Posted on

Performance Evaluation: The critical component in bringing your product to market and keeping it there

Abingdon Health and IVDeology Ltd have decades of  In-Vitro Diagnostic (IVD) regulatory compliance experience where our teams support your entire product journey from ‘cradle-to-grave’ to ensure you are getting your product to market in the quickest timeframe possible, reducing cost and strain, and keeping it compliant through its lifetime.

Abingdon Health also offer full-service contract development and manufacturing for lateral flow assays, bringing your idea to commercial success, with the benefit of an integrated regulatory and quality approach.

In our latest blog, Candice Vendettuoli Head of RAQA at Abingdon Health covers the importance of getting your Performance Evaluation (PE) right to streamline your route to market, and ensuring compliance to keep it there.

What is Performance Evaluation?

The In Vitro Diagnostic Regulation (IVDR) 2017/746, which entered into force in May 2017 and applied in May 2022, has introduced significant changes to the way in vitro diagnostic (IVD) medical devices are regulated in the European Union. One of the key aspects of this regulation are the new requirements for documenting the performance evaluation of IVD medical devices using a prescriptive document structure mandated within the Regulation.

Performance evaluation under IVDR is expected to be a continuous process throughout its entire lifecycle of the device. This process is crucial for ensuring that the device meets upon entry to the market, and continues to meet, the intended clinical benefits and safety as claimed by the manufacturer.

The mandated documents should be written to provide a comprehensive and structured narrative for the reviewer giving a clear and logical explanation of how the device was developed, verified and validated against the intended use/purpose claimed by the manufacturer. These documents are a requirement of the Technial Documentation described in Annex II and forms an essential part of the submission to the Notified Body

The mandated documents, unless they can justify why such studies are not applicable are as follows:

Performance Evaluation Plan

Ideally written during the early development of the device and updated regularly, this document has content prescribed within Annex XIII section 1.1 of the Regulation. Manufacturers are required to establish and regularly update the performance evaluation plan that outlines the device’s characteristics and performance, as well as the process and criteria used to generate the necessary clinical evidence.

Scientific Validity

The concept of scientific validity under the In Vitro Diagnostic Regulation (IVDR) 2017/746 is a cornerstone in the performance evaluation of in vitro diagnostic (IVD) medical devices. It refers to the association of an analyte with a clinical condition or physiological state, which must be substantiated with a medical-scientific rationale evidenced through a systematic literature search

Analytical Performance

Analytical performance refers to a device’s ability to accurately and reproducibly measure an analyte, marker, or molecule, which is a strictly technical performance without the need for correlation with a targeted pathology.  There are analytical performance characteristics mandated within Annex I section 9.1(a) including assessing the accuracy, sensitivity and specificity,

Clinical Performance

Clinical performance is defined as the ability of a device to yield results that are correlated with a particular clinical condition, physiological or pathological process, or target population and intended user. Manufacturers must demonstrate clinical performance through one or more of the following:

  • Clinical performance studies, carried out according to the IVDR requirements on clinical performance studies described in Articles 57-77, Annex XIII section 2 and, if applicable, Annex XIV for studies other than those using leftover samples
  • Scientific peer-reviewed literature on the device under evaluation, or
  • Published routine diagnostic testing.

Performance Evaluation Report

The report (also known as a ‘PER’) provides a summary of the clinical evidence collected through the previous reports. An assessment can then be made against the current state of the art in diagnostics and medicine that a positive benefit-risk ratio of using the device for its intended purpose has been met and then all data has been collected.

This rigorous approach ensures the reliability and effectiveness of in vitro diagnostic devices within the European Union, with the primary aim of protecting public health by requiring high levels of safety and performance of these devices to be evidenced.

For manufacturers, understanding and adhering to the IVDR’s performance evaluation requirements is vital for successful market introduction of their IVDs in the European Market. It involves a comprehensive understanding of the general safety and performance requirements (GSPR), as well as the specific guidelines on performance evaluation stipulated in Article 56 of the IVDR.

Abingdon Health and through its subsidiary IVDeology Ltd , can offer support and guidance to help companies navigate these new and complex EU Performance Evaluation requirements.

We offer a full-service solution for all your regulatory and quality requirements including:

Contact Us today to book some time with one of our industry experts to understand how we can support you bringing your product to market and keeping it there.


 

Posted on

The MedTech Summit: A reflection

The IVDR journey is a long and difficult path but look how far we have come. Stuart Angell, Managing Director and co-founder of IVDeology attended this years 2024 MedTech Summit in Brussels and shares his thoughts below on the event as it happened.

I was lucky enough to attend the annual MedTech Summit in Brussels this week. I have now attended this event either in-person or virtually since 2019 and the event continues to provide enormous value to regulatory professionals in the medical device and IVD sector.

I was asked to chair the in vitro diagnostic medical device (IVD) track on day 2, including presenting on the regulation of IVDs in the United Kingdom; and I also listened intently to great presentations on the current US (FDA) and European (IVD Regulation (IVDR)) regulatory landscape.  Suffice to say there is a great deal of positive change and complexity; and it was great to get a refresher on the current state of play!

Here are my overall thoughts on the event.

1) The UK remains a key market of interest

Much of my focus this year has been on the regulation of IVDs in the UK, including the utilisation of international recognition, and the domestic under UKCA marking.  I remain a strong advocate of the benefits of UK market access, and the potential for the UK being a world leader in the regulation of IVDs and medical devices. The UK medical device market is worth over €17 billion per annum and potentially offers a route to early adoption of new IVD technology; and it was encouraging to hear the overwhelming support and interest in the UK. The International Recognition is generally considered a positive and progressive step, however, there continues to be uncertainty in the domestic UKCA mark, and its role in global recognition.

2) The US offers a higher degree of certainty; IVDR remains in transition but will come good

This year had much more focus on US Regulation, and with good reason! While the IVDR continues to be implemented, the US is now considered a stable and predictable choice for market access. However, the US 510(k), De Novo and PMA routes should never be seen as an easy route to market. It still requires a great deal of effort to effectively achieve compliance.

For the last few years, l have been highlighting the challenges of IVDR, and the ongoing infrastructural issues that is making the uplift to IVD Regulation from IVD Directive so challenging. While many questions remain, I am taking this opportunity to reflect on the progress that has been made. Ask yourself: “what do I know now about IVDR than I did 12 months ago?” – The chances are quite a lot! So as an industry, we are all heading in the right direction albeit with many miles still to go.

3) We should all encourage and support structured dialogue

One of the challenges with the IVDR is the inability for Notified Bodies to offer advice and consultation.  This has cut off access to technical experts who may have been utilised to provide essential feedback on how to compile and construct technical documentation and performance studies. Developing a structured process for engaging with Notified Bodies, offers a chance for early dialogue on how to successfully achieve compliance. This is especially important for SMEs, or novel devices where the route to compliance is less well understood. Similar models have been employed as part of the US FDA Pre-submission process, and more recently, the UK MHRA IDAP Pilot.

Building this into the IVDR process would allow greater clarity to the industry, making IVDR more understood and ultimately lead to a higher chance of success.

In recent years (and I am guilty of this), we have pointed the finger at what is wrong with IVDR be it lack of guidance from the commission, resources from the Notified Body, or the inactivity of Manufacturers. And yes, some challenges remain, but what I am noticing this year is the desire to bring all stakeholders together to understand areas of weakness and opportunities for improvement which we can all learn from.

One key takeaway for me is the challenges of dealing with the regulatory complexity. This is a challenge for the largest multinationals dealing with a variety of products at different stages of their lifecycle; but also, for SMEs looking to launch one or two products; and considering which markets; and whether to manage the process internally or outsource. Certainly, managing the regulatory process, including post-market surveillance, has become more complex under IVDR; and outsourcing this has got to be a serious consideration; the positive is that these requirements are increasingly aligned across the UK, EU and the USA.

Overall, we all have a part to play in ensuring new innovative products get to market in the UK, Europe and the US; and improving health outcomes. Whilst the recent years have been challenging there is light at the end of the tunnel which should being to offer more certainly and more alignment of regulatory requirements across these jurisdictions which should be a real positive development. So, while the road remains long and challenging, why not take a moment to look back and see how far we have come.

IVDeology’s team has over 30 years’ experience supporting customers on quality assurance and regulatory compliance within the medical device and IVD market.  IVDeology’s services include supporting customers on regulatory filings in a range of territories including EU CE-marking (IVDR), USA (FDA), UK (UKCA) and other jurisdictions, including technical file build, regulatory submissions, regulatory gap analysis, analytical and clinical performance evaluation.

Stuart Angell, Managing Director, IVDeology

We also provide a range of quality assurance services including quality management system (QMS) build, QMS audit and full outsourcing or remote management of QMS systems. We also can be your UK or EU Responsible person.  If you would like to discuss any specific requirements, please contact IVDeology’s highly experienced team or click here.


 

Posted on

Role of the UK Responsible Person and the importance for future regulations

Following on from the Statement of Policy intent on international recognition of medical devices released by the MHRA on 21 May 2024, it is clear that the role of the UK Responsible Person will still be important in the future regulations for the UK.  This will be irrespective of whether devices will be placed on the market under the UKCA mark or using one of the recognition pathways from a comparable regulator country (CRC).

A UK Responsible Person (UKRP) is “a person established in the United Kingdom who acts on behalf of a manufacturer established outside the United Kingdom in relation to specified tasks with regard to the manufacturer’s obligations under these regulations.”

There has been a requirement for non-UK medical device & IVD manufacturers to appoint a UKRP in order to place their devices on the Great Britain (England, Wales & Scotland) market since the beginning of 2021. 

A letter of designation must be created and signed by both the manufacturer and the UKRP to officially appoint the UKRP to act on behalf of the manufacturer.  This letter is required to be uploaded as part of the registration process with the MHRA.

The UKRP responsibilities include:

  • ensuring that the declaration of conformity and technical documentation are correct and available if required by the MHRA
  • register the manufacturer, device and any importers with the MHRA
  • liaise with the MHRA for any requests of documentation, samples of devices and with regards to any preventative or corrective actions
  • inform the manufacturer of any complaints or any incidents related to the device
  • terminate the agreement and inform the MHRA if the manufacturer does not comply with the regulations

Selecting your UK Responsible Person should take careful consideration.  It is important that manufacturers appoint someone with the right experience to help with this process.  The manufacturer needs to be confident that the UKRP will be fulfilling their obligations on the manufacturer’s behalf and consequently the UKRP should be considered a critical supplier.  It is important that the manufacturer is assured that if there is a vigilance case identified on the Great Britain market, the UKRP knows how to engage with the MHRA and will communicate the issue in the correct time scales. The manufacturer also needs to be assured that the UKRP can assist with post market reporting and may also deliver regulatory updates which may affect the ability to continue to place devices on the Great Britain market. 

This especially will become more important as the new regulations come into effect.  The government responses to the consultation on the future regulations released in June 2022 indicates that a “Qualified Person” would be required to be permanently and continuously at the disposal of a UKRP.  This “Qualified Person” would need to meet minimum qualifications and/or regulatory experience in the field of medical devices or IVDs. This role is expected to be similar to the Person Responsible for Regulatory Compliance (PRRC) for the IVD Regulation and therefore it will be important for manufacturers to ensure that the selected UKRP can fulfil this requirement.  The UKRP name will also need to be included on the label, although this may be via over-labelling and the MHRA are also investigating the possibilities around digital labelling.

At IVDeology we offer a UK Responsible Person service.  We currently have a number of different customers from across Europe and the US and between them we have registered 489 products with the MHRA to date.

Our onboarding process involves the appropriate contract and letter of designation, followed by a technical review of the devices to be registered by one of our team.  Once confident that everything is in place, the manufacturer and devices are registered with the MHRA.  The process can and has been completed very quickly when a complete technical file has been provided to us for review.

One of the biggest challenges we have faced is around GMDN codes.  The MHRA registration process utilises GMDN codes to register the devices.  Often this has not been considered by manufacturers or the selected codes haven’t been reviewed to ensure that they are still current and appropriate for the device in question.  This can often lead to a delay in being able to register and ultimately placing the device on the UK market.

As a UKRP, we also provide Post Market Surveillance reports for our customers annually and keep them updated with any new relevant information released from the MHRA on future regulations.  This will be more important as the Post Market Surveillance is implemented and also to ensure that our UKRP customers continue to meet the changing regulatory requirements for the UK.

In summary, to place medical devices or IVD’s on the Great Britain market, there is already an established requirement to have a UK Responsible Person.  Whilst currently there are limited restrictions on who this person can be other than they have to be based in the UK and many manufacturers have enlisted their distributor or a UK office to fulfil this role, moving forward it will be more important to ensure that the UKRP that you have selected has the right level of expertise and experience to help support you place your device on the Great Britain market.

You can find out more about our UK Responsible Service here or book a call with one of our team.


Written by Regulatory Specialist Fiona Thompson, IVDeology Ltd and IVDeology UKRP

 

Posted on

Consultation on UK Common Specifications

On the 21st May 2024, the Medicines & Healthcare products Regulatory Agency (MHRA) launched a consultation on common specification requirements for invitro diagnostic devices. The aim of this consultation is to gauge industry opinion over a 4 week period on introducing common specifications requirements for certain high risk IVD devices placed on the Great Britain (GB) market.

What are common specifications?

Common specifications (CS) set out a minimum set of performance requirements for specific high risk IVDs, principally to ensure a higher level of patient safety. These common specifications will replace the existing ‘Common Technical Specifications’ described under the current Medical Device Regulations (UK MDR 2002).

The consultation asks the following questions:

  • Should GB common specifications align with the European equivalent, as set out under (EU) 2022/1107
  • Should monitoring for common specifications be included within a Post Market Performance Follow-up Plan (a key document to describe post market performance data collection)?
  • Should Covid-19 IVD devices meet a common specification rather than meet the existing CTDA requirements?

The consultation is an opportunity for industry to offer a view on how aligned GB common specifications should be to the EU. In addition, feedback can be given for the potential removal of the much-discussed CTDA process, which could mean that Covid-19 IVD devices will undergo the general process for conformity assessment via UK approved bodies.

You can submit your views and include comments on the consultation here. The consultation is due to end on the 18th June, so I would encourage any interested parties to submit their views – this is an opportunity to shape the way CS are used in GB.

As a UK provider of quality and regulatory services, IVDeology are proud to engage with the IVD diagnostic keen to support IVD manufacturers on IVD market access. For further information on how we can help, please contact [email protected]

Written by Stuart Angell, MD and Co-founder of IVDeology Ltd and IVDeology UKRP Ltd

Posted on

EU IVDR Transition Update 2024

IVDR Transitional Provisions – Something had to give!

On the 23 April 2024, the European Parliament unanimously approved the proposal to amend the EU MDR (2017/745) and IVDR (2017/746) regarding the gradual roll out of Eudamed, information obligation in case of interruption of supply and the transitional arrangements for certain in vitro diagnostic medical devices (IVDs).

The amendment has been requested by industry to ensure continued access to critical diagnostic products, essential for a smooth running European healthcare system, and offering a hight level of protection to patients and users of diagnostic tests.

Why was change needed?

The IVDR has applied for placing IVDs onto the EU market since 26 May 2022, replacing the existing IVD Directive 98/79/EC, this required that all devices, including legacy devices, must meet a higher level of regulatory compliance. In January 2022, the European Parliament and Council adopted an extension to the transitional arrangement, with extended timelines based on the risk classification of devices:

Risk ClassCurrent deadlines for compliance
Class D (Highest Risk)26 May 2025
Class C26 May 2026
Class B, Class A Sterile26 May 2027
New devices, Class A (Lowest Risk)26 May 2022 (No extension)
Devices used in Healthcare Institution26 May 2028

The original transitional extension was intended to ease the pressure on implementation issues and delay experienced with infrastructure (including Eudamed), Notified Body availability and manufacturing readiness, all of which were impacted by the Covid-19 outbreak.

While the transitions had allowed some breathing space, the industry is facing an uphill struggle to be ready to meet these dates.

What is changing?

  1. Further transitional extension for some devices

With the exception of legacy devices that do not require conformity assessment (Class A and devices used on Healthcare Institutions), additional time is being added to the transition time for IVDR, and existing devices can continue to be placed on the EU market until the following dates:

Risk ClassCurrent deadlines for compliance
Class D31 December 2027
Class C31 December 2028
Class B, Class A Sterile31 December 2029

To use these timelines however, manufacturers must comply with certain conditions including:

  • The devices are CE marked under the IVD Directive,
  • There are no significant changes to the design or intended purpose,
  • A Quality Management System compliant to IVDR shall be put in place by 26 May 2026,
  • A formal application shall be lodged with a notified body 2 years prior to the dates above.

2. Bringing forward the mandatory use of Eudamed

The Eudamed database includes seven electronic elements including UDI, Vigilance and Market Surveillance. The earlier mandatory use of some Eudamed module would offer an enhanced adoption for this critical element of IVDR deployment.

3. Prior notice if supply of IVD is stopped

To reduce the risk of device shortages, the proposal includes a requirement whereby Manufacturers are required to inform their relevant competent authority and health institutions if there is a temporary, or permanent interruption in the supply of their IVDs, especially if there are few or no alternative products, or where there is a risk of serious harm to patients or public health.

How will this impact industry readiness to IVDR?

The proposal offers a short term solutions for the current state of readiness in the industry for IVDR, especially for Class D devices, which often include low volume, but highly critical diagnostics which were at risk of not meeting IVDR compliance before the deadline of May 2025.

The proposal also encourages an increased usage of Eudamed, which has seen low adoption (caused in part by the delays to each module) by manufacturers within the UDI and Devices module.

In a wider sense, the commission is trying to mitigate the risk of supply shortages as a result of the IVDR transition, although it is currently up to the manufacturer to determine the severity of risk to supply for their products.

Don’t delay

The proposal allows a collective sigh of relief, allowing the industry more time to prepare the technical documentation and engage with a notified body. However in reality, the additional timelines do not offer time to pause. The additional 2 year delay allows the completion of the conformity assessment process, it does not provide any further time for getting the QMS ready for the IVDR. The amendment also allows manufacturers to also ensure their clinical evidence is compliant as we know that legacy devices require additional performance testing before they are IVDR compliant.

In the long term it remains to be seen how significant this amendment will elevate the challenges facing the industry as they transition from IVDD to IVDR. It remains to be seen to what extent the industry will be ready in another 2 years time.

While this should be seen as a positive, we would encourage Manufacturers to press forward with their IVDR transition planning now. For more information on how IVDeology have supported our customers achieve IVDR compliance, contact [email protected].

Note: This blog contains a summary of the key changes within the proposal, it is important that Manufacturers read and understood the proposal in full, and get independent legal advice if required.

Posted on

New Regulations Amendments for IVD’s in Northern Ireland

Under the terms of the Windsor Framework, the rules for placing devices on the Northern Ireland market have been different from the rest of Great Britain.  For IVDs, these rules have followed the EU In Vitro Diagnostic Medical Device Regulation (IVDR) 2017/746 since its date of application of 26th May 2022.

A Statutory Instrument (SI) 2024 No. 221 The Medical Devices In Vitro Diagnostic Devices etc. Amendment Regulations 2024 has now came into force as of the 21st March 2024 which enables the IVDR to be fully implemented within Northern Ireland.

This SI sets out the requirements that can be determined according to the IVDR by the competent authority such as fee structures and enforcement provisions.  It also amends other domestic legislation to reflect that IVDR applies in Northern Ireland.

It also:

  • appoints the MHRA as the authority responsible for Notified Bodies,
  • includes the requirements for documentation to be provided in English
  • sets out the requirements for performance studies within Northern Ireland
  • the provision that an IVD testing for SARS-CoV-2 that complies with the EU common specification does not require the separate CTDA approval from the MHRA
  • the requirement for the UK(NI) mark to be affixed if the conformity assessment for CE marking has been completed by a Notified Body established in the UK.
  • The provision for continued unfettered access for Northen Ireland traders to place devices on the GB market with no additional barriers providing the devices meet the requirements of the IVDR and are Qualifying Northern Ireland Goods.

So if you are either a manufacturer that sells into Northern Ireland or based in Northern Ireland, it is worth making sure that you fully understand the requirements set out in the above SI as it is now in effect and how they impact your organisation.

More details can be found at Regulation of devices in Northern Ireland – GOV.UK (www.gov.uk) or you can reach out to us and we’d be happy to have a chat.