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The U.S. Food and Drug Administration (FDA) has released an ambitious agenda for advancing new technologies in the diagnostics and medical device arenas, actions that are certain to impact clinical labs as well as device manufacturers.
One proposal explores a new pathway for demonstrating substantial equivalence in the Abbreviated 510(k) program. Currently, any device manufacturer seeking 510(k) clearance must first prove the safety and efficacy of new devices through comparative testing against predicate devices. Some of these previously approved devices, however, are too old to qualify as “substantially equivalent” to a newer, more modern device. An FDA draft guidance calls for a new voluntary program for certain well-understood device types.
A set of objective, transparent, and well-validated performance metrics would serve as the benchmark for evaluating some new devices. Instead of proving that their devices meet equivalence with a possibly outmoded technology, companies under this new option could demonstrate that the tests meet FDA-identified performance criteria. The goal is to create a more efficient process for 510(k) device approvals without compromising safety, and to ensure that these devices meet modern performance standards.
The new option would not change existing review processes that already work for FDA and manufacturers, FDA spokesperson Deborah Kotz clarified. Instead, “it focuses on the part of the substantial equivalence analysis that requires a 510(k) submitter to demonstrate that, despite technological differences, the device is as safe and effective as a predicate device,” she told CLN Stat. A 510(k) submitter would still need to identify a predicate to show that it has similar characteristics to the predicate device and the same intended use.
As FDA seeks comments this summer on this new device approval proposal, final guidance documents issued in the spring seek to drive the efficient development of novel next-generation sequencing (NGS)-based tests. The first guidance, “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics,” describes a streamlined regulatory approach that allows test developers to rely on clinical evidence from FDA-recognized public databases to support clinical claims for their tests and provide assurance of the accurate clinical evaluation of genomic test results.
“The rapid adoption of NGS technologies in research and clinical settings is helping to identify countless new genetic variants. However, information about genetic variants is generally stored in a manner that is not publicly accessible,” said Jeffrey Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, in a statement. The final guidance on genetic variant databases will encourage data sharing and accumulate evidence supporting the clinical validity of genomic tests in public databases. Such actions will provide an even more efficient path to market, Shuren added.
The second guidance, “Considerations for Design, Development, and Analytical Validation of NGS-Based In Vitro Diagnostics Intended to Aid in the Diagnosis of Suspected Germline Diseases,” offers recommendations for designing, developing, and validating NGS-based tests used to diagnose individuals with suspected genetic diseases. The document also clarifies how FDA evaluates premarket submissions to determine an NGS-based test’s analytical validity, including a test’s ability to detect the presence or absence of a particular genomic change.
In another development, FDA has proposed a streamlined submission process for determining the risk of vitro diagnostics (IVD) in oncology trials involving investigational drugs or biological products. “The use of these diagnostics can allow providers to identify which patients may respond best to new treatments. In recognition of the opportunities offered by these scientific advances, the FDA is streamlining the agency’s review of cancer diagnostics that are developed in conjunction with drug trials,” said FDA Commissioner Scott Gottlieb, MD, in a statement.
Under this approach, FDA would consolidate pre-market information about the investigational IVD and drug into one application to better assess their scientific relationship. Various FDA centers would then coordinate with one another to determine if the IVD in question has a significant or nonsignificant risk, or is exempt.
The agency has also issued an action plan to improve the safety of medical devices. “Our aim is to make sure that the new advances in technology that are enabling better capabilities and benefits are also harnessed to bring added assurances of safety, so that more patients can benefit from new devices and address unmet needs,” said Gottlieb in a statement.
The plan’s five-step process would establish a robust patient safety net, encourage new innovation to develop safer devices, advance cybersecurity, look at methods to streamline and modernize timely implementation of postmarket mitigations, and advance the use of a total product life cycle approach to device safety.