The FDA is considering changes in its regulations for analyte specific reagents, Steve Gutman, the director of the agency’s Office of In Vitro Diagnostic Device Evaluation and Safety, part of the Center for Devices and Radiological Health, this week.
The FDA’s ASR regulations were written in 1997 and enacted in November 1998 (read the original document here).
“We are working on a notice of proposed rule making, so we are in a very public manner going to discuss possibilities for rewriting” the 1998 document, Gutman said. He said it would take “months, or possibly a year or so” before his group has enough information to compose new regulations.
FDA experts “have identified what they thought were gaps in the regulation in genetic tests,” and will therefore rewrite the ASR document either as an amendment to the original regulation, or as a completely new document, he said.
Gutman’s comments follow a July 8 letter, drafted by his group, addressed to the chief of Roche Diagnostics, taking issue with the company’s marketing of its AmpliChip CYP450 product as an ASR and inviting Roche representatives to come to the agency’s office to discuss the matter.
The letter may mark the beginning of a process that will ultimately determine the path that microarrays must follow in order to make the leap from the research laboratory benchtop to the lucrative clinical marketplace. Today, microarrays are an evolving technology some eight years old, and one that is just beginning to attempt to match up against rigid scientific standards of reproducibility and accuracy.
FDA officials freely admit a lack of deep and intimate knowledge of this technology, which is just beginning to come to the diagnostics market packaged as an ASR. However, FDA followers say that Gutman has been hinting for some time that companies may be stretching the definition of ASR in order to ease a product into market, and the untitled letter to Roche, which can be read here, is seen as the first manifestation of these hints.
The FDA “has known about [alleged rule bending] for a while, but hasn’t done too much unless very, very specific diagnostic claims were made” in advertising or other literature, said Ron Eisenwinter, a regulatory specialist at Boston Healthcare Associates-Expertech.
The Roche Letter
The FDA’s letter to Roche has not touched off a blizzard of coverage in the mainstream media even roughly comparable to the number of stories that followed the launch of the product at a Basel, Switzerland, event in June. However, it is an issue of importandce for the molecular-diagnostics industry, and microarray manufacturers with sights set on a more lucrative market than the labs of pharma, biotech, and academia.
At the crux of the OIVD letter to Roche Diagnostics General Manager Heinrich Dreismann is the FDA’s questions over how the company can market its AmpliChip product as an ASR. In the letter, the FDA said that Roche claimed in a June 25 press release that the AmpliChip is a multi-signal device that may only be used on the Affymetrix platform [read the press release here].
“The AmpliChip microarray appears to be an assembled device that is part of a specific test system,” the letter said.
The letter also intimated that the AmpliChip is a “‘diagnostic tool’ that provides information about an individual’s genetic make-up for selection of drug therapies to treat ‘cardiovascular disease, high blood pressure, depression, ADHD, and more.’
“Given these claims,” the FDA letter continues, “it appears that the AmpliChip CYP450 is a medical device” that may require pre-market approval. “Based on the press release and other materials about the AmpliChip obtained from your company, FDA is concerned that your device would not properly be classified as an ASR,” the FDA said.
“I think that is where Roche is going to get into trouble — that they made diagnostic claims” about a product they claim is an ASR, said Eisenwinter.
Meantime, Bill Pignato, vice president of regulatory affairs at Exact Sciences, agreed, saying he believes the FDA thinks there has been a “misrepresentation of the [ASR] rule.”
A regular attendee at OIVD roundtable discussions, Pignato said that the AmpliChip issue is not the spur that will lead the agency to rewrite the lengthy regulatory document. The agency has been considering amending it “for the past six months,” he said.
“Because of the change in the landscape in the technology, I think the FDA really feels there’s a need to revise the rule and bring further clarity on what an ASR is and what an ASR is not,” Pignato said.
Upside, or Downside
It remains to be seen whether Roche will be censured — or what its punishments might be — if the FDA concludes the diagnostics giant overstepped its bounds. The agency does not comment on ongoing compliance issues.
Roche may encounter one of three likely outcomes, according to interviews with industry insiders, analysts, and consultants. One option is that nothing will happen, and that both parties will agree “it was a misinterpretation on the part of the FDA,” according to one analyst.
Another potential outcome is that the AmpliChip, as it is currently marketed, will undergo a pre-market review. The third option lay someplace between the first two.
Expertech’s Eisenwinter said, hypothetically, that if the FDA concludes that the AmpliChip could not be marketed as an ASR, Roche would be required to halt selling the product and submit a 510(k).
But if Roche’s product is the first of its kind on the market, “then it’s a PMA, and you’re talking three years-plus” to get approved, Eisenwinter said.