NEW YORK – As the scope of the SARS-CoV-2 outbreak became apparent early this year, clinical labs across the US scrambled to develop and implement molecular tests for the virus.
The effort presented labs with a number of challenges, ranging from difficulties obtaining reagents and other materials needed for test development to the complexities of navigating unfamiliar regulatory regimes.
Gregory Tsongalis is a professor of pathology and laboratory medicine and director of clinical genomics and advanced technology at Dartmouth College's Geisel School of Medicine. Last week he and his colleagues published a paper in the Journal of Molecular Diagnostics detailing their lab's work getting molecular testing for SARS-CoV-2 up and running, offering, as they wrote the perspective of "a mid-sized, rural, academic medical center."
360Dx spoke with Tsongalis this week about the paper, his lab's work on SARS-CoV-2 testing, and the preparedness of the country's public health infrastructure to ramp up infectious disease testing more generally. Below is a transcript of the interview edited for length and clarity.
Did you have previous experience from any prior infectious disease outbreaks that helped with this process?
I have been doing this for 30 years, and this is kind of the first time that we have had to do anything this significant as far as ramping up and providing high-throughput testing. In the past we [in the US] haven't really been affected by some of the other pandemics or epidemics. So this was really kind of an eye-opening experience.
How familiar were you with the US Food and Drug Administration's Emergency Use Authorization process and what was involved?
I think most labs on the clinical side were familiar with the EUA designation and the status. I'm not sure that everybody was familiar with what the process was. We don't have a lot of experience dealing with the FDA outside of [laboratory-developed test] regulation, but I think they really did a great job in communicating and trying to communicate all the changes and all the things laboratories needed to do as much as they could, and in an environment where things seemed to be changing on almost a daily basis.
How flexible was FDA in terms of changing their requirements in response to issues that emerged like difficulties obtaining controls and other reagents?
I think because things were changing so fast and demand for testing happened so quickly, the guidelines the FDA was providing became more and more lax as things went on. They tried to keep it pretty strict with a known control, a known assay, and then as demand grew they knew pretty quickly that the supply and demand for the reagents and controls was just not being met. And so they had to open it up little by little to different extraction methods, different control materials, different assays that they were granting EUA status to pretty quickly just to keep up.
When did you become concerned about access to the various test components — controls, reagents, swabs — that have proved a challenge?
I think people knew that these were potential issues. I think one of the things that really caught everybody off guard was how quickly this happened. How quickly demand for testing sprang up. How quickly the virus spread. How quickly vendors ran out of supplies and things like that. I think people recognized that those were potential problems, but I don't think they realized how quickly they would be problems.
How did you find the EUA process? In the beginning when the country was struggling to ramp up testing there was a lot of commentary calling out FDA for being too slow to approve SARS-CoV-2 tests. On the other hand, the recent experience with serology tests perhaps shows what can happen when you have too little regulation of testing.
That's the fine line. You want more testing and you want it fast, but at the same time you want good testing because a bad test is probably worse than no test at all. So the FDA is kind of straddling that fine line of how to maintain some regulation of quality of assurance of these things versus trying to get them out quickly.
I was concerned that the EUA process was a little bit lax. If you look at what clinical labs do on the molecular side to validate a regular test outside of the pandemic, it is far above what we did for the EUAs.
If you had been developing a molecular LDT, your validation would have been much more rigorous than what you had to do for the EUA?
Absolutely, absolutely. The other thing that was pretty obvious in all of this was how under-resourced FDA is to be able to handle oversight and regulation of LDTs. You could just see day after day that they were loosening up the regulations to allow people to run tests. This was one test in a pandemic that happened very quickly, but I'm not sure they would have the resources to be able to oversee and regulate LDTs if they couldn't do it for this.
How big an issue to your mind was the initial problem with the Centers for Disease Control and Prevention test and the inability of the public health system to quickly ramp up testing.
I think it was a setback. I think after that, everyone recognized that there had to be other options available and started pursuing other kits from other vendors.
If anything comes out of this interview, it should be that the system is badly broken. The CDC, with all the experience they have, is not resourced to deal with this on their own. The public health labs, as good as they are at what they do, are way, way under-resourced to be kind of the sole frontline laboratories for these types of things. I think we in the US need to think about that whole system and how to fix it. I don't think we can just patch it. I think the whole system needs to be fixed so that we can have a much better response the next time something like this happens.
I've spoken to other lab heads who said that the public health system ran into similar, though less severe, testing capacity problems during the H1N1 pandemic in 2009. It seems this has been recognized as an issue for a while. Any thoughts on why that lesson wasn't taken to heart?
I think the problem was we didn't learn from that [H1N1 experience], and we thought that we could put together a better response by just piecing some things together, and it wasn't enough. This COVID-19 pandemic kind of proves that we need to have a much, much better, concentrated effort around the laboratory response in the US. It's not enough to say, well, we can throw $100 million at this and have it distributed around to labs. The labs have to have the capability and resources to be prepared to do this all year long every year. And that has just not happened. And I don't know if it is a political issue or an interagency issue or what, but somebody has to take a close look at this and realize that this is not going to work the next time around.
Do you have any thoughts on what could be done to enable a more effective response?
I think you need a system where you can have the CDC be kind of central command for what is happening, but they have to have a way through the public health laboratories in each state to coordinate and organize efforts not just with the public health labs but with the academic medical centers, the larger hospitals, and with the private lab sector.
This round it was just completely chaotic. Nobody knew what anybody was doing. Everybody was trying to do what they needed to do for their institution or their patient population, but it was chaotic. It was a circus.