Tag: 510K

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US IVD Classification – How different can it be?

IVDeology have decades of IVD (invitro diagnostics) compliance support experience within the Quality and regulatory industry, with backgrounds from microbiology to lab based experience, and recently becoming part of the Abingdon Health PLC to offer a more holistic range of services from cradle to grave of diagnostic products. Co-founder and Director of training Nancy Consterdine talks about the US classifications of devices, having worked recently with US 510K submissions including pre-submissions.

The Global Harmonisation Task Force (GHTF) published their classification guidance in June 2006 proposing a risk based, 4 tier classification system for In Vitro Diagnostic Devices. This guidance has been widely used since 2006 for new regulatory systems being set up around the world e.g. the IVD Regulation in Europe 2017/746.

However, the United States of America (US) had already introduced a 3-tier risk-based classification system back in 1976 with the amendments to the Food, Drug and Cosmetics act (FD&C) to include medical devices. This system has now been in place for 48 years, despite amendments having been made around the regulatory pathways e.g. introduction of the 510K De Novo program, enacting of the Small Business Determination program and electronic submission processes. So, how does the classification system work currently and what are the future changes that the FDA are proposing?

Figure above shows class |, || and ||| and risk (explained below)

Class 1

  • Low to Moderate Risk devices e.g. Transport culture medium, immunoelectrophoretic equipment, Biological stains
  • Subject to General Controls (Regulatory Requirements which apply to all medical devices) all covered under a quality management system:

    – Registration of producers of medical devices.
    – Notifications and other remedies e.g. recall.
    – Records and reports on devices e.g. adverse event report.
  • Manufacturers are still visible to FDA and may be subject to audit.
  • Devices may be exempted from a General Control as stated in the classification regulation for that device e.g. they may be exempt from GMP other than keeping records and complaint files.
  • Devices are submitted via the 510K pre-market notification process but some are exempt.

Class II

  • Moderate to High Risk e.g. Blood Culture Assay, Rubella ELISA Test
  • Subject to General Controls and Special Controls:
    – Device specific
    – Evidence of meeting performance standards
    – Post market surveillance
    – Adherence to guidelines
    – Special labelling requirement
  • General Controls are considered insufficient to provide assurance of safety and effectiveness.
  • Devices are submitted for pre-market notification via 510K process.

Class III

  • High Risk e.g. Cancer Biomarker companion diagnostic assay
  • Subject to General Controls and Premarket Approval:
    – Quality Management processes and controls
    – Software design, development and cyber security
    – Analytical Verification data
    – Clinical Performance Data
  • Pre-Market Approval (PMA) application is required

Recent Developments

In January 2024, a press release from Jeff Shuren, the director of the Centre for Devices and Radiological Health (CDRH) announced the intent to initiate the reclassification process for most IVDs which are currently class III (high risk) into class II (moderate risk). They identified that the majority of these tests are infectious disease and companion diagnostic IVDs. This is in line with the FDA least burdensome approach allowing manufacturers of some devices to seek marketing clearance through the 510K premarket notification route. In the release it also talked to the FDA desire to encourage more manufacturers to develop the test and in turn increase competition and access to these important tests.

The process of reclassification has already started with a panel meeting in September 2023 identifying 3 types of infectious disease diagnostic IVDs

  • Nucleic acid and serology based IVDs to aid diagnosis of Hepatitis B Virus infection and management of infected patients.
  • Serology based IVDs for detection of human parvovirus B19.
  • Cell mediated immune reactivity IVDs to aid identification of in vitro responses to peptide antigens associated with TB infection.

Conclusion

The IVD industry can only welcome these moves by the FDA in conjunction with the amendment of the Quality Management System regulation (QMS) to be more closely aligned to the ISO 13485:2016 standard. It makes the USA a far more inviting prospect for initial market authorisation applications. The costs are transparent, the timelines are clearly identified and there is a process in place to present and discuss the device with the FDA in a pre-submission meeting.

There are however other considerations that need to be taken, Jeff Shuren has recently announced his retirement and Dr Michelle Tarver will assume the role of CDRH Acting Director. Also, there are presidential elections this year, will these changes impact the current trajectory of the CHRH? We at IVDeology will continue to monitor the situation across the pond, it is evident that since Brexit the UK government has been eager to foster recognition of other regulatory body approvals and it does feel that the movement of the FDA approval process is going in the same direction as that of the UK MDR.

Next steps to consider, and how we can help.

IVDeology Ltd can support with all of the above, please contact us for a friendly conversation to identify how we can support you with your compliance journey via our contact page

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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.

 

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Laboratory Developed Test regulation – how the US FDA has moved on since 1976


Laboratory Developed Tests (LDT) have been used for decades. However, it is clear that regulatory authorities have seen the misuse of these tests. They are now moving to close the loopholes in regulation that have exploited over the years and the implementation of the European IVD Regulation (2017/746) introduced those controls.

On 29 April 2024, the US FDA published the Final Rule amending the US Food, Drug and Cosmetic Act (FD&C). There are two main purposes for this update:

• To formally identify that IVDs are devices under the FD&C Act, including if they are manufactured in a laboratory but updating the definition of an IVD.
• To phase out the general enforcement discretion approach for LDTs over 4 years. This means that they will now generally fall under the same regulation and enforcement approach as other IVDs.

This update was long overdue, curiously the last time LDTs had been considered was under the Medical Device Amendments of 1976 which amended the FD&C act to ensure the regulation of devices intended for human use. Since then, the FDA has exercised enforcement discretion for LDTs meaning that laboratories designing and manufacturing LDTs did not need to comply with those requirements.

Exceptions to the Rule

The change in rules do not apply to all devices, the following exemptions have been included for some circumstances:

LDTs marketed before Final Rule was published on 06 May 2024

  • Laboratory must still have Medical Device Reporting in place.
  • Must have Establishment and Device Listing in place.
  • Must comply with record keeping requirements.

Tests meeting unmet needs, Nonmolecular antisera LDTs

  • Record keeping requirements must be followed.
  • Other aspects of QMS are expected.

Understanding the Transitional Timelines

The transition will be a graduated process over the next three years. It is important that manufacturers understand what changes are expected, and when they are required.

Conclusion

Bringing LDTs under regulatory control can only be a good thing, the increase in high-risk, high-volume tests being offered to the public e.g. cancer risk prediction under LDT umbrella has forced regulators to act. There is no doubt that the future enforcement of regulatory controls will mean increased costs and resource requirements for those laboratories manufacturing LDTs in the US.

Unlike the EU IVD Regulation, it is clear that the FDA is using a less burdensome approach providing exceptions to the requirement to formally submit applications and wait for approvals if the LDT was already on “on market” before 06 May 2024. This does seem to be their current direction of travel in that they are actively seeking to down classify devices from PMA to 510(K) and to implement ISO 13485 to align Quality Management System requirements going forward.

Control is clearly moving to laboratories offering this type of test having QMS procedures in place to ensure that records are kept, and traceability is maintained. Oversight will be delivered with quality audits identifying issues and Medical Device Reporting highlighting issues to the FDA. The FDA will have the ability to show up on the doorstep of any facility they believe is having issues and this may be identified via market surveillance and/or patient/physician reporting of issues.

Next steps to consider and how we can help

IVDeology Ltd can support with all of the above, please contact us for a friendly conversation to identify how we can support you with your compliance journey by clicking here

By Nancy Consterdine, Co-founder and Director of Training at IVDeology Ltd and UKRP