The Roche Molecular Diagnostics' microarray, the AmpliChip CYP450, may not enter the market without an agency premarket approval, the US Food and Drug Administration said this week.
The agency opted not to make a determination on whether or not the AmpliChip is an analyte specific reagent.
In a letter dated Nov. 4, 2003, and signed by Steve Gutman, director of the Office of In Vitro Diagnostic Device Evaluation and Safety of the agency's Center for Devices and Radiological Health, the FDA said it completed a review of the status of the AmpliChip CYP450, which was launched into the market on June 25. Click here to view the letter.
"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 said.
"The AmpliChip cannot be commercially distributed without an appropriate premarket determination from FDA. We recommend that Roche submit a premarket notification," the letter said.
In July, as first reported by BioArray News (see BAN, 7/10/2003) the FDA summoned Heinrich Dreismann, the general manager for Roche Molecular Diagnostics, to come to the agency to discuss why the company was marketing its AmpliChip microarray as an analyte specific reagent. Gutman issued what is termed an untitled letter to Dreissman, and had it delivered by overnight courier.
The letter was in response to statements made in a June 25 announcement issued by Roche Diagnostics at the official launch of the AmpliChip CYP450, a microarray of its own design, manufactured by Affymetrix.
The first FDA letter said that, based on review of the press release and other Roche materials, 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. The Nov. 4 letter determined that the product is subject to the agency's pre-market review.
Roche told SNPTech Reporter, BioArray New's sister publication, that the company has decided not to sell its AmpliChip product as an ASR. However, the company still expects to seek regulatory approval in the US in 2004 so that the AmpliChip may be sold as an in vitro diagnostic. And, based on receiving that approval, the company still targets revenues over $100 million by the year 2008.
"Roche will not make the product available as an ASR," a Roche Diagnostics spokeswoman said. Roche, however, will continue to provide it as a research product for use by pharmaceutical companies in clinical trials, which does not require FDA approval.
"The OIVD has determined that it is unnecessary to decide whether the product is an ASR or not. It is a very fuzzy thing for them to say," said Melinda Baker, the Roche spokeswoman. "We clearly accept the agency's position on this."
Last week, Joseph Hackett, associate director of the Division of Clinical Laboratory Devices of the US Food and Drug Administration's Center for Devices and Radiological Health, in a presentation at the Chips to Hits conference in Boston, said "We do not think microarrays are ASRs." He said the agency's lawyers were reviewing the matter and with hopes of producing a document before Thanksgiving.
Those seven words now seem to be the epitaph for Roche Diagnostics’ hopes of getting its AmpliChip CYP450 microarray out into the marketplace quickly.
FDA Steps Up
Hackett’s remarks came at a time of increased visibility for officials involved in the integration of genomic tools and data into the agency’s regulatory efforts. They seem to signal that the agency is preparing to make decisions that will affect the path that microarrays will have to travel from the relatively unregulated world of the laboratory benchtop to the regulated environment of the US healthcare system.
Previously, FDA officials have been candid in admitting a lack of expertise within the agency in how to regulate early-stage genomic technologies and their data, and have reached out to industry for dialogue and input in framing regulatory policy.
Last week, BioArray News reported that the agency, based on advice from its general counsel, had opted not to approve (See BAN, 10/29/2003) for comment an industry proposal for creating a regulatory category, a new class of analyte-specific reagent called an in vitro analytic test (IVAT). Some saw this category as a new route for microarray-based tests to gain regulatory approval without first completing clinical trials.
Then, on Monday, the FDA released a draft of a guidance (pdf) document on industry pharmacogenomics data submissions that “encourages drug and biologic developers to conduct pharmacogenomics tests during drug development and clarifies how FDA will evaluate the resulting data,” the agency said in a statement.
“Pharmacogenomics is a new field, but we intend to do all we can to use it to promote the development of medicines,” Mark McClellan, the FDA commissioner, said in a statement.
The FDA’s statement said the draft guidance is the agency’s “first step toward integration of this new field into the process of demonstrating that new drugs are safe and effective, and thus the regulatory guidance is intended to facilitate this integration.”
The guidance, the FDA said, provides specific criteria and recommendations on submission of pharmacogenomics data to investigational new drug applications and new drug applications, and biological license applications. The guidance includes information on what data is needed, and how the FDA will or will not use such data in regulatory decisions. The agency is asking for voluntary submissions, and says that it will not use such data in regulatory decisions.
While the guidance document may be the first step toward integration, it is not the FDA’s initial foray into genomics. The agency has a robust research agenda for using microarrays in-house; it is creating an informatics infrastructure to accept genomic data with new drug submissions; and it has actively been seeking industry counsel in how to evaluate genomic data.
But perhaps the FDA’s most high-profile regulatory effort involving microarrays have come to bear on Roche Diagnostics.
“A PMA [Premarket Approval], and you’re talking three years-plus” to get approved, Ron Eisenwinter, a regulatory specialist at Boston Healthcare Associates-Expertech, told BioArray News in July (See BAN, 7/23/2003).
— MOK and KL