MDR/ IVDR CLINICAL EVALUATION TOOLKIT; PART II

minion happy sadI am very happy that as of April, we have more time until the date of application of the Medical Device Regulation, as well as more clinical guidance to work with. In my previous post I addressed my observations on the guidance for the clinical/ performance evaluation of Medical Device SoftWare, in this one I will focus on the one for equivalence (MDCG 2020-5).

MEDDEV 2.7/1 REV 4

This guidance provides directions on the use of clinical evidence from equivalent device(s) for the purpose of the clinical evaluation. While highlighting and clarifying the differences, it uses MEDDEV 2.7/1 Rev 4 as a basis; which is great, since we are all familiar with that one and we updated (almost) all our clinical evaluations accordingly, right?

In fact for information on how to analyze clinical data from scientific literature it actually refers one to it, so we still need the current MDD guidance. Mind you, there is a conditional note though that

“In the event that the data do not meet the MDR definition of clinical data these are not clinical data and cannot be subject to data appraisal, analysis and evaluation for the purpose of providing clinical evidence”,

and given the MDR definition of clinical data, I wonder where that leaves us with clinical experience collected via physician testimonials or surveys; a tool we have been using to quite some extent the last few years to collect clinical experience in daily practice in a low-resource-consuming fashion.

Good thing is, that, similar to the MDSW clinical/ performance evaluation guidance, pending the development and publication of further MDR/ IVDR guidances, it seems a good strategy to continue using the existing ones including those from the IMDRF as long as they are in line with the MDR/ IVDR.

SAME

Screenshot_20200515_193924Also conform MEDDEV 2.7/1 Rev 4, clinical, technical, and biological characteristics need consideration for demonstration of equivalence to another device with respect to safety and performance. At first sight the same as before, but here the devil is in the details since instead of  similar some of the characteristics are explicitly mentioned as must be the same under the MDR. Especially the

BIOLOGICAL CHARACTERISTICS

are getting attention in this respect (3 pages!), and particularly noteworthy is the remark that

“the exceptions outlined in the MEDDEV 2.7/1 Rev 4, to NOT use the same materials are NOT  acceptable under the MDR”

(capitals are not mine). So for biological characteristic to be considered equivalent the equivalent device should use the same materials or substances in contact with human tissue or fluids. The guidance also stresses that since processing may affect the materials, the assessment should concern the final device.

On the clinical characteristics the guidance emphasizes that for equivalence the devices shall have the same kind of user (underlining that it makes a big difference whether users concern HCP’s or lay people due to their knowledge and competences), and that the devices should be used for the same clinical condition or purpose. That a

GAP ANALYSIS

needs to be performed within the context of a clinical evaluation is nothing new, but thus far this was to determine whether clinical data was sufficient to verify that the device is safe and performing. The current guidance adds in this respect (providing an insightful equivalence table as an example), that also a gap analysis has to be performed evaluating

“any clinically significant differences”,

and their possible impact on safety and performance (note that clinical significance is NOT the same as statistical significance, so obtaining expert input is essential here), but also that

“considerations of equivalence shall be based on proper scientific justification”,

telling me once more that showing equivalence is no longer a simple paper exercise, and one will not be able to get away with a simple statement saying that despite some small differences devices can be considered the same.

SUFFICIENT LEVEL OF ACCESS TO DATA

opendoorAnother topic that received much attention since publication of MEDDEV 2.7/1 Rev 4 concerns the need for access to the technical documentation of assumed equivalent devices. Also here the MDCG 2020-5 guidance leaves no room for debate, and once more underlines that under the MDR a manufacturer must be able to demonstrate sufficient level of access to the data of the equivalent device, and that for Class III and implantables this means a contract must be in place with the manufacturer of the equivalent device allowing for ongoing access to the technical documentation.

MDR CERTIFIED

Moreover for these devices the guidance requires that the

“clinical evaluation of the equivalent device has been performed in compliance with the requirements of the MDR”,

and that therefore equivalence with a device CE-certified under the MDD or AIMDD is no option. Basically making it almost impossible to bring Class III or implantable devices to the EU market on the basis of equivalence, unless the equivalent device concerns a modified version of a device already marketed by oneself.

In contrast for devices other that Class III or implantable devices , the equivalent device does not need to be CE-marked as long as clinical data are collected in line Good Clinical Practices and data are transferable to the EU population.

CONCLUSION

So while happy at first sight with a flood of MDR clinical guidance being published lately (another one on safety reporting in clinical trials was published this week), the details bring us back to earth, making one realize that clinical evidence has to meet higher, tougher standards, and that the reversed Christmas tree of clinical evidence with equivalence as its base has finally been brought down.

Feel free reaching out for a discussion on the above, or in case you need support with your clinical evaluation or investigation.

Annet

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MDR/ IVDR CLINICAL EVALUATION TOOLKIT; PART I

mdcg 2020-1 imageAfter a long period of waiting, several delays, and the MDR deadline without proper guidance hanging above our heads like the Sword of Damocles, as of end of April we have one more year until MDR date of application and a ‘flood’ of guidelines to work with.

So while keeping the clinical work on track as good as possible in the almost ‘fluid’ COVID-19 environment, I thought I’d give the ones regarding clinical evaluation a look.

At first sight there is not a lot of news, but a couple of things stood out from my perspective, especially since after a closer look they appear to give us a taste of the MDCG’s thinking and what we may expect from further guidance. In this blogpost I will address my observations on the guidance for the evaluation of Medical Device SoftWare (MDCG 2020-1), later this week followed by the guidance for equivalence (MDCG 2020-5).

IMDRF

Besides that MDCG 2020-1 addresses MDSW of all medical devices, including IVD’s, it is interesting to see that, although emphasizing that it “solely” applies to MDSW, this guidance uses IMDRF concepts as a starting point, such as N41. With several medical device guidances still pending, this gives us an idea of the MDCG’s thinking, and in the run-up to further publications it seems a good strategy to continue using existing guidelines at our disposal including the ones from the IMDRF.

SCOPE

The guidance includes a helpful table clarifying the clinical/ performance evaluation requirements in relation to intended purpose of the MDSW, indicating that MDSW with an independent medical purpose and MDSW with an intended purpose driving a medical device require an evaluation.

The scope also has a note specifying that

“If a software is driving/ influencing more than one medical device, an independent CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) is required for each foreseen and clinically viable software – device combination”.

So in case you are using certain MDSW for multiple medical devices, you are unfortunately not done with just one evaluation, which makes perfect sense since the MDSW should meet the intended purpose in a real-world environment (also refer to below).

Also of interest I find the acknowledgement that

“the final clinical outcome for the patient is dependent on further diagnostic and/or therapeutic options which could be available”,

in other words the clinical benefit for MDSW may be indirect and just lie in providing accurate information.

PROCESS

MDSW EVALUATION PROCESSMDCG 2020-1 nicely (re-)visualizes the general evaluation PROCESS, which is the same regardless whether we are dealing with medical devices, in vitro diagnostics devices, or MDSW, and describes the 6 stages we are (supposedly) familiar with: planning/ scoping, data identification, data appraisal, data analysis within the context of the Essential Safety and Performance Requirements, reporting, and updating throughout the product life cycle.

SUFFICIENT

I am delighted seeing in this guidance we finally get a sense for what will be considered sufficient evidence. Something we have been waiting for for ages by now, and clarifying (at least for MDSW although it reads pretty generic with the exception of one example question) that the assessment of what is sufficient data should be determined based on answers to questions regarding the amount as well as quality. Example questions proposed include:

Sufficient amount

  • Does the data support the intended use, indications, target groups, clinical claims and contra-indications?
  • Have the clinical risks and analytical performance/ clinical performance been investigated?
  • How big is the body of scientific evidence?

Sufficient quality

  • Were the type and the design of the study/ test appropriate to meet the research objectives?
  • Was the statistical approach appropriate to reach a valid conclusion?
  • Were all ethical, legal and regulatory considerations/ requirements taken into account?

In fact no big surprises here, since the questions simply reflect aspects that we are supposed to take into account during the general process of appraisal and analysis of clinical data.

REAL WORLD DATA

With respect to the performance analysis, it is interesting to see the emphasis that is placed on the translation of MDSW performance into daily practice: in the section on technical as well as clinical performance it is emphasized that the manufacturer should verify and test that the MDSW meets the intended purpose in real-world usage, in the intended use environment and with the intended users, telling me that Human Factor testing  basically is the bare minimum that one needs to have data on.

A little misplaced seems the statement that

“CLINICAL EVALUATION of class III and implantable devices (MDR), shall include data from a CLINICAL INVESTIGATION unless the conditions of Article 61(4), (5) or (6) of the MDR have been fulfilled”.

While no-one will dispute that typically a pre-market clinical study is required for class III medical devices and implantables under the MDR unless it can be scientifically justified to rely on existing data, based on the text as it is right now, I find it puzzling whether this statement is meant to be applicable for MDSW, and, if so, for what type (stand-alone MDSW up-classified to class III and/or MDSW influencing a class III medical device?). I  anticipate  some clarification in this respect upon revision of this guidance.

CONCLUSION

To conclude this post, while at first sight this guidance seems a repetition of what we already know, and it indicates to be subject to revision upon the publication of other “horizontal” guidance for other devices that MDSW, it has interesting new elements worthwhile to take note of which are potentially also supportive for evaluations beyond the scope of this guidance.

Annet

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COVID-19 CLINICAL EVIDENCE DOWNTIME: HOW TO MAKE USE OF IT!

evidence downtimeTo date numerous guidances, blogposts, webinars have been published addressing what one must and cannot do in the process of clinical evidence collection due to the COVID-19 pandemic (for overviews see here and here), and with this post I have no intention repeating that, but rather want  to focus on the things we CAN do and actually use this downtime to increase the quality of our clinical evidence base.

Clinical Evaluations

With my medical device background, I cannot help but address the fact that following the Coronavirus pandemic the MDR date of application is likely to be delayed with one year (mind you, the IVDR DoA still stands, with an even bigger clinical evidence EU MDR IVDR timelinechallenge, or quoting Erik “another crisis in the making”), and as (hopefully) known, an important activity concerns (re)assessment and updating your device clinical evaluation(s). The extension of the deadline does not only give you more time to do a better, more thorough, job updating your clinical evaluation report(s) (after all, literature and database searches, and writing can still be done), but also, if recently discovered that your (accessible) clinical evidence base is too small (maybe the equivalence did not work out that well, or the available clinical data of the equivalent device is not as good as expected, or…, basically something you should have assessed much earlier), it gives you more time (3-6 months or so, also see below) to collect and process your own clinical data on the safety & performance of your device, and depending on the specific situation in a pre- or post-market setting.

Clinical Trial start-up

Over the years I have been mentioning that the clinical investigation start-up process is like getting a baby, didn’t I? Roughly the study start-up process will take 9 month from conception (idea) to birth (FPI) (anything faster thumbs up!), so when near to, or in the process of initiating a clinical trial, now is the time for a thorough discussion (video, phone, e-mail, …) with your (candidate) study PI’s, steering committees, etc, on the details of your study design and endpoints, write-up the corresponding documentation, and initiate the applicable EC/ IRB, R&D Committee, Competent Authority approval routes.

In absence of the usual pressure to get that done (in the current situation every-one including management will understand that FPI takes more time than usual), you now can take the time needed, thereby enhancing quality and reducing mistakes, and consequently the number of protocol amendments with related consequences in the course of the study.

Indeed, in the current situation EC & CA review takes more time than usual due to coronavirus trial priorities and people involved working remotely, but everyone is getting used to it by now, and the process is still ongoing (actually even better since processes are more tweaked towards fully digital submissions instead of using paper), so there is nothing to keep you from submitting your clinical trial package for review.

If well timed, you will be ready for study kick-off as soon as the pandemic is under control.

Clinical Trial execution

Excluding coronavirus related trials, the execution of clinical investigations and specifically patient enrolment has come to a grinding halt, and several companies actually put their trials for that reason on hold.

safety helmetProvided there is study personnel available, however, participant visits can be converted from a  physical visits into a phone or video visit. In times like these study participants tend to be even more open to (extra) attention, and by phone you will be able to capture key parameters, obviously not with the details as when the subjects are on site, but for sure you will capture big events (Safety!), and with a little luck some other key parameters on your study, while also keeping the participants engaged for the remainder of the study when it picks up speed again when the pandemic is under control.

In addition, this to my opinion is also THE moment to apply and gain experience with risk-based and centralized monitoring. As mentioned in my preceding blog on this topic, options for remote SDV are  limited, especially when there is no dedicated study personnel able to give insights into study participant source data, but partially due to the fact that there will be little to no new data coming in, the timing for the other aspect of it centralized monitoring, i.e. checking for consistency, data completeness & trends, identification of sites with high (or low for that matter) PD and AE rates, is excellent. So review and (internally) discuss your study data and follow-up with the concerning sites, if possible, now, or otherwise right after the coronavirus downtime is over, thereby enhancing the quality of your data.

Clinical Trial closure

Being in the wrap-up phase of your clinical investigation, on-site close-out visits will hardly be possible at the moment, but (provided you have digital study files) you can still prepare for it by performing a TMF reconciliation, making sure all files are in order at sponsor’s as well as site’s end when performing the on-site close-out visit after the coronavirus downtime is over. Alternatively, when the reconciliation shows the files are in order, and publicationssite data review is finished, you could consider  performing the close-out by phone.

In case you are in the ‘fortunate’ situation that final  (or interim for that matter) and clean study data are available, you can also use the downtime to prepare the final/ interim study report and publication, and subsequently ensure the applicable regulatory bodies submissions/ notifications are done. The latter is still a neglected child as I unfortunately know from experience, in spite of the fact that (timely) reporting of the study results is an ethical and scientific duty partially imposed by GCP standards. So what better way to use this clinical evidence collection downtime than to write your reports when stuck at the (home) office?

Conclusion

In short, depending on the phase of clinical evidence collection process you are in, I believe there are several things we can still do to keep the processes reasonably on track. Limiting the amount of time lost and picking up speed once the pandemic is under control, and actually using this down-time to increase the quality of your clinical evidence base, working on your clinical evaluations, clinical study start-up documentation, performing centralized monitoring, and writing clinical study reports and publications where possible.

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CORONAVIRUS AND CLINICAL STUDIES: WHAT TO DO?

20200316 CORONA HOPKINS

By now the Coronvirus outbreak is affecting everyday life worldwide (see latest statistics Johns Hopkins University), and to avoid patient exposure or to reduce the burden on clinical services it also started impacting clinical trials; their execution, monitoring, and publications. Study staff re-allocated to clinical care or requested to stay at home, study participant enrolment and follow-up delayed to limit contact, and monitors being kept out of the hospitals.

With respect to clinical trial management more and more governmental guidance’s are safetyappearing in a hard to keep up pace, indicating what is the best approach with respect to study suspension, protocol amendments, deviations, and study participant recruitment and follow-up. Suggesting for example changing participant site visits to phone calls or paper questionnaires by post where possible, keeping in mind that study participant’s safety has the priority.

In this blog post I would like to address another tool at our disposal for monitoring: Remote (or centralized) monitoring, which depending on the local situation and study security arrangements can be extremely helpful to keep the ‘clinical motor running’ as far as possible given the current situation.

BACKGROUND

Besides training, Site File review, etc., one of the main reasons for the on-site monitoring is proper source data verification (SDV), i.e. the process to ensure that data are verifiable, correct, and complete. On-site monitoring, however, represents at least 15% of the total clinical study budget, and digitization and evolving regulatory insights nowadays allow for remote monitoring (remote evaluation carried out at a location other than the sites at which the clinical study is being conducted),  as well. Although remote monitoring may not be considered the tool of choice for your current clinical trial and/ or described in the study monitoring plan, in the current situation it may be the best tool we have, keeping in mind that remote monitoring is not the same as

RISK BASED MONITORING,

although they do go hand-in-hand, because RBM allows for a lower than 100% SDV and it is extremely difficult to perform 100% SDV with remote monitoring and SDV (see below).

Key is to check whether your study allows for RBM, and what the monitoring plan says about remote monitoring. If it does include RBM, you may just need to adjust your timing or (temporarily) the degree with which you perform remote monitoring, or if it does not include RBM you may want to amend your monitoring plan, notify the applicable Ethics Committee on it (make sure to check their latest ‘Corona’ policy), and train your CRA’s. Especially do not forget the latter, since not all CRA’s are 100% familiar, yet, with remote monitoring procedures.

Good thing in this situation is that the

REGULATIONS

nowadays widely accept a risk-based approach for monitoring, and in parallel to the FDA, ICH-GCP, also the upcoming version of ISO 14155 allows for

“a combination of on-site and where justified, centralized monitoring, as appropriate”,

and see it as additional monitoring capabilities to complement or reduce the extend and frequency of on-site monitoring. So the ‘only’ thing to do is to ensure proper documentation and reporting to the applicable regulatory bodies (Competent Authorities as well as the Ethics Committees) of the ‘why and how’ to ensure you stay compliant with the applicable regulations.

While (temporarily) switching to remote monitoring, a few practical factors should be considered while performing remote monitoring, especially

REMOTE SDV

The study sponsor (eCRF or alternative), but ideally also the concerning sites (electronic patient files), should have electronic systems in place that are remotely accessible in a secured way. Working with a paper study and study staff at home will make remote SDV virtually impossible.

Annet_MarjoleinFor proper SDV the CRA needs to be able to review the patient files. That tends to create challenges due to the fact that most of the hospitals in Europe do not allow for remote (so off-site) viewing of patient files by the sponsor due to (possible) data-protection issues, and in fact most of the Informed Consents do not include permission of sharing of personal not coded data outside the study site.

Since these limitations typically include blockage of web-based tools like WebEx, Skype, GoTo, etc., the best option we have in this respect is that study staff uploads critical coded and signed reports into the study sponsor’s electronic system (eCRF or alternative) making it accessible to the CRA for review. The obvious down-sides being that this places yet a higher burden on the site study staff (so they should not be re-allocated to critical clinical care!), and this concerns a highly selective review of a copy of the source. It would, however, to my opinion be the best option we have for the current situation besides suspending all activities, and is in line with a risk based approach with a reduced amount of SDV.

CONCLUSION

The regulations nowadays allow for combination of remote and on-site monitoring, and given the current situation it seems best to assess the situation for your clinical study, and (re) consider (temporarily) applying remote monitoring, while ensuring ongoing study participant’s safety and well-being, using a risk based approach for SDV.

Annet

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2020 – THE 11th HOUR FOR THE MDR, ISO 14155, & OTHER EU CLINICAL MATTERS

 

NCIARA-MDR etcothing could have been more illustrative for the medical device clinical trial environment in Europe  than the storms Ciara and Dennis in February. With BREXIT as a kick off, the Coronavirus spreading around te globe, the MDR deadline less than 3 months away, and a new version of ISO 14155 coming out shortly, 2020 for sure guarantees a stormy year for any-one involved in medical device clinical trials

Per 31-January BREXIT finally is a fact, but what that actually means for clinical trials with sites in the UK is unclear to say the least. Without any say from UK’s end, EU regulations such as GDPR and MDR still apply, at least for 2020, but at the same time MHRA published an updated guidance regarding medical device clinical investigations indicating that a clinical investigation of a non-CE-marked medical device should at least be considered for certain circumstances, and notification to the MHRA will not be required if the medical device to be used is CE marked for the purpose under investigation. This comes across as less stringent than the MDR, that says that for class III devices and implantable devices safety and performance data, as a general rule, should be sourced from clinical investigations, and that PMCF studies that involve

“submitting subjects to procedures additional to those performed under the normal conditions of use of the device and those additional procedures are invasive or burdensome, the sponsor shall notify the Member States concerned”

So, in 2020, should we or should we not follow MHRA guidance when a UK site is involved in our clinical investigation?

As if we did not already have enough challenges in the EU medical device environment, there the CORONAVIRUS (or COVID-19) appeared, originating in China and spreading across the globe by now. By the end of last month, it started affecting device availability at the hospitals, but by now it also has a direct effect on our clinical study work due to travel restrictions and hospitals starting to keep out clinical trial monitors. Making remote monitoring in spite of its down sides, all of a sudden a much more attractive option. But are your EU clinical study sites ready for that, and how does that work again with the GDPR?

MDR appliesIn the meantime, let’s not forget the MDR DEADLINE being right around the corner. With a substantially higher demand for qualitative clinical evidence, and, as a brief reminder, reasons for this include that:

  • existing clinical evaluations need re-assessment following limitations on equivalence, state of the art, as well as clinical data that are considered suitable,
  • several devices have been up-classified, and will require a more solid evidence base than before,
  • planned activities for Postmarket Clinical Follow-up will require actual data collection, and are no longer a paper exercise, and
  • clinical trial/ investigations supporting the regulatory files need to be conducted in compliance with the MDR and other Good Clinical Practices, such as ISO 14155.

So in short, due to a broader scope, better follow-up, as well as limitations on the use of existing clinical data, ‘the pressure is on’, especially for the clinical evaluations. The problem is, that when you do not have (access to) a lot of clinical data there is nothing to evaluate. I already see issues appearing with lower class devices that have been on the market for ages, but where complaint data and some publications from equivalent devices were considered insufficient under the MDD: Where does that leave us under the MDR?

So, and I cannot emphasize this enough, when in the fortunate situation that your device still has a valid CE mark, please make sure to pro-actively collect clinical data on safety and performance appropriate for your device and its intended purpose now.

The MDR mentions ISO 14155 as the GCP for medical devices, and the 2020 version will be coming out soon. An obvious attempt was made to align the two, but one should pay attention though, since their requirements with respect to clinical investigations are not 1:1. The MDR is, for example, more ‘lenient’ with respect to AE documentation, requiring recording of any AE

“identified in the clinical investigation plan as being critical to the evaluation of the results of that clinical investigation”,

whereas ISO 14155 requires all AEs to be documented. Furthermore, there are some nuances with respect to pre- and postmarket clinical studies. I will write a separate post on this topic soon, but when planning your clinical investigation make sure to know what bucket your medical device clinical trial belongs to, pre- or postmarket, interventional or observational, feasibility or regulatory, and what that means for the applicable rules.

In CONCLUSION, 2020 for sure is an exciting year for those in the medical device clinical trial environment and beyond, with a lot of question marks. Unsure what to do? Stay tuned and feel free reaching out for advice, ACS can help you finding the most cost-effective way for your device through this clinical evidence labyrinth.

Annet

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6 MONTHS LEFT UNTIL MDR: MORE TIME FOR YOUR CLINICAL EVALUATION?

KlokUpdate 18-DEC-2019: The EU parliament adopted the second MDR corrigendum, giving manufacturers of Class I medical devices 4 years extra to bring their clinical evaluation in order, putting them in the same position as the other medical devices with a valid CE certificate.

With only half a year left until application, the implementation of EUDAMED delayed with 2 years, and slow progress on implementation of acts and guidances, there are calls for and rumors on extension of timelines of the EU MDR. But does that actually mean that medical device manufacturers have more time to bring their clinical evaluation in order?

Under the MDR all devices will require a Clinical Evaluation with clinical evidence

“appropriate in view of the characteristics of the device and its intended purpose”

including Class I devices.

Medical devices with valid CE certificates can be placed on the market under the current EU Directives as well as the new regulation during the transition period of the MDR. This means that CE certificates issued under the current Directives will remain valid for a period of four years post date of issue, so until 25th May 2024, unless there is a significant product update (then a clinical evaluation per MDR is needed).CE

Does that mean that for devices with a valid CE certificate there is plenty of time to update their clinical evaluation? The answer is that that depends on the device and the concerning clinical evaluation plan, since under the current directives manufacturers are required to actively update clinical evaluations

“.. when the manufacturer receives new information from PMS that has the potential to change the current evaluation; if no such information is received, then at least …. every 2 to 5 years if the device is not expected to carry significant risks and is well established”

so best case the manufacturer with devices in this category has time until the certificate expires.

LaidBackA laid back attitude towards product clinical evidence collection, however, is not advisable, since these manufacturers are in the fortunate situation they still have time to gather their own clinical evidence in a postmarket setting, which currently (changes are in progress everywhere though!) is still less complex than in a premarket setting, and might be a necessary evil since the equivalence pathway has become much harder under the MDR as technical, biological, and clinical

“characteristics shall be similar to such an extent that there would be no clinically significant difference in the clinical performance and safety of the device. Considerations of equivalence must always be based on proper scientific justification. Manufacturers must be able to clearly demonstrate that they have sufficient levels of access to the data on devices to which they are claiming equivalence in order to justify that claimed equivalence.”

More problematic is the situation for

class I medical devices since they have no CE certificate and will have to comply with the MDR and update all technical information including clinical evidence by May 26, 2020. Manufacturers of Class I devices may still self-certify, as long as MDR requirements are satisfactorily met, BUT an extra complicating factor is that several Class I devices have been up-classified to Class IIa, IIb or even Class III (including some health apps), SleepApnoeAppand the requirements with respect to pre- (and postmarket) clinical evidence are more strict under the current directives as well as the MDR.

Now, news is circulating for some time now that a second Corrigendum is in preparation, potentially introducing a transitional period for up-classified class l devices, including class I reusable devices, but, although projected for this month, thus-far unconfirmed as far as I am aware. So manufacturers better not bet on that, and, products with a valid CE certificate aside, all devices are still in the same boat as far as timelines for updating their clinical evaluation are concerned.

In conclusion, do medical device manufacturers have more time to update their clinical evaluation? Thus-far the answer is no, as nothing changed in that respect since the clarifying interpretation of the MCDG in beginning this year, and for the majority of devices the deadline of May 26th, 2020 still applies. So at this moment the key question is more whether 6 months will be enough to build or strengthen the clinical evidence base, if not already started working on it? For a full blown clinical investigation it typically will be too short (also refer to a previous post addressing time needed for a clinical trial), but when using alternative sources for your clinical evaluation it might just be tight, and key is to act NOW.

Feel free reaching out in case of questions regarding the above, or support needed concerning your clinical evaluation.

Annet

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THE EU MEDICAL DEVICE CLINICAL ENVIRONMENT: UNCERTAIN TIMES

beach-landscape-sea-coast-water-rock-917958-pxhere.comThe medical device regulatory environment in Europe is moving, but not always as timely and as clear as one would wish, certainly not from clinical perspective. The

MDR/ IVDR Rolling plan

has been updated and mentions clinicals a few times, and I find the part on Eudamed stating that

“It is estimated that modules for clinical investigation and market surveillance might be only partly or not at all available at the time of application of the two Regulations (due to workability issues) but few months after.”

a little disturbing, especially as that will not only affect new clinical investigations, but also the ongoing studies: Among other things the MDR states that clinical trials that have started under the MDD prior to 26 May 2020 may continue, but also that reporting of serious adverse events and device deficiencies shall be done according the MDR. Meaning that from 26 May on these events need to be reported via Eudamed per Article 73 (e). So, althought progress has been made drafting the functional specs for Eudamed, I am not sure where this will lead us.

MDCG guidances

More MDCG guidance documents have been published and of particular interest from clinical perspective is the one on the clinical evaluation consultation procedure, with an (not legally binding) interpretation of the 3 criteria exempting devices from the clinical evaluation procedure with expert panels, and especially the one regarding

“new devices designed by modifying a device already marketed by the same manufacturer for the same intended purpose…”.

The interpretation is that “a device already marketed” cannot be intended to refer to a device already marketed uniquely under the new Regulation, and so, as Erik Vollebregt put it

“scrutiny is only for devices that are new at the time of the conformity assessment application for the MDR”,

which will be of great help trying to get some control over the workload of the expert panels.

And last there is the never ending story of the

Brexit

Althought May is fighting it untill the bitter end, a no deal Brexit seems closer than ever, and the potential impact for those using or dealing with medical devices, and for UK patients requiring imaging and radiotherapy can be substantial.

Since UK Notified Bodies and competent authorities will no longer be recognized by the EU, medical devices and in-vitro diagnostics no longer can be brought to the EU market via UK: devices which enter the EU via or from the UK will be handled as import from a third country with all related consequences.

Patients with cancer in the UK are expected to face substantial challenges accessing the best care, as among other unfavorable developments, hospitals no longer carring out their own PET-CT services, deliveries of radiopharmaceuticals delayed and certain patients prioritised over others.

In conclusion,

the medical device environment in Europe is changing, with several moving parts and many uncertainties for manufacturers, users, and patients. We should keep in mind, thought, that most changes have been initiated for a better protection of patient safety.

Feel free reaching out to discuss any of the above or other aspects of the medical device clinical pathway in Europe.

Annet

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