By Jeff Overley

Law360 (August 7, 2020, 6:50 PM EDT) -- In this edition of Coronavirus Q&A, a leader of Hogan Lovells' medical devices team discusses school reopenings, client frustrations with a heavily burdened U.S. Food and Drug Administration, and mounting problems with COVID-19 testing volume and turnaround times.

Randy J. Prebula, a partner in Washington, D.C., is a co-director of the firm's FDA medical devices and technology practice. He advises a wide array of companies that are in the business of shoring up supplies of personal protective equipment and developing tests for the novel coronavirus.

Prebula, who has an undergraduate degree in biology, shared his perspective as part of a series of interviews Law360 is conducting with prominent attorneys regarding the evolving legal and regulatory challenges of the COVID-19 pandemic.

This interview has been edited for length and clarity.

What COVID-19 issues are you working on most for clients right now?

We are working on a whole series of issues on COVID-19 right now. In vitro diagnostic tests of all kinds. That includes the molecular tests, the antigen tests and the antibody tests. And for every imaginable use — from asymptomatic screening to symptomatic diagnosis to population surveillance testing to assessment of the ability of antibodies to neutralize the virus. If there's a diagnostic test of any kind relating to COVID in any context, we're working on it.

Outside of testing, we work a lot on personal protective equipment, and the reprocessing and sterilization of personal protective equipment — how to get the PPE to people, and then how to reprocess and sterilize the PPE so it can keep being used.

PPE shortages were a big problem early on, then not such a big problem, and then more of a problem again after cases began surging in June. Where do things stand now?

There are concerns being reignited there. Early on in an emergency like this, FDA takes more risks, because they have an immediate need. Later on, they start to focus on the additional science and data they need, and how they can make sure that products are truly safe and effective.

But as they get more strict and ask for more, they have to be cognizant of the fact that the situation might change again, and PPE is a good example of that.

They had the luxury of not accepting as many KN95 masks as they did before, or of limiting the number of reprocessors for sterilization of masks, because the needs were being met. But when the emergency ramps back up, the agency has to be willing to say, "Hey, I got a little too strict, and now I have a problem getting the product out there that's really needed."

I did just get an email from FDA saying that they're issuing an umbrella [Emergency Use Authorization, or EUA] process for surgical masks, specifically related to concerns about insufficient supply and availability of disposable, single-use masks. It literally just came across my inbox. So maybe they are going to be responsive. But I generally see that they have a harder time adjusting to heightened risks after they started to ask for more data than usual.

Your point is maybe still fair. We're almost two months into this second wave.

Exactly. We're two months into the second wave, and if they're just now starting to say, "Hey, maybe we need to do something here," it's a question worth looking at.

There have recently been extensive delays in processing COVID-19 tests. I actually got negative results back today after waiting 19 days. What's your sense of the situation?

I think FDA has recognized that as a risk, and they have incentivized ways of getting more rapid testing available. And seven states just announced a consortium that is trying to encourage the development of rapid tests.

To increase the amount of rapid testing is really, really important. We started by having laboratories run their own tests at the beginning of the emergency. And then we added in vitro diagnostic tests that can be run in laboratories. That was followed by allowing people to collect samples at home and send them in to labs. All of those things were funneling more people into testing without really fixing the back end of the pipeline, which is, how fast can you test them?

And now the efforts are being placed on testing more rapidly and in more locations. That's the next wave. I would imagine sometime in the next month to two months, we're going to start to see approvals that will significantly reduce the timeline.

So you don't expect a big improvement quickly?

I'm fairly comfortable that the entities that are currently doing testing are always looking at ways under their Emergency Use Authorizations to improve the throughput and reduce the time. I'm positive they're working on that, and I would expect to see incremental changes there.

Whether that's by increasing the instruments that are used, or the number of samples per plate, or pooling samples together. If you have a high enough incidence of negative samples, and a low enough incidence of positive samples in the general population, pooling is a really effective way to reduce your timeline because you're testing pools of four, five, 10, whatever it may be that's authorized. And then if you get them all negative, well that's it, you move forward.

All of those things are going to reduce the timeline, but I don't think any of those things alone is going to get the timeline reduced from 19 days to as little as one or two. But having hundreds of thousands, if not millions, of near-patient, non-laboratory, prescription or non-prescription instruments out there that can run in 30 minutes or an hour, and then you get the result, that's going to have a huge change in the timeline.

Could delays make the FDA more willing to authorize certain tests in order to add capacity?

It's a good question. I think we're going to continue to see unexpected approvals and authorizations.

Nobody expected FDA to approve pooling as rapidly as they did. To gather enough data to prove that your pooling system works is usually not something that's done overnight. To me, that means that either somebody really had a lot of insight into what data they needed to [demonstrate accuracy], or that the FDA's template [describing what data are required for an EUA] was developed while people were already in review and already discussing it with FDA, which is really appropriate.

And nobody expected FDA to approve asymptomatic screening as fast as they did. Asymptomatic screening requires that you demonstrate that a test is really sensitive, [meaning it doesn't generate too many false negatives], and many of the tests that were originally authorized were very sensitive. So it may have been they were able to leverage their existing data.

Testing volume declined almost 10% in the past week, according to the COVID Tracking Project. At the same time, fewer infections were being reported. What are the implications if volume doesn't pick up again soon?

The decline in testing is not happening because people don't need testing — they do, and probably more people need testing. [One issue] may be that more people are getting frustrated that they're not going to get a timely result. If you tell somebody they're not going to get a result for 19 days, then they may just monitor their symptoms.

I see that as a problem. From an epidemiological perspective, reduced testing is a nightmare. The less we know, the harder it is to control things.

I've spoken with attorneys who are concerned about the FDA's ability to manage its workload and efficiently review approval submissions amid this crisis. What's been your experience?

The response times from FDA on actual submissions are taking longer than they did earlier. And that's probably a factor of how busy they are. Having to wade through 200 submissions is different than wading through 2,000 submissions. That's got to be hard.

But what I'm more worried about is the tendency we're seeing for reviewers to say, "Follow the template." A company will then say, "My technology doesn't exactly fit that template. I really need a technical discussion with you to give you optimal data." And FDA says, "Well, I can't review your submission because I don't have optimal data. But I can't talk about it because I'm too busy."

If they're not willing to have a dialogue, they're going to get poorer submissions. I know it's hard because if they spend all their time having dialogues, they don't have time to do reviews. But if they don't invest a little time every day into dialogue with manufacturers, then they'll get poorer and poorer submissions. It makes it really hard to give the agency what they need if you need clarification and they're not willing to give it to you.

I know you've followed testing of asymptomatic patients and surveillance testing of specific sets of patients. Talk about those approaches.

I think that asymptomatic surveillance testing is absolutely going to be essential if we want to protect critical infrastructure like power plants, if we want to protect students going back to school, if we want to open up certain types of locations.

Without widespread and rapid asymptomatic testing, anyone going into one of those environments, with schools being a good example, is taking a significant risk. Pressuring people to open schools but not have testing in place is like telling people, "Take your chances."

That testing would also reduce the chances of large outbreaks that force schools or businesses to shut down, right?

More asymptomatic testing before people get into those environments would be useful. But again, it's all tied up into, "How fast can you do it? Where are you doing it? How are you doing it?" Right now, we don't have enough volume, enough test access or enough rapid turnaround, to do it effectively. It's going to hamper our ability to reopen.

There was lots of hype early on about rapid, toaster-sized test kits that could be widely deployed to pharmacies, doctor's offices and other sites. Where do things stand with that?

There are lots of organizations working on those issues. There are many companies that have approached [the Biomedical Advanced Research and Development Authority] and gotten funding, or they are saying publicly that they're developing rapid [diagnostic] testing and other technologies. I expect there to be more coming in that area quickly.

The progress that is being made is about what I would have expected. To go to a non-laboratory prescription test, or an over-the-counter test, there's more data that's needed. So I think where we are right now is about what we should have expected.

There was also lots of concern early on about false positives and false negatives, but I feel like we hear less about that now. Do you think test errors are less common?

I think people are starting to realize that any diagnostic test is more complicated than just, "I get a result and it's 100% accurate." That's never been true, even for HIV testing, which is really good. No tests are ever 100% accurate — they just can't be.

Let's say you were exposed on your way into the laboratory, and you haven't developed the disease yet, and you don't have enough of it in your nose to detect it. Was that a false positive? Or was that just poor timing?

I think people are realizing more and more that [various factors] impact the accuracy of the test. So they're less hung up about false positives or false negatives. They're understanding that those are a possibility. It's a low level of possibility, but it's still a possibility. As a scientist, I would like to hope that people are realizing that's actually the way testing works.

Is there anything your clients have experienced that hasn't received as much attention as it deserves?

The one thing my clients have been surprised by is in the area of the reprocessing and sterilization of N95 respirators. [Regulators] have approved several [submissions], they absolutely have. But I'm surprised they've approved as few as they have.

If you can't make more masks, getting them reprocessed so you can reuse them is vital to the protection of the health care providers.

My understanding is that they're asking questions about equipment, methods of sterilization, processing locations and other issues. I can't point to any one example without getting into confidences. But I would say that there's a need for focus on that area because of its ability to protect health care providers. There's been less attention paid to that than I thought there would be.

-- Editing by Kelly Duncan.

Check out Law360's other installments of Coronavirus Q&A.

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