The Diagnostics Pipeline: FDA Launches Pilot for Cancer Companion Diagnostic LDTs

On June 21, the FDA published a guidance document announcing the launch of a pilot program to regulate laboratory-developed tests (LDTs) used as companion diagnostics for oncology drug therapies.¹ The goal of this voluntary program is to minimize the risks associated with using LDTs for cancer treatment selection by providing greater transparency on the recommended performance characteristics of such tests.

Current Regulation of Cancer Companion Diagnostic LDTs

In vitro companion diagnostic tests provide information that helps determine whether a corresponding treatment is likely to be safe and effective in a specific patient. In the oncology setting, tests are used to identify patients who may benefit from certain types of cancer treatments—for instance, those who have genetic mutations that the treatment targets.

Oncology drug developers must indicate whether their products require use of an in vitro companion diagnostic. In many cases, these diagnostics are approved alongside the new drug—but if no in vitro test has received FDA marketing authorization, the agency may still clear the oncology drug. This would allow use of an LDT for the limited purpose of determining whether a particular patient might benefit from the treatment. In keeping with the FDA’s oversight of LDTs, this agency practice is a policy, rather than a formal regulation.

In the press announcement accompanying the new guidance, the FDA said it has become “increasingly concerned” that some companion LDTs “may not provide accurate and reliable test results or perform as well as FDA authorized tests.”² The agency has previously identified LDT issues such as insufficient evidence of clinical validity, poor or absent controls, and a lack of structure for adverse event reporting, all of which can negatively affect treatment decisions or outcomes.^{3, 4,5}

The New Cancer Companion Diagnostic LDTs Pilot

The guidance, “Oncology Drug Products Used with Certain In Vitro Diagnostic Tests: Pilot Program,” explains how the pilot will work. Specifically, the FDA will ask pharmaceutical manufacturers to furnish performance information for tests used to enroll patients in clinical trials. The agency will analyze the data and, if appropriate, extrapolate the clinical validity of tests used in patient selection “to other tests of the same type with similar analytical performance.” The resulting minimum performance characteristics for similar clinical tests will then be posted on a dedicated part of the FDA’s website so that laboratories can use the information when developing their own LDTs to identify biomarkers for cancer treatment selection.⁶

“We believe this guidance and the launch of the pilot program are important steps towards addressing safety risks posed by the use of poorly performing laboratory-developed tests,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “The pilot aims to help by making transparent performance recommendations for diagnostic tests used to select certain oncology drug treatments.”²

Toward a Comprehensive LDT Solution

Although the pilot program will only include up to nine pharmaceutical companies, the implication that the FDA will not approve LDTs that fail to meet the resulting benchmarks for biomarker performance means that the guidance will significantly impact labs and other LDT developers of companion diagnostic tests.

However, the real takeaway from the pilot guidance is that the FDA has once again signaled its intention to address all LDTs: According to the agency’s press statement, “This pilot program is one step that may be helpful in reducing the risk of using LDTs for oncology drug treatment decisions while we continue to work on a broader approach for LDTs, including moving forward with rulemaking.”²

Whether deliberate or unintentional, the likely end result of the FDA’s program will be to pressure Congress to pass the Verifying Accurate Leading-edge IVCT Development (VALID) Act or another bill to address LDT issues legislatively.⁷ Ironically, this dynamic may lead drug makers to balk at investing the time and resources necessary to enlist in the new FDA pilot, preferring instead to wait for a broader resolution, whether regulatory or legislative.

References:

1. https://public-inspection.federalregister.gov/2023-13134.pdf
2. https://www.fda.gov/news-events/press-announcements/fda-launches-pilot-program-help-reduce-risks-associated-using-laboratory-developed-tests-identify
3. https://www.fda.gov/media/102367/download
4. https://www.fda.gov/medical-devices/in-vitro-diagnostics/laboratory-developed-tests
5. http://wayback.archive-it.org/7993/20171115144712/https:/www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UCM472777.pdf
6. https://www.fda.gov/medical-devices/in-vitro-diagnostics/oncology-drug-products-used-certain-in-vitro-diagnostics-pilot-program
7. https://www.g2intelligence.com/despite-mdufa-setback-valid-act-is-back-on-track-for-passage/

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Here are the key laboratory testing and diagnostics products clearances announced since mid-June 2023:

New FDA Approvals & Emergency Use Authorizations (EUAs)

New CE Marks & Global Certifications

Notable European CE certifications announced in June 2023:

New Approvals in Europe

Other international clearances announced in June 2023: