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Majority Of Borderline/Combi Products To Escape Highest-Risk Classification In EU

This article was originally published in Clinica

The Association of the European Self-Medication Industry (AESGP) is relieved that many of its company members’ products – namely drug device combination products, or borderline devices - are no longer going to fall into the highest risk category of the Medical Devices Regulations and be subject to the strictest controls, as had been expected.

The latest text to emerge on the EU’s future Medical Devices Regulation includes a risk-based approach to the classification of substances that are absorbed by or dispersed in the human body, with these products falling into a range of different risk classes.

AEGSP had been lobbying against the original proposal by the European Commission for all such products to be placed into the highest risk class, and believes that text now agreed will ensure “the majority of such devices will be classified in classes IIb or IIa,” the medium risk classes.

Although it has not carried out an impact assessment, it says that it expects only “a few” substance-based medical devices will find themselves in class III now because of this ruling.

The revised new Rule 21 – as appears in the text of the Medical Devices Regulation as agreed by the European Parliament and Council but yet to be formally adopted


The European Commission’s original Rule 21 in In MDR proposal


Devices that are composed of substances or combinations of substances that are intended to be introduced into the human body via a body orifice, or applied on skin and that are absorbed by or locally dispersed in the human body are:

- in class III if they, or their products of metabolism, are systemically absorbed by the human body in order to achieve the intended purpose,

- in class III if they achieve their intended purpose in the stomach or lower gastrointestinal tract and they, or their products of metabolism, are systemically absorbed by the human body,

- in class IIb in all other cases, except if they are applied on skin, in which case they are in class IIa, or

- if they are applied in the nasal or oral cavity as far as the pharynx, and achieve their intended purpose on those cavities, in which case they are in class IIa.


Devices that are composed of substances or combination of substances intended to be ingested, inhaled or administered rectally or vaginally and that are absorbed by or dispersed in the human body are in class III.


Concern Over Delays And Notified Body Expertise

The association also comments that the requirement for the notified body to seek a scientific opinion from the European Medicines Agency (EMA) for devices that are systemically absorbed by the human body to achieve their intended purpose has the potential to significantly delay consumer access to substance based medical devices since it is scheduled to take up to 150 days after reception of the valid documentation.

AEGSP also questions whether notified bodies will have the internal expertise for assessing the requirements relating to the quality and safety of substance-based medical devices against Annex I of Directive 2001/83/EC on medicinal products for human use, where manufacturers will need to supply:

  • detailed information regarding test design;
  • complete test or study protocols;
  • methods of data analysis;
  • data summaries and test conclusions, notably regarding the absorption, distribution, metabolism and excretion as well as potential interactions with other devices, medicinal products or other substances.

Clarifying responsibilities for integral non-reusable combinations regulated as drugs

Clinica notes that a reading of the MDR text as agreed by the Council and Parliament shows that Directive 2001/83/EC on medicinal products will be amended by the Medical Devices Regulation as was being anticipated.

The medicinal products directive is being amended to clarify requirements, as well as stakeholder responsibilities, for non-reusable single integral product devices intended to administer a medicinal product and intended exclusively for use in the given combination.

These fall under Directive 2001/83/EC or Regulation (EC) No 726/2004 (relating to medicinal products and establishing the EMA), as applicable.

But this is the first time their regulation will have been clarified under medicinal product regulation.

At present, the current requirements fall under the Medical Devices Directive where it states that the Essential Requirements apply for safety and performance features of the device part.

However, at present, there is no rule requiring involvement of the regulatory authorities, and no rules to determine checks. This is considered by many as a potential safety shortfall.

The new Regulation as it now stands dictates a more formal co-operation between the drug and device authorities. The amendments to 2001/83/EC are drafted in Article 91 of the MDR.

There, it clarifies that manufacturers will need to submit evidence for the device element – namely the EU declaration of conformity or certificate issued by the notified body to demonstrate compliance with the new general “safety and performance” requirements.

The amendment states that the medicinal product marketing dossier must include the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements set out in Annex I of the MDR Regulation. The results are those contained in the manufacturer’s EU declaration of conformity or the relevant certificate issued by a notified body.

It goes on to say that where the dossier does not include this, and the notified body is required to be involved in the device element under the MDR, then the medicinal product authority will require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements of Annex I of the MDR issues by a notified body designated under the MDR for that type of device.


Other Issues Of Concern

AESGP has also raised at this point concerns over decision-making relating to borderline cases, and over device traceability.

Borderline Cases

AESGP says that it hopes that standing/temporary subgroups – which should be composed of industry representatives - within the Medical Device Coordination Group will be “appropriately consulted and involved” where the European Commission has to consult when deliberating the status of borderline products with the EMA, the European Chemical Agency (ECHA) and the European Food Safety Authority (EFSA).

Device Traceability

The association points out that while the European Unique Device Identification system is compatible with UDI systems used by major trade partners, there is no reference to the compatibility with the system used for medicinal products.

It also calls for clarification and potential exemptions to the ruling that UDI would need to be assigned to the device and “to all higher levels of packing”, which would potentially mean that each unit-dose packaging (for instance, lozenges in a pack) would have to bear the UDI code on its primary packaging.

Relief Over Transitional Arrangements

When it comes to how long manufacturers and other stakeholder will have to comply with the new requirements, AESGP says that it welcomes the agreed proposal that certificates issued, after the entry into force of the regulation, “presumably in early 2017”, will remain valid until the end of the period indicated on the certificate. (This will not exceed five years from its delivery.)

In addition, it says, it welcomes the fact that the Medical Devices Regulation contains a new clause to amend 2001/83/EC which states that devices lawfully placed on the market pursuant to Directives 90/385/EEC and 93/42/EEC prior to the entry into force of the regulation may continue to be made available on the market or put into service until five years after that date. This is likely to mean until 2025 if entry into force takes place in 2017, AESGP states.







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