The Medical Device Coordination Group (MDCG) recently published the Guidance on borderline between medical devices and medicinal products under Regulation (EU) 2017/745 on medical devices (MDCG 2022-5)

The guidance discusses the borderline between medical devices and medicinal products taking into account the relevant definitions and making practical examples, particularly focusing on herbal products, substance-based devices and combinations of medical device and medicinal product.

Below are listed the main novelties introduced by the guidance.

Substance-based medical devices

New definitions of pharmacological, immunological and metabolic means were introduced adding more precision to the respective definitions present in MEDDEV 2.1/3 rev 3. Focusing on pharmacological means the guidance lists the following examples:

• interaction between a ligand (e.g. agonist, antagonist) and a receptor;
• interaction between a substance and membrane lipids;
• interaction between a substance and components of the cytoskeleton.

Furthermore the guidance specifies that, when a substance-based device incorporates a substance, which, if used separately, would be considered a medicinal product and when the action of the medicinal product is ancillary to that of the device, a consultation with a competent authority or EMA is necessary.

Herbal products

Concerning the process of authorisation for (traditional) herbal medicinal products in the European Union, EU monographs (established by the EMA Committee on Herbal Medicinal Products - HMPC) must be considered. Also other official monographs, may be considered.

When a substance included in these monographs complies with the monograph regarding its composition/preparation, dosage and indication, it is a good indicator that the substance in question falls into the definition of herbal medicinal product.

However the fact that a monograph does not exist for a herbal substance in one of the abovementioned pharmacopoeias does not necessarily mean that it shall not be considered a herbal medicinal product.

Regulatory Pharma Net (RPN) is currently evaluating the impact of this new guidance on medical devices, directly involving the Notified Bodies. We are available to provide your company with any updates on the medical device regulatory framework and to assist on all regulatory needs.

Feel free to contact us at info@regulatorypharmanet.com

The Regulation 2017/745 (MDR) requires that the demonstration of compliance with the General Safety and Performance Requirements for the medical device includes a Clinical Evaluation. This applies to any medical device, including Medical Device Software (MDSW).

Clinical Evaluation is an ongoing process, conducted throughout the life cycle of a MDSW, intended to produce, collect, analyze, and evaluate clinical data on a device for the purpose of verifying its safety, performance, and clinical benefits when used as intended by the manufacturer.

In order to help the manufacturers in fulfilling this requirement, two documents have been published: the MDCG document MDCG 2020-1: Guidance on Clinical Evaluation (MDR)/Performance Evaluation (IVDR) of Medical Device Software and the FDA Guidance document “Software as a Medical Device: Clinical Evaluation”.

As stated in the MDCG 2020-1, the clinical evaluation process is structured into 5 stages: Planning, Data collection, Data evaluation, Data analysis, Documentation (Clinical Evaluation Report, CER).

The manufacturer must provide the following evidence:

• Scientific validity
• Technical performance/analytical performance
• Clinical performance

According to the FDA Guidance document, the essential conditions for proper clinical evaluation are the existence of a relationship between the software itself and a specific clinical condition, analytical validation of input and output data processing, verification of the clinical effectiveness of the device during treatment.

Regulatory Pharma Net (RPN) is available to provide your company with any updates on the medical device regulatory framework and to assist on all regulatory needs including the development of the clinical evaluation for your medical devices.

Feel free to contact us at info@regulatorypharmanet.com

Slightly more than a year after the Regulation 2017/745 (MDR) came into force, many medical device manufacturers are still struggling with the certification of their products in accordance with the new MDR, which is mandatory in order to place medical devices on the European market. This also applies to legacy devices whose validity period for placing on the market cannot extend beyond the expiration date of the previous certificate and in any case no later than 26/05/2024. Therefore, the issue of certification needs to be urgently addressed.

The MDR involves the addition of specific new requirements. In most cases, significant changes will have to be made to the compliance process, quality management system and technical documentation in order to achieve regulatory compliance.

RPN can support you for all of CE mark certification activities from development to CE mark:

• Strategic support for MD development, classification and clinical assessment
• Contacts with Notified Bodies
• Drafting of Technical Files, including Risk Analysis Report, Clinical Evaluation Report (CER), Biological Evaluation Plan and Report (BEP and BER)
• Quality Management System set-up according to ISO 13485
• CE mark Maintenance Activities (Technical File variations, Support for maintenance audit)
• Specific services to fulfil the Person Responsible for Regulatory Compliance (PRRC) obligation
• Support for promotional material review and submission in Italy
• Support for management of Italian MD Database and EUDAMED (European Database on Medical Devices)
• Support for Clinical Investigation Application submission to Italian ECs and MoH

Don’t get caught unprepared and contact us for your customized gap analysis; you will save time, money and you will be able to better plan the future of your devices.

Regulatory Pharma Net offers full regulatory support and is available for any clarification and assistance, please do not hesitate to contact us at info@regulatorypharmanet.com

The Regulation (EU) 745/2017 requires stricter classification rules for substance-based medical devices together with timely pharmaco-toxicological evaluation of components.

Classification Rule 21 and the guidance MDCG 2022-5 need to be taken into consideration for the proper classification and management of the substance-based medical devices.

In order to qualify a substance-based medical device, it is critically important to assess the ancillary nature of the pharmacological, immunological, or metabolic action of its constituent substances.

If their principal action is pharmacological, or immunological, or metabolic, the entire product will be considered a medicinal product and, therefore, will follow a different regulatory pathway, namely that outlined in Directive 2001/83/EC or Regulation (EC) 726/2004. However, when these substances have no pharmacological, immunological or metabolic action or this is ancillary, then the classification of the device will depend on the application of the rules of Annex VIII.

For example, the Rule 21 states that devices that are composed of substances or combinations of substances 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 in the human body must be classified as follows:  

• Class III: substance-based devices that 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;
• Class IIa: substance-based devices applied on the skin or in the nasal or oral cavity as far as the pharynx;
• Class IIb: all the other devices that comply with the requirements of Rule 21.

As stated in the MDCG 2022-5, a consultation procedure with a competent medicinal authority or the EMA (the European Medicines Agency) is required for:

• devices that are systematically absorbed to achieve their intended purpose;
• when a substance-based device incorporates a substance, which, if used separately, would be considered a medicinal product and when the action of the medicinal product is ancillary to that of the device
• medicinal products with an integrated device
• borderline products for which there is uncertainty about which regulatory framework applies.

Regulatory Pharma Net (RPN) is available to provide your company with any updates on the medical device regulatory framework and to assist on all regulatory needs in relation to medical devices including the support for a correct classification of your substance based medical device.

Feel free to contact us at info@regulatorypharmanet.com

EMA has launched a pilot to give scientific advice on the intended clinical development strategy and proposals for clinical investigation for all class III medical devices and class IIb active devices intended to administer and/or remove medicinal product(s). Manufacturers can submit their letter of interest to be part of the pilot on scientific advice which will be provided by the medical device expert panels.

The pilot will prioritise certain types of medical devices:

• devices that benefit a small group of patients in the treatment or diagnosis of a disease or condition, such as devices intended for the treatment of a rare condition, known as ‘orphan devices’, and devices for paediatric use;
• devices addressing medical conditions that are life threatening or cause permanent impairment of a body function and for which current medical alternatives are insufficient or carry significant risks;
• novel devices with a possible major clinical or health impact.

The expert panels will provide free advice to ten selected applicants on their clinical development strategy and/or proposals for clinical investigation. The pilot will last approximately one year and will help to establish an efficient scientific advice procedure.

More information on the process and the selection criteria is available on EMA’s website.

The first five applications will be selected in April. Small and medium-sized enterprises are strongly encouraged to submit their letters of interest.

Regulatory Pharma Net (RPN) is available to support in the procedure and to assist on all regulatory needs.

Feel free to contact us at info@regulatorypharmanet.com

With the publication in the Official Journal of the European Union, the amendment to Regulations (EU) 2017/745 and (EU) 2017/746 as regards the transitional provisions for certain medical devices and in vitro diagnostic medical devices was approved.

This gives more time to many manufacturers and avoids the exit from the market of a significant number of medical devices and in vitro diagnostic medical devices. The Regulation (EU) 2023/607 introduces the following main changes:

• Extension of MDR transition period until 31 December 2027 for class III medical devices and class IIb implantable devices (with some exceptions);
• Extension of MDR transition period until 31 December 2028 for class IIa, IIb devices (not covered by previous point), class I sterile devices or with measuring function, as well as devices qualified as class I under the directives but which conformity assessment procedure under the MDR requires the intervention of a Notified Body;
• Removal of the “sell-off” period in the MDR and IVDR;
• Introduction of a transition period until 26 May 2026 for class III custom-made implantable devices.

The above-mentioned devices will be allowed to benefit from the extension if the following preconditions are satisfied:

- such devices continue to comply with Directive 90/385/EEC or Directive 93/42/EEC, as applicable;

- there are no significant changes in design and intended use;

- the devices do not present an unacceptable risk to the health or safety of patients, users or other persons or to other aspects of public health protection;

- by May 26, 2024, the manufacturer has established a quality management system in accordance with Article 10(9) of the MDR;

- by May 26, 2024, The manufacturer – before the certificate’s expiration – has concluded a contract with a Notified Body for conformity assessment under the MDR or alternatively the manufacturer benefitted from an exemption under either Article 97 or 59 of the MDR, which provide derogations from applicable rules in particular cases.

Regulatory Pharma Net (RPN) is currently evaluating the impact of this new regulation on medical devices and in vitro diagnostic medical devices, directly involving the Notified Bodies. We are available to provide your company with any updates and to assist on all regulatory needs.

Feel free to contact us at info@regulatorypharmanet.com

Artificial Intelligence (AI) has been a true revolution in many sectors, but perhaps one of the most promising is that of medical devices. From a regulatory perspective, the classification of an AI-based software as a medical device depends on its specific intended use defined by the manufacturer. In general, only software with medical purposes, such as diagnosis, monitoring, or disease prevention, fall under the definition of medical devices.

AI has opened new frontiers in the field of medical devices, improving the accuracy of diagnoses and reducing human errors. This means that diseases can be identified more accurately, enabling more effective treatments. The efficiency of AI-based medical devices translates into shorter access times to care and better quality of healthcare.

There are several successful examples of AI-based medical devices. From assisting in the diagnosis of diseases to suggesting personalized treatment options based on specific patient data, AI has revolutionized medicine. For example, software analyzing radiological data can detect anomalies, while in surgery, surgeons are increasingly assisted by sophisticated devices for delicate procedures.

Moreover, the combined use of wearable devices and artificial intelligence algorithms simplifies the diagnosis of sleep disorders, especially insomnia, without the need for traditional polysomnography electrodes.

The European Union is currently discussing the AI Act, new legislation that will have a significant impact on medical devices containing AI-based software. According to the proposal, these products could be subject to dual regulation, both as medical devices and as AI-containing products. This will result in increased regulatory obligations for all actors involved in the manufacture and commercialization of such devices.

Regulatory Pharma Net (RPN) is available to provide your company with any updates on the medical devices regulatory framework and to assist on all regulatory needs in relation to medical devices including those AI-based.

Feel free to contact us at info@regulatorypharmanet.com

The Italian Medicines Agency (AIFA) recently introduced a guideline for Notified Bodies planning to submit a consultation for ancillary medicinal substances in Class III medical devices. This guideline aims to simplify the procedural, formatting, and dossier requirements for the consultation process, facilitating easier and clearer compliance pathways.

AIFA's guideline is a significant step towards enhancing regulatory clarity and ensuring patient safety in the development and approval of medical devices. By simplifying the consultation process, AIFA supports the industry's progress and innovation. For more details, visit AIFA's website.

Regulatory Pharma Net (RPN) can support you assess  the impact of this new guideline on your medical devices. We are available to provide your company with any updates on the medical device regulatory framework and to assist on all regulatory needs.

Feel free to contact us at info@regulatorypharmanet.com

The European Commission has proposed a targeted revision of the EU Medical Devices Regulations, aiming to simplify rules, reduce administrative burden and support faster access to safe and innovative medical devices across Europe.

The proposal addresses structural challenges identified in the implementation of the MDR and IVDR, including complex procedures, divergent application of requirements and certification processes that may affect predictability, competitiveness and device availability.

Key actions include:

• More proportionate conformity assessment requirements.
• Improved coordination among regulatory actors.
• Enhanced digitalisation of regulatory processes.
• Broader use of real-world evidence.
• Stronger EU-level scientific and regulatory support through expert panels and the European Medicines Agency.
• Dedicated support for SMEs, breakthrough technologies, orphan devices and AI-enabled medical devices.
• Continued focus on maintaining high standards for patient safety and public health.

For manufacturers and other economic operators, the proposed changes may have a significant impact on regulatory planning, technical documentation, conformity assessment strategies, post-market obligations and market access activities.

This initiative represents an important step toward a more efficient, predictable and innovation-friendly EU regulatory framework for medical devices and in vitro diagnostics.

RPN will provide any further update and is available to provide full support for Medical Devices regulatory activities across the whole product lifecycle.