This article has been updated from a previous version to clarify the current test menu for BD's platforms.
As Becton Dickinson's Diagnostics business unit continues to build out its molecular testing capabilities, the company is betting that it can be all things to all molecular diagnostic customers.
To wit, BD Diagnostics is gearing up to launch the next-generation version of its Viper XTR platform, which currently runs assays based on its isothermal strand displacement amplification method and is geared toward labs running high-throughput screening assays, primarily in the area of women's health.
The new version, called Viper LT and set to launch later this year, will feature both PCR and SDA capabilities and will run a human papillomavirus screening and typing test that BD believes will contend with established molecular assays from the likes of Qiagen, Roche, Abbott, and Hologic's Gen-Probe.
In addition, the company has a growing menu and rich pipeline of assays — developed both internally and with partners — for its multiplex real-time PCR-based BD Max system, which is designed to save clinical laboratory customers time and money by allowing them to either use these pre-designed commercial assays or develop their own tests in house.
According to at least one customer, the BD Max's sample-to-answer capability, high degree of flexibility, and relatively low cost positions it favorably as an all-around workhorse molecular testing platform in clinical laboratories, and will allow it to compete with the likes of well-established systems such as the GeneXpert system from Cepheid.
"There is a phenomenal amount of clinically impactful molecular content that's being made available to the market," Tom Polen, president of BD Diagnostics, told PCR Insider in a recent interview.
"Of course, it can be challenging for customers to understand which of that content is going to really help them improve the clinical and economic outcomes in their institution," Polen said. "And the amount of content … is expanding very quickly, more than most people's budgets can absorb. How do you navigate that, and find the right balance between molecular solutions … that are really going to [have] higher clinical impact and cost effectiveness?"
Polen said that the molecular testing market essentially breaks down into two major segments. The first is large-volume testing of samples generally taken from asymptomatic patients. "Screening" is the watchword here, particularly for sexually transmitted diseases. In this segment, "cost is a critical factor [as] high-volume productivity or workflow is very important," Polen said. "Menu breadth here is not as critical, because there are only so many of those specific types of tests."
On the other side of the coin, testing of symptomatic patients has a completely different set of requirements. "Now you've got a much smaller and much more diverse group," Polen said. "It's about how to get the information in a timely and accurate manner, and help get those patients on the right therapy, [both] for their benefit and from a healthcare efficiency benefit, particularly given new reimbursement trends."
In this segment, "turnaround time becomes very important; sensitivity and specificity of course are always very important; menu breadth becomes very important; and having the assay designed to be smart so it's not just looking for the assay for a specific organism, but … [maybe for] the [drug] resistance pattern of the organism, for example," Polen said.
For the first market segment — higher-throughput screening of asymptomatic patients — BD Diagnostics has for several years marketed the Viper XTR platform, a fully automated and integrated molecular testing system featuring BD's SDA technology.
The company's flagship Viper XTR test uses the ProbeTec CT/GC assay for detecting Chlamydia trachomatis and Neisseria gonorrhea from endocervical specimens. According to the company's website, Viper XTR can process up to 736 CT/GC results in an 8.5 hour shift. In September, BD also launched a ProbeTec Trichomonas assay for use on the Viper XTR in Europe, and hopes to launch a US Food and Drug Administration-approved version "later this fiscal year," Polen said (BD's fiscal year begins on Oct. 1). Additionally, BD offers Viper XTR tests for herpes simplex viruses 1 and 2.
According to Polen, the Viper XTR is "best in class from a cost and performance perspective, and is very specifically designed for the screening market." However, the company is also gearing up to launch the next generation of Viper XTR, the Viper LT, which will have a smaller throughput than Viper XTR, but will fit on a laboratory bench and perform both SDA- and PCR-based assays.
"The Viper LT is the first platform that we're launching with PCR and SDA," Polen said. Eventually, he noted, BD plans to migrate existing Viper XTR assays to the Viper LT platform.
Concurrent to the development and launch of Viper LT, BD Diagnostics will expand into the HPV screening market with what it claims will be "the first fully automated HPV with genotyping assay," which will run on Viper LT, Polen said. The company has stated that it hopes to launch the HPV typing assay outside the US by the end of this year, and in the US at an unspecified date after that.
The market for HPV molecular testing is already extremely crowded, with Abbott, Hologic's Gen-Probe, Qiagen, and Roche already offering automated tests. Some of these assays are for detection, while some are for detection and typing, but BD believes its test, once launched, will offer several advantages over rival assays.
"It's really HPV with genotyping on demand," Polen said, adding that the assay will be very price-competitive with existing tests. However, "for every test that is performed, what's unique about our system is that we actually generate very specific individual genotypes for 14 specific genotypes of the virus. Then there is a smart card reader in the instrument that one purchases smart cards for."
Physicians can then monitor whether patients are infected with a genotype known to have a high risk for the patient developing cervical cancer, and can determine whether these genotypes persist over time.
"We increasingly see interest in utilizing persistence as part of the clinical algorithm," Polen said. "It's been shown that an HPV infection by itself does not cause cervical cancer, and neither does a high-risk strain. It's a persistent infection with the same strain that causes that. And that's where we really see genotyping becoming increasingly utilized."
While other tests provide information on those genotypes by default, with the Viper LT HPV assay, "clinicians or laboratories will only pay for that capability in an on-demand manner, if and when it's appropriate within the clinical algorithm," Polen said. "Most other tests push those genotypes out whether you want them or not. We also utilize some different markers, which we believe will have better performance over the life cycle of an HPV infection."
Early reports from customers using the HPV typing test are promising. Several studies have been published comparing the assay favorably to existing commercial tests. One notable UK-based study, led by Jack Cuzick of the Wolfson Institute of Preventive Medicine-Queen Mary at the University of London, was published in March in the Journal of Clinical Microbiology.
In that study, Cuzick and colleagues from several UK-based hospitals and research institutions compared the ability of seven molecular tests – the five aforementioned tests plus two others that did not compare favorably in terms of sensitivity – to identify high-grade cervical intraepithelial neoplasia in 1,099 women referred for colposcopy.
The researchers found that all five tests generally had comparable sensitivity, specificity, and positive predictive value, with the BD test being the only one not yet commercially available.
"There are five tests that are all in a cluster in terms of sensitivity and specificity, and BD is one of those," Cuzick said. The same research group is also preparing a manuscript for a study of around 6,000 women that compared the assays in a screening setting, Cuzick told PCR Insider.
Initial results from that study have been presented at various scientific meetings, Cuzick said, adding that "the bottom line is that the BD test is very easy to use, the platform works well. We've had no problem loading it with sample and getting results out, so it's a nice platform to work on." The group performed its first study using the Viper XTR, but is using the not-yet-commercialized Viper LT for the second study, and plans to transition to that platform in the future, Cuzick said.
"We've really just focused on trying to establish the scientific parameters – sensitivity and specificity – of these tests," Cuzick said. "Ease of use is going to be important." In addition, he noted, "the platforms that you run these things on are relatively expensive machines. If you're going to have the platform there that you're using other things on, then it's going to be relatively easy to add the HPV test. If you're actually going to buy a whole new platform, then there is quite a bit of investment cost."
Cuzick noted that the jury is still out regarding the importance of the test's ability to detect different HPV genotypes.
"I think that's an open … research area at the moment – how useful is it going to be to know about these other types?" he said. "One of the things that I suspect [is that]… there are 14 types associated with a high risk of having precursor lesions. Of those, about six of them have much less predictive value than the other ones. And I'm a little hypothetical now, but I suspect that once we learn more about typing, we're going to want to act less aggressively if you've just got one of those intermediate risk types. But exactly how important that's going to be has not really been established yet."
Nevertheless, BD is betting heavily on Viper LT to help it snag market share in the rapidly crowding field of molecular testing for women's health. Polen and other company executives noted in an August conference call that they also plan to introduce this year a front-end automated sample processing system to facilitate CT/GC, Trichomonas, and HPV genotyping tests on Viper LT (PCR Insider, 8/9/2012).
"That's where the majority of the [molecular] screening testing is today," Polen said. "There are not a lot of, for instance, cancer screening tests out there. Many folks including ourselves are looking at that space, but [women's health] is really where the higher-volume tests are; those tests are really highly consolidated."
Even further down the road, BD plans to eventually replace its first-generation Viper XTR with a higher throughput version of the benchtop Viper LT that will also feature both SDA and PCR capabilities.
"The Viper LT is the first platform we're launching, but there will be a higher throughput version of that in development to which will be able to port over the HPV assay and all other assays," Polen said.
For the second major molecular assay market segment — testing symptomatic patients in more of an acute care setting — BD has put its eggs in the BD Max basket.
Formerly the HandyLab Jaguar system, the BD Max is a six-color, fully automated, benchtop system that performs cell lysis, nucleic acid extraction, and PCR set-up, amplification, and detection. Its hallmark is its ability to accommodate both pre-developed commercial assays and laboratory-developed tests. BD introduced the "open" version of the platform and its first development partner, Diagenode, in May 2011 (PCR Insider, 5/12/2011).
"We've really designed this to be the iPad of molecular diagnostics," Polen said. "It's … the only fully automated open system that allows app developers, or assay developers, around the world to develop assays … and make those available to users. We've announced a number of partnerships with those developers over the last two years and have begun launching those assays."
So far, the company has launched just one partner-developed assay: in November BD and Diagenode announced the European launch of an influenza A and B test for use on the BD Max (PCR Insider, 11/8/2012). Overall, the companies are developing several assays in three categories: respiratory (viral panel, Bordetella, pneumonia), gastrointestinal, and central nervous system diseases. Under the agreement, Diagenode is responsible for obtaining CE marking and launching the tests in Europe, while BD will seek FDA approval for the assays on the BD Max in the US.
Other participants in BD's partnership program include Lab21, which is developing an assay for Aspergillus fungal infections and Italy's Biodiversity, which is working on a menu of tests for infectious agents in immunocompromised patients. Polen said that in fiscal year 2013 BD or its partners plan to launch the assays for Bordetella and community-acquired pneumonia.
The second way that BD is building out the BD Max menu is through its own internal development program. Here, the company already has released FDA-approved assays for Group B Streptococcus and methicillin-resistant S. aureus, and a CE IVD marked test for C. difficile. BD has also submitted the C. diff assay for FDA approval.
The third facet of BD Max menu development comprises assays created by end users in clinical laboratories. Many of these end users require assays for less common infectious agents not typically covered by commercial tests.
"Some of those are very straightforward assays — [for instance], people have developed their own [tuberculosis] assays on Max," Polen said. "Others have developed [antibiotic] resistance marker [or] cystic fibrosis assays on Max. Some of those tests are pretty straightforward and just not offered by any companies commercially, so they've filled those gaps in themselves. And other assays developed by our customers are quite unique and cutting edge. We absolutely have discussions with them about taking those products commercially. We haven't disclosed any at this time, but that's part of the power of BD Max, the ability to do that."
One such user is Ray Widen, director of Esoteric Testing at Tampa General Hospital. Currently, Widen's lab is using a BD Max to both validate its own LDTs and run assays from BD and partners.
"Tampa General is the fourth busiest transplant center in the country," Widen said. "We have a lot of challenging patients, and that's why we develop so many LDTs. There are so many targets we have LDTs for that aren't commercially available anywhere. A few examples, like BK virus, have no commercially approved assay. Up until recently there wasn't anything for cytomegalovirus. I still don’t think there is one yet for Epstein-Barr virus. These are all things that a transplant center needs to be doing. It doesn't want to wait two to three days to get a result from a reference lab if it can avoid it. You save cost and a lot of time by doing it in house."
Widen added that the lab had been using Cepheid's GeneXpert for many of its assays, such as MRSA, but is switching to the BD Max primarily for cost and ease of use. "It provides pretty much the same level of automation, but at a lower cost, which is important to us. And, it's an open platform. [With] the GeneXpert, you basically … don't have a choice to put anything on it. The cartridges are sealed. There is no open mode for it."
The Esoteric Testing lab is looking at BD Max LDTs for vancomycin resistance, cystic fibrosis, and enteroviruses, among others. "Eventually we plan to move a lot of the LDTs onto the BD Max because it's just so much better use of the tech time to put a sample on the instrument and walk away and let it do the extraction and the PCR. We still use the GeneXpert for some things, and we have the [Quest Diagnostics] Focus Dx instrument that we use for some of our LDTs … and the Abbott m2000 instrument for viral load assays. We have a variety of instruments, but the BD Max is the one we're looking at the most because it does give you that sample-in/sample-out type of approach."
The last major frontier for BD in the molecular testing space is oncology. It could be argued that the company is already addressing this segment with its forthcoming HPV assay, since HPV testing is increasingly being eyed as a screening method for cervical cancer risk. However, the company is also working with partners to develop oncology assays on BD Max.
"We just announced in the last several months a partnership with Lab21 … about building capabilities within the oncology space," Polen said. "That partnership has two major components. The first is to develop open system extraction reagents for paraffin-embedded tissue on Max. That will allow us to offer open system reagents for our customers to develop molecular oncology assays."
The second phase of that agreement, Polen said, is for Lab21 to then "take those extraction reagents … and port over a series of molecular assays to BD Max, which we'll offer commercially to our customers. The first two assays we'll be launching are for KRAS and BRAF."
BD has not disclosed a development timeline for these reagents or assays.