Is Roche prepared to focus its considerable resources to test the US Food and Drug Administration’s regulatory framework in order to get its microarrays approved as analyte-specific reagents? That’s unclear, but microarray producers with hopes for penetrating the lucrative in vitro diagnostic and clinical marketplaces are watching closely the company’s response to an FDA letter questioning claims Roche made in launching the AmpliChip CYP450 microarray last month.
The FDA last week fired off a tightly-worded letter, posted at http://www.fda.gov/cdrh/oivd/letter-roche2.html, to question Roche’s effort to position this relatively new genomics tool as an analyte specific reagent as a first step to the diagnostic and clinical marketplace.
Steve Gutman, the director of the FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety of the Center for Devices and Radiological Health, signed what the agency terms an “untitled letter” to Heinrich Dreismann, the general manager for Roche Molecular Diagnostics, requesting that the company visit the 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.”
In the letter, the 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 in the letter.
Gutman told BioArray News that the agency cannot comment on open compliance issues.
Previously, agency officials have said the 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.
Gutman said that the agency posted the letter online, anticipating that there would be requests to see it under the Freedom of Information Act.
While such letters are of an informal and advisory nature, they do wield authority, Gutman said.
“I can assure you that in the few that I have dealt with, they are not without clout,” Gutman said.
He said the letter is the first the agency has issued dealing with microarrays applied in this manner.
“The FDA is very interested in the technology in general,” he said.
Seeking Public Comment
In May, the FDA issued a first draft of guiding principles for the development and marketing of multi-analyte-based diagnostic tests. The document, which is open for public comment until after July 21, is found on the FDA site at: http://www.fda.gov/cdrh/oivd/guidance/1210.pdf.
“While the full impact of this new technology is uncertain” and the agency has “little experience with multiplex or array device submission,” the draft reads, “the 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 is clearly well practiced in regulating the messages issued by companies, with in-house groups that are charged with reading and regulating the claims that regulated industry makes in press releases and in advertisements.
Roche’s rollout of the product was highly visible and “a lot of people provided comments about this,” said 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.”
Gutman said there is no standard operating procedure for this type of proceeding.
“We are a small group that has one or two companies visiting almost every day,” he said. “The formal process we have is to the extent of documenting who comes in, having the minutes [recorded], but there is nothing formally written about the process.”
The FDA letter bases much of its questions on claims made by Roche in its June 25 press release (http://www.roche.com/med-corp-detail-2003?id=999&media-language=e) issued from Roche’s headquarters in Basel, Switzerland, and announcing the launch of the novel array, which was designed by Roche and manufactured by Affymetrix (BioArray News 4/25/2003). The launch comes as part of the companies’ 18-year, $70 million non-exclusive licensing agreement announced in January (BioArray News, 2/7/2003).
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.”
The launch — presided over by Heino von Prondzynski, the head of Roche Diagnostics — was widely reported in the mainstream media.
Christiane Koesling, a Roche spokeswoman, said the company would work with the FDA. “They are not saying that our conclusions are not appropriate but they would like to discuss it. We look forward to working with the FDA.”
“Roche remains committed to working with the FDA to develop this exciting technology for clinical diagnostic applications,” said Greg Heath, head of clinical genomics at Roche Molecular Diagnostics of Pleasanton, Calif.
A Roche Molecular Diagnostics spokeswoman was unable to respond to a BioArray News request for information on when the com-pany would travel to the FDA, and who would appear at the agency.
Affymetrix, in a written response to a request for comment from BioArray News, said: “We believe there is a huge potential for these products to enable new solutions for improved diagnosis and patient care. It is the role of the FDA to set guidelines for the introduction of novel products, such as Roche’s AmpliChip product, to the marketplace.”
Amersham, which sells a CodeLink P450 SNP microarray product intended for the research market, noted in an email to BioArray News, “ASRs are under consideration, but we have made no decision at this point.”
An Agilent spokeswoman declined comment, saying the issue is very specific to Roche.
David Ludvigson, executive vice president of San Diego-based Nanogen, said that the company will be watching the process closely. The company has five microarray-based products it is marketing as ASRs, and Ludvigson said it has received no compliance letters from the agency.
A spokesman for Tm Bioscience, a Toronto, Canada-based microarray producer, said it hopes that any FDA action would keep a level playing field for all. Tm Bioscience has previously said it plans to roll out mutation detection kits for P450-2C9, to be launched at the end of the year, and a mutation detection kit for P450-2C19, to roll out in the first half of next year.
Charlie Barnett, an internist who founded diagnostic biochip startup Healthspex, of Knoxville, Tenn., said that Roche’s battle will not cause his outfit to readjust its course. Healthspex is building a prototype biochip that will initially go to market as an ASR for cystic fibrosis.
Barnett said that Roche’s effort at putting out its AmpliChip product as a comprehensive panel is at the cutting edge of a technological evolution that will create new questions for the healthcare industry to answer.
“New tests are desperately needed out there,” he said. “But, we don’t know how clinically important the information from [the test] is, and we don’t know about how to get people to reimburse for something that is bound to be an expensive test. And, if there is a test out there, and it reimburses, is it really important to have? That’s what doctors will have to be able to explain to patients.”
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.”
Links to previous stories
[BioArray News 7/10/2003] FDA to Roche: Your Presence is Requested. Agency Letter Seeks to Discuss AmpliChip
[BioArray News 6/18/2003] FDA Gates Swinging Open To Admit Standardized Gene Expression Data
[BioArray News 6/11/2003] CDER’s Woodcock: FDA To Publish Draft Guidance in August on Array Data in INDs
[BioArray News 6/4/2003] Expertech’s David Link on the FDA, In Vitro Diagnostic Regulations