As promised yesterday, here is a first impression of the IVD Regulation (IVDR) proposal that may lead to a general approach this Friday in the ESPCO Council.
In this post I will try to not repeat what I have blogged about yesterday given the large amounts of overlap between the two regulation proposals. Where things are the same under the IVD regulation proposal I will refer to the post on the Medical Devices Regulation (MDR) of yesterday.
By the way, the Annexes to both regulations have also become available in the mean time, see here for MDR and here for IVDR. So we have the whole picture now minus the recitals, but unfortunately I do not have time anymore to plow through 300 pages of annexes and produce a coherent blog about it this week.
The Dutch Minister of Health has written in the annotated agenda for the EPSCO meeting that there was much progress under the Latvian Presidency, that the Netherlands see achievement of the general approach on Friday as ‘a very realistic possibility’ (that’s Dutch political understatement for “this will work unless something very unexpected happens”) and that the large majority of the member states supports this (the MDR and IVDR) proposal currently on the table. She also confirms the timetable that I have mentioned as realistic and that it is likely that the Dutch Presidency will complete the project in an early second reading in the first half of 2016.
Chapter I Scope
Same provisions on national competence and freedom of information as in the MDR feature in the IVDR.
There is a new limb to the definition of IVD: “providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations.”. This information has to be for medical purposes (given the Commission’s amended definition) but not necessarily for diagnosis, prevention, etc.
A new borderline clause is setting out that “Products specifically intended for the cleaning, disinfection or sterilisation of medical devices and devices for the purpose of control or support of conception shall be considered medical devices.”
The definition of accessory is not changed as in the MDR and only the word “assist” has been struck out. I assume that this is an oversight as the concept of accessory should be consistent between the two regulations.
The definition of companion diagnostic completely changed to “a 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;”
That definition copies the FDA definition and description of a companion diagnostic device almost completely except for the limb
- “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”
New definition of ‘kit’ as “a set of components that are packaged together and intended to be used to perform a specific in vitro diagnostic examination, or a part thereof; ” This will be the IVD counterpart of the new ‘procedure pack’ under the MDR.
‘Safe’ under the MDR is ‘safety’ under the IVDR, otherwise the same definition. Definitions of risk and risk-benefit determination and definitions of compatibility and interoperability;
Refurbished definition of clinical evidence [bold indicates addition]: “clinical data and performance evaluation results pertaining to a device of sufficient amount and quality to allow a qualified assessment of whether the device achieves the intended clinical benefit(s) and safety, when used as intended by the manufacturer”
Identical mechanism to the MDR for Commission decisions in borderline cases.
Chapter II Making available of devices, obligations of economic operators, CE marking, free movement
The IVDR regime for in-house developed tests is now rather similar to the MDR home brew devices (surprise surprise) regime in its logic that the health institution establishes in its documentation that it has given due consideration as to whether the target patient group’s specific needs cannot be met or cannot be met at the appropriate level of performance by an equivalent device available on the market. There are additional controls for class C and D IVDs.
Like for the MDR there are more prescriptive rules for risk analysis and clinical evaluation (article 8 (1a) and (1b)) and for quality systems (article 3 (5)) and instead of mandatory product liability insurance proposed by the Parliament the Council proposes only a duty to consider insurance (article 8 (11)) – the Parliament was however very adamant on its proposal.
Same articles on authorized representative, qualified person and the same provisions on MAID as in the MDR.
Removal of article 18 about systems and procedure packs. This provision was apparently intended to harmonize current article 12 of the Medical Devices Directive to the IVD Regulation (there is currently no similar provision in the IVD Directive) but the Council will have none of it for IVDs. Apparently this is because the new definition of “kit” is included in the definition of IVD, and, consequently, all kits are to be treated as IVDs in their own right.
Chapter III Identification and traceability of devices, registration of devices and of economic operators, summary of safety and performance, European databank on medical devices
Identical to MDR.
Chapter IV Notified Bodies
Identical to MDR.
Chapter V Classification and conformity assessment
Scrutiny for IVDs (article 42): interesting change compared to the Commission proposal and to the MDR. Scrutiny still applies only to class D devices but the whole MDCG procedure proposed by the Commission is deleted, to be replaced by a notification procedure on a national level. Basically, the notified body notifies the granted certificate for a class D IVD together with assessment report and lab tests and that’s it. If there are concerns that the notified bodies are doing a bad job, “a competent authority and, where applicable, the Commission may, based on reasonable concerns, apply further procedures according to articles 33 [notified body oversight], 33a [new article on competent authority review of technical and performance evaluation documentation], 34, 35 [notified body oversight], 67 [Evaluation regarding devices suspected to presenting an unacceptable risk or non-compliance] and, when deemed necessary, take appropriate measures according to Article 68 [Procedure for dealing with devices presenting an unacceptable risk to health and safety].” This is a big deregulation step for IVDs.
Like under the MDR, notified bodies may impose restrictions to the intended purpose of a device to certain numbers or groups of patients or require manufacturers to undertake specific post-market clinical follow-up studies pursuant to Part B of Annex XIII (article 43 (2a)).
Improvement of certificate of free sale provision: the authorised representative can now also request it, which is helpful because in the Commission proposal these certificates could only be requested by manufacturers established in a member state (article 46), which is kind of discriminatory.
Chapter VI Performance evaluation and performance studies
The IVDR will feature performance evaluation that is mandatory for all IVDs, which looks a lot like clinical evaluation for ‘general’ medical devices, and which is the basis for the clinical evidence for the IVD (article 47).
Performance studies regime significantly amended – subject to IVD Regulation studies regime:
(a) where invasive sample taking is done only for the purpose of the performance study
(b) where it concerns an interventional clinical performance study as defined in Article 2(37)
(c) where the conduct of the study involves additional invasive procedures or other risks for the subjects of the studies
(d) in case of performance studies involving companion diagnostics.
Otherwise similar to MDR clinical investigation regime.
Chapter VII Post-market surveillance, vigilance and market surveillance
Similar to MDR. Manufacturers of class C and D devices have to submit PSURs directly to the notified body that will evaluate them.
Chapter VIII Cooperation between Member States, Medical Device Coordination Group, EU reference laboratories, device registers
At the request of a Member State, the Commission may also designate EU reference laboratories where that Member State wishes to have recourse to such a laboratory to ensure the verification of the compliance of Class C devices with the applicable CS when available, or with other solutions chosen by the manufacturer to ensure a level of safety and performance that is at least equivalent (article 78 (2a).
Detailed requirements for EU reference labs in article 78 (3a). Not a bad idea because these will play an important role in the application of the IVDR.
Chapter IX Confidentiality, data protection, funding, penalties
Identical to MDR.
Chapter X Final provisions
Similar to MDR. There are minor changes in transitional regime for UDI: for class D devices Article 22(4) [affixing of UDI carrier] shall apply one year after the date of application of this regulation. For class B and class C devices Article 22(4) [affixing of UDI carrier] shall apply three years after the date of application of this regulation (5 years transitional period plus 3 years post application date). For class A devices Article 22(4) [affixing of UDI carrier] shall apply five years after the date of application of the regulation (5 years transitional period plus 5 years post application date).
Largely the same as for the MDR. For the IVDR specifically there are no shocking broad stroke departures from the Commission proposal for the IVD specific items discussed in this post, except for abandoning scrutiny for IVDs completely in favor of post approval controls, which is basically the current situation. This is probably why the IVDR has been riding the comfortable back seat in the political discussion so far, unless the Parliament rekindles the political circus by sticking to the constitutionally impossible (genetic testing amendment) or the highly inadvisable (changing the definition of medical device to anything with an indirect medical purpose) amendments.
That does not mean however that the IVDR as such will not be a very major regulatory change for the IVD industry though, as I have discussed on occasions and as set out concisely in the BSI White Paper that I co-authored. The IVD industry has to start building up performance evaluations for each and every IVD currently on the EU market (no grandfathering!) and for each device to enter the market when the new regulation applies. That will be a really big job and I predict that it will be underestimated by many companies. Remember, 80% of the IVDs are expected to be notified body certified (as opposed to 20% currently) under the new regulation, and that also applies to the IVDs currently on the market. Getting all these devices through that process during the 5 years transitional period will be very difficult – the regulatory quantum leap, as it has been dubbed in the mean time.