In its first foray into medical diagnostics, Guava Technologies of Hayward, Calif., announced last week that it has commercially launched its EasyCD4 system for CD4 and CD8 T-cell enumeration in “nations outside the US, Europe, and Japan.”
Guava is expecting the system, which is based on its Personal Cell Analysis flow cytometer, to sharply reduce the cost — as much as 20-fold over existing methods — of T-cell enumeration tests in resource-poor countries.
Although the company’s official statement did not disclose in which countries the EasyCD4 is being launched, Jeff Harvey, Guava’s vice president of customer service, told Inside Bioassays that the systems are initially being distributed in several African countries, including South Africa, Botswana, and Kenya, with an eye on additional East African countries in the near future.
Guava also said that it plans to introduce a version of the EasyCD4 system for research use only in the US later this year, and that it will eventually seek FDA approval for the system as a clinical diagnostic product.
“We felt it was too important to roll out a reliable solution for CD4 testing to wait to do so until going through the rather lengthy process of gaining FDA clearance,” Harvey said. “So instead, we set up several very rigorously controlled multi-site evaluations of our system compared to those more conventional approaches, and we are using those results to establish to government officials [in Africa] that our system works as well as theirs.”
The platform, according to Harvey, has the potential to reduce the cost of individual blood tests to about $1 per test, depending on the number of individuals being tested with a given platform, and allow more remote laboratories to afford and install systems — perhaps saving clinicians from having to travel to centralized laboratories that are sometimes few and far between.
The number of circulating CD4, CD8, and other types of T-cells in an HIV-infected patient’s blood provides important information about the stage of disease, as well as whether or not antiretroviral treatments are working. The “gold standard” for counting such cells in a patient’s blood sample has for many years been flow cytometry, Harvey said.
Guava’s PCA is not a traditional flow cytometer, but it works under the same principle, with one major difference: It features a proprietary microfluidic system that greatly reduces the amount of reagents and sample necessary to perform an assay, translating into a cost reduction for each test. In addition, the company says a PCA user requires little training as compared to someone using a flow cytometer (For a more detailed description of Guava’s technology, see Inside Bioassays, 4/27/2004).
“Some of the HIV vaccine developers [we were working with] use our product for what you could call cellular quality control,” Harvey said. “And the thing that they started asking me … is: ‘Couldn’t you do a CD4 count on this system?’ And I said: ‘Sure we could, we just hadn’t really thought about it.’
“And they told me that I really should because there’s a real need out there for affordable CD4 counts, and your system is a great cell counter,” he added.
Harvey said he took the idea back to Guava’s headquarters, and the company quickly realized it could do such assays well and “very, very affordably.” Soon thereafter, about a year-and-a-half ago, Harvey said Guava embarked on a project to test the system against existing technologies and explore the deployment of systems in resource-poor countries.
Undercutting the Competition?
The market for CD4 testing outside of the US, Europe, and Japan has huge potential, and is highly dependent on the humber of people being administered antiretroviral therapy.
Tina Baumgartner, Guava’s senior manager of business development, cited the World Health Organization goal to have 3 million people outside these areas on antiretroviral therapy by 2005. Because it is recommended that such patients receive quarterly CD4 tests, this translates into 6 to 12 million tests per year.
BD Biosciences and Beckman-Coulter are two of Guava’s biggest competitors in this area. Both have FDA-approved platforms and a large presence in North America, Europe, and Japan, as well as some presence in African and other resource-poor countries.
BD has two major platforms, which it places under the category of “lymphocyte subsetting”: The FACS (fluorescence-activated cell sorting) MultiSet and FACSCount systems. The closest competitor to Guava’s instrument is the FACSCount, said Gloria Young, director of marketing for BD Biosciences. It analyzes two differently colored fluorescent labels at a time to count CD4+, CD8+, and CD3+ T-cells (the CD3+ is used to first distinguish T-cells from other CD4-expressing cells in blood). Guava’s instrument also analyzes two colors at a time.
The FACS MultiSet enables three- or four-color enumeration for all of the above markers, as well as for CD45. The US Centers for Disease Control last year issued a report recommending CD45 gating and three- or four-color assays to more accurately perform CD4 counts.
“[The FACSCount system] is really dedicated for CD4 testing, and is predominantly sold ex-US, though it is FDA-cleared,” said Young. “With the FACS MultiSet, you can have all of the markers you want to look at in one tube.”
Beckman Coulter offers two- and three-color assays which are intended to be conducted with the company’s flow cytometry instruments — in particular the Cytomics FC500 series and the EPICS XL flow cytometer. In fact, the company signed an agreement in January of this year with the Clinton Foundation to offer tests to developing nations on the EPICS platform for a substantially reduced price, and has already delivered instruments to South Africa.
In addition, Beckman recently licensed a new type of CD4 test called a PanLeucogating, or PLG test, from its developers at the South African National Health Laboratory Service. The PLG test reduces the steps involved in a CD4 assay from three to one, and allows whole-blood samples to be analyzed up to five days after collection.
“It has the capacity to run blood samples that are a lot older,” said Angela Vernon, marketing product manager for Beckman. “In addition, it uses whole blood, rather than someone having to prepare samples and store them. This is a huge benefit for remote sites.”
While both BD Bioscience and Beckman Coulter cited elements in their systems that confer increased productivity, throughput, and diagnostic accuracy, they declined to discuss with Inside Bioassays pricing of their assay systems — an area where Harvey believes the EasyCD4 really stands out, most importantly in resource-poor countries.
“Our platform costs around $35,000, which is the instrument plus the first 100 tests,” Harvey said. “When you consider that we have the potential of offering each CD4 test for $1, compared to $4 or $5 on the low side — although some will claim $2 … we’re at least twice as affordable as anybody else, and in some cases twenty times as affordable as other methods. On average, we’re about 6- to 8-fold more affordable,” he said. “The real benefit to the customer is if they’re going to do several thousand CD4s in the course of a year, then even the difference between $1 and $2 per test becomes significant.”
But does the Guava test perform as well as established methods? According to Harvey and several upcoming scientific abstracts, it does.
Guava said that it had tested the EasyCD4 against established methods at several institutions, including the CDC, Health Canada, and the University of California, San Francisco, and that in every case the Guava assay performed as well or better.
Inside Bioassays was able to obtain information about only the UCSF study, which stated that the EasyCD4 performed as well as the MultiSet for CD4+ cell enumeration. The abstract of that study is slated to be presented at the upcoming Congress of the International Society for Analytical Cytology, to be held May 22-27 in Montpellier, France. Calls to the UCSF researchers who performed the study were not returned by press time.
Harvey was quick to point out that the EasyCD4 does not necessarily trump existing technologies in terms of accuracy, but stressed that the reduction in cost is the largest issue.
“CD4 testing has been going on for a long time,” he said. “The BD’s and the BC’s of the world have been [in Africa], but more in centralized locations. But the question has always been ‘How do we get all the samples out there?’ Now, people are thinking about Guava, as well, when they are considering CD4 testing alternatives.
I’m a firm believer in competition, so if what we’re doing helps other companies figure out a way to reduce the cost of their testing, then I’m all for it,” Harvey declared.