26 Oct Interview Xavier Canals – Director Tecno-med Ingenieros, Vice-president SEEIC and independent consultant in Healthcare Technology
Xavier Canals: “Sometimes there is a very weak line to classify whether an-app is a medical application, SaMD, or an application for wellbeing”.
Xavier Canals is a Telecommunications Engineer by the UPC and member of the COIT (1983). He is currently Medical Device Consultant and Director of the Consultancy Tecno-med Ingenieros SL. specialised in health technologies. He is also vice-president of the Spanish Society of Electromedicine and Clinical Engineering (SEEIC) and president of the UNE Standardisation Subcommittee for Electromedicine and scientific evaluator of the ANEP – Ministry of Science and Innovation. He is a lecturer on the master’s degree in Biomedical Engineering and Electromedical Technician courses and a member of the Business Advisory Board of GENESIS Biomed.
The covid-19 pandemic has been a tough test for the entire healthcare system, including the Notified Bodies (NBs), responsible for certification as MDs (Medical Devices), and the Health Authorities, responsible for controlling their marketing and authorisations in the event of an emergency, as happened with pulmonary ventilators. Has the response of these organisations been swift and agile?
It is always difficult for the regulatory aspects to get adapted. We have also been caught in the change from directives to regulations. And the implementation date of the general directive has been postponed by one year: until 26 May 2021. All this because of the pandemic. The conformity assessment by a notified body audits the medical device factories and this has been interrupted because of the pandemic. We are always a bit behind on the regulatory side compared to reality. This can also be seen in emergency cases by health authorities. For example, the use of COVID antigens without a prescription took three or four months. However, in all the countries around us it was already on sale, even in supermarkets.
What changes has the Covid-19 crisis brought to light that should be undertaken within the MD (Medical Device) regulation in order to respond in times of health crisis and allow rapid commercialisation (e.g., IVD (In Vitro Diagnostic Device) regulation for antigen and Ac (antibody tests)?
One of the few good things about the pandemic has been to force us to digitise all processes and to do so based on a digital submission of documents. For example, in the new draft of the Spanish Royal Decree, there is a whole specific legislation that has included sections for its authorisation and use in case of emergency; it was not foreseen in the legislation and now it will be streamlined in the new Royal Decree. Therefore, there is a change not only at the Spanish level but also at the European level, which will effectively help these authorisations for use in the event of an emergency.
Digital Health is an area that has experienced a boom in recent years, especially as a result of the emergence of Covid-19. This has led to the need to certify a large number of software (apps) associated or not with an electronic device. Is the regulation sufficiently clear as to when software can be defined as Medical Device Software (MDSW) or Software as a Medical Device (SaMD)?
There is a very fine line between a medical health app and a wellness app. Sometimes, we find apps that have a medical purpose and a wellness or health treatment improvement purpose, but they are not directly a medical application. For example, I can have an app that alerts me to drink water regularly or to get up periodically when we telework so much: this would be a wellness app, it would not have a medical purpose because teleworking is not a disease and it is clear that it wants to prevent and promote a healthy lifestyle. On the other hand, an app that wants to correct my posture and establish a monitoring of my posture while I am sitting because I have an ailment associated with a postural issue would be a medical app. It is a difficult subject. There are several guidelines. Now we have the MDCG 2019-11, which is for this qualification first, whether it is medical software or not and, if so, to establish its classification according to the implicit risk that the app has for its medical application (according to MDR: classes I, IIa and III or according to IVDR: classes A, B, C and D).
In 2014, the European Commission launched a public consultation on mHealth in the form of a “Green Paper” document in which stakeholders gave their opinion on 11 different aspects (data protection, big data, interoperability, retributive models, market access, etc.) The result of this consultation in 2018 was the launch of the “digital transformation in health” which includes the need for greater interoperability and advocates the adoption of these How is this issue?
It is a very relevant issue. The FDA, in the United States is already regulating it but here in Europe the application depends more on each country, since the medical device regulations cover products not their clinical use. For example, Germany, England or France are already implementing it; and in these countries they have directories of medical apps, just as there is a repertoire of drugs to prescribe covered by the National Health System and which are subject to reimbursement, to funding, by the system. Therefore, it is now a question of having apps that the medical professional will be able to use. For example, if a man is diabetic, he will be prescribed medication, but he will also be told: ‘and to monitor your disease you have to use this app’. And they will only be able to choose from a directory of two or three apps, certified as such and approved by the National Health System.
Is regulation always several steps behind the needs? Does technological development make a regulation obsolete as soon as it is implemented?
Regulation has a conservative character because of its precautionary principle to maintain patient safety. The health technology assessment agencies and all these regulatory bodies try to look at the longer-term effect. Not only its efficacy but its effectiveness, its cost-benefit ratio, so it is not simply that the technique is safe and effective, but also that it has an acceptable cost-benefit ratio for the National Health System. Therefore, we are always going backwards, and this is normal. In the United States the FDA, in order to classify the risk of products, works with a system of lists of products which, in some way, are accepted; if there is a product which is not on the list because it is a disruptive or very new product, it becomes class III, and its risk may be low, but because it is class III it is considered to be high risk. In Europe, on the other hand, the CE marking system based on rules is intended to improve access to the innovation market and if a product is not on our list (as in the FDA system), it does not mean that it is high risk but that it is novel. Therefore, CE marking in theory, and it is so in practice in general, is a guarantor that products reach the European market before the US market. It is a problem to adapt to the new regulations because all the products that are now on the market lose their original CE marking and have to pass the test again. So, with this new regulation, we have gone backwards in terms of the promotion of new products. In vitro diagnostic (IVD) products, which have an application date next year, are having many problems to reach these deadlines and the disappearance of European manufacturers in this sector is foreseen, which is very serious for us.
What notable differences does Regulation (EU) 2017/745 MDR incorporate compared to the previous Directive 93/42?
There are now two major regulations. Before there were three directives. What the regulator did is to think: ‘let’s do the riskiest products first’. And it started with active implantable devices, Directive 90/385/EEC. This directive covered active implants, such as pacemakers, high-risk products with a high added value that it was in the regulator’s interest to regulate as soon as possible. At that time, the FDA had been regulating products for 20 years and in Europe there were very few regulated products, and this regulation was needed. What is being done now is to merge Directive 90/385/EEC, for active implantable devices, with Directive 93/42/EEC, for general medical devices, and we now have the MDR regulation, which is (EU) 2017/745. The problems in some types of products arose the first time they were used in patients, which was after their approval; in other words, they were already approved and that was when they were used in patients. Now, with the new regulation, all implantable products require prior clinical research, and, in addition, a legal obligation is added regarding their efficacy. We want to know that the product is safe and effective, both when it is submitted for evaluation and on a day-to-day basis, batch by batch, product by product that is being manufactured. So, we are obliged to monitor efficacy and safety, and to prove it in periodic audits with the notified body.
What notable differences does Regulation (EU) 2017/746 IVDR incorporate with respect to the previous Directive 98/79?
In in vitro diagnostic products what you get is diagnostic information not by applying it directly to the patient, but by applying it to a biological sample. So there has always been a certain condescension in its regulation in the sense that since I can’t harm the patient, nothing happens. Twenty-five years ago, the analytical part was not so frequent, and its use was not so intensive. Nevertheless, the number of biomarker parameters was expanded. The whole genetic part was totally new, and now with artificial intelligence there is much more information, and there was a need to regulate this part. But the risks of false positives and negatives remain for the patient. It is clear that these in vitro diagnostics, even if they are not applied directly to the patient and are associated with biological samples, also have a risk for the patient and have been regulated. The in vitro directive started with lists, just like the FDA: in an annex there was list A of the riskiest ones, such as sexually transmitted diseases (HIV, hepatitis, HTLV) and the part of blood typing for transfusions. Then there was a list B, which were more general diseases such as rubella or chlamydia, but also serious. And then there was a part of self-diagnosis, for example in the area of glucometers or INR meters, or pregnancy tests. All these list A, B and self-diagnostic products required notified bodies, but the rest were self-certified. What happens now with the regulation? Well, there are 7 rules associated with the classification and it is classified on a product-by-product basis. Before, we used to find that the same product, trisomy 21 evaluation software version or reagents for the same purpose, in one case was regulated with intervention by the Notified Body, in the other case it became self-certified. From lists, the rules for classifying these in vitro diagnoses have been changed, and the pyramid is inverted. From 80% self-certification and 20% with the intervention of a notified body, the pyramid is reversed: 80% will require intervention and 20% will be self-certified. With another handicap: there are few notified bodies, only 6 for in vitro and the application date is May 26, 2022.
What notable differences does the next Royal Decree incorporate with respect to the previous Royal Decrees?
They are associated with the regulation. There are practices in the market that we did not want to see, and the solution was to ban them. For example, the reprocessing of single-use medical devices. There are single-use products that do not deteriorate and could be used for more uses. In other countries it was allowed, as in Germany. Products such as a syringe are not reprocessed; products that have a high cost are reprocessed. For example, interventional cardiology catheters that are high cost. These when they are used, they are inserted and removed, and they are practically intact. So, it will be possible to reuse them: they are cleaned, sterilized and reused. What the regulation and the Royal Decree do is to prohibit the reuse of simple products such as syringes; however, for others they provide other option. This is one of the major sections of the Royal Decree. It includes more elements: manufacturing within the hospital itself; now, with 3D printing, the hospital has become a manufacturer of many parts. To make anatomical models, surgical guides, spare parts and even masks or protective visors. All these items can be made, but it will be regulated. In order to do not become a hospital factory, the scope is limited: during an emergency or in cases of innovation. In addition, the use of the implantation card has been extended, it means more traceability. There will also be a European database in which all medical devices will have a bar code or a scannable data matrix that will make it possible to verify in the Eudamed database whether it is a product normally marketed or whether it has been withdrawn from the market or whether there is an incident associated with it. Transparency will be much greater and therefore patient safety will be improved.
What is the effort (financial and resource dedication) for companies that already had their MDs certified under the old regulations to update them to the new regulation? What are the deadlines?
We note that this change in legislation has been underestimated by the various stakeholders, as the requirements to adapt to this new certification with the regulation have been greatly increased. And the same has happened for manufacturers: it is no longer enough to ‘pass the test’. Now they want to know if you make implants, how many fail and have been explanted or how many have given problems. It also regulates medical devices without a medical purpose (listed in Annex XVI of MDR), for example, breast implants for aesthetic purposes, hair removal equipment and electro-aesthetic equipment. And associated with this, we have been given additional deadlines as well. The application date was May 26, 2021, but we have a grace period until May 26, 2024, for legacy products: that is, those that comply with the directive and maintain the certificate in force but require post-marketing follow-up, surveillance, notification of incidents or withdrawal of products from the market according to the regulation. There are also new elements to be reviewed. For example, for equipment and software, in addition to interoperability and data integrity, cybersecurity is now included as a very relevant element. Before, it was not a critical element; now, there are people who hack into medical devices. We must protect ourselves.
You are now part of the Business Advisory Board of GENESIS Biomed. What do you think you can contribute with your experience to the projects we work on and how do you value this type of initiative?
We are used to be on the dark side of all projects, and we do not usually take the lead, but when GENESIS Biomed invites us to be part of this group we do not hesitate, and we are honoured and delighted because our task is to help all projects from the Backoffice always trying to maintain regulatory compliance and not to give work to lawyers. We help to comply with all the requirements, avoiding bottlenecks and allowing access to the market as soon as possible. So, I am very grateful to GENESIS Biomed for this visibility.