By Mo Krochmal
Can Roche convince the US Food and Drug Administration that its micro-arrays should be approved as analyte-specific reagents? That remains to be seen, but microarray producers with hopes for penetrating the lucrative in vitro diagnostic and clinical marketplaces have been watching closely since FDA sent Roche a letter in July questioning its claim that the AmpliChip CYP450 microarray qualifies as an analyte-specific reagent.
Steve Gutman, director of FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, signed an “untitled letter” to Heinrich Dreismann, the general manager for Roche Molecular Diagnostics, requesting that the company meet with FDA at its earliest convenience to “discuss the basis for your apparent conclusion that this microarray is properly regulated under analyte-specific reagent (ASR) provisions of FDA regulations, 21 CFR 864.4020.”
FDA contends that Roche’s claims for the AmpliChip appear to be for a multi-signal device that may only be used on the Affymetrix platform. “The AmpliChip microarray appears to be an assembled device that is part of a specific test system,” Gutman wrote. FDA defines an ASR as a reagent “intended for use in a diagnostic application for identification and quantification of an individual chemical substance or ligand in biological specimens.”
While such missives are generally considered to be informal advisories, Gutman says they “are not without clout.” Although this letter is the first of its kind to deal with microarrays, agency officials have said in the past that FDA is working to get up to speed on genomics tools, data, and applications, and is actively seeking industry feedback as it prepares to craft policies that guide the way these tools move from the lab bench to the regulated environment of the clinic.
In May, FDA issued a first draft of guiding principles for the development and marketing of multi-analyte-based diagnostic tests. “While the full impact of this new technology is uncertain,” and the agency has “little experience with multiplex or array device submission …” the document states that “FDA is anxious to provide clear guidance to assist sponsors in developing submissions that will support marketing of safe and effective products using this technology.”
Despite its inexperience in genomics, the agency, with in-house groups charged with reading and regulating the claims that the industry makes in press releases and in advertisements, is clearly well practiced in regulating the messages issued by companies. Roche’s rollout of the product was highly visible and “a lot of people provided comments about this,” says Gutman. “We don’t peruse all of the press releases that come out in the world. What happens is that, commonly, companies watch each other, and many issues are brought up that way.”
The FDA letter bases much of its questions on claims made by Roche in its June 25 press release issued from Roche’s headquarters in Basel, Switzerland, announcing the launch of the novel array, which was designed by Roche and manufactured by Affymetrix. According to Roche, the AmpliChip “enables clinical diagnostic laboratories to identify certain naturally occurring variations (called polymorphisms) in two genes, the CYP2D6 and CYP2C19, which play a major role in drug metabolism.”
Christiane Koesling, a Roche spokeswoman, says the company would work with FDA. “They are not saying that our conclusions are not appropriate, but they would like to discuss it.” Adds Greg Heath, head of clinical genomics at Roche Molecular Diagnostics in Pleasanton, Calif.: “Roche remains committed to working with the FDA to develop this exciting technology for clinical diagnostic applications.”
Meanwhile, much research remains to create a clinical-standard tool. Kenneth Goldman, a Lehman Brothers analyst who follows Affymetrix, said that at $20 billion to $30 billion, the in vitro diagnostics market is a “great opportunity for a new life-science enabling tool — if one could penetrate that market.” But, he said, there are issues of reproducibility and accuracy that must be solved before it can be used as a pharmacogenomics tool. “The bottom line,” he said: “Roche jumped the gun.”
A version of this article appeared in the July 16 edition of BioArray News.