NEW YORK – In August, the US Department of Health and Human Services said that the Food and Drug Administration would not require premarket review of laboratory-developed tests without notice-and-comment rulemaking.
The announcement surprised many in the lab industry, and since then, industry stakeholders have scrambled to parse the implications of the move.
One question of interest is the status of home collection devices used in sampling for LDTs and the extent to which such devices remain subject to FDA regulation.
HHS has not provided detailed guidelines regarding the status of home collection, but several observers suggested that while FDA might still technically retain the authority to regulate these devices, it was unlikely do so in most cases given the current political climate.
This could impact labs across the industry and is at the moment especially relevant to SARS-CoV-2 testing, where a number of laboratories have developed or are developing tests using home sample collection.
Take, for instance, a saliva-based LDT for SARS-CoV-2 where patients collect and send in samples for testing. Prior to the HHS announcement, the entire test, from sample collection through to the laboratory portion of the assay would have been subject to the FDA Emergency Use Authorization process. Following the HHS move, SARS-CoV-2 LDTs no longer have to receive EUA. The question is whether a home collection device can be considered part of the larger LDT or if it is considered a separate device, in which case it could still fall under FDA's purview and require EUA.
In response to an inquiry about the status of home collection devices, an HHS spokesperson said that "generally, a collection device by definition is a device unto itself and subject to regulation notwithstanding the status of the LDT. Swabs, for example, used for standard PCR testing are devices without regard to the nature of the underlying test."
This would seem to indicate that collection devices remain subject to FDA oversight and, in the case of SARS-CoV-2 LDTs, the EUA process. However, Jeff Gibbs, a director at the law firm Hyman, Phelps & McNamara, who formerly served as FDA's associate general counsel for enforcement, said that the HHS statement did little to clarify if FDA would continue to regulate the use of such devices in LDTs.
"While it is true that a product designed to collect samples is a device, that does not necessarily mean that it needs to be separately regulated when incorporated into an LDT," he said. "LDTs often incorporate products that have not undergone FDA review, including RUOs, general purpose laboratory equipment, and devices that are not labeled for use with the test being offered by the laboratory."
"Even pre-COVID, pre-EUA, you had labs that were saying, we have a new collection device, just like there is new software, just like there might be a new instrument that is RUO, a reagent that is RUO, and we are going to consider this [collection device] to be part of the entire assay," Gibbs said, "which is reasonable, because FDA thinks of assays as systems from collection to the final result."
In some cases, FDA has gone after labs taking such an approach, he said, though more often, the agency did nothing. "You had many companies that were offering lab-developed tests that had samples collected by new devices that did not come through the FDA process."
He said that there was no obvious distinction between the cases in which FDA did decide to regulate an LDT collection device and those where it did not.
Gibbs said that a lack of action by FDA does not mean the agency has determined affirmatively that something is permissible, but it was unlikely the agency would attempt to tighten its standards following the HHS announcement pulling back its authority over LDTs.
"It would be surprising if FDA said, we're not going to regulate the lab, but we are going to regulate the collection device the lab uses," he said, adding it would be a way of regulating LDTs through the backdoor. "FDA could do that, but in light of what HHS said, it would be surprising if they did it."
James Boiani, an IVD, drug, and medical device life sciences attorney at Epstein, Becker & Green in Washington, DC., similarly suggested FDA would likely take a hands-off approach to the question.
Had HHS not intervened and "we were just dealing with [FDA's] normal LDT enforcement discretion policy, I would say it was very likely that FDA would act," he said. "But given that HHS overruled them and apparently wants to get more tests out there, whatever way possible, I think enforcement is less likely unless and until there is a problem."
Like Gibbs, he highlighted FDA's past inconsistency around regulating collection devices. For example, Boiani said, a lab could bring in a collection device for general use and distribute it with its LDT.
"If FDA wanted to, they could come in and argue, this isn't a general use product anymore, you are the manufacturer of the LDT and you are distributing this specifically for that use, and you don't have FDA approval specifically for that use, so we can ding you."
In such cases, the agency has often either looked the other way or treated the collection device as part of its LDT enforcement discretion, he said, but if he were advising the developer of a SARS-CoV-2 LDT, he would still recommend they take their test through the EUA process.
"I would be concerned not really about the FDA piece but about liability protection," he said, noting that tests that receive an EUA qualify under the Public Readiness and Emergency Preparedness (PREP) Act for limited liability immunity.
If something were to go wrong using the collection device with the LDT without having received Emergency Use Authorization, "could become a really big problem, not just for the people it affects, but for the [lab] client," he said.