February 2024 Introduction to Medical Device Regulation
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3 www.gandlhealth.com Objective MDR Comprises: • 10 Chapters • 123 Articles • 3 Annexes The objective of today’s presentation is to provide an understanding of the European Medical Device Regulation 2017/745, and the requirements to be fulfilled to place a medical device on the market.
4 www.gandlhealth.com Regulation (EU) 2017/745 of the European Parliament and of the Council Of 5th April 2017 on medical devices amending Directive 2001/83/EC, Regulation (EC) No 1223/2009 and repealing Council Directive 90/385/EEC and 93/42/EEC Regulation (EU) 2017/745
The Medical Devices Regulation was passed in April 2017 with an implementation date of 2021 for medical devices and 2022 for In Vitro Diagnostics.* This regulation amended the directive on medicinal products for human use MPD, the regulation on food law and the regulation on cosmetic products. While also repealing the directive on active implantable medical devices and the MDD. The MDR is significantly more comprehensive and detailed compared to the MDD. While the MDD comprises 23 Articles and 12 annexes over 60 pages, the MDR has 123 articles and 17 annexes over 175 pages. Throughout the course of this presentation, we will take a brief look at the requirements of the different chapters and annexes. The word safety appears almost 300 times in MDR, it appeared 22 times in MDD. * There have been some extensions to the implementation of the regulation for legacy devices which will be discussed later in the slide deck.
6 www.gandlhealth.com Guideline? Regulation? Directive? Guideline Advisory. To be considered; scientific rationale often required when deviating from recommendations or guidelines. Directive EU level legislation but interpreted at the local level and translated into local country laws at a time of the member state choosing. Regulation EU level legislation must be implemented word for word by each member state on stated date.
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8 www.gandlhealth.com Mar 20, 2023 May 26, 2026 Dec 31, 2027 Dec 31, 2028 MDR amendment effective for legacy devices Custom made Class III implantable devices Other Class IIb, Class Is (MDD certified legacy devices) and Class I devices before May 26, 2021 Class III and Class IIb implantable (MDD certified legacy device) MDR Transition Period – Legacy Devices
As previously mentioned, the MDR is a recent piece of legalisation and is a significant expansion on the previous directives with an added emphasis on the safety and efficacy of devices places on the market within the EU. The increased requirements from MDD to MDR has been challenging for both the manufacturers and the Notified Bodies who issue the CE marks. Due to the challenges faced by manufacturers and the limited capacity of the certified Notified Bodies (NB) it became clear that across the EU member states implementing the original timelines was not probable and to ensure the safety of patients and prevent shortages of key medical devices in hospitals across the union the transition timeline was revised. The original date of May 2024 has been extended to December 2027 for high-risk devices such as pacemakers and hip implants, and December 2028 for medium and low-risk devices such as syringes or reusable surgical instruments.
10 www.gandlhealth.com 4. Regulatory status of products Scope and Definitions Articles 1 - 4 2. Definitions 3. Amendments of certain definitions 1. Subject matter and scope Chapter I
Article 3 currently specifically amends the definition of nanomaterials for the purposes of MDR This Regulation shall also apply, as from the date of application of common specifications. The necessary common specifications shall be adopted by 26 May 2021. They shall apply as from six months after the date of their entry into force or from 26 May 2021, whichever is the latest. Grandfathering is a term used to describe the practice whereby a device copied a design of another product on the market and claimed essential similarity and inferring if that product was safe and effective (not necessary to provide this evidence), then, my product is equally safe and effective. It is permissible to claim essential similarity but only if the maker of the “parent” product provides approvable evidence. This change has proved difficult for many manufacturers as they don’t have access to such data or the means to run a clinical trial. Most of the legacy device's CE marked under the MDD will require recertification because of Annex I, General Safety and Performance Requirements (GSPR).
12 www.gandlhealth.com • Includes medicinal products derived from human blood or human plasma, • Includes derivatives of non-viable tissues or cells of human or animal origin Active implantable medical devices (AIMDs) Devices incorporating an ancillary medicinal product Devices incorporating ancillary nonviable tissues or cells of human origin Devices manufactured utilizing tissues or cells of animal origin, Products specifically intended for the cleaning, disinfection or sterilization of devices Aesthetic products without an intended medical purpose accessories for cleaning, disinfection or sterilization characteristics similar to medical devices with an aesthetic only Article 1 - Scope of the MDR
The scope of the MDR is wider than that of the MDD and covers medical devices for human use and their accessories including: • Active implantable medical devices (AIMDs) (previously controlled by a dedicated directive) • Devices incorporating an ancillary medicinal product, including a medicinal product derived from human blood or human plasma, • Devices incorporating ancillary non-viable tissues or cells of human origin or their derivatives, • Devices manufactured utilizing tissues or cells of animal origin, or their derivatives, which are non-viable or are rendered non-viable, • Products specifically intended for the cleaning, disinfection, or sterilization of devices - These were previously covered as accessories to medical devices. The change means that accessories for cleaning, disinfection or sterilization are now in scope of the MDR.
• Annex XVI to the MDR specifies devices with non-medical indications such as: 1. Contact lenses or other items intended to be introduced into or onto the eye. 2. Products intended to be totally or partially introduced into the human body through surgically invasive means for the purpose of modifying the anatomy or fixation of body parts with the exception of tattooing products and piercings. 3. Substances, combinations of substances, or items intended to be used for facial or other dermal or mucous membrane filling by subcutaneous, submucous or intradermal injection or other introduction, excluding those for tattooing. 4. Equipment intended to be used to reduce, remove or destroy adipose tissue, such as equipment for liposuction or lipolysis . 5. High intensity electromagnetic radiation (e.g. infra-red, visible light and ultra-violet) emitting equipment intended for use on the human body, including coherent and non-coherent sources, monochromatic and broad spectrum, such as lasers and intense pulsed light equipment, for skin resurfacing, tattoo or hair removal or other skin treatment. 6. Equipment intended for brain stimulation that apply electrical currents or magnetic or electromagnetic fields that penetrate the cranium to modify neuronal activity in the brain without a specific medical purpose.
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16 www.gandlhealth.com Foods Food supplements additives, flavourings Human Blood Products Radiopharmaceuticals Toys In Vitro Diagnostics Cosmetic Products Products Outside Scope of MDR Advanced Therapy Medicinal Products Biocides
Most importantly Article 1, defines what is out of scope of the MDR. It is Important to note that the following items are not considered to be medical devices though some may bear CE Marking. • Toys (Directive 2009/48/EC) – many toys bear CE mark but this does not infer that it is a device • Biocide products - Regulation (EU) 528/2012 • Human Blood products - Directive 2002/98/EC • Radiopharmaceuticals (2001/83/EC and EMEA/CHMP/QWP/306970/2007 • Foods - Regulation 178/2002 • Supplements - Directive 2002/46/EC • Additives - Regulation (EC) No 1333/2008 • Flavourings - Regulation (EC) No 1334/2008 • Advanced Therapy Medicinal Products - Regulation 1394/2007 • Cosmetic Products - Regulation 1223/2009 • Medicinal Devices - Regulation 2017/745 • In Vitro Diagnostics - Regulation 2017/746
18 www.gandlhealth.com investigation, replacement or modification of the anatomy or of a physiological or pathological process or state diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease Providing information by means of in vitro examination of specimens derived from the human body, including organ blood and tissue donation diagnosis, monitoring, treatment, alleviation of, or compensation for an injury or disability Article 2 - Definition of a medical device
Article 2 defines what is a medical device ‘Medical Device’ means any instrument, apparatus, appliance, software, implant, reagent, material, or other article intended by the manufacturer to be used, alone or in combination, for human beings for one more of the following specific medical purposes and does not achieve its principal intended action by pharmacological immunological or metabolic means in or on the human body, but which maybe assisted in its function by such means When trying to identify if a product falls within the criteria to be considered a medical device, it should be determined if the product in question follows one or more of these specific medical purposes. It should also be notes that in line with the MDR The following products shall also be deemed to be medical devices: • Devices for the control or support of conception, • Products specifically intended for the cleaning, disinfection or sterilisation of devices as referred to in article 1(4) and those referred to in the first paragraph of this point.
20 www.gandlhealth.com The nit comb has a specific medical purpose The normal comb does not have a specific medical purpose For medical devices compliance to the regulation is needed before a CE mark can be attached However, having a CE mark does not always denote a medical device Definition of a medical device
21 www.gandlhealth.com Medical Devices for Drug Delivery Empty Syringe Drug Delivery Pump Nebulizers Measuring Spoon/Syringe Sterile Wound dressing Medicinal Products Vaccine solution Delivery syringe Morphine IV Solution Ventolin solution for Nebulizer Calpol Solution Topical disinfectants Povidone/Iodine Wound Dressing Medical devices which may accompany a medicinal product and medicinal products that would utilise medical devices Examples Medical Devices and Medicinal Products Article 117 - Products should be regulated by either the device or medicine review process. Not both.
22 www.gandlhealth.com Skin peeling products (device or cosmetic) • Depends if a medical claim (appearance vs scar removal) • Depth (top layer of skin or deeper action) • Frequency of application Insect repellent (device or biocide) • Manufacturer wanted a medical claim of prevention of injuries from insects • Primary action is to repel insects (and not humans) and so not a medicinal claim. It is a biocide. Borderline with Other Directives
Borderline cases are considered to be those cases where it is not clear from the outset whether a given product is a medical device, an in vitro diagnostic medical device, an active implantable medical device or not. Or alternatively, borderline cases are those cases where the product falls within the definition of a medical device but is excluded from the Directives by their scope. Borderline and Classification Working Group (BCWG) is chaired by the European Commission and consists of representatives of competent authorities from all Member States with a number of stakeholder associations as observers. Manual on borderline and classification for medical devices under Regulation (EU) 2017/745 on medical devices and Regulation (EU) 2017/746 on in vitro diagnostic medical devices (Version 3 – September 2023 ) The interpretations within the manual are not legally binding as only the Court of Justice of the European Union can give an authoritative interpretation of Union law. This Manual only serves as one of the support tools for case-by-case application of the Union legislation by the Member States in their respective jurisdictions. It remains for the national competent authorities and the national courts to reach decisions at national level.
24 www.gandlhealth.com Babies' nappies N Walking stick Y and N Breast pump N Stair lifts N Wig N Hearing aid Y Nonprescription sunglasses N Bandages Y Baths with doors N Cycling helmet N Prescription contact lens Y Artificial tears N Is it a Medical Device?
Medical devices are considered to be specifically intended for a ‘medical purpose’, products that do not have such a principal intended purpose are not considered to be medical devices, even if they may be considered to be used for the prevention of disease as a secondary purpose. Wigs have been classified by manufacturers as medical devices but technically, while fulfilling an important need in chemotherapy and other patients who have lost hair, there is no corrective or preventative action. Not actually correcting hair loss. While baths with doors and stair lifts are aids for daily living, they are generally not considered to be devices since they may be used ‘by all’ (rather than having a direct link with the individual concerned). A walking stick could fall into this daily aid category also, but some are specifically designed and MARKETED as being intended for alleviation of, or compensation for a disability. The determining factor will be whether or not there is a direct link between the corrective function of the equipment and the individual concerned and that there is a stated medical purpose. Prescription contact lenses are considered medical devices as they correct a person's sight. However, there are contact lenses that change the colour of people's eyes these are not corrective or preventative and hence are not medical devices.
26 www.gandlhealth.com Chapter II Making available on the market and putting into service of device, obligations of economic operators, reprocessing, CE marking and free movement Articles 5 - 24
Chapter 2 details the obligations, regulations, which must be observed in order to bring a CE certified product to the market in the EU under the MDR. Chapter 2, leaning on the scope of the regulation and the definitions defined in Chapter 1, provides security to the end-user that any MDR CE Marked device, brought to the EU market, has been designed and controlled to ensure that components used in the manufacture of the product are fit for purpose, the effective operation of the product has been validated and verified, through the lifetime of the product and the product is clinically effective. The implementation of the regulation to ensure that importers and distributors have a legal responsibility to ensure that any product they import/market/distribute is new throughout the manufacturing and distribution process and that there are appropriately qualified representatives available.
28 www.gandlhealth.com Article … 5. Placing on the market and putting into service 6. Distance sales 7. Claims 8. Use of harmonised standards 9. Common specifications 10.General obligations of manufacturers 11.Authorised representative 12.Change of authorised representative 13.General obligations of importers 14.General obligations of distributors
29 www.gandlhealth.com Article … 15.Person responsible for regulatory compliance (PRRC) 16.Cases in which obligations of manufacturers apply to importers, distributors or other persons 17.Single-use devices and their reprocessing 18.Implant card and information to be supplied to the patient with an implanted device 19.EU declaration of conformity 20.CE marking of conformity 21.Devices for special purposes 22.Systems and procedure packs 23.Article 23 Parts and components 24.Article 24 Free movement
30 www.gandlhealth.com ISO 13485: Medical Devices ISO 14971: Risk Management ISO 14155: Clinical Investigation of MD FOR human subjects ISO 15223: Medical devices - Symbols to be used with information to be supplied by the manufacturer ISO 10993: Biological Evaluation of medical devices IEC 60601: Medical electrical safety ISO11607: Packaging material for devices to be sterilised ISO 5840: Cardiovascular implants ISO 18250: Medical devices - Connectors for reservoir delivery systems for healthcare applications General Standards Specific Standards Product Specific Standards Harmonised Standards Article 8
Under Article 8 • A harmonized standard is: • A European standard developed by a recognised European Standards Organisation: CEN, CENELEC, or ETSI. • Following a request from the European commission • Many are also ISO standards (EU deviations - Annex ZA is incorporated into the EU version EN ISO to confirm it’s a harmonised standard) • Can be used to demonstrate that products, services, or processes comply with relevant EU legislation. • Use is voluntary* • Presumption of compliance to relevant requirements of directive or the MDR References of Harmonized Standards are published in the Official Journal of the European Union • The standards or sections of standard applied need to be explicitly stated in the Technical Document and in any associated validation or verification reports and identified against the corresponding section of the GSPR Note: * Though use is voluntary, in reality, it is difficult to argue against following a standard unless the path to certification uses even more stringent methods of validation or verification to demonstrate safety and efficacy of the product.
32 www.gandlhealth.com General obligations of manufacturers Key elements required by the MDR Article 10 a) Regulatory Strategy for compliance h) Verification of UDI b) General Safety and Performance Requirements (GSPRs) i) Post Market Surveillance(PMS) system c) Management responsibilities j) Communication with Competent Authority (CA’s) Notified Bodies (NB’s) Economic Operators (EO’s) ……etc. d) Resource management k) Vigilance e) Risk Management l) Corrective Action Preventive Action (CAPAs) f) Clinical evaluation m) Product improvement G) Product realisation Article 10
Under Article 10 of the MDR Manufacturers must have a robust Quality Management System (QMS) in place to support these key obligations. Article 10 through to Article 16 of Chapter II define specific activities and stakeholders within the supply chain who have legal obligations in terms of their activities in facilitating the placing of a medical device on the EU market, these stakeholders are collectively referred to as Economic Operators (EO). Manufacturer The natural or legal person with responsibility for the design, manufacture, packaging and labelling of a device before it is placed on the market under his own name, regardless of whether these operations are carried out by that person himself or on his behalf by a third party. Manufacturers are obligated to: • Draw up the appropriate documentation and amend it as standards change, and the product changes. • Maintain a quality management system to manage processes (e.g., reporting obligations).
European Authorised Representative (AR) • If the manufacturer is outside community, they need a natural or legal person to act on their behalf. • Article 11 describes obligations. Record in the mandate between AR and manufacturer tasks. • A UK AR is no longer possible post BREXIT. Importer • Responsible for the placement of a non-EU product on the EU Market Distributor • A distributor is defined as being any natural or legal person in the supply chain, other than the manufacturer or the importer, that makes a device available on the market, up until the point of putting it into service. Person Responsible for Regulatory Compliance (PRRC) • Manufacturer needs someone responsible for compliance of MDR(PRRC-m) and the AR needs access to someone in the community (PRRC-AR). MDCG 2019-07 Rev.1 Guidance on Article 15 of the medical device regulation (MDR) and in vitro diagnostic device regulation (IVDR) on a ‘person responsible for regulatory compliance’ (PRRC) (December 2023)
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36 www.gandlhealth.com Declaration of Conformity (DoC) Article 19
DoC Is a document generated by the CE holder and specifies the CE number issued by the NB The “DoC shall state that the requirements specified in this Regulation have been fulfilled in relation to the device that is covered.” “By drawing up the EU declaration of conformity, the manufacturer shall assume responsibility for compliance with the requirements of this Regulation and all other Union legislation applicable to the device.” 1.Information about the device 1. Name of the device, registered trade name or registered trade mark 2. Unique reference, e.g., the name, product code or catalog number, where appropriate also a photo 3. Intended purpose of the device 4. The device’s Basic UDI-DI 5. The device´s risk class 2.Information on the conformity of the device 1. Number of devices the declaration of conformity refers to (e.g., via lot, batch or serial numbers, unit quantities).
2. A statement from the manufacturer that the EU declaration of conformity is issued under its sole responsibility 3. A statement that the device conforms with the requirements of the MDR “and, if applicable, with any other relevant Union legislation that provides for the issuing of an EU declaration of conformity” 4. References to any CS used and in relation to which conformity is declared 5. Name and identification number of the notified body involved in the conformity assessment procedure 3. Information about the manufacturer 1. Name and address of the manufacturer and/or its authorized representative 2. If already issued, the SRN of the manufacturer and its authorized representative 4.Other 1. Place and date of issue 2. Name and function of the person signing the declaration 3. Signature DoC permits the manufacturer to affix the CE Mark.
39 www.gandlhealth.com • All devices must bear the CE mark except: • Custom made devices • Investigational devices • Demonstrations at trade fair or similar (disclaimers required) • Affixed to the device or the sterile packaging or the packaging (if not applicable/possible) • Must appear in any instructions for use and any sales packaging • Shall be accompanied by the NB number (where applicable) (check NB rules on their logo) • Form of the CE mark per Annex V Article 20 Affix the CE Mark
40 www.gandlhealth.com Chapter IIa - UKCA Making available on the Market in the UK and Northern Ireland and the transition from CE mark to UKCA mark
The MHRA is responsible for regulating medical devices, since January 1st, 2021, they have issued guidance on the procedure laid out to for manufacturers putting devices on the market in Great Britain (England, Wales and Scotland) under the newly designated UKCA mark. This guidance only applies to medical devices and does not cover other CE or UKCA marked products, in this guidance medical devices includes In Vitro Diagnostic Medical Devices and Active Implantable Medical Devices. Government has put into place measures to allow CE marked devices to be placed on the GB market, ensuring consistency of supply during the transition to UKCA in so doing, safeguarding the patients needing to avail of these products. •general medical devices compliant with the EU medical devices directive (EU MDD) or EU active implantable medical devices directive (AIMDD) with a valid declaration and CE marking can be placed on the Great Britain market up until the sooner of expiry of certificate or 30 June 2028 •in vitro diagnostic medical devices (IVDs) compliant with the EU in vitro diagnostic medical devices directive (IVDD) can be placed on the Great Britain market up until the sooner of expiry of certificate or 30 June 2030.
•general medical devices including custom-made devices, compliant with the EU medical devices regulation (EU MDR) and IVDs compliant with the EU in vitro diagnostic medical devices regulation (EU IVDR) can be placed on the Great Britain market up until 30 June 2030. UK notified bodies are not able to issue CE Certificates – They have become UK approved Bodies. In England, Wales and Scotland devices are regulated under the Medical Devices Regulation 2002(SI 2002 No 618, as amended(UK MDR 2002) which brought into effect in UK law: •Directive 90/385/EEC on active implantable medical devices (EU AIMDD) •Directive 93/42/EEC on medical devices (EU MDD) •Directive 98/79/EC on in vitro diagnostic medical devices (EU IVDD) As such the requirements for a UKCA mark application are based on the legislation.
43 www.gandlhealth.com Manufacturers wishing to place a device on the Great Britain market need to register with the MHRA Manufacturers not established in the UK must appoint a UK Responsible Person to register and act on their behalf Manufacturers must comply with relevant product marking and conformity assessment requirements for medical devices Requirements for UKCA mark application
MHRA’S registration guidance: https://www.gov.uk/guidance/register-as-a-manufacturer-to-sell-medicaldevices-from-1-january-2021 The responsibilities of the UK Responsible Person are set out in the UK MDR 2002. In summary, in addition to the registration requirements, the UK Responsible Person must: •ensure that the declaration of conformity and technical documentation have been drawn up and, where applicable, that an appropriate conformity assessment procedure has been carried out by the manufacturer •keep available a copy of the technical documentation, a copy of the declaration of conformity and, if applicable, a copy of the relevant certificate, including any amendments and supplements for inspection by the MHRA •In response to a request from the MHRA, provide the MHRA with all the information and documentation necessary to demonstrate the conformity of a device •where they have samples of the devices or access to the device, comply with any request from the MHRA to provide such samples or access to the device
•where they have neither samples of the device nor access to the device, communicate to the manufacturer any request from the MHRA to provide such samples or access, and communicate to the MHRA whether the manufacturer intends to comply with that request •cooperate with the MHRA on any preventive or corrective action taken to eliminate or, if that is not possible, mitigate the risks posed by devices •immediately inform the manufacturer about complaints and reports from healthcare professionals, patients and users about suspected incidents related to a device for which they have been appointed •if the manufacturer acts contrary to its obligations under these Regulations: • terminate the legal relationship with the manufacturer; and • inform the MHRA and, if applicable, the relevant Approved Body of that termination. If an importer is not UK Responsible Person, the importer is required to inform the relevant manufacturer or UK RP of their intention to import a device. It is either the manufacturer or appointed responsible person to provide the MHRA with Importer details.
46 www.gandlhealth.com Northern Ireland CE Mark
The rules for placing a medical device on the NI market differ from those in GB. Since 26th May 2021, the EU MDR has applied in Northern Ireland Since 26th May 2022, the IVDR has applied in Northern Ireland CE marking is required for marketing in NI. In addition, the UKNI indication is required if a UK NB undertakes mandatory third-party conformity assessment. Certain medical devices, including In Vitro Diagnostic Medical Devices(IVD’S) placing on NI market to be registered with the MHRA. When placing devices on the Northern Ireland market, Great Britain- based manufacturers must be appoint on EU or Northern Ireland – based Authorised Representative.
48 www.gandlhealth.com Eudamed Traceability UDI Registering Devices Chapter III Identification and traceability of devices, registration of devices and of economic operators, summary of safety and clinical performance, European data base on medical devices Articles 25 - 34
Article 25. Identification within the supply chain 26. Medical devices nomenclature 27. Unique Device Identification [UDI] system 28. UDI database 29. Registration of devices 30. Electronic system for registration of economic operators 31. Registration of manufacturers, authorised representatives and importers 32. Summary of safety and clinical performance (SSCP) 33. European database on medical devices 34. Functionality of Eudamed
50 www.gandlhealth.com Article 27 Unique Device Identifier (UDI)