NEW YORK (360Dx) – Last summer was a notable one for the clinical mass spectrometry market as three major vendors — Sciex, Thermo Fisher Scientific, and Roche — announced plans to release instruments specifically targeting the clinical market.
Perhaps most significantly, the latter two firms said they intended to develop fully automated instruments analogous to current clinical analyzers, which could drive mass spec's move into the clinic by fitting it more seamlessly into existing workflows and eliminating the need for expert users.
Despite this vendor activity, though, mass spec's route to the clinic remains uncertain, said Victoria Zhang, director of the clinical mass spectrometry and toxicology lab at the University of Rochester Medical Center and founding chair of the American Association for Clinical Chemistry's Mass Spectrometry and Separation Sciences division.
Zhang is senior author on a paper published this month in Clinical Mass Spectrometry looking at the potential of mass spec in the clinical lab. The paper uses a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis to discuss where and why the technology might or might not fit into clinical practice.
As the paper notes, mass spec offers potential advantages in terms of improved accuracy and reproducibility; the ability to measure molecules not amenable to existing techniques; and the possibility of lower per-test costs. On the other hand, current mass spec instrumentation is expensive; challenging to operate, troubleshoot, and maintain; more labor intensive than many established assay systems; relatively low throughput; and poorly standardized.
Among the opportunities the authors cite as potentially driving increased use of mass spec are increased recognition of the limitations of existing clinical technologies; demand for the shorter assay development times enabled by mass spec; and the development of new clinically focused instruments like the aforementioned systems from Sciex, Thermo Fisher, and Roche.
That said, the paper also notes that immunoassay performance continues to improve, while clinical mass spec efforts could be derailed by a failure to focus on basic issues like service response times, instrument robustness and user-friendliness, and the reluctance of existing in vitro diagnostics companies to move towards mass spec for fear of cannibalizing their current business.
Speaking to 360Dx this week, Zhang observed that clinical mass spec has been strongest in small molecule applications like inborn areas of metabolism, drugs-of-abuse testing, therapeutic drug monitoring, and endocrine testing, adding that she expected these areas would continue to drive the technology's growth.
A look at the tests Sciex and Thermo Fisher highlighted as likely initial offerings on their clinical platforms bears this out. Sciex's first test for the Topaz was its Vitamin D 200M Assay. A vitamin D test is also the first assay available on Thermo Fisher's Cascadion, which in May received the CE-IVD mark and is now available for sale in Europe. Commercialization in the US will be based on the completion of clinical studies and pending FDA 510(k) clearance, the company said this week.
In addition to vitamin D, Thermo Fisher said last year it was developing Cascadion assays for testosterone and immunosuppressant drug monitoring and has targeted future assays for monitoring of therapeutics, testing for drugs of abuse, and various endocrinology assays.
Zhang said she also believes there will be increased clinical use of mass spec for targeted protein analysis and of imaging mass spec for tissue analysis, complementing traditional anatomical pathology.
This latter application is still in the relatively early stages, but according to researchers like Richard Drake, director of the Medical University of South Carolina Proteomics Center, the technology has advanced to the point where clinical implementation is now plausible. Speaking last year, Shannon Cornett, mass spectrometry applications development manager at Bruker, which has collaborated with Drake on MALDI imaging work, noted that the company has begun working with commercial and academic pathology labs in Europe with the aim of developing MALDI-based assays that could prove clinically useful and that it has identified several initial clinical assays it is pursuing.
In addition to its MALDI imaging work, Bruker is a major player in the move of MALDI mass spec into clinical microbiology with its MALDI Biotyper instrument. That technology, "revolutionized the [clinical microbiology] field overnight," Zhang said, adding that she had "never seen a single technology change a field that quickly and dramatically and with such tangible, significant impact."
Whether mass spec can ultimately play a similar role in other parts of clinical practice remains to be seen, but Zhang said she expects the technology to make its mark in enabling new tests or replacing existing tests with poor performance. She said she sees it as less likely that mass spec will displace established tests not suffering from performance issues.
Some have argued that the technology's multiplexing capabilities will allow it to run panels of existing tests more cheaply than is possible with current approaches, but Zhang said she doesn't believe these cost savings will actually materialize.
"I don't think [mass spec-based] multiplexing will be cheaper," she said. "I think that it is going to take a lot more effort, the reason being that if you are multiplexing, you have challenges [around] quality control and processing that you don't perceive in the immunoassays that become very prominent."
"I think the two technologies will continue to be complementary," she said.
Of the three clinical mass spec instruments announced last summer, Sciex's Topaz was the first to come to market, becoming available in Q4 2017. James Ritchie, professor of pathology and laboratory medicine at Emory University and director of the core laboratory at Emory Crawford Long Hospital, has had a Topaz in his lab for more than a year as an early-access user. He suggested that while the instrument is an intriguing one for clinicians, it isn't necessarily the sort of advance that will drive a large number of new users to the technology.
The system "is still a little cumbersome," Ritchie said, comparing it to Thermo Fisher's Cascadion, which, he suggested, could have a more significant impact if it lives up to its billing as a fully automated, walkaway system equivalent to existing clinical analyzers.
"The Cascadion would be a total break" with existing clinical mass spec instrumentation, he said. "I think people would sit up and say, 'I didn't think I could do mass spec before, but now it looks just like a chemistry analyzer, and I know I can do that.'"
Ritchie said that his lab would likely do a refresh of its clinical mass spec instruments in the near future and that they would consider the Topaz.
"Right now we are a Waters shop on the clinical side, but the instruments we are using are almost 15 years old," he said. "They are working fine, but discretion being the better part of valor, we need to start replacing them."
"I think Sciex would be a good contender with the Topaz" to win his lab's clinical mass spec business, he said. Among its advantages, he said, is the fact that it is relatively simple to operate compared to other mass spec systems, and that Sciex has taken an assay through US Food and Drug Administration clearance on the platform.
Those factors might not be enough to lead his lab to switch from Waters to Sciex, Ritchie said, noting that he and his colleagues are already familiar with the former's instruments and have them well integrated into their clinical workflows.
"Not that we couldn't get there with Sciex, but it might just take a little bit more work," he said.
Regarding the Topaz and Cascadion comparison, a key difference between the two is the fact that the Topaz will allow labs to do their own LDT development, while the Cascadion is a totally closed system.
Ritchie said it was hard to say how that distinction would play out in the market. On the one hand, "the early [clinical mass spec] adopters are all used to doing LDTs," and might be reluctant to surrender that option, he said. "On the other hand, buying everything off the shelf and just putting your samples on and walking away is hard to beat."
Zhang said she expected that open systems like the Topaz and closed ones like the Cascadion will coexist in the near term, though she said she believed the market would shift over time towards higher levels of automation and ultimately towards closed systems.
"Automation is a huge challenge for mass spec," she said. "It's the bottleneck and hurdle for broader applications of [the technology]."
One advantage of an open system is your customers will essentially do a portion of your test development for you, suggested Leigh Anderson, CEO of clinical mass spec firm SISCAPA Assay Technologies. "You are going to be able to expand your menu quicker than someone with a closed system."
He added that purely from a lab footprint perspective, the Cascadion will likely need a substantial test menu to win adopters.
"It is the same size as a Siemens or Roche machine that will run 90 different tests," he said, "so just on the basis of floor space, I can't imagine anyone has the need to run that much vitamin D that they would devote that much space to it [for that test alone]."
"I think it is going to have to have a wide-ranging menu when it comes out," Ritchie agreed.
Anderson noted, however, that traditionally IVD companies have made a significant proportion of their profits off consumables, as opposed to instrument sales. The Cascadion, he noted, fits into this conventional business model, but given the Topaz's open design, Sciex might not control the majority of reagent kits for tests developed on that system.
On the other hand, Anderson noted that one of the arguments for clinical mass spec has been that it doesn't require a lot of expensive consumables.
"If everyone is developing [mass spec] LDTs with no antibodies in them, then maybe there isn't so much business to be had on the reagent side," he said.