Roche and two competitors, Gen-Probe and Becton Dickinson, are asking the US Food and Drug Administration to consider a new category of in vitro diagnostic test — in vitro analytical tests, or IVATs — and a new path for companies seeking regulatory approval to market these devices, BioArray News, a SNPtech Reporter sister publication, has learned.
The request was made in the form of a 19-page submission to the FDA signed by Bradley Merrill Thompson, a partner of the Indiana-based law firm of Baker Daniels, on behalf of regulatory officials from Roche Diagnostics, Roche Molecular Diagnostics, BD, and Gen-Probe.
The companies’ suggested draft defines an IVAT as “an in vitro diagnostic test for which analytical validity has been established.” It suggests that IVATs should be approved for marketing through an analytical 510(k) clearance “based on review of the same analytical data that FDA now examines in premarket notification submissions.”
What the draft suggests “is a traditional 510(k) minus the clinical trial, and a claim for a normal range,” said Glen Freiberg, vice president of regulatory quality and government affairs at Gen-Probe. “The forms are the same, and the analytical claims are the same. It is just shortening the time to get something to market that is usable and of value without the clinical information” — precisely the sort of change that would benefit Roche’s AmpliChip, an ASR, if it is required to undergo a 510(k) approval process, which the FDA has intimated may be the case.
Microarrays, Freiberg said, are a different challenge.
Indeed, the suggested guidance, obtained by BioArray News, does not address microarray-based technologies specifically but does give examples where microarray-based technology is commonly used today in research laboratories — for example in genetic tests measuring the presence or absence of an analyte like a gene or a gene product.
The document speaks of innovative technologies, and said that the authors will submit “technologies for which this proposed guidance would seem suitable” and would consult with other members of the IVD industry, trade associations, and members of the clinical industry and clinicians.
Roche’s AmpliChip is not mentioned, and the link between IVATs and ASRs is not fully clear. However, some industry insiders who have read the suggested draft and are familar with the existing ASR regulations said some items in the new draft “may” directly impact ASRs [read the draft here: www.snptech.com/LINKTO/IVATdraftguidance.pdf. An analysis appears on page 4].
The companies’ draft guidance suggestion comes at a time when one of them, Roche Diagnostics, is facing an FDA-requested meeting to discuss why its AmpliChip microarray product is marketed as an analyte- specific reagent. Roche rolled out the CYP450 AmpliChip with a press release on June 25 that triggered a letter from the FDA two weeks later requesting the meeting.
For Roche and its ASR plans — not to mention the broader molecular diagnostics and pharmacogenomics drive — the stakes are high. The Swiss drug and diagnostics giant has entered into an 18-year, $70 million collaboration with Affymetrix to produce the AmpliChip. In introducing the product, Roche said it expects revenues of $100 million within five years. If the FDA rules that the AmpliChip requires a premarket approval, rollout could be delayed by years, and potential benefits to patients delayed even more.
Representatives from Roche and BD did not return multiple telephone calls seeking comment.
The FDA has regulated ASRs for use in in vitro diagnostic devices since 1998, but the AmpliChip case may represent a challenge to its ability to define and regulate ASRs that are microarray based. The agency has been candid in admitting a lack of expertise about how to regulate this, and other, early-stage genomic technologies. However, the FDA is working to learn through workshops and meetings with industry.
The date printed and stamped on the draft’s cover letter — June 17, 2003 — suggests that it was submitted days before Roche introduced its AmpliChip CYP450 microarray product.
The document is presented in the form of an official agency guidance, down to the front-page e-mail address of Steven Gutman, the director of the agency’s Office of In Vitro Diagnostic Device Evaluation and Safety. Gutman’s office has been spearheading the agency’s regulatory initiatives for ASRs.
Gutman on Monday told BioArray News that the agency has received the document and is reviewing it. He said he could not comment on the specifics of a document under review.
“We are working as proactively as we can to consider the regulatory options for helping expedite the transfer of technology to the marketplace, and we are working as proactively as we can to get products approved,” he said. “There is a clear end-point, but the journey there is quite colorful.”
Gutman said the document’s formatting in the form of an official guidance is not unusual. He said there are no standard-operating procedures for the FDA to consider such a draft, and would not guess at any time frame for a decison.
According to the document’s cover letter: “Our intent was to describe a process that would bring ‘innovative technologies’ to market.” The suggested draft should apply to new technologies as well as improvements on existing devices.” The authors saidd the agency should be flexible in the application of this process.
Manufacturers would have the option to pursue this analytical clearance, based on the establishment of analytical validity. The FDA would have 60 days to make a determination on clearing the IVAT for marketing.
Recently, Henry Nordhoff, CEO of San Diego-based Gen-Probe, which manufactured the first nucleic acid-based testing products, approved by FDA in 1985, pointed to Roche and Becton Dickinson as its chief competitors in the DNA probe testing market.
In that context, the draft’s signatories exist on the periphery of the microarray industry, but their collaboration indicates the financial potential of a clinical marketplace where mass-produced, microarray-based diagnostic devices are in every doctor’s office and clinic, helping realize the far-off dream of personalized medicine.
Gen-Probe’s Freiberg said the FDA’s OIVD will discuss the suggested draft during an industry roundtable on Oct. 24.