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MDx Systems Integrate LDTs With IVD Kits for Labs Seeking Greater Efficiency


NEW YORK (GenomeWeb) – A number of diagnostic companies are providing systems that consolidate routine laboratory-developed tests with pre-manufactured in vitro diagnostic test kits on a single molecular platform, enabling automation of manual tasks and lab efficiencies.

Laboratory-developed tests are a vital part of the clinical laboratory's repertoire, and substantial time, cost, and performance advantages can be gained when they are incorporated into routine workflows alongside IVD test kits.

Among the systems that offer this functionality are the Roche Cobas 6800 and 8800 featuring the Cobas Omni Utility Channel. According to Jill German, vice president of molecular systems at Roche Diagnostics International, the channel operates following the addition of lab primers and probes to a reagent cassette prior to loading it into the Cobas systems, which is similar to the preparation and use of an IVD reagent cassette provided by Roche. By selecting this option, laboratorians are able to automate a number of LDT process steps that normally require manual handling, increasing efficiency and operational gains for the labs, she said.

All labs that run both LDTs and IVD test kits are target users for systems that offer this functionality, German said in an interview. The labs that will benefit the most are those that are "in the middle of responding to a significant patient need. But any laboratory that wants to ensure consistency and get its high-valued staff back to doing high-valued things" is a suitable user, she said.

The US Food and Drug Administration definition of an LDT is an in vitro diagnostic test that is designed, manufactured, and used within a single laboratory. Currently, LDTs don't need premarket approval or 510(k) clearance from the FDA, but firms that run them can pursue a regulatory path if they want.

Among other companies that offer this functionality, which is sometimes called open channel capability, Abbott supplies the m2000 molecular diagnostic batch analyzer. It can operate in open mode to run laboratory-developed assays and in vitro diagnostics, and in closed mode to run just in vitro diagnostic tests.

In May, at the American Society for Microbiology Clinical Virology Symposium in West Palm Beach, Florida, Frederick Nolte, medical director of clinical laboratories and molecular pathology at Medical University of South Carolina, spoke about consolidating IVDs and LDTs on the Abbott m2000 molecular diagnostic test platform. Nolte said during a webcast CVS presentation that in 2017 his lab processed around 60,000 lab samples, up from 37,000 in 2009. The m2000 lends itself well to the integration of both IVDs and laboratory-developed tests, which has "been the big selling point for us," he said. 

In open channel mode, the m2000 has protocols for extracting several different sample types, and his team has used whole blood, urine, serum, plasma, and cerebrospinal fluid while developing tests, he noted. In this mode of operation, different sample extraction protocols are optimized for human genomic DNA, bacterial DNA, viral DNA, and total nucleic acid testing. The system enables customized cycling and detection conditions, and features user-defined thresholds and settings for data analysis, among other options. The instrument runs quantitative or qualitative assays in open mode and provides validation of results using internal controls and calibration.

On the Alinity m, Abbott's next-generation molecular diagnostic system in development, the IVD and open mode are planned to run in a random, continuous fashion, Abbott told 360Dx.

Hologic, another Roche competitor, confirmed that it has open channel functionality on the Panther Fusion system. A spokesperson said that the firm has not yet "commercially launched the open access capability" but declined further comment.

High throughput

Designed for high-throughput applications such as viral load monitoring, blood screening, microbiology testing, and women's health, the Roche Cobas 6800 runs up to 384 tests in an eight-hour shift, Roche said. For blood screening and other applications that require very high throughput, the Cobas 8800 system runs up to 960 tests in eight hours. Clinicians develop and run laboratory-developed tests on these systems when approved in vitro diagnostic kits are not available, Roche said.

When labs decide to develop or conduct their own tests, they deploy highly trained people to follow complicated manual procedures, German said, adding, "Every step in that process can introduce an error or contamination, and when an outbreak occurs, resources in the lab are pushed to their limits."

The Omni Utility Channel integrates sample handling, testing, result reporting, and reagent handing — areas where manual steps are usually required, German said. A lab operating without an automated system such as the Cobas "might have to run their LDTs on five to more than 15 different instruments," she said. "In these times of emerging pathogens, many companies develop a single assay and one instrument system to run that assay. You can imagine the challenges in training your staff to develop an LDT that has a slightly different profile than another one on a separate instrument. There's value to a laboratory in consolidating that onto a single automated platform."

Disparate instruments frequently are not linked to central laboratory information systems, but the Cobas Omni Utility Channel, through its connection with the LIS, provides for full process automation and traceability, German said. "Customers have the confidence in running tests that are monitored continuously and for which they don't have to attend to paperwork. With high throughput and fast time to result, the lab can more easily respond to peak demand and seasonal outbreaks," she noted.

Marc Luetgehetmann, a physician at the center for diagnostics at the University Medical Center Hamburg-Eppendorf, said in an interview that he and his colleagues have used the Cobas 6800 system for the past two and a half years, and they have successfully  implemented several LDTs with RNA and DNA targets using the Omni Utility Channel. The open channel software allows users to modify PCR cycles and settings, such as extraction volumes, he said.

Among its benefits, the Omni Utility Channel enables the automation of single or multiplex qualitative and quantitative LDT assays, Luetgehetmann noted. Further, apart from providing convenience and safety features, the channel eliminates manual steps, provides a structured PCR analysis process, and enables traceability of all steps.

Luetgehetmann noted that the channel also enables easy scale-up of LDTs throughput, an important feature when clinicians at the medical center encounter new or existing pathogens. His team recently used the Omni Utility Channel to implement an influenza LDT using primers and probes sourced from Danaher's Integrated DNA Technologies. The Utility Channel "was essential for us in dealing with this … influenza season," he said.

In April, based on studies sponsored by Roche, Luetgehetmann and his colleagues presented a series of posters at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Madrid describing their use of the Cobas Omni Utility Channel for quantitative analysis of BK virus, a significant risk factor for renal transplant dysfunction and allograft loss. The researchers said that using the Cobas Omni Optimization Kit and LightCycler 480 system — a medium- to high-throughput PCR platform that provides methods for gene detection, gene expression analysis, genetic variation analysis, and array data validation — they adapted and transferred to the Cobas 6800 a recently published BK-PCR assay targeting the large T antigen.

In their poster presentation, the researchers compared their results with those obtained using the Realstar BKV PCR Kit from Altona Diagnostics, a CE-marked PCR test. The Cobas Omni Utility Channel "is a convenient solution to automate quantitative and qualitative LDT workflow for multiple clinical specimens, including plasma and urine," they wrote, adding the LDT "showed a good linear correlation with our current CE-IVD based reference method."

There are a few challenges with using the system, however, Luetgehetmann said, including that not all LDT assays can be adapted to it without primer modification. "The unique master mix does require special attention to the primer design and primer concentration," he said. "Furthermore, low background fluorescence is important to have optimal results. Therefore, the use of either double-quenched probes or [short minor groove binder (MGB)] probes is required."