By the end of next year, all of the large array vendors could have US Food and Drug Administration-cleared products on the market for postnatal constitutional cytogenetics.
Representatives of Agilent Technologies told BioArray News during a recent visit to the firm's headquarters in Santa Clara, Calif., that the company is taking part in several studies that will inform part of a future cyto-focused submission to the US regulatory agency as soon as next year.
Affymetrix and Illumina, Agilent's main competitors in the market, have both said recently that they intend to submit similar packages to the FDA later this quarter, with an eye on gaining clearance by the middle of this year (BAN 1/15/2013).
Should all three vendors achieve clearance, it will cap years of speculation about the regulatory status of the method, which has become the standard of care for postnatal cytogenetics in the US. Arrays have been used in cytogenetic testing for the past decade, but in 2009, the FDA notified vendors of its intent to review the use of the technology as part of laboratory-developed tests (BAN 10/13/2009). The discussions that followed placed the onus on vendors to obtain clearance for their platforms, while CLIA-compliant labs continued to buy arrays marketed for research use only and use them as a component of their cytogenetic testing services.
Kathleen Shelton, senior director of genomics at Agilent, said that the company has been working with the FDA over the past few years to agree on a feasible path to obtaining clearance.
"Initially, what they requested we do [to obtain clearance] was cost prohibitive, but now we're at a stage where we have agreed on something [that] we can do, something that is manageable that will satisfy them," Shelton said.
Heidi Kijenski, the firm's director of clinical marketing, said that Agilent has proposed multi-tiered studies, some of which will be run at its facility in Cedar Creek, Texas, and others that will be processed at a third-party site. She declined to name Agilent's partner. Affy has also worked with an external partner to obtain data for its submission. CombiMatrix CEO Judd Jessup acknowledged last summer that his company has been processing samples for Affy (BAN 8/14/2012).
According to Kijenski, Agilent's studies will be taking part this year and into 2014 ahead of its planned FDA submission. She said that the company will submit its SurePrint G3 CGH+SNP platform to the agency for review. She also said that Agilent may rely on resources gained through its recent acquisition of Danish diagnostics firm Dako to aid in the submission process.
"They have large regulatory staff, we had a pretty limited one, and it was across all of Agilent, so now we can have more dedicated attention, which will help us streamline the process as opposed to having us learn as we do it," Kijenski said of Dako's role.
While FDA clearance will allow Agilent, Affy, and Illumina to market their chromosomal microarray products for clinical use, it will not mean that all labs performing chromosomal microarray analysis services will need to use those cleared devices, according to Kijenski.
"There is a set of customers who don't want to use an FDA-cleared design because they have their own content on the arrays," Kijenski said. "These customers and their colleagues have identified content of interest and would like to offer it in their labs, but the array we will submit to the FDA is a very specific one, and to add that content would mean that we would have to go through another clearance," she said. "So some customers will not necessarily want the FDA-cleared arrays."
Affy also doesn't believe that the clearance of its CytoScan product will compel its clients to abandon their own designs. Andy Last, director of Affy's genetic analysis business, said last month that having an FDA-cleared product will instead allow the company to approach smaller labs and to market it for clinical use in other regional markets.
"A lot of labs that cannot go through the certification and validation [associated with introducing an LDT] will now have an FDA-cleared product they can offer themselves," said Last, adding that clearance in the US "becomes a baseline for adoption around the world," as some countries, such as China, require that products achieve clearance in their country of origin before they can be submitted to local agencies for regulatory clearance as clinical assays (BAN 1/15/2013).
Agilent's Shelton expressed doubt that having a cleared product on the market a year after its two competitors could negatively impact the firm's business. At the same time, it could increase adoption of the firm's CGH+SNP platform over other chromosomal arrays it offers.
According to Kijenski, some Agilent customers continue to use CGH arrays, despite the availability of newer chips that also have SNP content, which is useful in detecting loss of heterozygosity and uniparental disomy. Since Agilent added that SNP content, there has been some debate about the future role of CGH arrays (BAN 4/17/2012).
"The customers who are using CGH arrays already probably won't transition to CGH+SNP because they don't need to," said Kijenski. "If you are looking for constitutional abnormalities, there is probably no reason to use a CGH+SNP or a SNP array," she said. However, "most new customers that we bring on will implement the CGH+SNP array because there is more information there," Kijenski added.