FDA officials attempted to allay concerns about the agency's pending regulatory framework for laboratory-developed tests at a meeting hosted by the American Clinical Laboratory Association Nov. 22.

But until draft guidance detailing FDA's thinking on the matter is released, members of the laboratory community say they are left with more questions than answers.

"We all agree that we want to provide the highest quality testing to our patients," Franklin Cockerill, chair of the laboratory medicine and pathology departments at Mayo Clinic, said at the meeting. "What we don't want to get into is redundancy and added costs."

The meeting participants honed in on three questions: what constitutes an LDT; what are the key issues involved with registering clinical labs as medical device manufacturers and listing LDTs as medical devices; and what are the potential overlaps, gaps and efficiencies between future FDA regulations and existing laboratory oversight.

The meeting in Washington, D.C., was the first in what ACLA hopes will be a series exploring issues related to FDA regulation of laboratory testing services.

What Is An LDT?

"This is going to be a long-term process," FDA diagnostics chief Alberto Gutierrez said.

Most recently, FDA defined an LDT, for the purposes of adverse event reporting, as "a clinical diagnostic test for use in the diagnosis of disease or other conditions that was developed by a CLIA-certified clinical laboratory for use in that laboratory."

An LDT is not an analyte-specific reagent, nor are its components for research use only, FDA stated.

That definition, which FDA says it is not necessarily committed to using across-the-board, would capture thousands of tests, many of which have been in use for decades, cautioned Peter Kazon, an attorney with Alston and Bird.

Further, an LDT is not a "thing," Kazon emphasized at the meeting. "It's not a kit in a box.”

The attorney and other lab stakeholders at the meeting questioned what aspects of lab testing services FDA proposed to oversee.

"An LDT is a process," Kazon said. "What is it that we're looking at regulating? Is it that entire process? Is it the thing that is comparable to the [test] kit?"

Courtney Harper, director of the division of chemistry and toxicology devices in FDA's diagnostics office, said any test performed in a lab is an in vitro diagnostic device, so the real question is over what products FDA will begin to exercise oversight.

"We've been fairly clear that in developing a plan for additional FDA oversight, we'd like to take a risk-based approach," Harper told meeting attendees. More information on which tests are considered higher risk would be most helpful to the agency, she said.

OIVD Director Alberto Gutierrez said the framework will be issued in the form of draft guidance, and that oversight would be phased in over time. FDA will attempt to address public comments and concerns in the draft, and there will be opportunity for additional comment before the document is finalized, he said.

Gutierrez could not predict when the document would be released. Another public meeting likely will follow.

"This is going to be a long-term process," Gutierrez said. "You'll have plenty of time to respond to the details and we will move forward from there."

No Conflict Between FDA And CLIA – Feds

Another key concern among lab workers is how FDA's regulatory plan will address and hopefully eliminate overlap with existing requirements under the Clinical Laboratory Improvement Amendments (CLIA).

"We can't have multiple different quality systems [or] multiple different validation approaches," Mayo Clinic's Cockerill said.

The CLIA program is meant to establish quality standards for laboratory testing to ensure the accuracy, reliability and timeliness of patient test results. CMS principally oversees the CLIA lab oversight process.

"A lot of the … activities that a laboratory might do to address the CLIA requirements probably will actually fulfill many of the requirements of the FDA quality system regulation" – FDA's Katherine Serrano

Lab stakeholders are concerned that additional requirements to comply with FDA's quality system regulation for device manufacturers would be redundant and costly.

The purpose of the quality system regulation is to ensure that devices consistently meet applicable requirements and specifications and are generally safe and effective for their intended use, FDA explains.

OIVD staffer Katherine Serrano presented general take-aways from a "crosswalk analysis" performed by FDA and CMS to determine how the various CLIA and FDA regulations overlap.

The agencies found that there were no conflicting requirements between the two sets of regs and that many CLIA requirements partially fulfill FDA's requirements, or are analogous to the FDA QSR requirements.

"A lot of the elements and activities that a laboratory might do to address the CLIA requirements probably will actually fulfill many of the requirements of the FDA quality system regulation," Serrano said.

However, there are some cases where CLIA requirements do not address necessary elements of the FDA regs – namely FDA's requirements for the test development process and for use of appropriate statistical techniques in validation studies.

Also, CLIA inspections are "not a prospective review, so tests can be offered and test results be reported before an outside reviewer from the CLIA program would come in and take a look at them," explained Penny Meyers, a CMS/CLIA analyst.

Further, CLIA does not consider the clinical validity of tests, so inspectors are not trained to look for such data, she said.

Some meeting attendees questioned whether CLIA could not beef up its own requirements to address some of the FDA questions, thus eliminating the need for duplicate inspections.

But because CLIA is user-fee funded, CLIA surveyors could not tack on FDA requirements to their inspections, Meyers said.

FDA says it is considering whether it could rely on third-party groups like the College of American Pathologists to conduct inspections on its behalf, but has made no final decisions. The groups would need to be trained on FDA procedures and the agency would have to sign off on results of the inspections, OIVD's Gutierrez said.

FDA Seeking More Than It Can Handle?

Stakeholders also questioned whether FDA should be taking on LDT oversight at all given its current resource constraints.

But the OIVD staffers said they are ready and able to take on the additional workload.

"We're not intending to ask for something that we can't handle," OIVD's Harper said. "It's not our intention to have a five-year backlog or anything on the tests. … We do meet the timelines we commit to and we intend to do that going forward as well."

"We think we have enough resources to do this in a rational way," office director Gutierrez added.

ACLA says it hopes to hold further workshops in early 2011 on other key issues, such as how to stratify lab-developed tests by risk, and what evidentiary requirements would be appropriate for different types of tests.

The group also hopes to hold those meetings before FDA issues its draft regulatory framework.

By Jessica Bylander

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