Clinical laboratory groups plan to mount a major push against the FDA’s efforts to regulate lab-developed tests at a Jan. 8 and 9 public meeting, arguing that the FDA’s plans will hinder LDT development and use.

Some groups even question whether the FDA has the statutory authority to regulate LDTs. “We have always maintained that we do not believe these are medical devices,” says Alan Mertz, president of the American Clinical Laboratory Association. “These are laboratory services, used during the practice of medicine, and are not sold commercially.”

And even if the FDA did have authority over LDTs, the ACLA believes the agency can’t regulate them simply by issuing a guidance document, the approach the agency is taking, but only through formal rulemaking. Using the guidance process allows the FDA to avoid rulemaking provisions that require the agency to respond to each comment on a new rule, as well as conduct an economic analysis of how regulations will impact industry, Mertz says.

Labs Challenge Use of Guidance

Attorney and FDA regulatory expert Gail Javitt agreed the decision to proceed with guidance may not be legal. She noted that the regulations defining medical devices exempt clinical laboratories from FDA registration and listing requirements.

The proposed guidance advises LDT makers to voluntarily notify the FDA of LDTs being developed; it makes no reference to listing or registration. However, the notification standards would ask for more extensive information than is typically required in device registration and listing, such as updating the information every time the laboratory makes a significant change. She says the agency is disregarding longstanding principles of agency law and administrative procedure in the way it is proposing the new requirements.

But AdvaMedDx President Andy Fish says the FDA’s authority to regulate LDTs is covered under longstanding diagnostics rules, so guidance is appropriate. The comment period on the guidance, which ends Feb. 2, and public meeting will allow adequate opportunities for all stakeholders to be heard, he says.

AdvaMedDx firmly supports FDA regulation of LDTs because the tests are now increasingly sophisticated, are relying on molecular diagnostics, and are now being used to diagnose and choose treatment for critical life-threatening conditions even though there is no FDA or other third-party review for the tests. Further, he says, the FDA’s plan to phase in the requirements over nine years and apply a risk-based approach to overseeing the LDTs provide LDT makers with enough protection against being overwhelmed by new regulatory requirements.

The proposal has been controversial since it was announced this summer, with some touting FDA regulation as a win for patient safety while others see it as an FDA overreach that could be expensive for industry and destructive to patient access. A total of 83 representatives from manufacturers, trade groups, research organizations and patient advocacy organizations are scheduled to offer public comment during the meeting.

Revisions Rather Than Overhaul Urged

Roger Klein, president of the Association for Molecular Pathology, says his group proposes modernization of the Clinical Laboratory Improvement Acts instead of an FDA takeover of LDT regulation. He believes that several of the FDA’s proposed changes would impose high costs on labs for little benefit.

For example, he says he has never seen death or a serious injury directly caused by the design of a lab test, and notes that CLIA already requires problems with tests be reported to physicians. The costs of maintaining a formal adverse event reporting program would be substantial for a lab and offer no benefit. If adverse event reporting is imposed at all, he believes it should be limited to labs making FDA-cleared tests.

The ACLA’s Mertz also expresses concerns over the costs, noting that diagnostics makers who obtain FDA approval often spend $10 million to $20 million on the process – more revenue than many LDTs ever generate, he says.

Several speakers say they plan to urge the proposal be modified in ways that would place labs and IVD manufacturers on equal footing. Sam Rua, vice president of regulatory affairs and quality systems at genomic testing start-up HTG Molecular Diagnostics, says he supports most of the guidance but finds parts of it overly restrictive. For example, the proposed guidance would say tests only qualify as LDTs if they are designed and manufactured entirely within a lab. “The FDA allows IVD manufacturers to use contract manufacturing,” he says. “Labs should be allowed to do the same thing.”

Sharing LDTs Should Be Allowed

The FDA’s proposal to exempt tests used within a single research hospital from oversight also caused some concern. High-quality programs such as those at the Mayo Clinic or Cleveland Clinic sometimes share tests they have developed with smaller hospitals via outreach programs, Roger Klein of AMP says. But that informal sharing would seem to be banned under the FDA proposal.

Klein also questions a provision in the regulations that would define any lab that modified a cleared test as a re-manufacturer and subject to clearance requirements. “It’s important to understand these types of modifications happen very regularly,” he says, noting that sometimes tests are validated on one specimen type but may be modified to accept others as well. If labs had to notify the FDA every time they did this, labs would simply stop doing it. He wants the FDA to allow labs to use LDTs off-label, just as physicians may use drugs off-label.

Despite all the disagreement, HTG Molecular’s Rua says he hopes the meeting allows industry and the FDA to find common ground. “Everybody understands that laboratories can get tests out much quicker than IVD manufacturers and that’s in part due to the regulatory hurdles,” he says. “I hope this will get more parity so the FDA is looking at the IVD community and labs under the same lens, with a similar least-burdensome approach.”

The meeting is set to be webcast. View a speaker list and other information at www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm423537.htm. — Elizabeth Orr