FDA Authorizes Tumor Assay Through New Streamlined Pathway

The FDA announced that it has approved the IMPACT tumor profiling assay, while also making it easier for some device manufacturers to bring their products to market.

The IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) tumor profiling test developed at Memorial Sloan Kettering Cancer Center, is an in vitro diagnostic test that can identify more tumor biomarkers than any test previously reviewed by the agency. The assay uses next-generation sequencing (NGS) to rapidly identify the presence of mutations in 468 unique genes, as well as other molecular changes in a tumor’s genomic makeup.

The IMPACT test compares a patient’s tumor tissue with a sample of normal tissue to detect genetic alterations. While the test is intended to provide information on cancer biomarkers and help guide treatment options, the FDA cautions its results should not be taken as definitive when making treatment decisions.

The FDA determined that IMPACT is >99% accurate and capable of detecting a mutation at a frequency of approximately 5%. Compared with traditional methods of detection, detection of microsatellite instability was concordant >92% of the time across multiple cancer types in 175 cases.

“NGS technologies can examine hundreds, if not millions, of DNA variants at a time; and we are only at the beginning of realizing the true potential for these devices to assist patients and their healthcare providers in learning about the genetic underpinnings of their disease,” Jeffrey Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, said in a press release.

The agency reviewed the assay through the de novo premarket review pathway, a regulatory pathway for some novel low- to moderate-risk devices for which there is no predicate device.

The agency recently approved the New York State Department of Health (NYSDOH) as a third-party reviewer of in vitro diagnostics. Going forward, laboratories producing NYSDOH-approved NGS-based tumor profiling tests are no longer required to submit a separate 510(k) application to the FDA. Instead, developers may choose to request that their NYSDOH application, as well as the state’s review memorandum and recommendation, be forwarded to the FDA for possible 510(k) clearance.

“The goal of allowing NGS-based tumor profiling tests to undergo review by accredited third-parties is to reduce the burden on test developers and streamline the regulatory assessment of these types of innovative products, FDA commissioner Scott Gottlieb, MD, said in a press release. “As this field advances, we are modernizing the FDA’s approach to the efficient authorization of laboratory tests from developers that voluntarily seek 510(k) clearance.”

NYSDOH previously reviewed IMPACT and approved its use on samples coming from patients in the state of New York. Memorial Sloan Kettering had not previously submitted the test for FDA review because the agency has generally not enforced premarket review and other applicable requirements for laboratory-developed tests. The center submitted a de novo application for the IMPACT test to the FDA that included information submitted to NYSDOH to expedite FDA authorization.

Other accredited, third-party FDA reviewers also may become eligible to conduct such reviews and make clearance recommendations to the agency.

“Recognizing the significant effect information about an individual’s biomarkers can have on their care planning and outcomes, the FDA worked closely with NYSDOH and MSK to help ensure that the IMPACT test is accurate, reliable and clinically meaningful,” Shuren said. “This collaboration is an excellent example of how the FDA can partner with the medical and development communities to review innovative tests as quickly as possible.”

The FDA is also establishing a Class II regulatory pathway for the review of other NGS-based tumor profiling tests for use in patients diagnosed with cancer. Class II designation allows these types of tests to be eligible to use the FDA’s 510(k) clearance process, either by submitting the application to the FDA directly or through an accredited third-party reviewer, such as NYSDOH.