As a growing number of cancer treatments focus on specific genetic mutations, the FDA has authorized a next-generation sequencing (NGS) test than can rapidly identify genetic biomarkers in 468 genes––more than any test previously reviewed by the agency.
IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets, Memorial Sloan Kettering Cancer Center) is a tumor profiling test (assay), an in vitro diagnostic test. The IMPACT test can rapidly identify the presence of mutations in 468 unique genes, as well as other molecular changes in the genomic makeup of a person’s tumor.
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 health care professionals with useful insight that may help inform how best to treat the cancer.
Today’s action advances a policy framework that paves the way for the efficient review and availability of other NGS-based cancer profiling tools. The FDA also announced the accreditation of the New York State Department of Health (NYSDOH) as an FDA third-party reviewer of in vitro diagnostics, including tests similar to IMPACT. Moving forward, laboratories whose NGS-based tumor-profiling tests have been approved by NYSDOH do not need to submit a 510(k) application to the FDA. Instead, developers may 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. Other accredited, third-party FDA reviewers also may become eligible to conduct such reviews and make clearance recommendations to the agency.
“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. 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,” said FDA Commissioner Scott Gottlieb, MD.
Unlike many cancer diagnostics that are designed to detect one cancer biomarker for use with a single drug, IMPACT 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 on cancer biomarkers, its results are not conclusive for choosing a corresponding treatment.
“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 health care providers in learning about the genetic underpinnings of their disease,” said Jeffrey Shuren, MD, director of the FDA’s Center for Devices and Radiological Health.
IMPACT was reviewed by the FDA through the de novo premarket review pathway. Its ability 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 the authorization, the NYSDOH previously conducted its own review of IMPACT and approved it for use on samples coming from patients in New York state. Memorial Sloan Kettering Cancer Center 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. The cancer center submitted a de novo application for the IMPACT test to the FDA, including and extending the information submitted for NYSDOH’s prior review.
Along with this authorization, the 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 the FDA’s 510(k) clearance process, either by submitting the application to the FDA directly or through an accredited third-party reviewer, like NYSDOH.
Source: FDA; November 15, 2017.