The new European Regulation 2017/745 on medical devices will introduce new activities and a new approach in the management of vigilance and post-market surveillance of medical devices.

A new definition of an “incident” will be introduced. In fact, according to the Regulation 2017/745, there will be a clear distinction between “incident” and “serious incident” based above all, on the gravity of the consequences.

In particular, it will be classified as “serious incident” any incident that, directly or indirectly, caused or could have caused the death or the serious temporary or permanent deterioration of the health condition of the patient, of a final user or of other person, or that represented or could have represented a serious threat for the public health.

It will be defined “incident” any malfunction or deterioration in the characteristics or performance of a device made available on the market, including use-error due to ergonomic features, as well as any inadequacy in the information supplied by the manufacturer and any undesirable side-effects.

Another news is the introduction of an electronic system on vigilance and on post-market surveillance. As defined by the Article 92 the database will be created by the European Commission, with the collaboration of the Member States and it will serve to ensure a fast collection and management of the reports in a centralized process. Manufacturers will have to use this electronic system to report any “serious incident” to the relevant competent authority. Furthermore, manufacturers shall also report any field safety corrective action.

Other new activities on vigilance and post-market surveillance that manufactures should perform according to the European Regulation 2017/745 includes:

• Reporting trends on incident frequency
• The implementation of a Post-Marketing Surveillance Plan and of a Post-Marketing Clinical Follow Up Plan
• The PSURs preparation for class IIa, IIb and III Medical Devices
• The post market surveillance report preparation for class I Medical Devices

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The new European Regulation 2017/745 will introduce a new clinical document: the “summary of safety and clinical performance”. This document will be mandatory for all implantable devices and class III devices.

The “Summary of safety and clinical performance”, is described in the Article 32 of the new European Regulation 2017/745. In this document, manufacturers shall summarise the main safety and performance aspects of the device and the outcome of the clinical evaluation, as well.

The Article 32 of the new European Regulation 2017/745 also describes the different aspects that should be considered in the “Summary of safety and clinical performance”, included among these:

• The identification of the device and the manufacturer related data
• The description and the intended use of the device
• The available diagnostic or therapeutic alternatives
• Warnings and information concerning potential residual risks

The summary shall be clear and comprehensible to the intended user or to the patient; it should be noted that the document will be made available to the public via Eudamed database, once the database will be active. It should include the place of the device in the context of diagnostic or therapeutic options taking into account the clinical evaluation of that device when compared to the diagnostic or therapeutic alternatives and the specific conditions under which that device and its alternatives can be considered.

The manufacturer shall mention on the label or instruction for use where the summary is available. Furthermore, for class III devices and implantable devices, the “summary of safety and clinical performance” shall be updated at least annually by the manufacturer.

Finally, the draft of the summary will be part of the documentation to be submitted to and evaluated by the notified body involved in the CE conformity assessment.

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The RPN team is ready to support you in the transition from the old Directive to the new European Regulation and in the preparation of the Clinical Evaluation Report and related documents.

The new European Regulation 2017/745 will bring many innovations. One of these concerns the extension of the Regulation application field. According to Article 1, the Regulation 2017/745 will apply also to groups of products without an intended medical purpose listed in Annex XVI. These products will be classified as “devices”, although they do not have any medical purpose. A summary of the categories of products listed in Annex XVI of the European Regulation 2017/745 is reported below:

• Contact lenses or other items intended to be introduced into or onto the eye;
• 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, except for tattooing products and piercings;
• 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;
• Equipment intended to be used to reduce, remove or destroy adipose tissue;
• High intensity electromagnetic radiation emitting equipment used on the human body such as lasers and intense pulsed light equipment, for skin resurfacing, tattoo or hair removal or other skin treatment
• 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

These products will be classified as medical devices; this means that the manufacturers will have to classify, register and manage these products as medical devices according to the requirements of the new European Regulation 2017/745. However, the manufacturers could state that the intended use of the device is different from medical purpose.

It should be noted that due to the specific nature of these devices, the clinical evaluation will be principally be based on the safety data, whereas the requirement related to the demonstration of the clinical benefit will refer to the demonstration of the performance of the device.

Considering that most of the products listed in Annex XVI of the European Regulation 2017/745 do not currently fit into clearly defined categories, the New Regulation could be of great impact for many companies.

RPN is at your disposal to offer you support to better manage the transition from the current directive to the new regulation.

Starting with the entry into force of the new European Regulation 2017/745 on May 2020, the information on medical devices to be supplied by the manufacturers will be more detailed and regulated. The Annex I of the current Directive 93/42/CEE will be in part maintained even in the new Regulation, but it will be implemented with new essential requirements and an entire chapter. The chapter III “Requirements regarding the information supplied by the manufacturer” indeed, has been introduced into the Annex I of the MDR 2017/745 and it deals with this fundamental theme for the manufacturers in a more detailed and precise way.

This means that the new introduced requirements will impact, for example, on the medical devices labelling and leaflet.

The presence of CMR substances of categories 1A and/or 1 B within the allowed limits shall be labelled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging with the list of substances.

Some other changes will interest the information to be stated on the label. In particular, the labels will have to be more detailed and shall contain the UDI carrier and the other relevant information according to the type of medical device, such as:

• The indication that the device contains or incorporates human or animal origin tissues or cells;
• The indication related to the reprocessing in case of a single-use device;
• The composition in case of device composed by substances or combinations of substances;
• The serial number for the active implantable devices.

As just anticipated, even the instruction for use shall report further information. The main novelties regard the description of the expected clinical benefits and the links remanding to the “summary of safety and clinical performance” referred to in Article 32 of the new Regulation 2017/745 (for further information on this topic, please click here) that shall be indicated in the leaflet.

Moreover, concerning the safety, the information related to any preparatory treatment or handling of the device before it is ready for use shall be stated in a more detailed manner, including the required levels of disinfection to guarantee the safety. Even the frequency and modality of maintenance, calibration, indication on the consumable components shall be described in detail.

Furthermore, another very interesting novelty regards the medical device users, who will be called to participate actively as concerns the surveillance.

In fact, the instruction for use shall contain a note that indicates to the patient/user the need of reporting to the manufacturer and to the competent authority any serious incident related to the device. Moreover there are some other information that shall be included in the leaflet such as the indication regarding the devices intended to be used by lay persons, the devices referred to in Annex XVI (for further information on this topic, please click here), the devices which incorporate electronic programmable systems and other more.

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One of the main changes that will most affect the Medical Device regulatory field is included in Annex VIII of the new Regulation EU 2017/745 (MDR 2017/745).

This Annex concerns the Medical Devices new classification rules that will be stricter than those currently stated in Annex IX of the Directive 93/42/CEE. The new rules will lead many devices to be classified in a higher risk class starting from the entry into force of the MDR 2017/745.

The new classification Rule 21 refers to the medical devices composed of substances or combinations of substances and that are intended to be introduced into the human body through a body orifice or applied to the skin and that are absorbed by or locally dispersed into the human body.

Rule 21 will apply to medical devices as follow:

• all the devices that comply with the requirements of Rule 21 shall be classified as class III (highest risk) if they are systemically absorbed by the human body in order to achieve their intended purpose, or if they achieve their intended purpose in the stomach or lower gastrointestinal tract and they are systemically absorbed by the human body;
• if instead, this kind of devices are applied on the skin or in the nasal or oral cavity as far as the pharynx, they shall be classified as class IIa;
• all the other devices that comply with the requirements of Rule 21 shall be classified as class IIb.

This new classification rule will affect a wide cluster of medical devices, part of them currently in risk class I according to the Directive 93/42/CEE. For medical devices currently classified as class I, this rule may have a great impact. In fact, up to now these devices can be easily CE marked with a self-certification by the Manufacturer, who has only to declare the compliance with the requirements of the Directive 93/42/CEE. Whereas, applying the new classification rules of MDR 2017/745, the risk class of this kind of devices will increase with an unavoidable consequence: demonstration of MDR 2017/745 requirements by the Notified Body conformity assessment (for further information on this topic, please click here).

Regulatory Pharma Net offers regulatory support to the Medical Devices companies to be compliant with the requirements of the new MDR 2017/745. We are available for any clarification, do not hesitate to contact us!

26 May 2020 is the date of the definitive application of the European Regulation 2017/745 (MDR 2017/745) on Medical Devices. The new MDR 2017/745 will bring many changes that will affect all the involved economic operators.

One of these novelties concerns the introduction of a new figure in the enterprises organizational chart: the “Person Responsible for Regulatory Compliance” (PRRC).

The responsibilities and obligations of the PRRC are well defined in Article 15 of the MDR 2017/745 (please click here for further details on the PRRC features and requirements).

The PRRC has to be an employee of the organization and it is possible to appoint more than one PRRC. Indeed, it is possible to split the obligations established by the Article 15 of the MDR 2017/745 between more PRRCs, provided that all the obligations laid down by the Article 15 are fulfilled.

Micro and small enterprises are an exception to the above, as they are “not be required to have the PRRC within their organization but shall have such person permanently and continuously at their disposal”.

Micro and small enterprises have the possibility of subcontracting the PRRC responsibilities to a third party that would be a single freelancer, or an employee of an external organization. In order to demonstrate and document the permanent and continuous availability of the external PRRC, it is fundamental for the manufacturer to establish a contract with the PRRC. In this contract should be mentioned the PRRC qualification in compliance with the requirements established in Article 15.

It is also advisable to point out the relevant obligations and responsibilities of the PRRC in the contract (especially if the manufacturer disposes of more than one PRRC). For micro and small enterprises are intended those with fewer than 50 persons employed and whose annual turnover and/or annual balance sheet total does not exceed EUR 10 million.

The MDR 745/2017 points out that the obligation of having a PRRC available within the organization refers to the individual legal manufacturer. This means that organizations with more than one legal manufacturer under the parent company need to ensure at least one PRRC for each legal manufacturer.

No obligations are specified as concerns the location of the PRRC, but it is fundamental a close linkage between the PRRC and the manufacturer activities. This means that it is suggestable to have the PRRC located in the same country of the manufacturer, therefore the PRRC could be located outside the EU in case of extra-EU manufacturer.

As for the micro and small enterprises, even the Authorized Representatives are not required to have the PRRC within their organization but shall have such person permanently and continuously at their disposal. Therefore, even the Authorized Representative may subcontract the PRRC responsibilities to a third party.

It should be highlighted that the PRRC and the Authorized Representative for an extra-EU manufacturer cannot be the same person and the PRRC of a micro/small enterprise and the PRRC of the Authorized Representative of that same enterprise shall not belong to the same external organization.

RPN is available for any clarification or support on this topic. Do not hesitate to contact us to receive more information!

The date of the definitive application of the Medical Device Regulation (MDR) 2017/745 is close at hand and starting from 26^th May 2020 all the Manufacturers will have to comply with several new regulatory requirements.

The current low number of Notified Bodies (NBs) designated for the conformity assessment of medical devices according to the new MDR 2017/745, the resulting long waiting list by these NBs and the reclassification of many class I medical devices in higher risk class with the consequent involvement of a NB in the conformity assessment for the first time would have caused a bottleneck effect for the CE mark applications according to the MDR.

This would have entailed unavoidable delays and the following risk for many Manufacturer of not obtaining the CE mark for their own medical devices in time.

In order to avoid this scenario, on 25^th November 2019 the European Council proposed a 2^nd Corrigendum to the MDR to the Member States competent authorities and to the European Parliament.

The 2^nd Corrigendum has been approved and published on 27 December 2019.

The main change concerns the Article 120 relevant to the transitional provisions. In particular, the paragraph 3 has been changed by extending the so-called Grace Period also to the class I medical devices subject to the up classification with the NB’s involvement according to the new classification rules of the MDR.

The Grace Period is referred to the transitional disposition that allows the medical devices complying with the Directive to be placed on the market until 26^th May 2024 and be made available on the market or put into service until 26^th May 2025.

However, in order to exploit the Grace Period it is required to fulfil the following conditions:

• The conformity assessment of the class I medical device will require the NB involvement
• A declaration of conformity was drawn up prior to 26^th May 2020
• No significant changes in design and intended purpose occurred

According to the 2^nd Corrigendum, manufacturers of the class I medical devices subject to up classification will have much more time to prepare the required documentation and apply for the NB’s conformity assessment in order to obtain the CE mark according to the MDR.

Anyhow, it should be highlighted that the Grace Period concerns exclusively the medical devices and it is not addressed to the manufacturers that shall comply with the MDR requirements immediately from 26^th May 2020.

This means that all the manufacturers should update their own Quality Management System in order to fulfil the MDR dispositions concerning at least the Post-Marketing Surveillance (for more details click here), the Vigilance (for more details click here), the registration of the economic operators and medical devices, the traceability of the medical devices and the nomination of a Person Responsible for Regulatory Compliance (for more details click here).

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The Directive 93/42/EEC did not regulate in depth the clinical investigations with medical devices and most was delegated to the technical standard ISO 14155.

However, starting from the full application of the new Regulation 2017/745 (MDR) on 26^th May 2020, the legislation on this aspect will acquire its own legal autonomy.

The MDR has introduced and defined the following points:

• Informed Consent
• Substantial and Non-Substantial Amendments
• Specific Rules for Risk Populations (e.g. pediatric population, pregnant or breastfeeding women)
• Damage Compensation
• Electronic System (EUDAMED) for the notification and management of the clinical trials (including vigilance and incidents reporting)

The MDR clearly distinguishes the clinical investigation between pre-market clinical trials in the context of the clinical evaluation for the conformity assessment; post-market clinical trials on CE marked medical devices according to the intended use and post-market clinical trials in the context of the clinical evaluation with different purposes from the conformity assessment (e.g. addition of a new indication).

The pre-market clinical investigations have become a cornerstone of the clinical evaluation according to the MDR. As a matter of fact, class III and implantable medical devices are clearly required to have substantial clinical investigation data to demonstrate the conformity with the relevant safety and performance requirements (for further details on this topic read our dedicated article).

The approval procedure for a pre-market clinical study foresees the validation and the following assessment of the trial application submitted by the sponsor to the interested Member State’s Competent Authority.

The trial application basically consists in the documentation pointed out in Annex XV, part 2 of the MDR, and it should be submitted to the interested Member State through the new electronic system EUDAMED (once it will be activated).

In particular, the trial application should contain:

• Application form
• Investigator’s Brochure
• Clinical investigation plan
• Other information (e.g. the opinion of the ethics committees)

The Member State shall inform the sponsor whether the application is validated (i.e. the application falls within the scope of the MDR and can be evaluated) within 10 days from the notification date.

• For class I, and not-implantable medical devices of class IIa and IIb the sponsor is immediately allowed to begin the clinical investigation starting from the validation of the application (unless a negative opinion by an ethic committee).
• For class III and implantable medical devices the Member State has 45 days starting from the validation date to perform the clinical investigation assessment and transmit the relevant report to the sponsor. The sponsor will be allowed to start the clinical investigation once he receives the Member State authorization (unless a negative opinion by an ethic committee).

Regulatory Pharma Net is available to support companies in each of the regulatory steps for the clinical investigations. Do not hesitate to contact us for further information!

In order to better manage the emergency due to the COVID-19 and ensure the supply of protective device against the virus, the Italian Authority has taken some extraordinary measures.

A special manufacturing authorization procedure has been set up to speed up and simplify the authorization for the production and supply of protective masks that are not bearing the CE mark.

The ISS has created the special working group “Gruppo di lavoro dispositivi medici COVID-19” with the task of assessing the safety compliance to the current Directive for the use in derogation of protective facial masks, including those that are not CE marked, with a medical intended purpose.

The procedure foresees the submission to ISS of a reduced documentation to demonstrate the conformity to the safety requirements expected by the relevant technical standard. This authorization will remain valid until the end of the COVID-19 emergency. Also, evidence of a ISO 13485 quality system suitable for manufacturing management must be provided.

This working group is already full operational and in direct contact with the Italian Ministry of Health in order to provide the interested companies with all the required information and clarification.

The technical and administrative procedures are described in the explanatory note at the following link: Art. 15 del Decreto Legge del 17/03/2020 n.18.

RPN is available to assist companies in the preparation and submission of the documentation to obtain the special authorization for the manufacturing and commercialization of protective masks with medical purpose. Please do not hesitate to contact us for any support.

With the II Corrigendum of the Regulation 2017/745, the transitional provisions of the Article 120 (point 3 and 4) of the Regulation 2017/745 (MDR) have been extended also to some class I medical devices (further details on our blog The impact of the II Corrigendum).

However, the class I medical devices are required to meet the following conditions in order to take advantages of the transitional period:

• The device continues to comply with Directive 93/42/EEC (MDD),
• A notified body will need to be involved under the MDR (e.g. re-usable surgical instruments or up-classified devices),
• A valid Declaration of Conformity, according to Annex VII of the MDD, must be drawn up before 26 May 2020,
• No significant changes to the design or intended purpose of the device after 26 May 2020,
• The requirements of the MDR relating to post-market surveillance, market surveillance, vigilance, registration of economic operators and of devices shall apply in place of the corresponding requirements in Directive 93/42/EEC. This shall be in place on 26 May 2020.

The Medical Device Coordination Group (MDCG) issued a guideline (Class I Transitional provisions under Article 120 (3 and 4) – (MDR) that clarifies the information to be provided within the Declaration of Conformity of the class I medical devices and the management of the Declaration of Conformity, in order to make use of the transitional provisions.

According to the guideline, class I medical devices manufacturers shall perform a conformity assessment on whether the device is in compliance with the current MDD.

On the basis of the result of the conformity assessment, the manufacturers have to issue a Declaration of Conformity to state that a conformity assessment has been performed and that the device complies with the MDD requirements. All these steps must be performed before 26 May 2020, otherwise it will not be possible to make use of the grace period reported in the II Corrigendum of the MDR.

In order to demonstrate that the Declaration of Conformity has been lawfully issued before 26 May 2020 and no significant changes have occurred after that date, the Manufacturers must keep the Technical Documentation, that include the technical file of the device and allows the conformity assessment of the product, at disposal of the competent authorities for a period of 5 years at least, after the last batch manufactured.

Documenting on the technical file the conformity of the device to the MDD prior to 26 May 2020 is crucial as this is the only way to be included in the grace period and also because the features of the device reported in the technical file cannot be changed. In case of changes a CE mark procedure according to MDR will be required.

Regulatory Pharma Net offers regulatory support to the Medical Devices companies. Should you require more information or clarification on this topic or on medical devices quality system and regulatory affairs do not hesitate to contact us!