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AACC Announcements Mark Steps Forward for Clinical Mass Spec

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This story has been updated to correct Sally Benton's title and institution.

NEW YORK (360Dx) – Last year's American Association for Clinical Chemistry annual meeting saw announcements by several major mass spectrometry and in vitro diagnostic players regarding their plans to develop clinical mass spec platforms.

A year later, some of those plans have progressed to concrete realities as both Sciex and Thermo Fisher Scientific have clinical instruments up and running in customer labs.

Sciex launched its Topaz LC-MS/MS clinical mass spec system and an accompanying US Food and Drug Administration-cleared Vitamin D test in Q4 of 2017. At this year's AACC annual meeting, the company followed up with the launch of its Topaz Prep Station, an automated sample prep workstation for use with the Topaz, as well as its Vitamin D 200A assay kit, a version of the Topaz Vitamin D assay designed for automated use with the new sample prep workstation.

Thermo Fisher, meanwhile, received in May the CE-IVD mark for its Cascadion system, making it available for sale in Europe. According to Robert Dewitte, VP research and development and clinical mass spectrometry at Thermo Fisher, the company has begun beta installations of the system, which it has placed in two European labs.

Roche, which last year announced plans to develop a turnkey LC-MS system in collaboration with Hitachi, said relatively little about this effort at this year's AACC meeting, but it did reiterate its intentions in this area during an analyst meeting.

Both Thermo Fisher's Cascadion and Roche's proposed instrument are modeled after traditional clinical analyzers — fully automated and closed systems. The platforms are (or will be, in the case of Roche) also random-access, meaning single samples can be run in whatever order as needed. While this is the most commonly used workflow for many clinical labs, mass spec workflows have more typically used a batch approach, wherein a group of samples is prepared together and then run.

The Topaz uses a batch approach, making for a workflow more in line with those traditionally used in clinical mass spec applications. More generally, the Topaz retains more of the appearance and function of a conventional mass spec system, while the Cascadion operates like a traditional clinical analyzer. The Topaz also allows users to run both premade, closed test kits like the Vitamin D assay and to develop their own laboratory-developed tests on the platform, while the Cascadion is strictly a closed system for running test kits sold by the company.

Both approaches have potential pros and cons. As Topaz early-access user James Ritchie, professor of pathology and laboratory medicine at Emory University and director of the core laboratory at Emory Crawford Long Hospital, noted previously, the Cascadion represents a more dramatic step for clinical mass spectrometry — one that is perhaps more likely to draw interest from clinicians without mass spec experience.

"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.'"

With the release of the Topaz Prep Station and the Vitamin D 200A assay kit, Sciex, part of Danaher, has further streamlined the platform, allowing for "completely unattended sample preparation," according to Aaron Hudson, VP and general manager, global marketing at Sciex Diagnostics. Nonetheless, the system does not move as far in the direction of a conventional clinical analyzer as the Cascadion. 

On the other hand, Ritchie noted that labs, such as his, that have mass spec experience might like to maintain the ability to develop their own tests, which the Topaz affords. This could also help the company more rapidly expand the test menu for the platform, as its user base would be active in developing content for the system.

In an investor note published during AACC, Leerink analyst Puneet Souda cited expansion of the Cascadion's test menu as one key to its success, echoing previous observations by clinical mass spec researchers like SISCAPA Assay Technologies CEO Leigh Anderson.

Thermo Fisher's Dewitte said the company believed "there are plenty of labs who see sufficient demand and volume for Vitamin D [currently the only assay for Cascadion] for us to get a great start."

He added that the company expects that when it adopts its next planned tests, for immunosuppressant testing and testosterone, "the scope of customers who are keen to adopt [Cascadion] grows significantly. And those three [tests] create enough growth for us in the near term."

Also important to the Cascadion's success will be developing the ability to link the platform to the automated track systems used in clinical labs to sort and process samples and deliver them to the appropriate instruments for testing, suggested Sally Benton, consultant biochemist at Berkshire and Surrey Pathology Services, Frimley Park Hospital, which is one of the beta sites for the Cascadion. Peter Van Overwalle, senior manager of market development at Thermo Fisher said this was something company was working on although he couldn't give a timeline for when a track-compatible system might be available.

An experienced mass spectrometrist, Benton has implemented clinical mass spec assays in a variety of labs and said she can envision a place for the Cascadion in both labs with mass spec expertise, as well as mass spec-naïve labs.

In the case of the former, LC-MS instruments "are being overrun with these very routine assays [like Vitamin D] that [clinicians] want to keep on mass spec because of the superior [analytical] quality of LC-MS," she said. "But the labor-intensive nature of the sample prep becomes very tedious and quite prohibitive."

Moving routine mass spec assays like Vitamin D to the Cascadion would free up instruments and operators to focus on more esoteric test development, she said.

"The workload of [routine mass spec tests] has just increased so dramatically that you're spending a lot of time doing a specialist assay for something that has now become very routine," she said. "When you work in an LC-MS lab, you want to develop new assays to support your clinical teams."

The random-access workflow will also prove advantageous, especially as the company expands its test menu beyond Vitamin D, Benton said, noting that the approach allows prioritization of urgent samples — something a batch approach is less amenable to.

"I don't think I've ever been asked for an acute Vitamin D test … but certainly with immunosuppression you might get a patient where you need an immunosuppressant result pretty urgently," she said. "And that's where the benefit of this sort of system comes in as well. Rather than having to find a member of staff to do the sample prep at a time when they're not running a batch, you can just stick it on the analyzer as an urgent, and the analyzer enables you to push the sample through. You might have 80 samples all loaded up, but if this one sample comes in and you wanted it to go before those 80 vitamin Ds, you can just put it on and analyze it straight away."

In the case of a mass spec-naïve lab like the Frimley Park lab, Benton said the system does appear straightforward enough for technicians with no mass spec experience to operate it with relatively little training, making it a feasible option for non-expert labs interested in adding mass spec testing capabilities.

She said the instrument is currently run by two operators who, though experienced clinicians generally, had no previous mass spec experience. The two learned how to run the system during a training session over several days, she said, and have now begun to train other lab staff, including laboratory assistants with no scientific background.

"It's as easy to run as a chemistry analyzer," Benton said. "It's all been remarkably straightforward."

She suggested that in labs already doing a large amount of routine mass spec testing, the system would be "almost a no-brainer" as it would allow substantial reductions in the staff required for running those assays.

In the case of a facility like the Frimley Park lab, which didn't previously use mass spec, the cost of the system and assays will be key to determining whether it makes sense to adopt the system or not, she said.

She noted that the higher quality of mass spec assays compared to immunoassays provided a strong incentive to switch over, but that this would have to be balanced against whether the system is able to compete on price while also delivering the throughput and efficiency required.