International regulatory news in brief

UK

13 June

Guidance: Transparency for machine learning-enabled medical devices: guiding principles

In 2021, the U.S. FDA, Health Canada and the UK MHRA jointly identified 10 guiding principles for good machine learning practice (GMLP).

GMLP supports the development of safe, effective and high-quality artificial intelligence/machine learning technologies that can learn from real-world use and, in some cases, improve device performance.

The FDA, Health Canada and MHRA have further identified guiding principles for transparency for machine learning-enabled medical devices (MLMDs). These principles build upon the GMLP principles, especially:

• principle 7: focus is placed on the performance of the human-AI team
• principle 9: users are provided clear, essential information

You can read the guidance here.

In this document:

• ‘transparency’ describes the degree to which appropriate information about an MLMD (including its intended use, development, performance and, when available, logic) is clearly communicated to relevant audiences
• ‘logic’ refers to information about how an output or result was reached or the basis for a decision or action
• ‘explainability’ refers to the degree to which this logic can be explained in a way that a person can understand

Logic and explainability are aspects of transparency.

Effective transparency:

• ensures that information that could impact risks and patient outcomes is communicated
• considers the information that the intended user or audience needs and the context it is used in
• uses the best media, timing and strategies for successful communication
• relies on a holistic understanding of users, environments and workflows

Source: MHRA

Guidance updated: Software and artificial intelligence (AI) as a medical device

This guidance has been updated to include reference to guiding principles on transparency for machine learning-enabled medical devices. You can view it here.

Source: MHRA

21 May

MHRA announces a proposed framework for international recognition of medical devices

The MHRA:

• has today published a statement of policy intent for international recognition of medical devices. It describes how the UK Government intends to recognise regulatory approvals from other countries (see CRCs below)depending on device type, class, and prior approval.
• continues to review the list of comparable regulator countries and is in active discussions with the Pharmaceuticals and Medical Devices Agency (PMDA) to explore the recognition of medical device approvals from Japan.
• statement of policy intent focuses on ensuring safe access to quality-assured medical devices and reducing the duplication of assessments by comparable regulators to enable resource to be focused on more innovative products for the benefit of patient health.

The proposed framework is still in draft, and the final version would be integral with the future core regulations.

With reference to the intended policy on international recognition, the comparable regulator countries (CRCs) for the proposed framework will be:

Country	Agency
Australia	TGA
Canada	Health Canada
European Union	National competent authorities in the member states of the EU/ European Economic Area (EEA)
USA	FDA

On this page, you can see the eligibility criteria for the framework and the exclusions from international recognition.

Source: MHRA

---

MHRA announces consultation on improved safety for high risk in vitro diagnostic devices  

The MHRA has today launched a four-week consultation which will support improved safety for certain high risk in vitro diagnostic (IVD) devices.

The new policy that the MHRA is consulting on would require manufacturers to comply with additional measures for certain high risk IVDs, such as blood tests used to identify blood type before transfusions or tests which identify life-threatening diseases, introducing harmonised requirements for these products.  

The agency is also seeking views on the removal of the Coronavirus Test Device Approval (CTDA) process to avoid duplication of regulatory requirements for COVID-19 tests against the Common Specification requirements.   

The consultation is for the MHRA to seek views on the possible amendments to the Medical Devices Regulations 2002 to include Common Specification requirements for manufacturers of high-risk IVD devices.

This consultation builds upon public views after an initial consultation in November 2021 and will help inform further policy decision-making in this area. The scope of this consultation is specific to the Common Specification requirements for high-risk IVD devices. 

You can respond to the consultation online here.

The deadline to complete this consultation is Friday, 14th June 2024.

Source: MHRA

9 May

MHRA launches AI Airlock to address challenges in regulating medical devices that use Artificial Intelligence

The MHRA has launched AI Airlock, its new regulatory sandbox for AI as a Medical Device (AIaMD).

Last month, the MHRA set out its strategic approach to AI in response to a white paper published in 2023 by Government.

• This pilot project is a key part of that approach.
• It will help the Agency to identify and address the challenges for regulating standalone AI medical devices (AIaMD), initially seeking out and supporting 4-6 virtual or real-world projects through simulation.
• This will allow the Agency to test a range of regulatory issues for these devices when they are used for direct clinical purposes within the NHS.

The AI Airlock

The regulatory sandbox model is a recognised mechanism to help address novel regulatory challenges across sectors.

• The AI Airlock is a world-leading version in healthcare, designed to assist in safe development and deployment of AIaMDs, and this project will follow that robust process so manufacturers can deliver what is required to ensure the real-world viability of these devices.
• The MHRA’s regulatory AI Airlock takes into account evidence-based work produced by other bodies with a similar focus and the Agency will work collaboratively with the NHS AI Lab and the Department of Health and Social Care (DHSC).
• AIaMD products are deployed via NHS infrastructure, making the Devolved Nations crucial to regulatory discussions around deployment and post-market surveillance.
• The findings from this partnership between government, regulators and industry will inform future AI Airlock projects and influence future UK and international AIaMD guidance, including how we work with UK Approved Bodies on UKCA marking and with trusted regulatory partners on international recognition of medical devices.

You can read more about the AI Airlock here.

Source: MHRA

7 June

Proactive monitoring of highest-risk medical device clinical trials

As part of its commitment in the 2019 Action Plan for Medical Devices,the TGA is reviewing the safety information supporting notifications of the highest-risk implantable and cardiac invasive medical devices used in first-in-human clinical trials. Changes have been made in response to feedback from the consultation on proposed regulatory changes for clinical trials of medical devices.  They include:

Clinical Trials Notification (CTN) form enhancements 

The CTN form now includes new mandatory fields to:

1. Better characterise the medical device in the clinical trial, for example:
   • risk classification
   • intended purpose
   • whether it’s an invasive or implantable medical device.
2. Identify first-in-human trials and trials halted overseas for safety reasons. 

There is also a new attachment upload feature, which sponsors are encouraged to use to upload the Investigator’s Brochure (or another equivalent document) to minimise requests for further information. 

These changes came into effect on 5 April 2024. 

The updated CTN form will help the TGA to identify first-in-human trials for the following devices at high risk of immediate, catastrophic consequences if they fail to perform:

• cardiac assist devices (artificial hearts, ventricular assist devices, intra-aortic balloon pumps, cardiomyoplasty devices)
• heart valves and valve repair devices (surgical/percutaneous/mechanical valves, annuloplasty rings, valve repair clips)
• pacemakers and leads
• implantable cardiac defibrillators 
• transcatheter cardiac occluder devices 
• cardiac mapping and ablation catheter devices
• implanted intracerebral/subcortical stimulator devices
• aortic stent and aortic graft devices.

The TGA considers‘first-in-human’ to mean trials in which the investigational device has not been used in humans previously. 

Legislative changes

Legislative changes have been made to:

1. Enable the TGA to require information about the safety of medical devices used in clinical trials. For example, information regarding materials, engineering and sterility.
2. Enable inspection of medical device trials conducted under a CTN, and the documentation supporting them, to make sure they’re compliant with Good Clinical Practice.

The Therapeutic Goods Legislation Amendment (2023 Measures No. 2) Regulations 2023, which included these changes, came into effect on 28 November 2023.

Further information is available at the link below.

Source: TGA

15 March

Companion diagnostics guidance update- public consultation

The TGA is seeking feedback on the updated draft Companion Diagnostics (CDx) Guidance document.

The proposed updates aim to provide sponsors and manufacturers of medicines, biologicals and IVD medical devices further clarification regarding the requirements for companion testing, including:

• A CDx testing identification guide to assist them in identifying whether their medicine or biological indication requires companion testing,
• An introduction to the concept of the ‘companion testing plan’ to recognise the CDx component evaluations undertaken as part of the medicine application.
• Improved clarity on clinical and analytical performance requirements for CDx, and
• Case studies to assist sponsors of medicines and devices on the regulatory process and the technical documentation required for an IVD CDx.

You can respond to the consultation here.

Source: TGA

Consultation start date: 15 March 2024

Consultation end date: 17 June 2024

Ireland

5 June

HPRA Medical Devices Newsletter – Issue 58 – June 2024 published

The newsletter is packed with information provided under the following headings:

• 2024 Regulatory Milestones
• EU Regulatory Updates
• HPRA focus for 2024
• HPRA Updates for Health Institutions – In-House in vitro Diagnostic Medical Devices
• Economic operator registration obligations
• HPRA distributor and importer inspections 2024
• Clinical investigations update
• Published documents

There is information in the newsletter that applies to anyone in the EU working on Medical Devices.

Source: HPRA

24 May

Guide for Health Institutions which Manufacture and Use In-house in vitro Diagnostic Medical Devices in Ireland

The first guide for Health Institutions which Manufacture and Use In-house in vitro Diagnostic Medical Devices in Ireland has been published.

The purpose of this guide is to provide an overview of legislation and key concepts relevant to in-house IVDs. This guide is targeted towards health institutions in Ireland that manufacture and use in-house IVDs. The requirements of the IVDR are described here, including details on when they apply, taking into account national legislation for IVDs (S.I. No. 256 of 2022 and S.I. No 365 of 2022).

Source: HPRA

17 May

Guide to applications for a variation to a manufacturer’s authorisation

HPRA has published a new guide for the above. You can download it here.

Source: HPRA

16 May

Guide to Clinical Investigations Carried Out in Ireland

This guide has been updated. There are changes throughout the document. Here, you can view the track changed (18 Nov 2022) and clean (16 May 2024) versions of the document. The guide:

• provides an overview of the legislation on clinical investigations (CIs) involving medical devices.
• also provides guidance on how to submit applications to carry out CIs in Ireland to the Health Products Regulatory Authority (HPRA).
• is primarily targeted towards CI sponsors (e.g. manufacturers, academic groups, clinical research organisations), who wish to carry out CIs involving medical devices in Ireland. The information may also be useful for ethics committees and other stakeholders.

Source: HPRA

PMDA (Japan)

30 May

Pamphlet published – Develop your innovative medical product in Japan and Bring it to the world

In order to achieve realization of innovative drugs, medical devices, and regenerative medical products, PMDA launched the Regulatory Science Consultations, mainly for universities, research institutions, and venture companies that possess promising “seed-stage” researches or technologies.

During the consultations, advice will be provided on the tests needed in the early product development stage and the necessary clinical trials.

To support this initiative, the PMDA has published a comprehensive 52 page pamphlet entitled Develop your innovative medical product in Japan and Bring it to the world. The pamphlet concerns both of the following types of consultations:

• Regulatory Science General Consultation
• Regulatory Science Strategy Consultation(Pre-consultation meeting+ Consultation)

Source: PMDA

23 May 2024

European Medicines Agency

Questions & Answers for applicants, marketing authorisation holders of medicinal products and notified bodies with respect to the implementation of the Regulations on medical devices and in vitro diagnostic medical devices (Regulations (EU) 2017/745 and (EU) 2017/746)

Revision 4 (May 2024) of the above document has been published. The document has been updated substantially, inclding the following new Q&As:

• 1.3 How to obtain advice on the qualification/classification of my drug-device combination, especially for borderline products?
• 2.4. Can I provide a notified body opinion concluding on partial compliance with the GSPR? What is the scope of the notified body opinion ?
• 2.7. How should I submit minor changes to the terms of the Marketing Authorisation for integral DDC following changes to the device (or device part)?
• 2.8. Will I need to provide a new/updated notified body opinion for changes related to the medicinal product (e.g. extension of indication, new strength, new pharmaceutical form) in an integral drug-device combination?
• 3.2.1 If co-packaged medical devices class I and class IIa, are supplied without an individual packaging and it is not technically feasible to implement the labelling requirements on the device itself, what alternative solutions could be considered to display the labelling requirements?

Here, you can view the track changed (Nov 2023) and clean (May 2024) versions of the document. The blog post entitled The importance of Article 117 of the MDR, for Drug-Device Combination (DDC) products has been updated in line with Revision 4 (May 2024).

Source: EMA

22 May

Revised Q&A for applicants, marketing authorisation holders of medicinal products and notified bodies with respect to the implementation of the Regulations on medical devices and in vitro diagnostic medical devices (Regulations (EU) 2017/745 and (EU) 2017/746) published

Revised Q&A (Rev 4 May 2024) has now been published. Here, you can view the track changed (Nov 2023) and clean (May 2024) versions of the document.

The document will guide marketing authorisation holders, applicants and notified bodies through some of the changes introduced by the medical devices and in-vitro diagnostics regulations. It includes the following:

• insights on integral drug-device combinations and their lifecycle management
• labelling requirements for medical devices co-packaged with medicinal products
• information on the consultation procedures for medical devices with ancillary medicinal substances and companion diagnostics

Further information is available in this blog post.

Source: EMA

2 April 2024

Scientific Advice Pilot for high risk medical devices

EMA is running a pilot that enables the expert panels to provide scientific advice for manufacturers of high-risk medical devices.

EMA invites EU-based manufacturers or their authorised representatives to apply for a third phase of the pilot by 30 June 2024. They can use the following application form:  

• Scientific advice pilot application form

For the third pilot phase, applicants can indicate if they would be willing to have an HTA body observe their project. In such cases, EMA will inform them whether this will be possible.

Source: EMA

Mexico

27 May

Cofepris approves software for cardiac monitoring in smart watches

Cofepris authorized the second software for use as a medical device, which will benefit thousands of patients diagnosed with atrial fibrillation (AF) by alerting about any irregularity in heart rhythm.

• This software , used in a smartwatch, is aimed at people aged twenty-two and older, diagnosed with AF, a condition that includes an irregular and commonly fast heartbeat. When detected early, it can be treated effectively.
• With this tool, patients will receive real-time information about their heart rate, allowing irregular episodes in heart rhythm to be identified. Additionally, the software facilitates ongoing monitoring and recognizes trends in estimated AF burden.
• They will also be able to access data about their lifestyle to understand the impact of their habits on that condition.
• It should be noted that this software is intended for self-care; However, it does not replace conventional methods of diagnosing, treating, or monitoring AF. If irregularities in the heart rhythm are detected, it is recommended to notify specialist medical personnel.
• Cofepris issued this authorization under the equivalence agreement with the US FDA after an evaluation carried out by the specialized ruling team of this health authority, in accordance with the Guide for obtaining the health registration of medical devices .

Source: Cofepris

20 May

Cofepris authorizes first high-tech software for the treatment of myocardial infarction

Cofepris has authorized its first high-tech software that improves the precision and prognosis of the most common treatment for myocardial infarction, marking a milestone in therapeutic innovation in Mexico in favor of the health of millions of patients.

This is the first software that the health authority has authorized as a medical device, which uses an interactive screen that receives, processes and transmits aortic and distal blood pressure signals, providing medical personnel with the ability to personalize treatments and significantly improving patient outcomes.

This authorization was issued based on the equivalence agreement with the US FDA and after the evaluation carried out by Cofepris’ specialized judging team, in accordance with the Guide for obtaining the health registration of medical devices .

Source: Cofepris

European Commission

17 May

Study supporting the monitoring of availability of medical devices on the EU market – 8th notified bodies survey on certifications and applications (MDR/IVDR)

The European Commission’s Directorate-General for Health and Food Safety (DG SANTE) – through the European Health and Digital Executive Agency (HaDEA) – has commissioned a “Study supporting the monitoring of availability of medical devices on the EU market”.

• The study started in December 2022 and will be running for 36 months (December 2025). The study has been contracted to a consortium led by the Austrian National Public Health Institute (Gesundheit Österreich GmbH/GÖG), in collaboration with Areté and Civic Consulting.
• In the context of the study, a dashboard has been developed. The dashboard presents an overview of the data gathered from different stakeholders. In addition, comparable data from previous surveys of notified bodies conducted by the European Commission have been integrated in the dashboard.
• You can view the latest update on the study here.

Source: European Commission

USA

9 May

FDA final rule will include IVDs manufactured by laboratories under FD&C act

The FDA is issuing a final rule to amend its regulations to make explicit that in vitro diagnostic products (IVDs) are devices under the FD&C Act including when the manufacturer of the IVD is a laboratory.

• In conjunction with this amendment, the FDA is phasing out its general enforcement discretion approach for laboratory developed tests (LDTs) so that IVDs manufactured by a laboratory will generally fall under the same enforcement approach as other IVDs.
• This phaseout policy:
  • includes enforcement discretion policies for specific categories of IVDs manufactured by a laboratory, including currently marketed IVDs offered as LDTs and LDTs for unmet needs
  • is intended to better protect the public health by helping to assure the safety and effectiveness of IVDs offered as LDTs, while also accounting for other important public health considerations such as patient access and reliance.

This rule becomes effective on 5 July 2024.

Brazil

8 April

Anvisa will use assessments from foreign regulatory authorities to register medical devices

Anvisa published, in the Official Gazette of the Union this Monday (8/4), Normative Instruction (IN) 290/2024 , which establishes the optimized procedure for the purposes of analyzing and deciding petitions for registration of medical devices.  

With this measure, the Agency now has more agility in the evaluation process of products already approved by equivalent foreign regulatory authorities , consolidating a major step in the adoption of regulatory trust mechanisms.  

The text of the IN stipulates that, as of 3 June 2024, medical devices authorised for markets regulated by four equivalent foreign regulatory authorities (Australia, Canada, the USA and Japan) may have their assessments shortened, based on the requesting companies.

To this end, documents must be presented demonstrating that products intended for the Brazilian market have the same production characteristics, indications and intended use approved by the recognized regulatory authority. 

Source: Anvisa