In a setback for Roche Diagnostics — as well as the growing analyte-specific reagent component of molecular diagnostics — the Swiss drug and diagnostics giant has succumbed to US Food and Drug Administration pressure and has decided not to sell its AmpliChip CYP450 product as an ASR.
“Roche will not make [the AmpliChip] available as an ASR,” Melinda Baker, a spokeswoman for Roche Diagnostics, told SNPtech Reporter. She said Roche will continue to provide it as a research product for use by pharmaceutical companies in clinical trials, and said it has sold it to one company for this purpose.
“The OIVD has determined that it is unnecessary to decide whether the product is an ASR or not,” said Baker. While this may seem ambiguous to the reader, she said “We clearly accept the agency’s position on this.”
According to the FDA letter, which can be seen here, the agency believes that the “technological differences of the AmpliChip would cause it to differ from existing or reasonably foreseeable ASRs such that the AmpliChip would not be exempt from pre-market notification.”
Baker said Roche has concluded its discussions with the FDA regarding the AmpliChip product as an ASR. “We’re continuing to work with the agency to determine the appropriate mechanism for submitting the in vitro diagnostic application,” she said. “This is such a new area.”
She said the company still expects to seek regulatory approval in the United States in 2004 so the AmpliChip may be sold as an in vitro diagnostic.
In the letter, dated Nov. 4 and signed by Steve Gutman, director of the the FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, the FDA said the AmpliChip “cannot be commercially distributed without an appropriate premarket determination from FDA. We recommend that Roche submit a premarket notification.”
“You have contended that under certain circumstances, the AmpliChip would fit within the definition of ASR in 21 CFR 864.4020(a) and would, therefore, be class I and exempt from the Act’s requirement of premarket notification under 21 CFR 864.4020(b),” the FDA wrote in the letter. “OIVD has determined that it is unnecessary to decide whether this assertion is correct. Even if the AmpliChip were to qualify as an ASR under the regulation, the product would lose its class I, 510(k)-exempt status by operation of other provisions of the Act and of FDA regulations.”
However, OIVD stresses that “the intended use of the AmpliChip, to identify polymorphisms related to drug metabolism, is of substantial importance in preventing impairment of human health.”
“Moreover,” the letter continues, “according to information provided by Roche, the AmpliChip is a unique, highly processed, multi-signal device with unusual quality control features. It requires unique and sophisticated configurations of both hardware and software to make accurate use of those features.
“Even if the AmpliChip were to fall within the definition of ASR in 21 CFR 864.4020(a), OIVD believes the technological characteristics of the AmpliChip would cause it to differ from existing or reasonably foreseeable ASRs such that the AmpliChip would not be exempt from premarket notification,” the letter states.
It concludes: “The AmpliChip cannot be commercially distributed without an appropriate premarket determination from FDA. We recommend that Roche submit a premarket notification and, if the AmpliChip is found not substantially equivalent, seek de novo classification under section 513(f) of the Act (21 U.S.C. § 360c(f)). The device classification of the AmpliChip depends on the outcome of FDA’s premarket review.”
Baker said that Roche continues to expect the AmpliChip to generate annual revenues of more than $100 million by 2008 [see June 25 press statement by Roche here].
This week’s letter, which was addressed to Heinrich Dreismann, general manager for Roche Molecular Diagnostics, caps almost four months of speculation over the fate of the AmpliChip — not to mention the fate of other similar ASRs. In mid-July, the FDA summoned Dreismann to the agency to discuss why the company is marketing its AmpliChip microarray as an analyte specific reagent [see 7/10/03 SNPtech Reporter ].
The original letter, which can be found here, illustrates the gulf that lies between microarrays as a research tool and the promised land of clinical diagnostics — supposedly by way of the ASR route. If the AmpliChip were to have been marketed as an ASR, then it would have stood as an important initial step toward a time when microarrays could be used in doctors’ offices to do a quick gene-expression profile for diagnostic or treatment purposes.
In the July letter, the FDA apparently took issue with statements made in Roche’s June 25 press release announcing the official launch of the AmpliChip. The Swiss drug and diagnostic giant designed the microarray, which is manufactured by Affymetrix.
“We would like to invite you to come in to discuss the basis for your apparent conclusion that this microarray is properly regulated under the analyte specific reagent provisions of FDA regulations, 21 CFR 864.2020,” the original letter said.
In the letter, the FDA said that after reviewing the press release and other Roche materials, it believed that the AmpliChip is not a reagent, but a multi-signal device, and one that is intended for use with a specific configuration of a proprietary accessory — the Affymetrix microarray platform. Therefore, the letter said, the AmpliChip is an assembled device that is part of a specific test system.
If this is the case, it would be subject to FDA review.
“They are not saying that our conclusions are not appropriate,” Christiane Koesling, a Roche spokeswoman, said at the time. “But they would like to discuss it. We look forward to working with the FDA.”
The FDA’s recent decision may also have implications for a number of other companies that hope to cash in on the so-called metabolism genes: For example, Finnish company JuriLab said it has developed its own cytochrome p450 chip, which is currently in beta testing and is due out at the end of the year; and Toronto-based Tm Bioscience said it plans to roll out the Tag-It Mutation Detection Kits for P450-2C19 in the first half of next year, and the Tag-It Mutation Detection Kits for P450-2C9 at the end of the year. However, it was not immediately clear whether any of these products will be marketed as ASRs.
Roche has placed a $70 million bet on the Affymetrix platform, announcing an 18-year licensing agreement with the Santa Clara, Calif., microarray giant in January, and then just months later, launching its first product, the CYP450 chip, to be sold in the US as an ASR, with the promise of more to follow. As SNPtech Reporter has said, the launch was delayed by four weeks (see 6/6/03 SNPtech Reporter].
— KL and MOK