This story has been updated with a statement from Beckman Coulter.
CHICAGO – More makers of clinical decision support software in genomics and in vitro diagnostics may have to submit their products for US Food and Drug Administration (FDA) review, thanks to new guidance spelling out how the FDA will regulate such technology.
As required by the 21st Century Cures Act, the FDA recently finalized guidance for industry and agency staff on what kinds of software it will consider medical devices and what types are exempt. The Cures Act made changes to section 520 of the Food, Drug, and Cosmetic (FD&C) Act regarding the definition of different kinds of medical devices.
While the document is nonbinding, it indicates current FDA thinking on how it will regulate clinical decision support software and what kinds of technology should to be submitted to the agency for 510(k) review.
However, 510(k) clearance is not necessarily required. "You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations," the agency said in the guidance.
"I think primarily what the guidance is now attempting to do … is interpret that statutory carve-out instruction from the definition of a medical device in law," said Gregory Levine, a Washington, DC-based attorney with Ropes & Gray who specializes in FDA regulation.
Levine said that the document is essentially a roadmap for what the FDA plans on regulating. "Just because something is not statutorily exempt from being a device doesn't mean that FDA is going to choose to regulate it," he said.
Levine noted that the FDA has considerable leeway in what it can or cannot regulate. "They can still exercise enforcement discretion, which they do all the time," he said.
The FDA cited several examples of device software functions that it would concentrate its regulatory oversight on, including analysis of digital pathology images, treatment recommendations based on VCF files for identifying variants and mutations, and identification of chemotherapies based on "pathologist-confirmed" biopsy results.
The guidance document referred to next-generation sequencing as a "signal acquisition system" that does not meet all four FD&C Act criteria for exclusion from regulation, and therefore is subject to FDA scrutiny. Software that processes and analyzes NGS data to identify variants also may be regulated.
Other non-device CDS software functions the FDA cited in the guidance included the recommendation of therapies and preventive screening based on specific genetic mutations including BRCA1 and EGFR.
Kyle Faget, a healthcare and life sciences attorney with Foley & Lardner in Boston, said that this document in some ways goes farther than an earlier draft in 2019 in that it introduces the idea of "automation bias," or what Faget called "time-critical decision-making." Software that identifies or quantifies risk for a specific patient probably will be regulated, she said.
"Any time that the software functionality is going to be used with a certain level of software automation, and there's a time-critical nature of the healthcare provider's decision-making, FDA is leaning on the concept of automation bias to make a determination that that should be regulated," Faget said. "That wasn't even a concept that was raised in the 2019 draft guidance."
The FDA did say, however, that it would be more hands-off with consumer-facing devices than it called for in the 2019 draft.
Shortly before issuing the draft guidance three years ago, the FDA began stepping up regulatory actions against laboratories offering pharmacogenetics services without premarket clearance or approval in an apparent attempt to prod more firms to submit their tests for regulatory review. Many industry players said then that the agency's communications had been vague, lacking specific guidance as to what companies should do to come under compliance.
"As history shows, burgeoning healthcare sectors benefit from clear and effective regulatory pathways," Kelly Sager, VP and general manager of clinical decision support solutions for Beckman Coulter, said in a statement provided to GenomeWeb. "The US FDA guidance ... provides yet another level of clarity when it comes to CDS software function. We are aligned with the agency’s guidance and are developing our solutions accordingly.”
Several other medical device, electronic health records, and clinical decision support software vendors contacted by GenomeWeb declined to comment on this new, final guidance, as did two industry associations.
While some — perhaps most — will object to having their software treated as medical devices, Faget suggested that some may take comfort in having clarity rather than the ambiguity that was present in the draft. "Clarity can, in the long run, actually lead to greater efficiencies, because at least you know where you stand," she said.
Regardless, they will have to review their own products. "I think all developers, because it's different than what was [presented] in 2019, are going to have to go back and think through their regulatory strategy and make a determination anew whether or not they're subject to FDA oversight," Faget said.
Levine agreed that the decision to regulate CDS recommendations around risk scores may be controversial. "Clearly, what FDA's judgment is there is that they think they need to do that from a patient safety perspective," he said.
He also suggested that medical device and bioinformatics software developers reassess their standing in the eyes of the FDA in the wake of this guidance.
"Do you feel still comfortable with your position either because you think it's still congruent with FDA current guidance or frankly because the guidance is nonbinding and you think your software is actually within the statutory provisions?" Levine said. "Software developers need to look at their individual situations and see where they stand."
Faget said that she is advising clients to look at how much risk they are exposing themselves to by having or not having FDA clearance for their product.
"Anything that is providing specific preventative diagnostic or treatment output or directives is going to be regulated," Faget said. "I think that it's going to be more expensive for developers to go to market."