Posted May 11, 2022 | By
Left to right: Sabina Hoekstra-van den Bosch, Laura de Vries and Suzanne Halliday
AMSTERDAM – European healthcare product regulators should begin to focus on harmonizing guidance on artificial intelligence/machine learning (AI/ML) across regulatory regimes, according to a panel of health authority representatives at a townhall meeting at the 2022 RAPS Euro Convergence.
On 11 May, a high-level group of representatives from health authorities, notified bodies, and regulatory agencies opened themselves up for questions from delegates who asked them a range of questions including how they collaborate within and across regulatory agencies to develop guidelines. They were also asked pointed questions about their thoughts on the current regulatory environment.
Koen Cobbaert, senior manager for quality, standards and regulations at Philips, asked whether the International Coalition of Medicines Regulatory Authorities (ICMRA) is working with the International Medical Device Regulators Forum (IMDRF) to develop complimentary guidance on AI/ML. He also noted that further complicating matters is the proposed AI Act from the European Commission that would include three layers of risk-based legislation each with their own set of regulations and standards.
The panel agreed that it was important for guidelines on AI/ML to align, regardless of whether they are for drugs or medical devices.
“I think there is cross fertilization surely between the groups … looking at what the other groups are doing,” said Falk Ehmann, chair of the European Medicines Agency (EMA) innovation task force. “But I think the point you highlight is extremely important because indeed, for the combination products where software is being used, how does it define the software and who looks at it?”
“There needs to be an adjoined assessment at the end,” he added
Ana Hidalgo-Simon, head of advanced therapies at EMA’s human medicines division, emphasized that every time guidelines are developed, they are based on massive commitments between experts and regulators from different countries. She went on to say the process often means getting a working guideline out first to give everyone a chance to chime in and pinpoint areas where alignment is essential.
“Sometimes you try to align all these different groups and doing that with something which is so high level that it is less helpful,” Hidalgo-Simon added. “So, the compromise will be there. The good thing is that you are aware [for the need] to continue pushing and then let’s see what is the most effective way to move forward.”
Another delegate, Ronald Boumans, a medical regulations consultant, raised issues with the performance of notified bodies. As the European authorities have implemented the Medical Devices Regulation (MDR) and work to implement the In Vitro Diagnostic Medical Devices Regulation (IVDR), notified bodies have struggled to keep up, which has slowed new products from getting to market.
“I think notified bodies are cracking under pressure and from a distance [the solution] looks like a very simple thing: Get rid of notified bodies and make them into a central European agency,” he said.
Laura de Vries, an inspector at the Dutch Health Care Inspectorate, argued against a centralized system stating that notified bodies give the regulatory system more flexibility and that it is very hard to find experts qualified to serve on them. She also defended notified bodies stating there are a lot of pressures on them with extra requirements due to new regulations.
“The question is, when you centralize the market approval for medical devices, will it be able to get the experts into one organization and keep the expertise in that organization?” she asked. “The process to get designated is a heavy one. It’s a lot heavier than it was under the directives, of course.”
de Vries asked the audience to consider the cause of why notified bodies were struggling and what the effect would be if they were nixed.
“In the end, if the system stands, and we need to get through this, I think it will be more flexible than a centralized system and that’s the way I look at it now,” she added.
Suzanne Halliday, vice president of the European Association for Medical devices of Notified Bodies, also defended notified bodies. She said they were just about to release their annual data which will show notified bodies have issued their first 1,000 certificates to the MDR and IVDR, while also increasing their staff by 25% over the past year.
“There is a rapid increase in the number of people, the number of certificates is starting to ramp up, and once people have done their first reviews, they get better and faster,” she added
Halliday also said they need manufacturers to apply for certificates, adding that it’s unclear how many manufacturers want to place products on the European market.
“I agree with Laura, it’s a challenging time. There’s 30 years of current European legislation and we’ve got three years to transition… it isn’t going to be perfect, but we’re getting a bit better,” she added.
On the topic of notified bodies, another audience member asked why they couldn’t adopt a similar system such as the US Food and Drug Administration’s Q-Submission process that lets regulators talk to sponsors about what they’re looking for in product applications.
Sabina Hoekstra-van den Bosch, session co-moderator and regulatory strategy principal at TUV SUD Medical Health Services, noted the topic would be covered in a separate panel the following day but Tom Melvin, associate asked professor of medical device regulatory affairs at Trinity College Dublin, to give the audience a sneak preview.
Melvin noted that based on his previous experience as medical devices clinical manager for Ireland’s Health Products Regulatory Authority, there have been instances where regulators potentially violated conflicts of interest by tacitly acting as a consultant for device companies before they submitted their product application. While the US has ways to avoid such unfair practices, the EU still hasn’t addressed the issue.
“I’ve seen practices where manufacturers would send a completely empty technical file and get kind of nonconformities and that was kind of a form of consultancy,” said Melvin. “I guess then there had been somewhat questionable practicing in the past where people could have kind of strategized together from the regulator on the regulated side of the conversation.”
Melvin notes newer regulations explicitly state that consultancy activities are not permitted. However, he also said that he empathizes with medical device-makers as they tend to be smaller and often are reliant on venture capital funding where they require clear clinical development plans that need to include details such as clinical trial designs and market entry points.
“That is all really important information that I think in the United States the US FDA can be extremely clear with, so people can have the predictability and fund the pathway,” said Melvin.
“On a member state by member state basis, in some countries you can get advice that almost approximates that, but a competent authority can’t tell you what’s sufficient for the notified body decision for market access,” he added.
Melvin did also note that under MDR, Article 61, expert panels could provide that kind of support for high-risk products.
Ehrmann noted, however, that in some cases the EMA is exploring providing such help such as in the case of certain combination product application where the sponsor can bring a notified body and ask regulators for scientific advice. He said there are some working groups exploring the idea.
“My hope would be again, maybe it’s political, in the future we harness approaches how we can provide advice for better products for the patients in the end,” he added.
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