With the COVID-19 pandemic expected to worsen in the U.S. in the coming weeks, and testing capacity still playing catch-up, federal emergency use authorizations have reached an inflection point.
Late last week the first two tests from the private sector were granted EUA, and early this week the U.S. Food and Drug Administration loosened its guidelines to make it easier for commercially developed tests to receive rapid approval.
Meantime, some kit makers have announced the launch of tests in the U.S., but it is unclear how and to whom those could be distributed, although some developers are working directly with labs to make tests available as EUA lab developed tests.
The new guidelines state that commercial test developers can launch an assay as soon as it is validated to previously guided standards, provided the companies subsequently pursue EUA within 15 days. This is similar to the guidance issued to labs seeking authorization for laboratory-developed testing.
The landscape for commercial testing for infectious diseases could be roughly divided into developers of instrument-agnostic test kits and developers of tests that run on a designated test system or instrument.
For example, five of the assays that have been granted EUA as of Wednesday this week—from Roche, Hologic, Abbott, GenMark, and DiaSorin Molecular—can only be run on those companies’ test systems, while two others—from Thermo Fisher Scientific and Quidel – are test kits that could potentially be run on other PCR systems.
But there are many companies—including makers of agnostic kits, syndromic panels, and point-of-care diagnostics—that have disclosed they are seeking EUA.
For some, the new guidelines do not appear to be enough to accelerate the launch timeline, since ramping up production and distribution is actually what limits speed, not the regulatory process.
Max Masucci, an analyst at Canaccord Genuity, explained in an email this week that while big players like Roche, Thermo Fisher, Hologic, and Quidel have all been granted EUA, there are a number of smaller companies that have submitted their COVID-19 tests for EUA approval and are now waiting to hear back. And, there are also companies, like Becton Dickinson and Chembio, that are developing point-of-care immunoassay testing, he noted.
“While I expect the diagnostics titans like Roche and Thermo Fisher to supply the lion’s share of tests, I expect smaller companies to help fill pockets of demand for COVID-19” testing, Masucci said.
The availability of reagents has been the key factor limiting the mass distribution of COVID-19 tests. “If large companies are using their full capacity of reagents, the role of smaller diagnostics companies will become increasingly important [because] several smaller diagnostics companies use several different sources of reagents,” Masucci said.
Overall, he said it is hard to estimate the exact number of tests that will be needed to adequately surveil the U.S., as this will depend on the effectiveness of social distancing and the consequent shape of the U.S. epidemic curve.
“What we do know is this—we’d rather overshoot than undershoot that target,” Masucci said, adding, “We think this will require a ‘team effort’ from diagnostics companies of all sizes.”
At a granular level, Masucci said tests from companies like Roche may resonate well in large reference labs like Laboratory Corporation of America and Quest Diagnostics, while tests from companies like GenMark, which provide an instrument geared toward the hospital inpatient setting, may serve as an attractive solution for hospitals that don’t anticipate having enough of a COVID-19 testing need to warrant a send-out to a large reference lab.
Masucci said he sees potential for COVID-19-specific instrument placements. Demand for pandemic-related testing may also be a catalyst to motivate hospitals and labs that may have already taken an instrument in but have not yet validated it and gone live with testing.
“We expect these incremental instrument placements to serve as a long-term driver of consumables utilization,” Masucci said. And, given that point-of-care tests offer rapid turnaround time and improved patient accessibility, he also sees utility for these tests in doctor’s offices, pharmacies, and potentially at the borders, if and when they attain EUA.
Companies like BioFire, GenMark, Rheonix, and Aldatu represent the spectrum of different types of testing and company sizes, and they are each pursing EUA in a milieu of evolving guidelines.
BioFire, a BioMérieux subsidiary, was the first commercial test to achieve EUA on an assay for the Ebola virus during the 2015 outbreak, and has previously disclosed it is bringing a COVID-19 test to market.
The new FDA guideline change is a “welcomed, and pretty aggressive move by the FDA,” Wade Stevenson, senior vice president of global marketing at BioFire Diagnostics, said in an interview. “I think it is appropriate, given the magnitude of the COVID-19 pandemic and ensuing crisis.”
Stevenson confirmed that the guidelines permit BioFire to commercialize its product 15 days before it submits it to the FDA, assuming the validation data looks good, but added that his understanding is that the firm also needs to post the validation data on its website.
Information on sensitivity and specificity of the COVID-19 tests available to date has been sparse in the public domain, so this could be a welcome change for customers, if it is the case.
BioFire is now far enough along in its test validation and manufacturing scale-up to provide a limited number of COVID-19 assays to the U.S. Department of Defense starting next week, Stevenson said. “As we ramp up manufacturing capabilities, we will be able to provide that test more broadly beginning in April,” he said.
Accelerating the regulatory authorization part of the timeline has been somewhat helpful, “but still, internally, there is a lot of ordering of raw materials, ramping up and production planning that still has to take place,” Stevenson said.
“As a manufacturer and developer, you try to coordinate all these different processes, and just because one has been accelerated, it doesn’t mean that they all can be,” Stevenson said, adding, “Many can, but you are at the mercy of the slowest one.”
At the other end of the spectrum, GenMark was also midway through the EUA process when the guidelines changed, but had already submitted its test on March 10, and then obtained EUA on Thursday. GenMark Senior Vice President of Marketing Scott O’Brien said in an email that prior to EUA submission the company had provided several partners with kits in the laboratory research phase of development (RUO), which they in turn validated for use in their labs and then submitted their own EUA to the FDA.
The new guidelines allow the firm to distribute EUA-labeled products ahead of formal approval, O’Brien said. “We are currently transitioning production from RUO to EUA and updating labeling accordingly,” she added. When the new guidance came out, the firm had already submitted its EUA application and was addressing initial questions from the FDA, and thus was “deep into the process and finalizing labeling” at that time.
Richard Montagna, CSO at Rheonix, said that from his perspective FDA has dramatically streamlined the EUA process. Montagna said he expects the process of validating its sample-to-answer test on its instrument will take another week or two.
Aldatu Biosciences—a start-up kit maker—has, meanwhile, brought its product to customers in a hospital in Boston.
The firm started working on its test three weeks ago and had a validated assay two weeks later. “Within another five days, the test was clinically validated in a CLIA lab and being used to test hundreds of patient samples per day,” said Aldatu CEO David Raiser.
One potential bottleneck to testing currently is the availability of sample collection materials, such as nasopharyngeal swabs and universal transport media (UTM) or viral transport media (VTM).
GenMark noted that the firm had already increased critical staffing “both to respond to demand and to mitigate if individuals have to stay home as a result of the COVID-19 outbreak.” And, from a manufacturing and supply chain perspective, the firm had also already planned for an extended and heavier-than-usual respiratory and influenza season, “so the increase in demand was something we are prepared to manage,” O’Brien said.
Aldatu’s Raiser also said the firm has planned ahead for bottlenecks. “We have gone to great lengths to work with our long-time suppliers to ensure timely delivery of our critical reagents so that we can guarantee an uninterrupted supply of kits to our CLIA lab partners,” he said. “We are also seeing impressive innovation from the hospital customers to circumvent their own bottlenecks, such as repurposing swabs from other specimen collection kits and generating large quantities of VTM alternatives on site.”
BioFire’s Stevenson said the company is ramping up production capabilities to meet the increased demand for testing instruments.
Stevenson noted, however, that many hospitals in the U.S. have closed their doors to sales reps during the pandemic. “We understand, and we want to support them in that, but that’s not all hospitals, and on top of that we still have field application specialists who are busier than they’ve ever been in their lives going out and installing new instruments.”
The firm is also accepting orders and staying in touch with customers online in cases where quarantine has been put in place.
For the BioFire respiratory panel, an increased demand in Asia has leveled off, Stevenson said, but has now ramped up in the rest of the world. “Overall demand for our respiratory infectious disease testing products is about 200% ahead of what we forecasted for the month of March, so it’s been a lively time here, and a challenge to manage that when a good part of your workforce is working from home,” he said.
The global number of BioFire FilmArray instrument placements was reportedly 10,400 at the end of last year.
GenMark sells direct in the U.S., which is the largest market for multiplex molecular diagnostics and the primary market for the firm. The company also has approximately 30 distributors globally who are also requesting COVID-19 test kits. So far, the firm has taken a phased approach to global distribution, with a focus on Hong Kong, but it will now expand distribution with the new EUA.
“At this stage, we have not experienced any disruption of our technical team’s ability to install new instrumentation, but we are doing this urgently now to ensure we get ahead of potential tighter restrictions,” O’Brien noted.
Like BioFire, GenMark has seen an increase in demand for its syndromic respiratory panel testing. “Initially all the focus seemed to be on getting a COVID-19 test, but once laboratories realized the majority of patients are negative for COVID-19 they realized it is important to be screening for a broad range of respiratory pathogens [and] as a result, we have seen many hospitals recently update their testing algorithms to include more syndromic panel testing rather that starting with FluA/B,” O’Brien said.
Rheonix plans to install and service workstations and ship kits as required. The company is also continuing to manufacture and ship its other products to customers. And, at this point Aldatu is also selling directly to the hospital that is currently using its test.
GenMark said that the changing EUA landscape has not really impacted any decisions the firm has made in regards to development, production, and commercial strategy.
That said, the changing EUA landscape has been “challenging and frustrating for clinical lab directors and hospitals.” The initial guideline required clinical labs to build their own lab-developed test “and effectively conduct a mini-clinical study in order to submit their own EUA,” O’Brien said. “This led to significant delays for many labs and more importantly, ruled out the majority of labs as they did not have the ability or resources to meet the EUA requirements.” Now, the shift in guidance “really helps clinical labs … start using a test rapidly and complete the studies for EUA submission while in clinical use.”
Aldatu’s Raiser commented that some of the ambiguity and lack of clear guidance in the EUA requirements, in particular around how to acceptably generate contrived samples, resulted in some frustration, but “In general, the documents were clear and provided an unprecedented avenue for a company like ours to get a solution implemented in truly record time during a pandemic crisis.”