FDA has granted premarket notification (510(k)) clearance to the integrated mutation profiling of actionable cancer targets (IMPACT) tumor profiling test, an in vitro diagnostic that can identify a greater number of genetic mutations found in various cancers than any test previously reviewed by the agency. The test was developed by Memorial Sloan Kettering Cancer Center (MSK).

According to FDA, cancer profile tests are gaining wider acceptance. By identifying what genetic mutations are present in a particular tumor, the test results can provide patients and healthcare professionals with useful insight that may help inform how best to treat the cancer. The IMPACT test uses next-generation sequencing (NGS) to identify the presence of mutations in 468 genes, and to detect other molecular changes in the genomic makeup of a person’s tumor.

FDA says that authorization of the IMPACT test advances a policy framework that paves the way for the efficient review and availability of other NGS-based cancer profiling tools. The agency also announced the recent accreditation of the New York State Department of Health (NYSDOH) as an FDA third-party reviewer of in vitro diagnostics, including tests similar to the IMPACT test. Moving forward, laboratories whose NGS-based tumor profiling tests have been approved by NYSDOH do not need to submit a separate premarket notification (510(k)) to FDA. Instead, developers may choose to request that their NYSDOH application, as well as the state’s review memorandum and recommendation, be forwarded to FDA for possible 510(k) clearance. Other accredited, third-party FDA reviewers may also become eligible to conduct such reviews and make clearance recommendations to the agency.

Scott Gottlieb, MD, FDA.

Scott Gottlieb, MD, FDA.

“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,” says FDA Commissioner Scott Gottlieb, MD. “As this field advances, we are modernizing FDA’s approach to the efficient authorization of laboratory tests from developers that voluntarily seek 510(k) clearance.

“This is another example of where FDA is working to find creative and flexible approaches to regulation that spurs development and efficient delivery of innovative technology,” Gottlieb adds. “We’ll continue to look for opportunities to create regulatory efficiencies where possible to drive broader access to tools that improve American health, while maintaining the safety and efficacy standards that patients should expect from their FDA-reviewed products.”

According to the National Cancer Institute, approximately 38.5% of American men and women will be diagnosed with a form of cancer at some point during their lifetime. Unlike many cancer diagnostics that are designed to detect one cancer biomarker for use with a single drug, the IMPACT test works by comparing tumor tissue to a ‘normal’ sample of tissue or cells from the same patient to detect genetic alterations that might help guide treatment options. While the test is intended to provide information about cancer biomarkers, its results are not conclusive for choosing a corresponding treatment.

Jeffrey Shuren, MD, JD, Center for Devices and Radiological Health.

Jeffrey Shuren, MD, JD, Center for Devices and Radiological Health.

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

FDA reviewed the IMPACT test through the de novo premarket review pathway, a regulatory pathway for some low- to moderate-risk devices that are novel and for which there is no legally marketed predicate device. The ability of the test to detect genetic mutations (analytical performance) was evaluated for precision, accuracy, and limit of detection.

Results indicated that the assay is highly accurate (greater than 99%) and capable of detecting a mutation at a frequency of approximately 5% (range of 2% to 5%). Additionally, detection of certain molecular changes (microsatellite instability) using the IMPACT test was concordant more than 92% of the time across multiple cancer types in 175 cases, when compared to traditional methods of detection.

Specific to authorization of the IMPACT test, NYSDOH previously conducted its own review and approved the test for use on samples coming from patients in the state of New York. However, MSK had not previously submitted the test for FDA review because it is a laboratory-developed test, for which the agency has generally not enforced premarket review and other applicable requirements. MSK submitted a de novo application for the IMPACT test to FDA, including and extending the information submitted for NYSDOH’s prior review, to inform and expedite the recent FDA authorization.

Following the pattern of the IMPACT test clearance, FDA is 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 FDA’s premarket notification (510(k)) clearance process, either by submitting the notification to FDA directly or through an accredited third-party reviewer.