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As Gutman s OIVD Debates Future of ASR Regs, Two Stark Options Emerge


As the US Food and Drug Administration continues debating how to revise the 1998 analyte-specific reagent regulations, a person familiar with the agency’s decision-making process increasingly believes it will choose one of two options.

Last year, Steve Gutman, director of the US Food and Drug Administration’s Office of In Vitro Diagnostic Device Evaluation and Safety, “had talked about revising the regulation,” said Thomas Tsakeris, president of Devices and Diagnostics Consulting Group of Rockville, Md. “Lately, he’s been falling back and saying, ‘Maybe we don’t need to revise the regulations.’”

The two most probable options that the agency will likely choose are issuing a notice of proposed rule making or releasing a draft guidance for industry, Tsakeris told SNPtech Pharmacogenomics Reporter this week. Each option is starkly different in its application, and will affect the molecular diagnostics industry in different ways.

The first option, which is also known as an NPRM, is a proposition to amend or modify an existing regulation. If approved and passed, “it means, ‘These are the rules, and if you break the rules, our enforcement of the rules will have more teeth,” said Tsakeris. The guidance option, on the other hand, is more flexible, and illustrates the FDA’s “current thinking” on a given topic. “If somebody has a different interpretation of what the guidance says, the FDA is always willing to entertain it.”

Tsakeris said the FDA “doesn’t want to be in a situation where their actions force a chilling effect on technology.” He recounted steps taken by the agency in the 1990s, a decade during which the FDA was known for being a strict enforcer of rules. “This took the form of stepping on a lot of toes, because there [were] a lot of egregious violations in the [research-use only, investigational-use only] area,” he said. “It was ripe for enforcement.”

So the agency made “a couple of examples of certain companies, and it had this chilling effect. The agency doesn’t want to be in that situation again, because they were actually creating a public health crisis.”

Asked if he believes that Gutman has begun to sense unease from the industry, and has therefore begun leaning toward the guidance option, Tsakeris said: “I would say that was probably true.”

“It’s much easier to issue a guidance, and then to use it, even in an enforcement way, than it is to go through an NPRM route,” he said. “That puts a lot of resource demands not only on the FDA and Steve Gutman and his group, but it ... has to clear the lawyers, it has to go through [the Office of Management and Budget]. All of that burns up resources.”

Like guidance documents, NPRMs require that industry has a chance to respond to it and suggest revisions or addenda. But while the FDA is not obligated to revise a draft guidance to include these suggestions, the agency is obligated in the case of a proposed rule “to specifically address every commenter, and then publish their response in the Federal Register,” Tsakeris said.

Asked to respond, Gutman said the NPRM and guidance choices “are certainly at least two options. I’m not sure that exhausts all the options, but those are reasonable options.”

He said other choices that OIVD currently faces include “doing nothing, less formal communications, statutory changes, and work through HHS and other mechanisms of incremental regulations.” He declined to say which the OIVD may likely choose.

The decision by the FDA to consider revising the ASR regulations was made after the agency questioned whether Roche Diagnostics could market its AmpliChip product as an ASR. Roche was recently forced to pull the product from the clinical market [see i>11/6/03 SNPtech Pharmacogenomics Reporter]. Read the ASR regulations here.

The FDA “has known … for a while” that some companies have been bending the ASR regulations, “but hasn’t done too much unless very, very specific diagnostic claims were made” in advertising or other literature, Ron Eisenwinter, a regulatory specialist at Boston Healthcare Associates, said at the time of the Roche letter.

“It’s no surprise to anybody in the diagnostic industry that the FDA is looking very closely at their regulation on ASRs,” Bill Pignato, vice president of regulatory affairs at Exact Sciences, added at the time. “For a number of reasons, the agency feels that … there’s a need to

Pignato, who regularly attends OIVD roundtable meetings, believs that Gutman’s group will wind up rewriting the regulation rather than go the guidance route.

He also stressed that the AmpliChip issue did not spur the agency to consider revising the document, but may have been the straw that broke the camel’s back. Although the agency had been considering amending it since January 2003, he said Gutman announced at a roundtable meeting July 11 — three days after sending the Roche letter — that he plans to rewrite it.

Commenting on that meeting, Pignato said it was “very clear that [the FDA is] in the process of rewriting the rule and issuing it as a proposed regulation.” He said it will be an amendment of the existing regulation, and will be through a public-comment period.

“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.

— KL


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