Tag Archive: SalivaDirect

  1. Blumenthal, Murphy praise SalivaDirect after visiting Yale School of Public Health

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    Connecticut Sens. Chris Murphy and Richard Blumenthal visited the Yale medical campus Tuesday morning and met with Yale scientists to discuss SalivaDirect, the new saliva-based testing protocol developed at Yale and validated with a study funded by the NBA. Among these Yale professionals were Dean of the Yale School of Medicine Nancy Brown and Dean of the Yale School of Public Health Sten Vermund.

    The initial research on using saliva samples was led by Anne Wyllie, associate research scientist in epidemiology, and Nathan Grubaugh, assistant professor of epidemiology. After obtaining promising results, they partnered with the NBA to validate the testing method on a larger cohort. The new saliva-based testing protocol received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) on Aug. 15.

    Both U.S. senators gathered on the lawn outside of Edward S. Harkness Memorial Hall after their meeting to reflect on how they envision SalivaDirect helping the state fight COVID-19.

    “This test is potentially a world-shaking, really game-changing breakthrough because it can reduce the cost, raise reliability and make detection and screening much faster,” Blumenthal said. “It can produce a low cost, very sensitive and very reliable kind of test that offers, right now, massive potential results for the country.”

    Blumental and Murphy applauded Yale researchers for committing to keep SalivaDirect inexpensive. After the protocol received EAU from the FDA earlier this month, Wyllie told the News that they sought to provide each test for $10 or less. A preprint published in early August estimated that the cost of reagents for each test would fall between $1.29 and $4.37 per sample.

    Blumenthal said his goal is to help scale up SalivaDirect while keeping it inexpensive. (Photo: Charlotte Zimmer)

    “Right now we have a set of reagents and instruments that have been included in the EUA,” postdoctoral fellow Chantal Vogels, who helped lead the EUA submission for the FDA, told the News last week. “By performing bridging studies, we can include other reagents, instruments [and] automated systems. We just have to show that that works equally well as compared to the components that we’ve already included and have authorized.”

    According to Vogels, the team is also planning on conducting bridging studies — supplemental studies that collect new data to expand the scope of the initial authorization — and working to identify equipment that other laboratories would find convenient and cost-effective for administering SalivaDirect. By identifying which bridging studies to conduct, the research team can validate the protocol with new instruments before submitting data to the FDA and seeking official approval to authorize a wider range of instrumentation for the protocol.

    Running a test according to this protocol will be much cheaper than the currently available tests kits that can cost around $150, according to Wyllie. Murphy emphasized that making testing more affordable will be the key to ending this pandemic and the damage it has caused.

    “There’s no amount of economic stimulus that Congress can provide to fix what’s broken in our economy, unless we beat the virus,” Sen. Murphy said. “And the only way you can beat this virus is to be doing ten to a hundred times more testing than we are today.”

    Murphy expressed frustration with the country’s inability to conduct population testing, but said he is “really grateful” to Yale researchers who are studying how to address testing shortages and lower the costs of testing. According to Murphy, tests are currently too expensive or hard to acquire, and businesses and schools in New Haven could have difficulties testing all essential workers and students. Large-scale population testing would help Connecticut reopen schools and the economy with more confidence, he said.

    The senators both discussed what their role would be in the next steps of developing SalivaDirect.

    “Our job now is to make it available to as many people as possible, as quickly as possible,” Sen. Blumenthal said. “And I think that my goal will be to enable that it be rolled out, scaled up [and] the intellectual property protected in a way that prevents a medical device company from profiting and exploiting this test, raising the price to put it out of reach from school systems or sports leagues…”

    “I’m going to be bragging to my colleagues down in Washington about the kind of test we developed here,” Blumenthal said. (Photo: Charlotte Zimmer)

    Researchers have already been addressing the challenge of disseminating the test. Unlike other testing kits that companies sell or distribute, SalivaDirect is the first testing protocol to receive an EUA from the FDA. The protocol is open source, and researchers at Yale have the right to authorize high-complexity U.S.-based labs seeking to begin testing with SalivaDirect, though any lab that receives approval must be certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). 

    Although the team initially directed requests to an email address, researchers have now set up a Google Form to field authorization requests. Hundreds of emailed requests came in the 72 hours following the announcement of SalivaDirect’s EUA, Annie Watkins MPH ’21 told the News last week.

    The Yale Pathology Clinical Molecular Diagnostic Lab was the first to receive approval to use SalivaDirect, earning authorization as part of the terms of the FDA EUA. According to Pei Hui, the director of the lab, his group partnered with Grubaugh and Wyllie’s team early on to carry out the clinical validation of the testing protocol necessary for the EUA, which is something the epidemiology researchers could not do on their own.

    Hui said the lab first officially started using the protocol on Thursday, Aug. 20 and added that the approval of the Yale Pathology Clinical Molecular Diagnostic Lab for SalivaDirect is a step in the right direction when it comes to scaling up the test.

    “This is beauty. This is really significant progress in my view,” Hui said. “Being able to do saliva, the value is tremendous. I think it will be changing the COVID testing landscape in the US.”

    The lab had already been testing nasopharyngeal swabs throughout the pandemic. Hui said they expect to maintain this testing platform as they begin to incorporate saliva samples. 

    The lawn outside of Edward S. Harkness Memorial Hall, where Murphy and Blumenthal spoke on Tuesday. (Photo: Charlotte Zimmer)

    He explained that his lab is currently “limited in space and manpower,” but that they hope to expand the operation. His lab will potentially buy automatic machines and use lab space at West Campus, although this would likely take a few months to set up, Hui added.

    The researchers involved in SalivaDirect also contacted the Yale Testing and Tracing Committee to propose that saliva samples could potentially be used in testing the Yale community in the future, according to Hui. Both senators expressed excitement about the prospect of working with Yale to continue scaling SalivaDirect and its use.

    “It is a source of enormous pride,” Blumenthal said. “I’m going to be bragging to my colleagues down in Washington about the kind of test we developed here … There is no pharmaceutical company that should profit; no medical device company should make money from it. The benefits should go directly to the public.”

    William McCormack | william.mccormack@yale.edu  

    Charlotte Zimmer | charlotte.zimmer@yale.edu

  2. Automation, pooling could come next for SalivaDirect as research team juggles authorization requests, media attention

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    Chantal Vogels was not expecting the news on a Saturday morning.

    A postdoctoral fellow in the Grubaugh Lab at the Yale School of Public Health, Vogels helped lead the Emergency Use Authorization submission process for SalivaDirect — a new saliva-based testing protocol for COVID-19 — detailing validation data in the application and collaborating with the U.S. Food and Drug Administration as the process moved along.

    By last week, she could sense the EUA was nearing. She was trading daily emails with the FDA, while Nathan Grubaugh — assistant professor of epidemiology, principal investigator in the Grubaugh Lab and the lead researcher behind SalivaDirect, alongside associate research scientist in epidemiology Anne Wyllie — was spending lots of time on the phone with the regulatory agency.

    On Saturday morning, word suddenly came through: the FDA had issued an EUA for SalivaDirect, permitting other high-complexity laboratories to acquire the testing protocol for use and igniting a flood of popular attention.

    “I think none of us would have expected it to be this big,” Vogels said. “We knew that we were getting to like the final stages … I was expecting it to be Friday or Monday. And then when it came, the media attention has just been crazy. We’ve been so overwhelmed. It’s really amazing to see how well it’s [being] received.”

    Since the EUA has been issued, the team of scientists, accustomed to spending hours inside the lab and out of the limelight, has been ushered onto live news segments and quoted across the internet. Vogels, who is from the Netherlands and completed her bachelors, masters and PhD there, said family and friends in Europe were excited to see her appear live on CNN Monday. Grubaugh spoke with CBS This Morning and ESPN, while Wyllie did interviews with ABC News, MSNBC and more. A Twitter thread describing the test and its benefits from former Obama health care aide Andy Slavitt had garnered more than 22,000 retweets by Tuesday evening.

    Yet as the media attention from Saturday’s EUA has continued into this week, researchers have been even more focused on what might come next, continuing explorations into improvements for the test and outlining a process for disseminating their open-source protocol to interested labs. Researchers are exploring the automation of sample processing, pooling of saliva samples for improved efficiency and modifications to SalivaDirect that would speed up processing by replacing the polymerase chain reaction step.

    “Although SalivaDirect is a big step forward, it’s definitely not the end of it,” Vogels said. “It’s not the solution to everything … It’s a huge step forward, but it’s just one step of the many steps that are still ahead of us.”

    Aside from improvements to the test, one of the most pressing steps for the researchers is distributing authorizations to labs and other groups interested in using SalivaDirect. Annie Watkins MPH ’21, who is helping to process correspondence from interested parties, told the News that the Grubaugh Lab had already received “hundreds of” emails inquiring about authorization by Tuesday morning.

    As part of the terms of the FDA EUA, Yale’s Pathology Clinical Molecular Diagnostic Lab, led by Pei Hui, became the first laboratory authorized to administer and process SalivaDirect. All laboratories that subsequently receive authorization must be certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).

    Vogels and Watkins were not able to provide the names of any specific institutions or laboratories reaching out seeking authorization — and could not comment on whether Yale has inquired about using the test for its regular testing of students returning to New Haven this fall — but said the interest originated from a wide spectrum.

    “It’s pretty broad [in terms of] who’s interested in things,” Watkins said. “There’s definitely some universities, university health systems that are interested in return to campus, potentially athletics. And there are one-off labs, there’s a few private practice type things [and some] international labs.”

    The rollout has been complicated by the unique nature of SalivaDirect’s EUA. According to the Grubaugh Lab’s CovidTrackerCT website, SalivaDirect — which is not a testing kit for sale — is the first protocol to receive an EUA from the FDA. The protocol is currently posted as an open source, but “testing is limited to laboratories designated” by the Yale School of Public Health, per the terms of the FDA EUA.

    SalivaDirect is the first protocol to receive an EUA from the FDA. (Photo: Sonia Ruiz)

    Grubaugh wrote in a Twitter thread on Tuesday evening that due to the novel nature of the EUA, his team has to work with Yale and the FDA to come up with the legal conditions surrounding authorization as well as formalizing the regulation of the whole process. Once these regulations are in place, they will start by authorizing labs that will test schools, Grubaugh wrote.

    The lead researcher, whose lab previously studied mosquito-borne viruses before the emergence of COVID-19, also addressed some misconceptions surrounding the testing protocols. 

    “What isn’t SalivaDirect?” Grubaugh wrote. “It isn’t a point-of-care or an at-home rapid test. It uses PCR, and thus requires a high-complexity lab … We don’t have products to distribute. Rather, for authorized labs, we can provide a protocol for doing inexpensive saliva-based RT-qPCR testing.”

    He also noted that while SalivaDirect testing is not yet available to the public, the lab is working to create partnerships to allow for this in the future.

    According to researchers, the next innovations for SalivaDirect include automation, rapid detection and pooling.

    Automation will require the validation of robotic systems and will hopefully be applied to the sample processing and/or PCR steps. With regards to the second goal, Grubaugh wrote that they are also working on replacing the PCR step altogether, with either loop-mediated isothermal amplification or recombinase polymerase amplification. Pooling would allow researchers to combine saliva from many people and test it simultaneously, which could increase testing capacity and utilize reagent resources more efficiently. 

    Watkins said that running one plate with PCR ideally only takes three hours. But other variables, including transport time and high volume, can lengthen the process.

    “It really depends on the lab,” Vogels added. “There’s a step between collecting the sample, getting it in the lab, doing the test, sending out a result, so in an ideal world the protocol itself might be a couple hours, but it’s not a rapid test.”

    All laboratories that receive authorization must be certified under the Clinical Laboratory Improvement Amendments of 1988. (Photo: Lukas Flippo)

    The lab’s study with the NBA — which offered funding for the validation process — is ongoing as researchers continue to explore how SalivaDirect works for asymptomatic detection. They are monitoring samples from one team outside of the bubble, according to Watkins, after players have stopped testing positive in the Orlando bubble. Vogels said the NBA study is also being used to study pooling. 

    SalivaDirect’s current EUA permits the test for “individuals suspected of COVID-19 by their healthcare provider.” The team could submit another EUA for asymptomatic screening with data from the NBA study, Watkins said, but FDA rules around tests for asymptomatic surveillance continue to evolve.

    “As far as I know, I think there’s only one test or a few tests that have been authorized for testing asymptomatics,” Vogels said. “So I think this is really a dynamic process of figuring out what does it really mean, where can we apply this, and how does that really work, so we’re still working closely with the FDA to figure that out.”

    Finally, performing bridging studies could also allow researchers to show the FDA that using different reagents or instruments down the road might work just as well, helping make the testing protocol more flexible for a wider range of labs. 

    But first come the emails that continue to pour in. For the researchers, this journey has been all-consuming but rewarding nonetheless.

    “I’ve kind of forgotten that I’m a student,” Watkins said. “I’m supposed to be registering for classes this week, and I forgot the classes were a thing to be completely honest. This has become my life, and the student aspect seems like a previous life.”

    William McCormack | william.mccormack@yale.edu  

    Charlotte Zimmer | charlotte.zimmer@yale.edu