September 2021 – Medical Devices Regulatory Insights

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 seventeen 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?

More information about the consultation, documentation, and how to respond can be found at:
https://www.gov.uk/government/consultations/consultation-on-the-future-regulation-of-medical-devices-in-the-united-kingdom

The MHRA have also scheduled webinars that provide further information on the consultation, for industry and for patients and the wider public.

Consultation closes on 11:45pm on 25 November 2021. The survey can be accessed through the following link: https://www.surveys.mhra.gov.uk/613cff3142a2b02700706bad

MHRA update on regulation of software and AI as a medical device in the UK

With software and artificial intelligence (AI) playing an increasingly prominent role within health systems, the MHRA has created an extensive work programme including eleven work packages. Eight of the packages cover reforms across the ‘software as a medical device’ life cycle. The aim is to implement a surveillance system and use real-world evidence. The three-remaining work packages consider challenges AI poses to medical device regulations. MHRA aims to address the adaptivity of AI, issues of human interpretability, and ultimately ensure its safety and effectiveness.

Published: 16 September 2021, Press Release:
https://www.gov.uk/government/news/transforming-the-regulation-of-software-and-artificial-intelligence-as-a-medical-device

Guidance documents issues by the Medical Device Coordination Group (MDCG)

MDCG has issued a large number of guidance documents over the last few months, aimed at providing clarification and support for manufacturer’s trying to meet new MDR and IVDR requirements. Highlights include FAQs on European Medical Device Nomenclature (EMDN),
explanations on IVDR codes, integration of UDI into QMS, and repackaging and relabelling rules for importers and distributors.

• MDCG 2021-6: Regulation (EU) 2017/745 – Questions & Answers regarding clinical
  investigation
• MDCG 2021-1 Rev.1: Guidance on harmonised administrative practices and alternative technical solutions until EUDAMED is fully functional
• MDCG 2021-7: Notice to manufacturers and authorised representatives on the impact of
  genetic variants on SARS-COV-2 in vitro diagnostic medical devices
• MDCG 2021-8: Clinical investigation application/notification documents
• MDCG 2021-9: MDCG Position Paper on the Implementation of UDI requirements for contact lenses, spectacle frames, spectacle lenses & ready readers
• MDCG 2021-10: The status of Appendixes E-I of IMDRF N48 under the EU regulatory framework for medical devices
• MDCG 2021-11: Guidance on Implant Card – Device types
• MDCG 2021-12: FAQ on the European Medical Device Nomenclature (EMDN)
• MDCG 2021-13 Rev. 1: Questions and answers on obligations and related rules for the registration in EUDAMED of actors other than manufacturers, authorised representatives and importers subject to the obligations of Article 31 MDR and Article 28 IVDR
• MDCG 2021-14: Explanatory note on IVDR codes
• MDCG 2021-15: Application form to be submitted by a conformity assessment body when applying for designation as notified body under the medical devices regulation (MDR)
• MDCG 2021-16: Application form to be submitted by a conformity assessment body
  when applying for designation as notified body under the in vitro diagnostic devices regulation (IVDR)
• MDCG 2021-17: Applied-for scope of designation and notification of a conformity
  assessment body – Regulation (EU) 2017/745 (MDR)
• MDCG 2021-18: Applied-for scope of designation and notification of a conformity
  assessment body – Regulation (EU) 2017/746 (IVDR)
• MDCG 2021-19: Guidance note integration of the UDI within an organisation’s quality management system
• MDCG 2021-20: Instructions for generating CIV ID for MDR Clinical Investigations
• MDCG 2021-21: Guidance on performance evaluation of SARS-CoV-2 in vitro diagnostic
  medical devices
• MDCG 2021-22: Clarification on “first certification for that type of device” and corresponding procedures to be followed by notified bodies, in context of the consultation of the expert panel referred to in Article 48(6) of Regulation (EU) 2017/74
• MDCG 2021-23: Guidance for notified bodies, distributors and importers on certification
  activities in accordance with Article 16(4) of Regulation (EU) 2017/745 and Regulation (EU) 2017/746
• European Medicines Agency Guidance: Questions & Answers for applicants, marketing authorisation holders of medicinal products and notified bodies with respect to the implementation of the Medical Devices and In Vitro Diagnostic Medical Devices Regulations ((EU) 2017/745 and (EU) 2017/746)

Outlook on companies ready to meet IVDR regulations

MedTech Europe, the European trade association for the medical technology industry, ran a survey in July 2021, gathering data from IVD manufacturers. The survey explored how manufacturers are expecting to transition to the IVD regulation within the following ten months. The data suggests only one-quarter of current IVDs will be certified in time for the upcoming deadline in May 2022. It is forecasted up to 22% of IVDs will be discontinued and lost in the transition to IVDR, with a further 17% not certified in time.

As few as 24% (worst case scenario) or as many as 61% (best-case scenario) of IVDs are expected to be certified by May 2022.

One concern highlighted is the small pool of notified bodies available to certify. This is particularly worrying as the new regulations have led to a ~10-fold increase in the number of tests needing Notified Body certificates compared to the current IVD directive. The lack of notified body capacity has resulted in 53% of IVD manufacturers, and 64% of small/medium-sized enterprises being unable to sign with a notified body to certify their IVDs and quality
management systems.

Serge Bernasconi, CEO of MedTech, stressed that the COVID-19 pandemic has shown how significant IVD medical tests are to healthcare systems and implores European leaders to “act decisively to put in place the right elements in the system and then give enough time to allow
all IVD medical tests to get certified to the new IVD Regulation”. Without this action, MedTech Europe predicts loss of a large number of critical diagnostics across every medical discipline and risk class.

Overall, the survey, which represents an estimated 90% market revenue coverage, indicates an urgent need for action in time for the fast-approaching date of application.

Original Source: MedTech Europe, Published: 9 September 2021, Full Press release:
https://www.medtecheurope.org/news-and-events/press/industry-survey-shows-an-urgent-high-risk-to-the-availability-of-ivd-medical-tests-once-the-new-ivd-regulation-fully
applies-in-eight-months/

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 an 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

Original Source: BusinessWire, Published: 10 May 2021, Full Article:
https://www.businesswire.com/news/home/20210510005036/en/Almost-Three-quarters-of-Medical-Device-Companies-Ready-to-Meet-the-European-Union%E2%80%99s-MDR-and-IVDR-Regulations

EC publication of IVDR joint implementation plan among calls for IVDR delay

A joint stakeholder letter from the European Federation of Pharmaceutical Industries and Associations (EFPIA), the European Cancer Patient Coalition (ECPC) and Diaceutics, calls for both postponement and a phased approach to IVDR implementation.

The potential for “serious disruption” to patient care, especially in targeted therapies for cancer patients has been highlighted. With the pandemic further compounding implementation problems, slower pace of on-site audits, and huge difficulties securing notified bodies, trouble is
said to inevitably lie ahead. Arguably, “the IVDR is in much worse shape (compared to the MDR roll-out), as all capacity has gone to the MDR,” said Erik Vollebregt, LLM, partner at Amsterdam-based Axon Lawyers in an interview.

Even with correct infrastructure in place, notified bodies are highly unlikely to be able to take on the ~700% increase in workload that accompanies the new regulations without market disruption. The letter highlighted downstream effects of these disruptions; up to 65,000 non-small cell lung cancer and ovarian cancer patients yearly would not receive testing that allows
targeted therapy for their conditions. Postponement and a phased approach that places priority on notified body assessment of “high risk impact” IVDs would be of great benefit.

EC maintains the May 2022 Date of Application despite calls for delay and has released a joint implementation plan. The plan acknowledges the remaining work before the DoA and establishes a timetable with priority on tasks that are vital for the implementation of the IVDR. Priority is placed on contingency planning, notified body availability and assistance, and designation of EU reference laboratories. Tasks that are of a lower priority include adopting common specifications (CS), publishing guidance for notified bodies specific to IVDs, clarifying the expert panel process for some IVDs, developing a template for the summary of safety and performance
(SSP) and working on MDR/IVDR harmonised standards.

Original Source: European Federation of Pharmaceutical Industries and Associations, Published: 26 May 2021, Full Article:
EFPIA ECPC and Diaceutics call for postponed application and phased implementation of the in vitro diagnostic Regulation

Original Source: Regulatory Focus, Published: 01 June 2021, Full Article:
https://www.raps.org/news-and-articles/news-articles/2021/6/industry-and-patient-groups-call-for-ivdr-delay

Original Source: Emergo by UL, Published: 16 June 2021, Full Article:
European Commission Publishes IVDR Joint Implementation Plan | Emergo by UL

Notified body capacity for MDR and IVDR audits

There are currently 23 notified bodies designated under the EU MDR and 6 under the EU IVDR. Manufacturers are finding it increasingly harder to find notified bodies with capacity under both MDR and IVDR. 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.

There is also no system in place updating manufacturer’s regarding notified body capacity, so time can be wasted in this process with bodies such as BSI Netherlands and TÜV SÜD turning them away. A further delay may be found in the process of conformity. Manufacturers are going into these new regulations for the first time, with little guidance, and notified bodies remain cautious with advice to prevent being seen as providing consultancy. This can lead to issues with achieving conformity, lengthening the process, and holding up capacity, preventing other manufacturers from accessing services.

Under the IVDR, as of September 2021 there are six notified bodies designated, despite up to
85% of the IVDR industry needing notified body services for the first time. In addition, very few notified bodies have been designated under the MDR for Class III and implantable devices. Not only is this affecting high-risk devices, but arguably it is impacting products that are highly innovative in nature, and potentially disrupting the EU’s standing in competitive global medtech markets.

One further consequence of the notified body capacity is feelings of tension where manufacturers feel they are being treated unfairly, and there is a sense of the notified bodies no longer seeing keeping clients as a priority, with more than enough customers available.

It is difficult to grasp the scale of the challenge with limited information on the number of certificates that have been issues and the number of products on the EU market.

Original Source: MedTech Insight, Published: 14 September 2021, Full Article:
https://medtech.pharmaintelligence.informa.com/MT144455/Industry-Needs-Direction-And-Support-As-Notified-Body-Powers-Strengthen

EUDAMED registration requirements under the MDR – current progress

The MDR, coming into force earlier this year, requires the registration of medical devices into a European database (EUDAMED). This database aimed to improve transparency and co-ordinate information flow between economic operators, notified bodies, member states and the wider public. It consists of six inter-connected modules:

1. Actors registration
2. UDI/Devices registration
3. Notified Bodies and Certificates
4. Clinical Investigations and performance studies
5. Vigilance and post-market surveillance
6. Market Surveillance

The development and implementation of EUDAMED was described to be a “high priority” for the Commission. Despite this, the first module is currently the only one that is fully functional. The second module on UDI/device registration (second module) and the third module on Certificates and Notified Bodies will become available this month, September 2021, except for the mechanism for scrutiny and the clinical evaluation consultation procedure (CECP) functionalities. According to the European Commission, “the remaining modules as well as the mechanism for scrutiny and the CECP will be released when EUDAMED is fully functional”.

Source: https://ec.europa.eu/health/md_eudamed/overview_en

First EU expert panel under the MDR, challenges notified body assessment The first medical device scrutinised by an expert panel under the new MDR regulations was a Class III implant
used in dentistry and maxillofacial surgery. The expert panel challenged the notified body’s assessment of the graft, with reservations about aspects of the device that were said to be “ not clarified appropriately resulting in possible negative effects”. A number of concerns were highlighted regarding the clinical evidence, impact of device failure, and some missing evidence. The notified body must now consider the opinion and advise the manufacturer on whether they are in agreement, providing full justification if the panel’s advice is not followed.

This was the first insight into the expert panel process, a new requirement for Class III implantable devices and Class IIb devices for administering and/or removing medicinal products under the MDR, and high-risk Class D diagnostics under the IVDR.

As of September 2021, EU expert panels have now started accepting applications from notified bodies for the evaluation of high-risk in vitro diagnostics. EU reference laboratories (EURLs) will also play a part in scrutinising these high-risk diagnostics, but these remain a work in progress, and are still being set-up.

Original Source: Medtech Insight, Published: 05 July 2021, Full Article:
https://medtech.pharmaintelligence.informa.com/MT144168/First-EU-Expert-Panel-Opinion-Challenges-Notified-Body-Assessment?vid=Pharma

Original Source: MedtechDive, Published 07 September 2021, Full Article:
https://www.medtechdive.com/news/eu-panel-accepting-applications-for-high-risk-ivds/606135/

EU MDR & IVDR chaos: Implications for combination products

The regulation of drug-device combination products could be seriously disrupted by the “chaos” involved in MDR and IVDR implementation. Medical devices have become increasingly important in drug delivery, and more so with technological advancement in AI. Under Article 117 of the MDR, notified body involvement is needed for EU market authorisation of combination products. Notified body opinion of the medical device aspect of the product must be submitted to the EMA. The huge changes brought about by the new MDR has created significant market access delays for combination products, with the MDR viewed as a serious block to these products and threatening EU’s position in the global market. There are some fears that innovators may prefer to place their products in markets that are more supportive of this “rapidly growing cutting-edge industry” such as the US. The delays could seriously affect EU industry and patients alike. It seems that developing guidance for combination products is currently a lower priority, despite the pharma sector keen to move forward rapidly.

Original Source: Medtech Insight, Published: 10 September 2021, Full Article:
https://medtech.pharmaintelligence.informa.com/MT144439/Why-The-New-EU-Medtech-Regulations-Have-Caused-Chaos-And-Concern-For-Combination-Products

EN ISO 13845 linked to MDR and IVDR

EU standards bodies, CEN and Cenelec, have published an update to the EU QMS standard “EN ISO 13485:2016+A11:2021”. The standard consists of annexes that map out the relationship of the standard with the following MDR and IVDR regulations requirements:

• The general obligations of the manufacturer in Article 10 (General obligations for manufacturers);
• The quality management system requirements in Annex IX on conformity assessment based on a quality management system and on assessment of technical documentation; and
• The quality management system requirements in Annex XI on conformity assessment based on product conformity verification.

The EU commission had made harmonizing standards, in particular those of risk management (EN ISO 14971) and QMS (EN ISO 13485), a priority. So far, some standards have been harmonized under the MDR and IVDR but there are up to 200 standards to process.

Original Source: Medtech Insight, Published: 13 September 2021, Full Article:
https://medtech.pharmaintelligence.informa.com/MT144451/EN-ISO-13485-Linked-To-MDR-And-IVDR-At-Last

Update on proposed and final FDA rules

The FDA prepares to implement proposed and final rules related to medical devices, drugs, biologics, and clinical trials. These rules were detailed in the Spring 2021 unified agenda released by the Office of Management and Budget in June. A final rule on the ‘de novo’ classification process for medical devices was released in June 2021. The rule “establishes procedures and criteria for the De Novo process and makes it more transparent and predictable for manufacturers”, thus reducing the associated time and costs. A proposed rule on harmonising and modernising Quality System regulation was released in June 2021 aimed at revising the existing requirements with specifications of ISO 13845:2016, to reduce regulatory burdens and increase harmonisation of domestic and international requirements. There are also proposed rules regarding the classification of OTC hearing aids (June 2021), spinal spheres used in fusion procedures (June 2021), human leukocyte, neutrophil and platelet antigen or antibody tests (September 2021), and allograft heart valves (December 2021). Another final rule slated for a
notice of proposed rulemaking (NPRM) in July 2021 includes “regulations regarding ‘intended uses’” which finalises the amendments to the intended use regulations, in particular, the language used.

Original Source: Regulatory Focus, Published: 17 June 2021, Full Article:
https://www.raps.org/news-and-articles/news-articles/2021/6/unified-agenda-a-look-at-fdas-upcoming-rulemaking

FDA grants de novo authorisation to AI software for prostate cancer

The FDA has granted marketing authorisation to ‘Paige Prostate’, an AI-based software than can help detect cancerous prostate cells. The potentials for AI in healthcare are vast, and in an increasingly competitive global medtech market, it seems the US is open to this innovation. Risks of the device were deemed acceptable because the device would only be used by trained
pathologists who can also take into consideration their expertise, and factors such as the patient’s medical history, and other test results before confirming diagnosis.

Interest in AI is also accompanied with concerns regarding safety, and how regulations can be bolstered to keep up to date with the advancements. This can also be seen in the recent news of the MHRA launching an extensive work programme related to AI in medical devices.

Original Source: MedTech Insight, Published: 21 September 2021, Full Article:
https://medtech.pharmaintelligence.informa.com/MT144487/Another-Set-Of-Eyes-US-FDA-Authorizes-AI-Software-To-Spot-Prostate-Cancer

TGA regulation changes in conformity assessment

Certain devices that have already obtained CE-marking, including Class D IVDs, may no longer require mandatory TGA conformity assessment certification, after an amendment to regulations.

The devices covered by the amendments include:

• Medical devices whose components include non-viable tissues of animal origin;
• Medical devices containing tissues, cells, microbial- or recombinant-based substances
  intended for use in or on the human body;
• Medical devices featuring stable derivatives of human blood or plasma that act upon the human body in an ancillary fashion;
• Class 4 IVD devices

Market applicants may submit conformity assessment documents issued by EU notified bodies for CE marking under the AIMDD, MDD, IVDD, IVDR, or MDR.

Original Source: Emergo by UL, Published: 20 September 2021, Full Article: https://www.emergobyul.com/blog/2021/09/australia-tga-accept-ce-mark-conformity-assessments-some-high-risk-medical-devices-ivds

ANVISA UDI requirements

In August 2021, ANVISA (Brazil) rolled out a proposed six year framework for meeting Unique Device Identification (UDI) requirements based on risk classification of devices. The framework has undergone public consultation and is likely to be finalised into regulation by December 2021.

The timeline is as follows:

• Two years for Class IV (highest risk) devices
• Three years for Class III (high risk) devices
• Four years for Class II (moderate risk) devices
• Six years for Class I (low risk) devices

If these estimates hold, manufacturers of Class IV devices would have to comply with UDI requirements by December 2023. Required UDI data, including Global Device Nomenclature (GMDN) codes, would have to be uploaded on ANVISA’s own UDI database.

Original Source: Emergo by UL, Published: 02 August 2021, Full Article:
https://www.emergobyul.com/blog/2021/08/brazils-new-udi-requirements-medical-devices-compliance-implications-manufacturers

Challenges with access to the Chinese MedTech market continue despite regulatory update
A recent revision to the Chinese RSAMD medical device regulations has been underwhelming in its approach to help foreign innovators gain access to the Chinese market. Though the revisions aimed to streamline the fast-track regulatory procedure known as ‘Green Channel’, it seems this has not been successful. Chinese domestic medical device manufacturers can apply for the Green Channel after only providing design concepts and conducting initial preclinical research. Foreign innovators, need to undergo a much more demanding process, and have to submit design verification information and clinical data to the same level as if they were seeking marketing authorisation. Consequently, over 114 domestic medical device manufacturers have obtained Green Channel status, yet only five foreign manufacturers.

Original Source: MedTech Insight, Published: 20 September 2021, Full Article:
https://medtech.pharmaintelligence.informa.com/MT144462/Chinas-Medtech-Regulatory-Update-Does-Not-Go-Far-Enough-For-Overseas-Innovators

References:
Image 1
https://compliancenavigator.bsigroup.com/en/medicaldeviceblog/ai-and-the-medical-devices-sector/
Image 2
https://morulaa.com/blog-morulaa/ivd-classification-system-2018/
Image 3
https://www.ipha.ie/wp-content/uploads/2020/05/efpia-logo-002.jpg
Image 4
https://www.celegence.com/wp-content/uploads/2019/04/EU-MDR-Checklist-Celegence-Life-Science.png