourses and consulting services designed to illustrate toeconomic operators and health professionals what arethe new rules for in-house devices, custom-made devices,and clinical investigations. Meditrial also provides strategicadvice and support for regulatory compliance and qualitymanagement system upgrade including digital tranformativeoptions.REFERENCES1. Regulation (EU) 2017/745 of the European Parliamentand of the Council of 5 April on medical devices, amendingDirective 2001/83/EC, Regulation (EC) No 178/2002 andRegulation (EC) No 1223/2009 and repealing CouncilDirectives 90/385/EEC and 93/42/EEC.2. Medical Devices Market Size, Share and IndustryAnalysis by Type, End User and Regional Forecast, 2019- 2025 Fortune Business Insights, April 2019.3. The European Medical Technology Market in Figures.Medtech Europe Report 20194. EU Commission EUDAMED 2 webpage s/newregulations/eudamed en5. UDI System in the US and in the EU, Mapping of thedifferences. Medtech Europe, January 20196. MHRA An Introductory guide to the MDR and IVDRhttps://www.gov.uk/guidance/Monica Tocchi MD, PhDFounder, Chief Medical OfficerMeditrial Europe Ltd.Birmensdorferstrasse 1988003 Zürich, SwitzerlandPh. 41 4178498 84 - Fax. 41 4178498 85Meditrial USA Inc.19W 34Th StreetSuite 1018 - New York, NY 10001Ph. 1 646 741 9156 - Fax. 1 646 741 9156What is your opinion on the proposed newMedical Device Regulation? Stay intouch!@meditrial-europeMeditrial www.meditrial.net
and new obligations span every aspect of the medical device lifecycle, from development and clinical evaluation to market access, surveillance and vigilance. Indeed, economic operators and health institutions in Europe are expected to comply with the applicable requirements of the MDR by the application date of May 26, 2020.
(7) Regulation (EU) 2015/2283 of the European Parliament and of the Council of 25 November 2015 on novel foods, amending Regulation (EU) No 1169/2011 of the European Parliament and of the Council and repealing Regulation (EC) No 258/97 of the European Parliament and of the Council and Commission Regulation (EC) No 1852/2001 (OJ L 327, 11.12.2015,
medical device clinical investigations. Manufacturers should also be aware of a European guidance document, MDCG 2021-6, Regulation (EU) 2017/745 - Questions & Answers regarding clinical investigation (April 2021), developed by the Clinical Investigation and Evaluation (CIE) subgroup of the Medical Device Coordination Group (MDCG). The CIE .
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who medical device technical series: to ensure improved access, quality and use of medical devices who medical device technical series human resources for medical devices the role of biomedical engineers development of medical device policies, strategies and action plans who medical device technical series
REGULATION (EU) No 231/2014 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 11 March 2014 establishing an Instrument for Pre-accession Assistance (IPA II) THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN CopenhagenUNION, Having regard to the Treaty on the Functioning of the European
medical device Medical Device Note: sterilization pouch used for the packaging and sterilization of a medical device prior to the supply of the device is part of the materials used in manufacturing process, and hence would not be classified as a Medical Device. Sterilization or disinfection 4) OPTHALMIC PRODUCTS
The ASSI device can be configured to act as a master device or as a slave: Master device A master device is configured as device number 1. The master device connects to the Pitot tubes. Slave device A device configured with device number 2,3 or 4 is to be used in multi engine setups as a slave (see later chapter).
Regulation 6 Assessment of personal protective equipment 9 Regulation 7 Maintenance and replacement of personal protective equipment 10 Regulation 8 Accommodation for personal protective equipment 11 Regulation 9 Information, instruction and training 12 Regulation 10 Use of personal protective equipment 13 Regulation 11 Reporting loss or defect 14
