British regulators tease new device regulations in informative live session

Quick background on medical device regulation in the U.K.

• In the wake of Brexit, the E.U. no longer recognized products certified in the U.K., but the U.K. still needed CE-marked products. To keep critical devices and in vitro diagnostics (IVDs) available for patients in Great Britain (England, Scotland, and Wales), a much smaller market than the remaining 27 Member States of the E.U., the U.K. government continued to recognize CE-marked products for a limited time. Originally planning to stop recognizing the CE mark in mid-2023, the U.K. government recently extended that recognition through 2028 for medical devices and 2030 for IVDs. [Read AgencyIQ’s analysis of that legal extension here.]

• There were myriad reasons for the extension. One was to align the phase-out of CE recognition with the transitional timelines for the European medical device (MDR) and IVD (IVDR) regulations, where the E.U. had also recently extended compliance timeframes. [Read AgencyIQ’s analysis of the most recent extension here.] But a main reason was the time it was taking to come up with the U.K.’s own new device regulations.

• The U.K. hoped to have those regulations in place by mid-2023, so it could transition to its own mark, the UKCA mark. Operating under The Medical Device Regulations 2002, which transposed the previous device and diagnostics directives (MDD, AIMDD and IVDD) into U.K. law, and updated them for Brexit as The Medical Device (Amendment etc.) (EU Exit) Regulations 2020, the U.K. planned for a new regulation that would be similar to, but not the same as, the European device and IVD regulations. The U.K. Medicines and Healthcare products Regulatory Agency (MHRA) introduced its concept for a new device regulation in late 2021 and responded to the public consultation on the regulations in mid-2022. Recently, it put forth the post-market part of that regulation, which is planned to be adopted in December 2023 and come into force in June 2024. [Read AgencyIQ’s analysis of the proposed U.K. post-market regulation here.]
• Separately, the government is piloting an innovative device access pathway (IDAP), designed to shepherd innovative devices from concept to acceptance into the National Health service. MHRA launched the pilot in late 2023 and ultimately chose eight products with different technologies that address life-threatening diseases with no equivalent solutions that also support the U.K.’s Life Sciences Vision. Ultimately, the pilot will provide a standardized process to support innovative devices and their manufacturers.

This week, the British regulator offered a sneak peek into where it’s going with its new regulations via a public webinar on the scope, classification and essential requirements for medical and diagnostic devices

• MHRA offered tantalizing new details on its planned medical device regulations in a stakeholder webinar this week. Presenters from the agency included EVE HUTCHINSON, head of regulation, who provided a status update on the future device regulatory regime. Additionally, CLARE THOMPSON, regulatory lead, JOSEPH BURT, head of diagnostics, and PAUL CAMPBELL, head of software and AI, outlined the scope of the regulations for general medical devices, diagnostic devices and software as a medical device (SaMD). They also covered changes in classification for the three product types in going from the old medical device and IVD directives to the future regulation, and what the new essential requirements would look like at a high level. The regulators answered questions on the new regulations at the end of the session.

The MHRA head of regulation provided context for the planned changes to its device regulations

• Hutchinson described MHRA’s intent for the new regulations, enumerating big goals for the regulator that include achieving status as a global leader while improving public and patient safety. Additionally, she said, MHRA hopes to come into better alignment with international regulatory best practices while maintaining transparency.
• MHRA consulted with the public on proposed new device and diagnostics regulations in 2021. AgencyIQ has written on this topic in the past, but in short, the U.K. government engaged a cross-section of stakeholders, including manufacturers, trade associations, healthcare professionals and the public to provide feedback on its proposal for a regulation. The proposal covered the future regulation’s intended scope and device classification; responsibilities of various economic operators; enhanced traceability including adoption of unique device identification (UDI); changes to how conformity is assessed; making clinical evaluations and investigations, including diagnostic performance evaluations, more robust; and new requirements for post-market surveillance.
• Software, artificial intelligence and international harmonization: The new regulations would encompass software as a medical device (SaMD), software in a medical device (SiMD) and artificial intelligence (AI) used in and with medical devices. The regulator also promised more international harmonization, such as leveraging the Medical Device Single Audit Program (MDSAP) and other guidance put out by the International Medical Device Regulators Forum (IMDRF). Initially, the regulator targeted July 2023 to transition to the new system.
• Public response supported the efforts but offered specific additional feedback. As Hutchinson reiterated in the webinar, there was strong support for the new regulations to improve patient safety and increase post-market requirements and traceability. Not discussed in the webinar but arising out of the consultation were clear messages from stakeholders to align with the European regulations and other international groups like the IMDRF to avoid duplicative efforts; those providing feedback also supported new pre-approval routes for innovative devices
• What’s happened since then: Following the consultation, MHRA pushed through a statutory instrument to recognize the European device CE mark through 2030, as discussed above. It also published the software and AI change program and drafted the post-market regulations and posted them on the World Trade Organization (WTO) website for public review. The regulator launched a pilot program for innovative devices – the Innovative Devices Access Pathway (IDAP) – and selected the eight technologies that will help the regulator solidify the program. In early January 2024, the MHRA offered its planned roadmap for the future regulations, describing the activities it plans for 2024 and 2025. This year will see the post-market regulations finalized and the WTO publication of the future core regulation addressing everything outside of post-market requirements, which the regulator plans to finalize in 2025. The third and final planned statutory instrument will be any needed enhancements to these regulations, with a public consultation planned for later in 2024.

Scope, classification and essential requirements of the planned regulations

• The planned future regulation would introduce new definitions, including those for medical device, intended purpose and SaMD. Thompson noted that the proposed regulations roll in certain products not previously regulated as medical devices, including products that clean, disinfect or sterilize devices and products used to predict disease or support conception, among others. In the future regulations, IVDs would encompass software, physical or mental impairment and include assays that provide information on the predisposition to conditions or diseases and those that predict treatment responses, according to MHRA’s diagnostics head Burt. Per Campbell, head of software and AI, SaMD would be defined as “a set of instructions that processes input data and creates output data.” The definition is broad in order to be flexible yet protect patients and the public. Notably, this definition would also include AI. MHRA intends to add special premarket requirements for software as well as enable pre-determined change control plans (PCCPs), which the regulator plans to describe in future guidance. Finally, certain products with no medical purpose will fall under the future device regulations, such as dermal fillers and colored contact lenses; this will likely occur under the enhancements to the future regulations.
• Risk is classified by level of contact and risk to patient and public, but there are also special rules for particular product types, including software. The classification scheme for medical devices didn’t change, with class I still being lowest risk and III the highest risk. Changes are meant to capture technology advancements and to align closely with the EU MDR, based on intended use, risk potential and technical and biological characteristics. The number of rules would change from 18 to 23 (the E.U. MDR has 22). Notably, though in vitro fertilization and assisted reproductive devices are non-invasive, these will be class III due to their high potential impact. Certain implantable devices have moved up to class III based on their risk profiles, such as surgical mesh and joint replacements. Finally, the special rules would address products that incorporate nanomaterials and substances that are absorbed in the body. For software, MHRA plans to use the IMDRF categories from document N12 on a framework for risk classification of SaMD, where IMDRF category I corresponds, under the future framework, to risk class I, II to IIa, III to IIb and IV to risk class III.
• IVDs would incorporate the IMDRF scheme, going from a list-based categorization to risk- and rule-based, as described by Burt. This would follow the IMDRF N64 document on IVD medical device classification, with parallels to the E.U. IVD Regulation as well. There are two U.K.-specific updates: Assays that monitor infectious loads for life-threatening diseases will be class D, and devices used to screen or diagnose neurodegenerative and cardiovascular disease will be class C. Burt reviewed the seven planned classification rules and where various products fall under each rule, also noting that only non-sterile class A devices can be self-certified under the future regime.
• Certain products, previously not regulated as IVDs, will be regulated under the future U.K. device regulations – Burt’s list included direct-to-consumer tests, companion diagnostics, assays that monitor therapeutic drugs (departing here from the E.U. IVDR), immunotherapies that use molecular methods, software and AI diagnostics, genetic tests, and wearables with a medical purpose.
• The new essential requirements will follow the European General Safety and Performance Requirements (GSPRs) closely, according to MHRA device specialist JENNY KEATING. Part of this is to align with international best practices, but it will also facilitate the supply of devices within Northern Ireland, following the European regulations. Keating did observe that the GSPRs will be tailored to U.K. requirements, although this primarily means citing U.K. rather than European regulations. An example: For GSPR 12 on devices that incorporate medicinal products, rather than citing the European pharmaceutical regulations (Directive 2001/83/EC), the U.K. version will cite the U.K. Human Medicines Regulation 2012.
• Changes to information provided with the device would focus on increased user and patient safety. CRISTINA SANTIRSO-MARGARETTO, MHRA diagnostics lead, outlined new labeling and instruction requirements planned for the future regulations. One of the first is the ability to use electronic instructions for use – eIFUs – rather than paper copies for most cases, though manufacturers will still need to provide paper copies if a user requests it and also need to verify that the delivery format is adequate for the intended end users. Overall, Margaretto pointed to an increased focus on usability to ensure intended users can safety and correctly operate devices, along with giving access to more robust information on warnings, contraindications and precautions. The MHRA plans UDI for labeling, similar to what Europe has done. The UDI transition should help with device traceability and vigilance, though the key part will be human readable UDI (machine readable would also be allowed).
• Differences in labeling between medical devices and IVDs: Certain medical devices would require biological safety information. These circumstances include where a device contains human blood derivatives, medicinal substances as integral part of the device, or if a device contains more than 0.1% of a carcinogenic, mutagenic or reproductive-harm substance (CMR) or an endocrine disruptor. Class III devices would have specific UDI requirements, active implantable devices would need serial numbers, and implanted devices serial or lot numbers. Certain IVDs will be treated differently; companion diagnostics used with drug therapies would have to include the international non-proprietary name (INN) of the medicine the test is used with.

Highlights from the Q&A session

• AgencyIQ highlights a few of the questions manufacturers will likely find most helpful. Interestingly, one of the first was whether MHRA would share the slide deck and that answer was no, though the recording would be available in the near future.
• Will MHRA align SaMD and AIaMD to the E.U. MDR and IMDRF? Per MHRA, it intends to align with Europe and the IMDRF on software classification.
• What is the rationale for differences between Europe’s GSPRs and U.K. essential requirements? The MHRA reiterated that it plans to align with the European GSPRs except where they cite European laws or standards. In these cases, MHRA would have to substitute reference to British laws and guidance.
• When will the draft U.K. MDR text be available? The regulator noted that it’s currently holding engagement sessions to give stakeholders insight into the content, but the first time the entire instrument would be available is when it’s posted to the WTO website, planned for late 2024.
• In the E.U., software seems to default to class IIa. Will the U.K. system have more flexibility in the U.K. system? Again, MHRA intends to follow the IMDRF classification system, where the device risk classes (I, IIa, IIb, III) align with the IMDRF categories (I – IV). Since device risk will be driven by the risk level of the software in relation to the intended purpose, it could fall anywhere from risk class I to III.
• Will sterile class A diagnostic devices be subject to limited conformity assessment by Notified Bodies, where just the sterilization validation and instructions are reviewed? In its response, the British regulator implied that class A sterile devices would be subject to full conformity assessment, rather than what is done in Europe. There, the Notified Body reviews only the technical documentation portion having to do with sterilization validation and instructions for sterilization.
• Will the new U.K. MDR support innovative devices? MHRA responded that it, and the government as a whole, are very supportive of innovation and the MHRA continues to work to ensure evidence can be generated in a proportionate way. The regulator held up the IDAP pilot as a demonstration of this support.
• In response to another question about the timeline for when the future regulation comes into force, the regulator observed that there is a general election within the next year that could impact the timelines discussed in the roadmap, but in general, the MHRA plans to adhere to these timelines.
• A question that came up more than once, and in a few different ways, is whether the different statutory instruments will be combined into a single regulation for ease of reference. In its response, the MHRA noted that the complete regulation is a “very large piece of regulation,” and splitting it into multiple instruments allowed the regulator to deliver high-quality regulations that are appropriate to the public’s needs. That said, the same teams are working on all of the instruments and the intent is that they are cohesive across instruments. The second time the question was asked, MHRA acknowledged that it likely would have a medical device regulation that would encompass all the instruments, but it might take a while to get to this point.
• Which medical devices will be able to make use of eIFUs? MHRA noted that its intent was to have international alignment, but it should be applicable for devices for professional use. This is a notable departure from Europe, which allows eIFUs in only a very narrow group of device types.
• Will there be a transition period once the U.K. MDR comes into effect, to give manufacturers time to comply? Yes, as was laid out in the government response to the 2021 consultation, MHRA intends to have a transition period, which will be built into the future regulations.

Analysis

• According to the MHRA in its webinar today, some parts of its planned medical e4w3device regulations will be quite similar to the European MDR. For instance, the E.U. MDR includes an annex describing certain products with no intended medical purpose that have been folded into the medical device regulations – so-called Annex XVI products; the U.K. will also include some of these, though whether the product types align perfectly isn’t yet known. In this webinar, MHRA did mention colored contact lenses and dermal fillers, which are also part of the European regulations. Similarly, the regulator promised that its medical and diagnostic device essential requirements would mirror the E.U. MDR GSPRs, except for references to specific national regulations. This would simplify conformance for medical device manufacturers, where they don’t have to try to address disparate requirements.
• It will be interesting to see if the U.K. diverges from Europe on class A sterile IVDs. In a response to an audience question, the regulator seemed to indicate that class A sterile IVDs would be subject to full conformity assessment of all of the technical documentation. This diverges from Europe, where sterile class A devices have limited Notified Body oversight, focusing only on the sterilization documentation, not the entirety of the technical documentation. However, given that the regulators aren’t done writing the regulations,it remains to be seen where this will settle out.
• In the feedback on the 2021 U.K. proposal for regulations, stakeholders asked for serious international alignment on the topic of international approvals, but we didn’t hear much about that today. In previous discussions, the regulator talked about its planned domestic assurance route in which it would recognize other regulators’ device approvals, but this topic was not mentioned by any speaker today. We did hear about recognition of quality management certificates issued under the Medical Device Single Audit Program and about the ongoing IDAP pilot, but nothing about recognizing, for instance, FDA clearances and approvals.
• The U.K. appeared to signal its intention to align with the IMDRF – and other regulators – on SaMD and AI questions. As part of its progress toward the future device regulations, the regulator talked about its software and AI change program and touted its publication, with Health Canada and the U.S. FDA, of guiding principles for pre-determined change control plans for software and AI-guided software. Based on this, we may see more of a focus on SaMD and AI in the U.K. regulations as compared with the E.U. MDR, but we’ll need to see the statutory instrument to confirm this.
• In its slides, MHRA made reference to 23 medical device classification rules, but Europe has only 22. We’ll have to wait to see the statutory instrument to understand that divergence as it wasn’t clear which rule the U.K. added.
• MHRA several times underscored its commitment to innovation and cited specific programs that it has already stood up, such as IDAP. It seems the British regulator is learning from the example of Europe, which is struggling to create new programs for innovative devices in the absence of a device and diagnostics regulatory framework that made room for innovation.

To contact the author of this item, please email Corey Jaseph ( [email protected]).
To contact the editor of this item, please email Kari Oakes ( [email protected]).

Key Documents and Dates

• MHRA MedTech Regulatory Reform Webinar – Scope, Classification and Requirements