FDA Lacks Capacity to Regulate Laboratory-Developed Tests, Senators Say

The FDA does not have the capacity to regulate the tens of thousands of laboratory-developed tests currently being used across the country, senators said during a committee hearing on the future of regulation in the age of precision medicine.

“Is there anybody here that believes that the FDA architecture or the FDA talent exists today to be able to handle the processing of an [LDT] application or an approval three years from now?” asked Sen. Richard Burr (R-N.C.), during a Sept. 20 hearing before the Senate Health, Education, Labor and Pensions Committee.

Currently, most tests that are developed and used within a single facility are regulated by the Centers for Medicare & Medicaid Services, under the Clinical Laboratory Improvement Amendments (CLIA). They can include in vitro diagnostics, blood tests, and assays evaluating whether a patient will respond to a specific drug.

However, following advancements in genomic and molecular science, and their increasing use in guiding high-risk treatment decisions, the FDA proposed draft guidance in October 2014 for the agency to begin regulating LDTs using a risk-based framework. That guidance document has not been finalized.

Industry criticized the proposed regulation as having the potential to stifle innovation. The FDA already struggles to process premarket applications for in vitro diagnostics and would be further slowed if resources are stretched to include LDTs, stakeholders said in comments on the guidance (IDDM, Feb. 6, 2015).

“In today’s ever-changing healthcare landscape, our mission is to help patients feel confident about the tests influencing their healthcare decisions — I’m not certain that the current FDA structure could provide that stability,” said Sen. Orrin Hatch (R-Utah).

Costs Prohibitive

The senators heard testimony from the chairs of two major pathology departments, who said that their labs would not be able to shoulder the costs of seeking premarket approvals for each individual test, if such requirements were imposed.

“We would close the lab,” said David Klimstra, the James Ewing Alumni Chair in Pathology at Memorial Sloan Kettering Cancer Center, whose department uses about 350 different LDTs. “There’s no way that the institution could afford the costs associated with formal FDA review and approval of all of those tests. It’s simply economically impossible.”

Karen Kaul, chair of the department of pathology and laboratory medicine at NorthShore University Health System, agreed: “I think the regulatory expense burden would be such that we wouldn’t continue personalized medicine. And I think it would have a big impact on the way that medical care is delivered today, for testing, in general. … [Patients] would not get the care they need.”

In its draft guidance, the FDA said compliance with CMS standards under CLIA is not sufficient by itself to protect patient safety. High standards for clinical laboratory practices and methodologies can provide assurances in clinical use, but those standards “were not developed to provide assurances regarding the design, manufacture, and validation of the diagnostic device itself,” the guidance said. The agency declared that premarket review and FDA regulations would ensure effectiveness.

“Most tests aren’t regulated by the FDA, and most tests aren’t reviewed by any external party to be sure that their results are accurate,” said Sen. Elizabeth Warren (D-Mass.). “And I’m concerned that that means a lot of uncertainty for patients and doctors who are making important decisions based on these test results.”

Potential Harm?

The committee’s ranking Democratic, Sen. Patty Murray (Wash.), said she is worried about potential harm to patients, and described how the FDA recently alerted women and doctors that lab tests marketed as screening tools for ovarian cancer lacked evidence to support their effectiveness.

“This may have led to women deciding to delay or forego treatment,” Murray said, and asked how the committee can help provide regulatory certainty for lab test developers.

Brad Spring, vice president of regulatory affairs and compliance at BD Life Sciences, said that FDA should be the regulatory body for LDTs, but not using the methods it has proposed.

“I don’t think the current construct and framework will work in this situation. I think we need to see legislative reform,” said Spring.

He listed several guidelines for future regulations, including equal application regardless of the type of entity, such as manufacturers, laboratories or research hospitals; test standards focused on analytical and clinical validity; clear jurisdiction between FDA, CMS, and state health departments and medical boards; and basing the level of oversight on each product’s risk to patients.

Regarding the more than 60,000 tests being used today, “we have to have some sort of grandfathering involved,” said Spring. “You can’t just automatically take them off the market.”

Jeff Allen, CEO of Friends of Cancer Research, said he supported FDA regulation, and recommended prioritizing the LDTs that address the highest risks to patients, such as large-scale genomic screening, or prostate-specific antigen tests. Also, professionals using the tests and interpreting the results may not know whether the test has been confirmed to work, he said.

“I think there’s an expectation that when you go into your doctor’s office, you’re going to be told the best information that a medical professional can provide to you — based on a whole host of tests and analyses, and their medical interpretation of the symptoms that you’re describing to them,” said Allen. “And frankly, patients shouldn’t have to worry about this.” — Conor Hale