Medical Devices - Major Challenges Ahead - by Adnan Ashfaq

Prologue/ Background

Basic Medical devices pre-industrial revolution date back as early as 7000bc with flint tipped drills and bowstrings used in dentistry, and in other examples in ancient Egypt ants would be used for wound closure prior to sutures being invented. At these times there were no regulations. It wasn’t until as late as the 1960s and 70s that the US introduced the Medical Device Amendments for safety and effectiveness of medical devices.

In Europe it wasn’t until 1993 that the Medical Devices directive formed and prior to this there was very little regulation for the safety of medical devices.?

So we can also see as technology has advanced the need for more formal regulations was necessary, and this has advanced considerably from 1993 to present day.?

So why the change in Europe from 1993?

Firstly the need for public safety to become more transparent has been called for, and this has been a result of a spate of cases where individuals in the global community have been traumatised or even died due to the failure of the efficacy of a medical device which may not have been tested appropriately.

Secondly, due to the leap in Technological advancement the directive was outdated and didn’t accommodate some of these recent developments in technology, specifically in Nano technology, Software, AI and Machine learning etc. There are some areas which have really left the directives behind and we needed a more up to date regulation.

As a result this has really tightened up the development of Medical Devices and eliminates the weak from the strong resulting in businesses that are really focused on patient safety and building in a level of high quality from the concept.

Due to the significant challenges that the Medical Device world brings many of my engagements are with companies who avoid being a medical device and during conversations its very apparent that they are developing a medical device but try and avoid it, but when we drill down to the definition its usually difficult to avoid. Therefore commercialising a product then becomes illegal and at the manufacturers risk. Its worth looking at the definition of a Medical Device.

The EU defines a Medical Device as:

A medical device means any instrument, apparatus, appliance, software, implant, reagent, material, or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:

? diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,

? diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,

? investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,

? providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations

and which does not achieve its principal intended action by pharmacological, immunological, or metabolic means, in or on the human body, but which may be assisted in its function by such means.

The following products shall also be deemed to be medical devices:

? devices for the control or support of conception;

? products specifically intended for the cleaning, disinfection or sterilization of devices as referred to in Article 1(4) and of those referred to in the first paragraph of this point.

The FDA defines a medical device as:

? "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part or accessory which is: recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,

? intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or

? intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes."

Its interesting to note that the EU MDR include Prediction, Prognosis and Monitoring which many devices are doing and will do more of in the future.

ISO 13485

If you are a medical device company then the recommended QMS is ISO 13485, very often start ups are confused between the QMS and the Technical Dossiers. The QMS is a basic building block of a companies management system, how you will conduct your daily affairs which covers everything from Hiring staff, to purchasing product, design and developing your product, shipping and storing your product and including post market affairs. This is often mixed up with the Technical File or Design History File. These are two separate activities however completely linked, the QMS is the predecessor and a prerequisite in most cases as some of the procedures will define how you will prepare your technical dossiers such as Design Control, Risk Management, Verification & Validation, Post Market Surveillance for example. The procedures in the QMS will outline how as a company you will meet the ISO requirements in general, while the technical file/ dossier needs to be specific about the product in hand being developed with all the details of its evidence of efficacy and performance. ISO 13485 is very carefully worded masterpiece for medical device companies, it really covers everything you need. The 2 key terms which were emphasised in the latest revision in 2016 were “regulatory requirements” and “Proportionate to risk”. A recent addendum has been released which incorporates the new EU regulations requirements for QMS.

MDSAP

Over the years there has been a significant effort of harmonisation globally, which resulted in the GHTF (Global Harmonisation Task Force) which now has become the IMDRF. MDSAP was introduced to act as a single audit programme, and 5 countries joined the programme – US, Brazil, Canada, Japan and Australia. Meaning in addition to ISO 13485: 2016 you also need to have the specific countries regulatory requirements met.

Brexit

Brexit brought a lot of challenges with it and we are facing some real difficulties now, lack of drivers to distribute produce and stock piling has resulted with shortages at supermarkets and fuel stations. However the Medical Devices regulations have been unclear as UK introduced the UKCA mark for the UK market, with a UKNI mark for Norther Ireland. However the complication is that since we are not part of the EU anymore we are not following the EU Medical Devices Regulations and instead following the UK MDR 2002 which in fact is the EU MDD 93/42 and IVDR 98/79. To me this doesn’t make any sense and is a plaster over the Brexit wound!, also the EU regulations have the answers to questions they are now asking as the government knows the directives are outdated, only recently the MHRA have released -?

MHRA Consultation on the future of regulating medical devices in the UK??

The UK Medicines and Healthcare products Regulatory Agency (MHRA) invites members of the public including patients, developers, manufacturers, suppliers, healthcare professionals and members of the wider public to provide their views regarding possible changes to the regulations for medical devices in the UK.?

The released consultation document has 17 chapters and covers all aspects of how medical devices are regulated in the UK. Questions include the following:

? The UK has no medical device regulations for devices claimed to be ‘non-medical’ but offering the same risks as medical devices. Examples include coloured contact lenses, dermal fillers, liposuction equipment and hair removal lasers, which involve risks such as infection and injury but are not regulated in the same way as medical devices. Should these products be regulated under the UK medical device regulations or are they out of scope?

? Can device classification be improved? For example, current IVD rules allow up to 80% of IVDs to be placed onto the UK market without involvement of an approved body. Should the regulations be amended to ensure alignment with international best practice.

? Health institutions in the UK are able to manufacture or modify medical devices for use ‘in-house’ without needing to meet requirements under the UK medical device regulations – should this be changed? If so, what kind of requirements should they be subject to??

? Should importers/distributors play a larger role in ensuring safe supply of medical devices into the UK? This could involve importing/supplying devices only if they are accompanied by the correct documentation, labelling and certificates, and stored/handled correctly

? Should assigning a UDI be required before entering the UK market? If so, what classification of devices should this requirement apply to?

? Should claims of equivalence in clinical investigations be governed under stricter requirements to avoid ‘product creep’? This is where devices originally claimed to be equivalent end up very different to each other.?

? Should UK medical device regulations require manufacturers to publish a ‘Summary of Safety and Clinical Performance (SSCP)’? This would allow members of the public, healthcare professionals and other economic operators to view clinical evaluation results, risks, undesirable side effects, and gain an overview of the medical device’s safety. If this was required, which classification of devices should it apply to?

? Should manufacturers whose QMS has been certified under the Medical Device Single Audit Programme (MDSAP), or who already have regulatory approval elsewhere, have a tailored pathway to market approval??

In my opinion the answers to all these questions lie in the EU MDR 2017/745 and EU IVDR 2017/746.

MDR/IVDR

The new European regulations were introduced in 2017 for Medical Device companies who were Manufacturing, Importing, Distributing into the European Union had to comply with these new regulations which superseded the old directives of 1993 for Medical Devices and 1998 for In Vitro Diagnostics. Over the past 4 years a lot has happened, firstly many companies had not taken the regulations seriously, the notified bodies then became a bottleneck, the EU had not provided full guidance in all areas, Common Specification were not released, for IVDs of High risk you need an external reference laboratory to review the files created and these are not in place even to this date. Then of course COVID-19 happened causing further complications and delays. As a result to date we have 23 NBs under MDR and 6 with IVDR designation. As a result, it is rare to hear of notified bodies declaring certificates. It can take from 9 to 18 months to issue a certificate. TüV Rheinland, designated as an IVDR notified body in December 2020, only announced its first issuance under the new IVDR at the beginning of September 2021. At this rate, it is likely most IVDR certificates may not be issued until 2022.?

RWS also produced a research report in May 2021, on the readiness of medical device manufacturers to meet EU MDR and IVDR deadlines. In contrast, the report highlights a fairly optimistic outlook, with 69% of organisations remaining positive about meeting the IVDR deadline in 2022. Other findings from the report include:

? 53% of organisations are impacted by both MDR and IVDR requirements

? 44% of organisations admit the regulations are their top priority?

? 45% of organisations felt COVID-19 had the most impact on their strategic planning for 2021

FDA for US market - rethink commercial strategy -> should you go to EU first?

The US is clearly the biggest global market of Medical Devices which captures around 45% of sales of $400 billion, while regulations were always seen to be the tightest in US and slightly easier in Europe which captures the second biggest market of over 25% of the global stake. The FDA seem to be quite creative in allowing new technologies with innovative programmes and this is quite attractive for start ups and new devices. However since the complications in Europe this could be a good option. The difficulty that arises is that start ups have innovation grants to launch the device in the UK or EU and so they have to go through the EU regulations.?

There are methods where the device can be used as research or education and not a Medical Device but claims have to be sacrificed, this way data may be gathered under an informal/ non clinical setting without patients. It may prove of some use when building evidence of a prototype working. This can be a non CE marked non medical device or even a self declared medical device with minimal claims to ease market launch. So there are some creative paths to market which can be explored. This needs consultants who are like accountants exploring loopholes in the tax system which is legal and safe.

Technological changes as well as ISO

Nanomaterials, Artificial Intelligence, Machine learning, Combination devices, Drug-Devices, Wearables, these are all terms we are hearing more and more which have changed the way we live and the way we interact in the modern world. The regulations need to keep up with modern living so this has along with it data confidentiality and cybersecurity concerns and finding skills can be challenging.?

I have a lot of clients who are Software as a Medical Device and often don’t see their software as a medical device and can be quite confusing where a device is for well-being and for health purposes, the take home point is if the device has a medically intended function that can be used in any decision making then most likely it’s a medical device.

Challenges ahead for medical devices

I would say:

1. If you think your device is a medical device then it probably is.

2. If you are developing a medical device don’t do this lightly as the regulations can be challenging, several medical devices don’t make it to market but several do and the ones that do followed the regulations.

3. Don’t underestimate the cost of quality and regulatory – build it in.

4. Know your market.

5. Get to know vertical or specific standards that apply to your device and the functionality.

But some challenges are underestimated that is skilled resource and training future talent is equally vital to ensure we can sustain the demands of the industry.

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