NEW YORK (GenomeWeb) — In cases where US Food and Drug Administration-cleared assays do not exist, clinicians often use their own lab-developed PCR assays to test for conditions of interest. This process can involve separate extraction and amplification steps, and extensive hands-on time.
Becton Dickinson has for the past few years promoted as a middle path its BD Max system, which runs FDA-cleared tests from the company and its partners but is also open to run lab-developed tests.
Now, clinicians at the Hospital of the University of Pennsylvania have provided a blueprint for their colleagues, describing how they transitioned tests for herpes simplex virus strains and varicella zoster virus onto the BD Max Open System. In a report published earlier this month in the Journal of Clinical Microbiology, they detailed each step they took to get their home-brewed assays to work on the BD Max Open System.
Ana Cárdenas, lead author of the study and current director of the virology laboratory at the Children's Hospital of Philadelphia, told PCR Insider in an interview this week that she appreciated that the BD Max system has these open capabilities.
Cárdenas' group brought the BD Max on board initially for doing Clostridium difficile and Group B Streptococcus testing in the hospital. "The idea was, if we already have a system in place that we could potentially put a lab-developed test on, then we don't have to buy a different platform or a different instrument," she said.
This can help in labs with limited space or funding, she noted. "If you have an instrument where you have the capability of doing an FDA-approved assay but also putting on lab developed tests, that allows the lab to have a little bit more flexibility," she added.
The JCM report detailed how her group transitioned testing for HSV-1 and -2, as well as VZV, the causative agent of chicken pox and shingles.
Quidel recently received FDA clearance for a similar assay, part of its Lyra brand of diagnostic assays. These tests are ready-to-use PCR reagent kits designed to be compatible with a lab's existing thermal cycler. Quidel's HSV1+2/VZV test is currently available to use on the Applied Biosystems 7500 Fast Dx, QuantStudio Dx Real-Time PCR Instrument, and Cepheid SmartCycler II, according to the company's website. The 70-minute test is a single-tube multiplex real-time PCR reaction with one-step reagent set-up and three-step sample prep.
The clearance of a related test was interesting, but not daunting to Cárdenas. "The field is always evolving, and always moving, so I think no matter what you do there's always going to be something in the pipeline," she said. Clinicians also consider how different protocols might fit with their own lab workflow, volume, and expertise, she said.
One of the reasons for putting the test on the BD Max was the ease of automated extraction and amplification, Cárdenas explained. It now requires much less technician interaction versus their previous protocol, which used one instrument for extraction and another for amplification and detection. Fewer procedural steps also minimize the risk of technician error, she noted.
The new method is now being used on patient samples from skin and mucosal lesions at HUP. These herpes viruses sometimes look similar in the lesions that they make, Cardenas said, and differentiating them is important because VZV is highly transmissible and a positive test would initiate hospital infection control and prevention protocols.
Open system business model
Mike Nugent, director of global partnerships and management for BD's Molecular Diagnostics division, told PCR Insider this week that users might ultimately defer to FDA-cleared tests when they are available. However, the open capability of the BD system fills a need for automated testing currently unmet by any other platform.
To enhance this offering, BD recently launched a set of reagents to enable and encourage porting of assays, called total nucleic acid, or TNA reagents. As reported in PCR Insider, the TNA sample prep chemistry is designed for extraction of both DNA and RNA, and the line includes basic master mixes that customers can use to develop their own assays on the BD Max platform.
"We have a variety of ways content is being developed on the BD Max," Nugent explained. "We're obviously very focused on internally developed assays for FDA-cleared IVD tests," he said, adding that his role includes working with BD's partners to develop this content.
"The content that they're developing could be either unique content that fills gaps in our portfolio, or it could be specific regional needs and niche requirements," he said. This content will be used to "continue to expand the BD Max test menu."
The partner program includes "different organizations and companies across the globe that are developing content in the molecular space," Nugent said. "They would use open system reagents as raw material, but they would end up going through a regulatory process … which could be either CE-marking [in Europe] or, ultimately, FDA clearance [in the US]," he said.
BD currently offers tests on BD Max with partner Diagenode that include enteric viral, influenza A/B, and Bordetella pertussis assays. Other partners have also included Lab21 and Biodiversity.
The HUP group is not a partner, in this sense, but rather a customer running an assay "on a more manual system that they wanted to port over to the fully-automated BD Max system for PCR testing."
For them, the platform removes the need for a separate extractor and systems for amplification and detection. "The BD Max incorporates all of that process into a single automated system," Nugent said. "It's end-to-end automation; that would be one of the driving reasons why they might want to move from a very manual system to an automated system like the BD Max," he said.
The cost-benefit analyses an individual lab goes through before making a major equipment purchase or changing established protocols are justifiably complex. However, echoing Cardenas, Nugent noted that the fact that a lab can run FDA-cleared IVD assays as well as automate its own lab-developed assays is an attractive selling point for BD Max.
In the long-term, Nugent said BD sees strong growth in the infectious disease market, with wholesale transformation of pathogen diagnostics from culture-based to faster and more sensitive PCR testing, for example. He cited BD's enteric bacteria panel, which was cleared by the FDA and launched in May, as an example of this trend. Emerging infections, or pathogens with novel or evolving resistance markers, can also be tackled in an automated fashion by open systems like BD Max, allowing people to address important clinical needs "in lieu of an FDA-cleared IVD," he said.
BD hopes to take this message to potential customers at the Association for Molecular Pathology annual meeting in Washington, DC, next month. The company will hold a workshop on its enteric panel, and host speakers who will discuss the company's IVD assays as well as their own work "in the open system space," Nugent said. These speakers will include Ray Widen of Tampa General Hospital, who has now ported numerous lab-developed assays onto the BD Max.