On June 19th, 2015, the Council of EU Ministers reached a partial General Approach on the review of the medical devices and in vitro medical devices (IVD) rules in the EU (an overview of the texts is accessible here).  The General Approach does not yet include the recitals to the new medical devices and IVD regulations.

The Council’s text on the new IVD Regulation significantly amends the Commission’s proposed definition of ‘companion diagnostics’, an evolution relevant to sponsors of both medicinal products and diagnostic devices.  The Council’s definition of companion diagnostics is almost identical to the definition used by the FDA, but significantly different from the European Commission’s proposal and the European Parliament’s suggested amendments.  An overview is set out below.  

New Definition of Companion Diagnostics

Under the current EU IVD Directive, there is no definition of ‘companion diagnostic’, creating uncertainty for device and medicinal product manufacturers.  The draft Regulation therefore seeks to clarify the situation.  Each EU institution seems to have a different view on the appropriate terminology to achieve this goal.

Definition in the current Council’s General Approach

The new definition of ‘companion diagnostic’ in the Council text reads:

“device which is essential for the safe and effective use of a corresponding medicinal product to:

– identify patients who are most likely to benefit from the medicinal product, or;

– identify patients likely to be at increased risk for serious adverse reactions as a result of treatment with the medicinal product, or;

– monitor response to treatment by the medicinal product for the purpose of adjusting treatment to achieve improved safety or effectiveness.”

The new definition mirrors the FDA’s definition for companion diagnostics, save for the latter’s last bullet point (Identify patients in the population for whom the therapeutic product has been adequately studied, and found safe and effective, i.e., there is insufficient information about the safety and effectiveness of the therapeutic product in any other population”).  By streamlining both definitions, the Council is responding to calls for harmonization between the US and EU regulatory approaches for this type of devices.

Definition Compared to the Commission and Parliament Position

The new definition is a major change in comparison to both the Commission’s proposal, and the amendments that the Parliament proposed.  In the Commission’s proposal, a companion diagnostic was defined as a device “specifically intended to select patients with a previously diagnosed condition or predisposition as eligible for a targeted therapy”.  Industry voiced concerns regarding this definition, pointing out that it was too broad and too narrow at the same time, particularly due to the unclear meaning of the word ‘therapy’ and the absence of a clear link with a ‘medicinal product’ as defined in EU law (see for example, the position paper issued by EFPIA and EBE).

The European Parliament further specified the proposed definition: according to its amendments adopted in October 2013, a companion diagnostic is (changes in comparison to proposal are underlined) a device “specifically intended for and essential to the selection of patients with a previously diagnosed condition or predisposition as suitable or unsuitable for a specific therapy with a medicinal product or a range of medicinal products.”  However, these additions also left many questions unanswered.

Additional Clarifications in the Recitals

The Council’s agreed texts only constitute a partial General Approach; it did not yet reach a common position on the recitals to the current texts.  Expectations are that the Luxembourg EU Presidency will finalize the recitals by September.  During past meetings, the Council already included a ‘compromise’ in relation to companion diagnostics: in its February meeting, it agreed to include the following recitals regarding companion diagnostics:

“Companion diagnostics are essential to identify patients for eligibility of treatment with a specific medicinal therapy (e.g. molecule, dose, scheduling) through the determination of a biomarker, either qualitatively or quantitatively, which is specific for a population of responders, non-responders or persons which will develop an adverse response towards this specific therapy. Such biomarker may be present in healthy persons or may be present or induced in the patient due to a condition or pathology”;

“It should be clarified that devices monitoring the response to treatment by the corresponding medicinal product are considered companion diagnostics where treatment adjustment to achieve improved safety or effectiveness is essential for the safe and effective use of a corresponding medicinal product, while devices that are used in treatment drug monitoring (TDM) to ensure that the drug concentration in the human body is within the therapeutic window of the drug are not considered companion diagnostics.”

These recitals, if and when they are adopted, would provide much needed additional information allowing companies to determine whether their devices qualify as companion diagnostics or not.

Companion Diagnostics: New Regulatory Framework

The definition of a ‘companion diagnostic’ is essential for industry, as this type of device will be subjected to a new array of regulatory requirements.  Overall, the Council kept the key aspects of the new regime proposed by the European Commission:

In the new rule-based classification system, companion diagnostics would qualify as a class C device, as stipulated in Annex VII (the Council’s text on the annexes can be found here).

  • Conformity assessment of class C devices requires the involvement of notified bodies. This is a major change to the current regime, where for most companion diagnostics, manufacturers can self-certify compliance with the IVD requirements.
  • Additional measures are described in Annex VIII section 6.2, which other class C devices do not have to comply with. Importantly, this includes the obligation of notified bodies to consult with the ‘medicinal product authorising authority’, e., the national authority or the EMA for centrally approved medicinal products.

Next Steps

The EU institutions are heading towards the final stages of the adoption of the revised medical devices and IVD rules.  In terms of timing, much will depend on the progress on the adoption of the recitals within the Council, which is expected in the next few weeks.  Once the EU Ministers manage to reach a common text, the trialogue negotiations with the European Parliament and the European Commission can kick off. It will be interesting to see what position the Commission and Parliament will take regarding the definition of companion diagnostics.

According to some reports, the new medical devices and IVD regulations could be adopted before the end of 2015.  While this is possible in theory, considering the magnitude of the proposals and the slow progress made in the file so far, adoption in 2016 seems more realistic.

The draft regulations contain transition periods: once adopted, the new rules on medical devices will enter into force three years later; those on IVDs will apply only five years after adoption.