A surge in premarket submissions during Covid-19 led the FDA to realign its review process for IVDs. Consequently, many device manufacturers need to revisit their regulatory strategies. In this insight piece, guidance is offered from Laurie Clarke, formerly an FDA partner, who now lead’s TSG Consulting’s established medical device regulatory team and works with Sagentia Innovation’s clients to deliver FDA-compliant medical devices across the patient care continuum.

The US Food and Drug Administration’s Center for Devices and Radiological Health (FDA; CDRH) recently outlined how it is prioritising its workload in light of the Covid-19 pandemic. Following a 38% rise in premarket submissions, it has taken decisive steps to ensure submissions for devices intended to prevent, diagnose, or treat Covid-19 (as well as other critical devices) are processed efficiently. This is resulting in delays in some other areas.

Pre-submissions for most non-Covid-19 IVDs will be declined

One of the biggest challenges facing the CDRH is the enormous volume of emergency use authorisation (EUA) submissions and pre-EUA submissions in the in vitro diagnostics (IVD) product space. The urgency surrounding these products means the Agency has only been able to process IVD pre-submissions related to Covid-19 and companion diagnostics or those with a breakthrough designation request or significant public health impact. Now, even as it is clearing the backlog, the CDRH is declining new IVD pre-submission requests for the remainder of 2021 unless they fall into those categories.

This announcement will undoubtedly impact the product development pipeline for many of Sagentia Innovation’s clients. So, what’s the best way forward?

To gain some expert insight on the matter, we spoke to Laurie Clarke from our sister company TSG Consulting. She heads up TSG’s medical device regulatory practice and previously worked as an FDA partner at several large law firms in the US.

How to adapt IVD product strategies

According to Laurie, there are some positive messages to take from the CDRH announcement. For instance, any IVD device that could integrate a Covid-19 diagnostic indication with its offering should reflect this in its pre-submission so the FDA will accept and review it.

The situation for non-Covid-19 IVDs is not as bleak as it might seem either. While pre-submissions are not being accepted, the premarket submission process has been streamlined to eliminate delays. The CDRH is providing applicants with the name and contact details of their lead reviewer within 30 days, rather than the standard 60 days. Laurie believes this could be of great benefit, but she says applicants should use the privilege wisely.

“Obtaining contact details for the lead reviewer after just 30 days represents a great opportunity to start an open dialogue at an early stage in the process. I’d advise any applicants in this position to reach out, make introductions and see if the reviewer needs further information. However, don’t overdo it and don’t make demands. If you do receive questions from the reviewer, aim to address them as quickly as possible.”

It’s Laurie’s view that IVDs which follow a tried-and-tested approach are likely to progress through premarket submission more smoothly than those with new indications or technologies. She advises product developers to take a step back, consider their overall objectives, and think about how they might need to adapt and pivot.

“It’s important to acknowledge the current situation and ensure your regulatory strategy reflects it. This is especially true if your product would not qualify for the ‘COVID review queue’ meaning the FDA will not accept a pre-submission for it this year.

“Under normal circumstances, pre-submission is a great vehicle for obtaining FDA feedback on a proposed regulatory plan. One advantage of this approach is the opportunity to meet with the FDA regarding the Agency’s written feedback on the document. However, these are not normal times. Waiting until 2022 to submit a pre-submission and hoping that the Agency will resume such meetings threatens to delay the device development process. It could also increase the risk that the device, as designed, will not meet FDA requirements and/or that testing will not yield the performance data needed for its evaluation.”

Alternative ways to gain FDA feedback

Laurie advises companies to think carefully about whether FDA feedback is critical at certain stages of the development process. If so, she says to consider whether a pre-submission is needed to obtain it.

“If the type of premarket submission your device requires is clear, and you know what data (bench, animal, or clinical) the FDA expects it to contain, then proceeding directly to the submission continues to be a reasonable approach. If that is not the case, you might consider whether there are other ways to obtain FDA feedback. For example, you could submit a 510(k) to determine whether your device requires de novo review, especially if you have a plausible substantial equivalence argument. The FDA has identified this as an alternative to the pre-submission/de novo path. Another route is to request breakthrough designation (if your device meets the criteria) to determine the type of premarket submission required.” 

Laurie says these alternatives offer the additional potential benefits of shorter submissions and review times if the FDA clears the 510(k) or at least determines that the device qualifies for a 510(k) review. Another benefit is a more interactive review if it is designated as a breakthrough device. 

In general, it takes longer and costs more to obtain FDA clearance or approval for a device with new or ‘risky’ indications and/or innovative features or functions. This is because they often need clinical data and require more intensive review. However, such devices are generally more marketable than ‘me too’ devices. Some companies opt to seek initial clearance or approval for the basic version of a device to obtain marketing authorisation and begin generating revenue as soon as possible. They then seek additional clearances or approvals for subsequent versions of the device. This approach is especially attractive to those with limited resources. However, the cumulative review time may be longer so a single submission for the ‘ultimate’ device might be more appealing.

Aligning device design and regulatory strategy

It’s clear that the CDRH is working hard to meet the unprecedented need and demand for its scientific and regulatory expertise during this public health crisis. Work related to Covid-19 remains a priority, but the FDA is taking measures to ensure that submissions for non-Covid-19 products also proceed as smoothly as possible. At Sagentia Innovation, we’re working closely with Laurie to ensure that our clients and internal teams understand the regulatory challenges that the current situation presents. We’re also suggesting ways to overcome these challenges through the development and implementation of regulatory strategies that meet clients’ individual needs.

Laurie concludes: “With everything that’s happened over the past 18 months, it’s reassuring to see such high levels of medical device innovation. Product development has accelerated to such a degree that the FDA had to change the way it works, and therefore we have to adapt too. Ultimately, we’re all focused on a common goal, improving access to products that protect public health.”

Laurie is available for consultation via Sagentia Innovation. Contact us if you’d like to arrange a session to discuss how your medical device development strategy could adapt in line with the CDRH’s revisions.

The full article outlining CRDH’s response to the pandemic workload is available here.