This article has been updated from a previous version to clarify information about the manufacturing and marketing of the Panther platform.
By Ben Butkus
Nucleic acid testing products marketed by Novartis Diagnostics and manufactured by Gen-Probe to screen donated blood for HIV and hepatitis have significantly increased the safety of the South African blood supply, according to recently presented data from the South African National Blood Service.
In addition, the data, which is currently being prepared for publication, suggests that nucleic acid testing of individual donors using the Novartis/Gen-Probe platform is more sensitive than pooled nucleic acid testing using a competing test from Roche for detecting HIV-1, hepatitis B, and hepatitis C, and is likely the most effective option for screening blood in countries with high infection rates.
"For ensuring blood safety now and for the next four or five years, the individual nucleic acid testing system that we're using is absolutely core to what we do," Ravi Reddy, chief operations officer at SANBS, told PCR Insider this week. "Without it, we would not be able to provide a safe blood service considering the current prevalence of HIV in the country."
According to UN AIDS, the joint United Nations program on HIV/AIDS, in 2007 there were 5.3 million HIV-infected people in South Africa, representing an overall national prevalence rate of 11 percent. Estimates have shown that in South Africa as many as one in 600 donated blood units is infected with HIV-1, the virus responsible for 99.6 percent of all HIV infections.
In order to curb the number of transmissions occurring through blood transfusions, in 2004 SANBS initially conducted modeling experiments that suggested that nucleic acid testing in general would pick up more infections in the blood supply than status quo methods such as immunological testing; and that individual nucleic acid testing could be more effective than testing of pooled samples, according to Reddy.
"Given the high prevalence in South Africa, and given the numbers that we were talking about, at that stage we were thinking that we would miss about eight detections a year … just using our current strategy of antibody testing and antigen testing," Reddy said. The group also predicted that about half of all infections detected with individual NAT would likely be missed if they were to conduct NAT on pools of eight donor samples.
As such, SANBS in 2005 partnered with Novartis Diagnostics to begin using the Procleix Ultrio assay — a qualitative, in vitro nucleic acid amplification test for HIV-1 RNA, HCV RNA, and HBV DNA in plasma and serum specimens — along with the Procleix Tigris automated nucleic acid testing platform.
Since that time, SANBS has screened 3.8 million blood donations for HIV-1 RNA, HCV RNA, and HBV DNA using Procleix Ultrio and Tigris. During that time, they collected data on test results and compared it to traditional serology methods, and found that 96 units of HIV-1-positive blood were detected using individual NAT that were not detected using serology.
"Since we've implemented individual NAT, we've picked up an average of about 20 [infections] per year," Reddy said. "Our prediction in 2005 was that we would miss only about eight or nine per year. Also, in the almost six years that we've been doing this, we haven’t seen a single case [of HIV from blood transfusions]."
The scientists also detected 3,007 HBV-positive units using Procleix Ultra, 346 of which were not detected with serology alone; and 250 HCV units, of which five were not detected with serology testing alone.
In addition, the researchers compared individual NAT using Procleix Ultrio with one of its main competing commercial products, Roche's Cobas TaqScreen MPX test, a multiplex, real-time PCR test that detects the presence of HIV-1, HIV-2, HCV, and HBV in plasma from blood, organ, and tissue donors. Cobas TaqScreen can be used to test individual samples or pools of no more than six individual specimens; SANBS performed a head-to-head comparison between Procleix Cultrio individual NAT and Cobas TaqScreen minipools of six.
According to Reddy, of 23 low viral load samples that were negative using serological testing but positive using Procleix Ultrio individual NAT, just over 60 percent were detected using the Cobas TaqMan minipool method. In addition, less than 60 percent of samples that tested positive for HBV using Procleix Ultrio individual NAT were detected using the Cobas TaqMan minipool method.
The bottom line, Reddy said, is that "in a country like South Africa, where there is a large prevalence of HIV and a large incidence of new infections, we cannot go with a system where we're missing 50 percent of infections."
The preliminary data that Reddy shared with PCR Insider was also presented last month at the 21st Regional Congress of the International Society of Blood Transfusion in Lisbon, Portugal; and will be the subject of a scientific paper that Reddy and colleagues plan to submit for peer-reviewed publication by the end of this year, Reddy said.
The new data contributes to a growing body of support for employing individual nucleic acid testing for infectious diseases such as HIV and hepatitis wherever they occur with a large prevalence rate. As such, it could also lead to Novartis Diagnostics increasing its already sizeable market share for NAT-based blood screening.
The company already has a long-term agreement with SANBS locked up, and Reddy said that the organization has now adopted the latest generation of the assay, the Procleix Ultrio Plus, which has a greater sensitivity for HBV than its predecessor.
In addition, "the American Red Cross is using our assay … and we have about an 80 percent market share in the US," Peter Maag, president of Novartis Diagnostics, told PCR Insider this week. "We also test 100 percent of all French blood donations and 100 percent of all Australian donations."
After that, "it comes down to market by market where there is a competition with alternatives" such as Roche's test and homebrew assays, Maag added. However, "when [an organization] like SANBS is looking at high-volume individual donor testing, with a high sensitivity, we feel we are the preferred [choice]," he said.
If an increased market for individual NAT materializes, Novartis and manufacturing partner Gen-Probe might not reap much benefit from it for another year or so, by which time the companies hope to launch Procleix Panther, a fully automated, higher throughput, sample-to-answer version of the Tigris system, in countries outside the US for blood screening.
Novartis and Gen-Probe began their blood screening collaboration in 1998. In 2009, the companies agreed to extend and expand the collaboration until 2025. Under the pact, Gen-Probe is primarily responsible for R&D and manufacturing while Novartis is responsible for sales and marketing.
Under the expanded agreement, Novartis also said that it would collaborate more closely with Gen-Probe on sales, marketing, and distribution strategies. The companies are sharing R&D costs and manufacturing expenses; and Gen-Probe receives a percentage of end-user revenue from product sales that escalates gradually from 2009 until 2015, and will remain constant thereafter.
Gen-Probe, which markets Panther for diagnostic purposes, launched the new platform with the CE Mark in Europe in December, and is still waiting for the instrument to significantly penetrate the market (PCR Insider, 12/2/10).
In February, as part of a conference call discussing Gen-Probe's fourth-quarter and full-year 2010 financial results, president and CEO Carl Hull noted that the company's blood screening sales declined 10 percent in Q4 2010 due to reduced shipments of Tigris to Novartis following an "exceptionally strong" prior-year period (PCR Insider, 2/17/11).
This decrease was expected, however, and Hull said at the time that Gen-Probe expects instrument sales to continue to decline from 2010 levels until Panther becomes available for blood-screening applications in 2012.
This week, Gen-Probe reported as part of its Q2 2011 financial results that its blood screening sales again declined compared to Q2 2010, as expected, due to nearly $11 million worth of lower shipments of assays and instruments to Novartis; and $3 million in additional supply chain fluctuations.
Despite this, actual total blood screening assay revenue for the joint business increased compared to the prior year period, Gen-Probe said.
"The underlying fundamentals of our blood screening business remain healthy, evidenced by the solid donation volumes, market share, and profitability we experienced in the second quarter," Hull said in a statement.
Novartis' Maag said this week that "while the Tigris instrument is now also adopting the new Procleix Ultrio Plus assay, [Novartis and Gen-Probe] are also proposing a continuous stream of innovation. On one hand we are developing new, powerful assays that will soon be available. But we also are developing new instrumentation [in] Panther, which is currently in development."
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