For the most part, the U.S. Food and Drug Administration (FDA) Office of In Vitro Diagnostics (OIVD/OHT7) kept laboratory developed test (LDT) regulation out of its fall IVD roundtable hybrid meeting November 12, instead drawing attention to IVD quality system requirements, complaint and adverse event reporting, and corrective and preventive actions (CAPA).
OIVD Director Courtney Lias, PhD, said the LDT exception was due to pending litigation.
IVDs offered as LDTs are expected to meet applicable FDA requirements for the first phase of the FDA's new enforcement policy by May 6, 2025.
Even though many in the medical laboratory industry are still fighting for new LDT rules to be vacated, efforts to comply with the phased approach set forth in the LDT final rule are already underway, according to the College of American Pathologists (CAP) and larger Coalition for Effective Diagnostics (CED).
Phase 1 involves labs developing a medical device reporting infrastructure, adverse event reporting processes, and quality system requirements regarding complaint files.
"That means the laboratory has to have a mechanism for receiving those complaints," stated Dr. Bobbi Pritt, professor of laboratory medicine and pathology, and chair of the Clinical Microbiology Laboratory, at Mayo Clinic in Rochester, MN, for a CAP educational webinar presented November 7. Pritt is also on the CAP Counsel on Scientific Affairs.
"Step two is that internal procedures are followed," Pritt continued. "You're going to need procedures for evaluating these complaints. So, SOPs, personnel, individuals need to be educated on where to bring any complaints that may be issued and also identify what a nonconforming event would look like.
"Step three would be then to determine whether the complaint or issue is reportable to the FDA," Pritt said, adding that if the complaint is not directly relevant to testing, it would not be reportable. "But laboratories are going to need those procedures so that they understand what is reportable and what is not.
"And then step four, of course, is report to the FDA if required," Pritt said, "and then also, importantly, maintain records so they could be pulled for that particular lab developed test."
A reportable event could be serious injury or failure of a device to meet its performance specifications or otherwise perform as intended, Pritt said. "And remember that your LDTs are going to be labeled as to what their intended use is, and the performance claims will also be part of that labeling."
When performance specifications include a certain analytical sensitivity or specificity and they are not met, then that is considered a device malfunction, according to Pritt.
CAPA, when necessary, will involve a root cause analysis of identified issues, actions to prevent recurrence, an effectiveness check for process fixes, and documentation of all results and related activities, the FDA explained during the roundtable.
With litigation pending over LDT regulation in the U.S., the CAP and CED urged the 118th Congress to pass comprehensive diagnostics reform this year to establish a regulatory framework that is uniquely tailored to diagnostic tests.
Dated November 12, the letter said "legislation is the only option that will provide regulatory certainty for developers and physicians to ensure continued patient access."
Furthermore, the CAP and CED suggested that comprehensive diagnostics legislation offer the opportunity to tailor premarket review pathways to unique characteristics and risk profiles of diagnostic tests, and to facilitate new regulatory paradigms that have gained broad stakeholder approval in the past.
The coalition also asked for some tests to be exempt from certain FDA medical device regulatory requirements to facilitate innovation of tests for rare and pediatric diseases.
Pursuing pediatrics indications for in vitro clinical tests raises regulatory questions, according to comments made during the FDA roundtable. To those pursuing FDA approval for pediatric tests, the FDA OIVD recommended they discuss their intended submission to determine what data is appropriate to extrapolate toward a pediatric test submission.
