Medical Devices Regulation

Regulation (EU) 2017/745 (Medical Device Regulation – MDR) has been adopted on the 5th April 2017.  It will apply to medical devices and their accessories after the transitional period of 3 years (May 2020).

The regulation sets essential health and safety requirements, while additional common specification and delegated acts will be drawn up at a later stage by the Commission. These specifications shall be taken into account by manufacturers as well as Notified Bodies. These Common Specifications will exist in parallel to the Harmonized Standards and the State of the Art.

Medical devices scope has been widened to include aesthetic purpose.

Devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose. They shall be safe and effective and shall not compromise the clinical condition or the safety of patients.

Manufacturers shall establish, implement, document and maintain a risk management system, and eliminate or reduce risks as far as possible through safe design and manufacture.

Manufacturer shall establish, document, implement, maintain, keep up to date and continually improve a quality management system that shall ensure compliance with the Regulation in the most effective manner and in a manner which is proportional  to the risk class and the type of device.

CE marking shall be affixed on devices complying with the MDR.  Devices will freely circulate in the European Economic Area and Switzerland provided that the manufacturer will continue complying with their obligations under the MDR and that the devices are safe.

Devices falling under the Medical Device Regulation (MDR) are 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 or more of the following specific medical purposes:

• diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,
• diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,
• investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,
• Providing information by means of in-vitro examination of specimens derived from the human body, including organ, blood and tissue donations.

And which does not achieve its principal intended action by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means.

The following products shall also be considered as medical devices:

• devices for the control or support of conception;
• products specifically intended for the cleaning, disinfection or sterilization of devices

Some aesthetic devices are now falling under the scope of the medical device regulation (MDR).

Accessories of medical devices shall be considered as medical devices.

Devices with both a medical and a non-medical intended purpose shall fulfill cumulatively the requirements.

The MDR classification system does not radically differ from the MDD, although it takes better into account the level of invasiveness and level of toxicity (e.g. absorbable sutures).

Any dispute between the manufacturer or authorized representative and the notified body regarding the classification should be brought to the competent authority for a decision.

The classification system might be subject to change by future implementing act from the commission.

Classes

The Medical Device Regulation divides MD into classes I, Is, Im, IIa, IIb and III, taking into account the intended purpose and risk as per Annex VIII :

• Class I-Devices low risk such as stethoscopes, bandages, etc. The devices are non-invasive, also some low risk software. The manufacturer must complete a technical file and shall self declare the conformity of their product
• Class I sterile-Devices are low risk such as sterile bandages, administration sets for infusion, The devices are non-invasive. The manufacturer must draw up a technical file and apply to a European Notified Body to get the sterilization process certified.
• Class I measuring-Devices are low risk such as measuring spoons and cups, etc. The devices are non- invasive. The manufacturer must draw up a technical file and apply to a European Notified Body to get certified in the area of manufacturing dealing with metrology.
• Class IIa-Devices low-medium risk devices such as a hearing-aid. The manufacturer must draw up a technical file and apply to a European Notified Body to get its its  quality management system certified. During the audit, the notified body will verify the technical file of  a representative device for each category of devices verified
• Class IIb-Devices are medium-high risk. Examples include ventilators and intensive care monitoring equipment. The manufacturer must draw up a technical file and apply to a European Notified Body to get its quality management system certified. During the audit the notified body will verify the technical file of a representative device per device generic device group.
• Class III These are high-risk devices. Some examples are balloon catheters and prosthetic heart valves, some high risk software. The manufacturer must draw up a technical file and apply to a European notified Body to get is Quality Management System certified. The notified body shall review the technical documentation. In addition prior to issuing the technical documentation review certificate, the notified body shall pass its summary of evaluation to the Commission which may decide together with Member States to require a further evaluation by a group of experts.

For all devices, manufacturer shall draw up an EU Declaration of Conformity.

18 Rules of Classification

The classification rules, which are based on the vulnerability of the human body, should take into account the potential risks associated with the technical design and manufacture of the devices.

• Rule 1– Non-invasive devices.
• Rule 2 – Non-invasive devices intended for channeling or storing (now includes cells)
• Rule 3 – Non-invasive devices that modify biological or chemical composition of blood, body liquids, other liquids and cells.
• Rule 4 – Non-invasive devices in contact with injured skin or mucous membrane.
• Rule 5 – Devices invasive in body orifices.
• Rule 6 – Surgically invasive devices for transient use.
• Rule 7 – Surgically invasive devices for short term use.
• Rule 8 – Surgically invasive devices for long term use and implantable (including any device administering medicinal products, surgical mesh or spinal disc).
• Rule 9 – Active therapeutic devices intended to exchange or administer energy.
• Rule 10 – Active devices for diagnosis & monitoring, emit ionizing radiation.
• Rule 11 – Software intended to provide information which is used to take decisions with diagnosis or therapeutic purposes (from class I to class III)
• Rule 12 – Active devices intended to administer and/or remove medicinal products, body liquids or other substances
• Rule 13 – All other active devices.
• Rule 14 – Devices incorporating a medicinal substance including human blood or plasma.
• Devices used for contraception or prevention of sexually transmitted diseases.
• Rule 15 – Contraception or prevention of the transmission of sexually transmitted diseases
• Rule 16 – Specific disinfecting, cleaning and rinsing devices.
• Rule 17 – Devices specifically intended for recording of diagnostic images generated by X-ray radiation
• Rule 18 – Devices utilizing non-viable tissues or cells of human origin or tissues of animal or derivatives.

Four new rules:

• Rule 19 – Devices incorporating or consisting of nanomaterial
• Rule 20 – Invasive devices with respect to body orifices to administer medicinal products by inhalation
• Rule 21 – Substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed
• Rule 22 – Active therapeutic devices with an integrated or incorporated diagnostic function which significantly determines the patient management

Annex XVI includes the following products as devices for the first time:

1. Contact lenses or other items intended to be introduced into or onto the eye. e.g. coloured contact lenses without correction of vision;
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, lipolysis or lipoplasty.
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.

A Technical File is proof that a medical device complies with the essential safety and health requirements set down by the relevant Directive(s) and Regulations. Technical Files are required for all classes of medical devices – Class I, Is, Im, IIa, IIb, III – and they must hold essential information about the medical device, and may include photographs and diagrams. The Member State in which the notified body is established may require the technical file to be made avaible in an official language determined by that Member State. In absence of such requirement, the technical file shall be provided in a language acceptable by the notified body

However, English is the most commonly used. An up to date electronic or hard copy of the file needs to be kept available in Europe allowing it to be presented to any EU Competent Authorities upon request. Manufacturers based outside the EU are to make it available at the address of their European Authorized Representative. As part of the CE Marking process, it is also advised that an external expert reviews the Technical File. For more information about Technical Files, please see our Technical File Compliance page.

ANNEX IX

• QMS assessment
• For devices class Is, Im, IIa, IIb, III : Manufacturer shall have a QMS assessed by a Notified Body.  For simple Class I and custom made devices, a manufacturer must have a QMS, but this is not checked by a Notified Body.
• For class Is, Im, reusable at least a yearly surveillance audit by Notified Body limited to sterility, measuring, reusability process
• For class IIa, IIb, III, at least a yearly surveillance audit by Notified Body

• Technical documentation assessment
• For devices IIa,: Manufacturer shall have technical documentation assessed by a Notified Body, including clinical evidence for at least one representative device for each category of devices.
• For devices IIb, Manufacturer shall have technical documentation assessed by a Notified Body, including clinical evidence for at least one representative device per generic device group
• For devices III, Manufacturer shall have the technical documentation of each device assessed by a Notified Body, including clinical evidence.
• Additional procedures :
• For the following class IIb and class III devices :
  • Implantable and active devices to administer / remove medicinal substances : notified body shall submit a clinical evaluation assessment report to the Commission expert panel for a scientific opinion (~60 days procedure) before issuing certificate.
  • Devices incorporating a medicinal substance : notified body shall consult the medicinal authority EMA/other designated CA (Directive 2001/83/EC) before issuing certificate (~210 days procedure).
  • Devices with viable or non-viable tissues or cells of human or animal origin, or derivatives : notified body shall consult the ‘human tissues or cells authority’ (Directive 2004/23/EC) or the medicinal authority EMA/other designated CA (Directive 2001/83/EC) before issuing certificate.

_

A Notified body shall prepare a clinical evaluation report and shall submit it to the Commission. The Commission will transmit the report to an expert panel which will decide whether to provide a scientific opinion on the clinical evaluation assessment report. (Annex IX 5.1) (Scrutiny process).

ANNEX X

• Type-examination conformity assessment for class IIa, IIb, III :  examination based on technical documentation vs prototype sample

ANNEX XI

• Product conformity verification for class IIa, IIb, III : complementary to the ANNEX X procedure, verification based on the prototype sample vs final product
  • Production quality assurance

or

• Product verification

Notified Bodies play a key role in supporting manufacturers to place only safe and compliant medical devices on the EU Market. They are controlling the manufacturers by carrying out conformity assessment procedures and grant conformity certificates to medical devices. There are certain expectations that a Notified Body must meet before being designated by the EU Authorities. A key aspect of their role is to audit the quality management system of the manufacturer and review the technical documentation of MDD Is/Im, IIa and IIb. Notified bodies will issue  before issuing CE Certificates and/or Technical Documentation Assessment or Type Examination Certificates depending on the class of the device. Manufacturers can consult the European Commission´s complete directory of Notified Bodies (available on the NANDO website).

Scrutiny by Competent Authorities over Notified Bodies has been reinforced with the MDR, the number of existing Notified Bodies have dramatically decreased throughout the years, therefore selecting a Notified Body device can be a complex process, it is also advised that an external expert supports this critical decision. For more information about Notified Body for medical devices, please see our Notified Body Selection page.

Notified bodies shall conduct surveillance on site audit at least on a annual basis as well as unannounced audit of manufacturer and where applicable subcontractors and suppliers.

The Medical Device Regulation (MDR) defines the “custom-made device” as any device which is specifically made in accordance with a duly qualified medical practitioner’s written prescription which gives, under his responsibility, specific design characteristics. A custom-made device is intended for the sole use of a particular patient. (MDR 2017/745 – Article 2 (3))

Examples of qualified medical practitioners: Dentist, Ophthalmologist, Orthotist, Ocularist.

Prerequisite to show experience of at least 2 years in manufacturing process

Example of custom-made devices: Orthopaedic footwear, Maxillofacial Prosthesis.

Special note: mass-produced devices which need to be adapted to meet the requirements of a healthcare professional, even though they are supplied for the sole use of a particular patient, are not considered as custom-made. (e.g., contact lenses).

Steps to place a custom-made device on the EU market:

Step 1: Non-EU Manufacturer appointing an Authorized Representative in Europe;

Step 2: Compliance with all the essential safety & health requirements that apply to the custom-made device (see compliance with MDR);

Manufacturers of custom-made devices shall:

• Comply with the essential requirements (MDR 2017/745 – Annex I)
• Shall establish, document, implement and maintain, keep up to date and continually improve a quality management system. (Article 10.9)
• Draw up Statement that the device conforms to the general safety and performance requirements (MDR 2017/745 – Annex XIII – section 1)
• Draw up technical documentation (MDR 2017/745 – Annex XIII – Section 2).
• PMCF as referred to in (MDR 2017/745 – Annex XIV, Part B)
• Report any Vigilance case (MDR 2017/745 – Article 87(1))

Step 3:

With the MDR, there is no longer pre-market notification of custom-made devices per se. However, it is likely that the commission will set-up guidelines in order to properly identify the market chain.

Custom-made devices do not bear the CE marking.

Custom-made devices do not require the intervention of a Notified Body.

Non-compliance:

A device may be placed on the market or put into service only if it complies with the Medical Device Regulation.

A device shall meet the general safety and performance requirements set out in Annex I which apply to it, taking into account its intended purpose.

Manufacturers and their Authorized Representatives shall cooperate with competent authorities to demonstrate the compliance of the device. If the manufacturer or authorized representative fails to cooperate or to provide complete or correct, the competent authority may take all appropriate measures to prohibit the device’s being made available on its national market, to withdraw the device from that market or to recall it.

The MDR (article 61 and Annex XIV) reinforces clinical data and evaluation process. Manufacturers shall provide sound clinical data and evaluation to confirm the device conformity with essential health and safety requirements.The clinical evaluation proves that the device is safe and performs according to its intended purpose, assesses the undesirable side effects, as well as the acceptability of the benefit-risk ratio. Manufacturers shall plan, conduct and document a clinical evaluation in accordance with Article 61 and Part A of Annex XIV.

How to obtain the clinical data:

• Published data on clinical experience with the device or equivalent
• Clinical investigation
• Clinical investigation with similar device
• Combination of the above

The medical devices must go through clinical evaluation which is the process of assessing clinical data and making sure that the data is in conformity with the harmonized standards and essential requirements that have been established by the European Union.

For all class IIb (Article 54(1)) and III devices, the manufacturer may, prior to its clinical evaluation and/or investigation, consult an expert panel with the aim of reviewing the manufacturer’s intended clinical proposals for clinical investigation.

The clinical evaluation must follow a certain procedure based on either:

1. A critical evaluation of the relevant scientific literature currently available evaluating the design characteristics, safety, and performance of the device all based on its intended use where:
   1. there is demonstration of equivalence of the device to the device to which the data relates and
   2. the data adequately demonstrates compliance with the relevant safety and performance requirements
2. A critical evaluation of results of all clinical investigations made with a consideration of alternative treatment options currently available.
3. A consideration of all current alternative treatments

When a clinical data not deemed appropriate, there must be adequate justification based on risk management output and under consideration of the specifics of the device/body interaction, the performances intended and claims of the manufacturer. In that case non-clinical testing methods alone, including performance evaluation, bench testing and pre- clinical evaluation, need to be appropriate.

The clinical evaluation shall be updated throughout the life cycle of the device with clinical data obtained from the implementation of the manufacturer’s PMCF plan in accordance with Part B of Annex XIV and the post-market surveillance plan referred to in Article 84.

For class III and implantable devices, a PMCF evaluation report shall be updated yearly, and a summary of the safety and clinical performance shall be uploaded to the EUDAMED and updated yearly.

Clinical investigation for class III and implantable devices

In the case of implantable devices and class III devices, clinical investigations shall always be performed except if:

• the already marketed device has been modified by the same manufacturer, and
• the modified device has been demonstrated by the manufacturer to be equivalent to the marketed device, and this demonstration has been endorsed by the notified body, and
• the clinical evaluation of the marketed device is sufficient to demonstrate conformity of the modified device with the relevant safety and performance requirements,
• In addition, NO obligation of clinical investigation for class III and implantable devices in case a manufacturer demonstrates that its device is equivalent to an already marketed device, this demonstration has been endorsed by the notified body and the following conditions are fulfilled:the two manufacturers have a contract in place that explicitly allows the manufacturer of the second device full access to the technical documentation on an ongoing basis, and
• the original clinical evaluation has been performed in compliance with the requirements of the MDR, providing clear evidence to the Notified Body.

In addition, NO obligation of clinical investigation for class III and implantable devices :

• If the devices have been lawfully placed on the market under the former directives and for which the clinical evaluation is based on sufficient clinical data and comply with Common specification where available

NO obligation of clinical investigation for devices such as : sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors for which the clinical evaluation is based on sufficient clinical data.

Manufacturer’s responsibility

Clinical investigation is the systematic study or investigation of safety and performance of a device being used by human beings in accordance with the device’s normal use. Where the sponsor of a clinical investigation is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative. Such legal representative shall be responsible for ensuring compliance with the sponsor’s obligations pursuant to this Regulation.

Manufacturer/sponsor is responsible for the:

• Design of the study
• Designation of principal investigator
• Insurance
• Application with ethical committee
• The non-EU manufacturer/sponsor may choose to appoint the Authorized Representative to complete the authorization of clinical investigation to EUDAMED.
• Incident Reporting-in the event of an incident during the clinical investigation, the reporting as such will need to be determined and performed by the appointed Authorized Representative through the EUDAMED database
• Documentation available-the clinical investigation data (reports) should be incorporated in the technical documentation that has to be kept available by the manufacturer of his appointed European Authorized Representative established within the Union.
• Sponsor (authorized representative) shall notify the competent authorities of the ending of the clinical investigation, and submit a report.

Clinical Investigation plan:

• Informed consent and ethical consideration
• Clear measurable objectives
• Criteria to stop the trial
• Statistical power
• Patient population equivalent to EU

The clinical evaluation and its documentation must continually be updated by its post-market surveillance information. If this post-market surveillance is not needed for some reason in following up on the medical device, an acceptable justification must be given and documented. For high risk devices, there must be a clinical follow-up report given with the final report.

Role of the Competent Authority:

Authorities are responsible to give authorization for the clinical investigation to start, after clinical investigation registration in the European Databank.  The authorization procedure should take less than a month according to the MDR.  Delegated acts may be taken by the commission to fine tune this procedure. The clinical investigation will receive a single registration number (SRN) for better follow-up and data exchange between member-states.

Role of the Notified Body:

Clinical investigation and evaluation are reviewed by the Notified Body who has such authority, as part of the technical documentation review before granting CE certificate:

• Assessment of clinical safety and performance
• Conclusion with justification
• Risk-benefit ratio
• Remove this bullet point

The Medical Device Regulation (article 22) refers to some specific ways in packing devices together while placing them on the market :

‘procedure pack’ or “kit” means a combination of products (from different manufacturers) packaged together and placed on the market to be used for a specific medical purpose

‘system’ means a combination of products, either packaged together or not, which are intended to be inter- connected or combined to achieve a specific medical purpose;

If you combine devices bearing a CE marking with another device bearing the CE marking, or an IVD bearing the CE marking, or other products for medical purpose which are in conformity with legislation, you will need

• to verify the compatibility between the devices in accordance with the manufacturers’ instructions,
• include manufacturers’ instructions in the system/procedure package, and
• ensure the activity of combining devices and if applicable other products as a system or procedure pack was subject to appropriate methods of internal monitoring, verification and validation. .
• draw up a statement

If you sterilize systems or procedure packs in order to place them on the market you must apply a conformity assessment procedure (Annex IX or Part A of Annex XI), involve a NB certificate for the aspects of of the procedure relating to ensuring sterility and draw-up a statement that sterilization has been carried out in accordance with manufacturer’s instructions..

These systems or procedure packs shall not themselves bear an additional CE marking but they shall bear the name, and address of the procedure/system “packer”.

Where the system or procedure pack incorporates devices which do not bear the CE marking or where the chosen combination is not compatible in view of their original intended purpose, or where the sterilization  has not been carried out in accordance with the manufacturer instructions, the system or procedure pack shall be treated as a device in its own right and shall be subject to the relevant conformity assessment procedure pursuant to Article 12.

The statements shall be kept at the disposal of the competent authorities for 10-15 years.

Basic UDI-DI are required for systems and procedure packs.

Steps to place a kit on the EU market:

Step 1:

Non-EU Manufacturer appointing an Authorized Representative in Europe;

Step 2:

• Manufacturer drawing a Statement (article 22)
• Label and instruction for use (Annex I – Section 23)
• NB if sterilization (statement of sterilization)

Step 3:

Registration to the EUDAMED, assignment of Basic UDI-DI and UDI-DI (article 22 and 29)