CEO SUMMARY: Since 2006, the FDA has said it has the authority to regulate lab-developed tests, but it has held off on doing so. Now the agency says it’s time, defining LDTs as being, “designed, manufactured, and used within a single laboratory. LDTs include some genetic tests and tests that are used by healthcare professionals to guide medical treatment for their patients.” Following its notification to Congress, the FDA is expected to issue draft guidance on LDT regulation within 60 days.
THERE WERE PLENTY OF HEADLINES when the FDA disclosed to Congress on July 31 that it intended to regulatelaboratory-developed tests. Buried in the reports, however, was the fact that the FDA had not yet released all the specifics about how it will regulate LDTs.
What triggered the news reports was a notice from the Food and Drug Administration to Congress that, within 60 days, it would issue draft guidance on how it would regulate LDTs. At that time, the FDA’s proposal to regulate LDTs would be open for public comment for 90 days.
Under the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), the FDA must notify Congress of its intent to regulate LDTs. Specifically, the FDA said it proposed a risk-based oversight framework for what it estimated are 11,000 LDTs produced by 2,000 medical laboratories in the United States.
Laboratory-developed tests , the FDA explained, are, “designed, manufactured, and used within a single laboratory . They include some genetic tests and tests that are used by healthcare professionals to guide medical treatment for their patients. The FDA already oversees direct-to-consumer tests regardless of whether they are LDTs or traditional diagnostics.”
FDA Offers Draft Guidance
In its notice to Congress, the FDA attached draft guidance titled, Framework for Regulatory Oversight of Laboratory Developed Tests, and a document titled FDA Notification and Medical Device Reporting for Laboratory Developed Tests. These documents and the letters to Congress are available online at https://tinyurl.com/lqxoyp9.
The FDA said it will use a risk-based, phased-in approach for oversight of LDTs. It further noted that its regulation of LDTs would be consistent with its regulation of in vitro diagnostic devices.
In response to the FDA’s action, the law firm of Wilson Sonsini Goodrich & Rosati of Palo Alto, California, issued an alert last week explaining that the FDA’s draft guidance has three regulatory levels for LDTs:
1) LDTs subject to full enforcement discretion (minimal regulation);
2) LDTs subject to partial enforcement discretion (moderate regulation); and,
3) LDTs subject to full FDA regulation.
Long Review, More Expense
“For companies that offer or plan to offer LDTs, the LDT classification is important because it determines the level of review by the FDA, with longer review times and more stringent review criteria translating into more time and expense to bring the LDT to market,” the WSGR alert said.
The Association for Molecular Pathology (AMP) has members who will be directly affected by FDA regulation of LDTs. AMP’s leadership has concerns about the FDA’s proposal. “What we have is potentially a perfect storm,” commented Elaine Lyon, Ph.D., President of AMP and Medical Director, Molecular Genetics; and Co-Medical Director, Pharmacogenomics, at ARUP Laboratories in Salt Lake City, Utah.
“Lab professionals should understand that the FDA is preparing to issue new regulations while—at the same time—the important questions about coverage and payment for molecular and genetic LDTs that were an issue last year continue to affect clinical laboratories today,” added Lyon. “In addition, the FDA released the final guidance for companion diagnostics at the same time that they gave notice to Congress of its intent to release the frame- work for LDTs.
“We appreciate the fact that, in giving the notice to Congress, the FDA also released much of what it will propose,” she continued. “AMP has found the FDA to be fairly open, despite the fact that the release is not final and the public comment period has not yet started.
“Having said that, we are deeply concerned that the FDA is making a significant change from the existing regulatory framework,” Lyon added. “This change could dramatically impact laboratories that offer LDTs. In turn, this could affect how laboratories perform these tests and ultimately affect patient care.”
The FDA said it will review the tests in the high-risk category first and then move to the moderate risk tests. Lyon observed that, “much remains unknown about the details of how the FDA will implement this draft guidance. For example, what is the definition of high risk and how many tests will be moved into this category? We don’t know that yet.
“Of course, the main concern of AMP members is how these new regulations will affect patient care,” she continued. “Often, laboratories offer LDTs for low-volume tests that have great importance for the few patients with uncommon diseases, yet these tests may not meet the FDA’s definition of a rare disease.
“If the FDA’s new regulations are overly burdensome, at what point would laboratories decide not to develop a test even though it’s medically necessary?” she asked. “The burden created by regulations is an issue that needs to be considered. We want to ensure that laboratories will be able to continue to provide the tests they offer. That’s a major concern.”
Thousands of LDTs
Lyon pointed out that another issue involves how the FDA would regulate the thousands of LDTs currently offered by laboratories across the country—while keeping up with the flood of new LDTs that continue to be developed in response to new scientific knowledge and advanced diagnostic technologies.
“The reality is that molecular laboratories today have few FDA-cleared assays available to them,” she said. “They rely on lab-developed processes to develop tests that incorporate new knowledge and new technology.
“These laboratories are directed by physician pathologists, meaning M.D.s, or they are medically-boarded clinical scientists, meaning Ph.D.s,” explained Lyon. “These well-trained individuals bring a strong professional component to the design, validation, implementation, review of the results, and the interpretation of the results based on clinical findings. This is significant and should be recognized by regulators and legislators.
Existing Lab Standards
“Further, the overwhelming majority of LDTs and laboratory-developed processes in use today come from CLIA laboratories,” said Lyon. “Many of those CLIA laboratories also are CAP accredited. These laboratories already meet rigorous state, federal, and professional standards.
“So, to imply that LDTs are not regulated is not true,” concluded Lyon. “In the United States, our laboratories are regulated and that regulation has worked very well since CLIA 1988.”
Now that the FDA has provided notice to Congress that it intends to release its draft guidance for regulating laboratory- developed tests, knowledgeable observers expect that the next step that the agency takes will be to release the proposed guidance for LDT regulation.
This information will then be published in the Federal Register and the time period for public comment will be announced. During that public comment period, pathologists, Ph.D.s, and lab executives will have an opportunity to provide comments to the FDA.
Five Senators Sent Letter to OMB, Asking It to Release FDA’s Draft Guidance on LDTs
WHY DID THE FDA CHOOSE THIS TIMING to commence the process necessary for it to regulate laboratory-developed tests? After all, it was as early as 2006 when the agency first proposed this idea.
The specific FDA draft guidance has been under review by the White House Office of Management and Budget (OMB), according to The New York Times. After the FDA proposed its plan to regulate LDTs in 2010, the idea ran into fierce opposition, reported The Times.
Did Politics Play a Role?
Politics may have had a role in the timing of the FDA’s actions. For example, on July 2, five Democratic senators demanded that the proposal be released, said The Times.
In their letter to the OMB, the senators urged the OMB “to take prompt action in releasing this draft guidance on the regulation of laboratory developed tests, to ensure appropriate and efficient oversight of diagnostic tools can move forward in an open and transparent manner.”
The five senators noted that “laboratories initially manufactured LDTs that were relatively simple, well understood pathology tests that could be used for low-risk diagnostics or for rare diseases for which adequate validation would not be feasible. These tests were traditionally developed to be used for a small population of local patients being evaluated by physicians at the same facility where the laboratory was located.”
What has changed, wrote the senators, is that LDTs have become more complex and are a “staple of clinical decision-making and are being used to diagnose high- risk, but relatively common diseases… [Thus], it is imperative that they perform as they are expected.” The senators asked OMB to release the draft guidance so that the FDA could solicit public comment and finalize the proposed rule.
Under law, the FDA must notify Congress 60 days before it plans to release the proposal. The agency delivered such a notice to Congress on July 31.