By Deborah Borfitz
September 24, 2020 | A better diagnostic platform enabling near-patient testing of disease biomarkers, including the presence of antibodies indicative of previous SARS-CoV-2 infection, as well as advice on how to build and fund new point-of-care (POC) platforms, were among the topics covered during last month’s virtual Next Generation Dx Summit. Pawan Jolly, senior scientist at Wyss Institute at Harvard University, and Helen Roberts, president of Seegene Technologies (a reagent maker for PCR-based molecular diagnostics) offered their perspectives on the dos and don’ts of developing and commercializing POC technologies and how to avoid some of the cost drivers such as devices that are needlessly complex or nano-sized.
A universal multiplex platform that has been repurposed to detect COVID-9 antibodies was the focus of a solo presentation by Jolly. “It’s about decentralizing diagnostics,” he says, which will be empowering patients of the future.
The eRapid technology being developed at the Wyss Institute seeks to apply electrochemical sensors to POC testing for conditions beyond glucometers for diabetes. But the sensing strategy is based not on ligands as biomarkers of human disease, which are limited in number, he explains. Rather, the sensors pick up molecular binding events, such as antibodies directed against specific biomarkers.
Importantly, a nanocomposite coating to which probes are attached are specific to the targeted biomarker, resolving the problem of “biofouling” on their conductive surfaces that can lead to false-positive readings—and doing it without sacrificing conductivity of the sensors themselves, says Jolly. Existing antifouling coatings are difficult to mass-manufacture, suffer from quality and consistency issues, and are not very effective, he adds.
The approach taken with eRapid is to combat biofouling with a 3D porous matrix composed of bovine serum albumin cross-linked with conductive nanomaterials, in essence creating a semipermeable membrane. Unlike enzyme-linked immunosorbent assay (ELISA), Jolly says, signals stay on the electrode surface to be measured “now or later.” ELISA measures signals in a solution, allowing cross-reactivity with neighboring electrodes.
More than 90 biomarkers have been detected with the eRAPID platform technology, says Jolly, including analytes as small as histamines, in one hour using only 10 microliters of human plasma. The platform has also performed well against ELISA in detecting interleukin-6 (a marker of immune system activation) and NT-proBNP (a cardiac biomarker).
The platform has additionally been used as a multiplex panel for sepsis with four electrodes dedicated to different markers of interest. “You can detect one, two, or all of them together,” says Jolly. “During COVID time,” he adds later, “we’re doing saliva molecular and antibody testing together.”
The ongoing pandemic has highlighted the importance of near-patient testing, as was noted in a subsequent panel session on POC technologies and systems. If a fast, accurate and affordable test for COVID-19 were available, students could be tested on their way into sporting events and employees as they arrive at work, says Roberts. Lives could be saved, and the infection better controlled, even if it took an hour to get results.
Seegene Technologies looks to acquire technologies or develop them in-house. “We’re always scouring for the best platform for our assays,” says Roberts, adding that the search over the past two years has been beset by acquisitions of their would-be partners and acting too slowly on buying out exclusivity rights with original equipment manufacturers. “On the point-of-care side, we have very specific needs, especially as it pertains to infectious disease.”
In urgent care and convalescent care settings, POC infectious disease testing is critical to organizations in terms of overall cost savings as well as containment of contagions and infections. This is true not only where speed is of the essence, such as sepsis, but also for high-occurrence sexually transmitted diseases among college students so they don’t need to make a return trip for test results.
Focusing on the right use cases is critical, says Jolly, since a POC device that doesn’t affect the clinical decision-making process would likely be neither useful nor cost effective. Physicians are also going to be “hesitant” to trust a device whose performance doesn’t compare favorably with results from a central lab.
Jolly’s take on “de-risking” POC technology is based on interest in either creating a spinoff company or pursuing licensing opportunities for the eRapid platform. Discussions with stakeholders help define technical and business risks as well as development milestones, he says.
Regulatory hurdles are a key consideration early on for Seegene Technologies, says Roberts. Before pursuing a partnership with another company, it will examine the design history file on a device in addition to conducting patent searches. It also looks at the cost structure for the cartridges “because the reimbursement on the infectious disease side is not very high.”
Manufacturing also must be scalable, she adds, since Seegene Technologies is a large company with a presence in over 60 countries. Financials of the intended partner also have to look solid because Seegene is a publicly traded company. The investment community has to see the move as “a positive thing … [and not] too risky” or the deal won’t proceed.
“First and foremost is the compatibility of the technology with our assay,” via some kind of feasibility testing, she stresses. The assays of Seegene Technologies have a reputation for being among the most sensitive and specific on the market, even when multiplexing, and the company won’t jeopardize that track record on accuracy.
Keep It Simple
Sooner is better than later when it comes to the time-to-market horizon for acquiring technology, says Roberts, noting that Seegene “lost a few very good opportunities” to competitors by not acting fast enough. “But if it’s the right technology, we’ll wait for it.”
From her purview, “the perfect system would be a little POC [device] that could do antibody work and molecular work” from a single sample, she continues. Depending on the assay, disease, and pathogen, as well as where patients are in the infectious cycle, antibody or PCR might be the better choice. “If I found that [platform], I’d be happier waiting six months or a year, but if it’s pure molecular I’d like to see it much more developed and… ready for market.”
Robert’s advice to people building new companies and systems is to “carve out the diseases you want to address, what the reimbursements look like, what the competitive landscape looks like, what the total available market looks like… [and] have solid final products in mind to back-calculate your development costs.” Companies can’t “sell” their technology to potential reagent partners without thorough research to establish final product goals over the next one, three, and five years, as well as an understanding of the financials required to recoup development costs, she adds.
The cost of consumables ultimately depends on how many biomarkers the platform targets, Roberts continues. A device with a cartridge cost of $1 to $2 would be ideal but is rarely the case. “We’ve heard $10, $30, even $100. At $100, it just doesn’t make sense for infectious diseases... for molecular PCR tests, reimbursements are fairly well established. Large syndromic panels are very hard to get reimbursed.”
So, what are the cost drivers? “The cartridge itself [tends to] have too much stuff in it,” Roberts says. The simpler and more plastic it is—meaning the instrument is doing most of the work—the better. Many POC devices are overly focused on the technology or nano. When they become too small, reagent companies will find it hard to accept that half a microliter of sample is sufficient to test for infectious disease without duplicate or triplicate experiments, she adds.
Finding the practical use cases is critical, Roberts reiterates. In addition to a reasonably priced cartridge, manufacturing has to be “very uniform” for a technology to be affordable for molecular-based assays for infectious disease.
Jolly concurs with the uncomplicated approach, noting that he has often been questioned about why eRapid uses such simple electrodes. The platform is “doing what it has to do” without any extraneous fancy instruments, he would reply. “It’s good enough.”
Editor’s Note: For a limited time, the 2020 Next Generation Dx Virtual Summit content is still available. Register now to access the event including all of the recorded sessions, presentations, and materials. Register for PREMIUM ON-DEMAND access.