The warning letter Nanogen received last week from the US Food and Drug Administration will not affect approval of the company's NanoChip 400 System, and it is unlikely to alter the company's plan to offer the device into the same lab market to which it is accused of improperly marketing its Molecular Biology Workstation.
"This letter does not impact pre-market clearance work," Steve Gutman, director of the FDA Office of In Vitro Diagnostic Device Evaluation and Safety, wrote in an e-mail to Pharmacogenomics Reporter this week.
"We intend to work with the FDA to explain our position, and we will modify our marketing or the wording of our website if it is jointly determined to be misleading," Nanogen's chief financial officer, Robert Saltmarsh, wrote last week in an e-mail to BioArray News, Pharmacogenomics Reporter's sister publication. "We have an ongoing dialogue with the FDA and take compliance and the FDA's opinions seriously."
The Aug. 12 OIVD warning letter said the company's test system was "adulterated ... for failure to obtain pre-market approval and misbranded ... for failure to notify the agency of your intent to introduce the device into commercial distribution as required" by the FDA's 510(k) clearance process. According to the regulatory office, materials on Nanogen's website described the firm's Molecular Biology Workstation, NanoChip microarrays, and analyte-specific reagents as clinical diagnostics tools.
"A review of our records indicates that you have not obtained clearance or approval for this test system as a whole or for the components separately."
According to the OIVD letter, the products "appear from the information on [Nanogen's] website to be marketed to work together as an integrated test system." This test system "is a medical device," according to FDA regulations, "because it is intended for use in the diagnosis of disease or other conditions," the letter stated.
Gutman wrote in an e-mail exchange with Pharmacogenomics Reporter that the FDA does not comment on active compliance cases. In most cases, companies in receipt of a similar letter "work with FDA to remedy outstanding issues, and after informal or formal interactions, in most cases these are resolved."
In an interview with BioArray News, Gutman declined to discuss what may have prompted the letter from the FDA, especially since Nanogen's system has been on the market since 2001.
If Nanogen and the FDA don't see eye to eye, the FDA "has a variety of tools that can be applied to encourage conformance with regulations and statutes. Besides warning letters, these tools include seizures, injunctions, and civil money penalties," Gutman wrote in the e-mail exchange.
What Did the Letter Say?
Interestingly, Nanogen said in an SEC filing last week that it had received an "untitled letter," while Gutman said that the company had been sent a "warning letter," which is more serious. The letter presented on the OIVD website reads, "warning letter."
"A warning letter tends to be a little more formal than an untitled letter, but they both are considered prior notice that the FDA wants to engage in dialogue with a firm," Gutman told BioArray News.
The letter itself contains numerous examples of instances in which the FDA believes Nanogen's marketing crossed the regulatory line. "A review of our records indicates that you have not obtained clearance or approval for this test system as a whole or for the components separately," it said.
The agency cited "contradictory statements" in Nanogen marketing materials that "suggest that these products are intended for research use, while others indicate that they are intended for use in clinical diagnostic applications."
The company "appears to be suggesting that its NanoChip System comprises research-use-only devices," but "it is not apparent that Nanogen is complying with the requirement applicable to research-use-only in vitro diagnostic devices," the letter said. The NanoChip platform "does not appear" to qualify as a class I system, which would exempt it from the pre-market approval requirement, the warning said. The FDA requested that Nanogen respond within 30 days of receipt of the letter.
In its SEC filing, Nanogen officials denied any wrongdoing, but pledged to work with the FDA to resolve the matter.
The NanoChip 400
It is fortunate for Nanogen that the warning letter will not affect pre-market approval of other products — the company is preparing its NanoChip 400 System for commercial release later this quarter [see BAN 8/10/2005]. The company plans to market the system for clinical diagnostic uses after it receives FDA clearance, which should happen next year, the company said.
"The [NanoChip 400] is an open platform [system] that can be used in both the research market and clinical diagnostic markets," Saltmarsh, Nanogen's CFO, told BioArray News last week. "FDA approval would broaden it to the clinical diagnostic market so we have planned to obtain FDA clearance. We'll determine a timeline and the specifics for FDA marketing clearance of the [system] after we respond to the agency's current questions," he said.
Saltmarsh said the company will not seek FDA approval for the NanoChip Molecular Biology Workstation. "The MBW has overwhelmingly been sold into the research market, so seeking FDA approval of this is unlikely," Saltmarsh said.
"The Molecular Biology Workstation was never built with the clinical lab in mind," Nanogen CEO Howard Birndorf said in an interview with BioArray News last autumn. "It's being used in clinical labs, [but] it was built for the research market. [The NanoChip 400] was built with the clinical research/diagnostic lab in mind" [see BAN 11/3/2004]. The MBW was designed for high-throughput experiments, said Birndorf, while the NanoChip 400 would allow users to tailor lower-throughput, specific assays.
Nanogen's letter comes approximately two years after the FDA asked Roche why it believed at the time that its AmpliChip product could be marketed as an ASR. The eventual result of that letter was the decision by Roche to forego its original plan to release the product as an ASR and instead to seek FDA clearance for the AmpliChip as an in vitro diagnostic. The FDA approved the AmpliChip as an IVD in January.
The FDA's Gutman recommended that companies with similar products "should review the ASR regulations and if they have questions about conformance with these, contact the FDA."
— Chris Womack ([email protected])