A PMA application usually requires manufacturers to submit clinical data showing that their device is safe and effective for its intended uses. For some tests, these clinical data can be published clinical studies and/or practice standards that can help determine the clinical performance of the test or retrospective comparisons of the diagnostic’s performance with that of another device that has already been clinically tested. But often the FDA requires prospective clinical studies to assess a new device’s safety and effectiveness.

The Safe Medical Devices Act of 1990 authorizes the FDA to request data on clinical sensitivity, specificity, and predictive value for diagnostic tests that undergo a PMA review. These data are costly and time-consuming to procure, and they require clinical research expertise that many small companies lack. Most manufacturers try to avoid the necessity of a PMA review of their diagnostic tests and may even forgo bringing their test to market if a PMA application is required.

Manufacturers can bypass the need for a PMA application if they can show that their device is substantially equivalent to one already on the market. This qualifies their device to enter the market via a 510(k) review process. This review requires manufacturers to submit data showing the accuracy, reproducibility, and precision of their diagnostic. Manufacturers also have to provide documentation supporting their claim that the diagnostic is “substantially equivalent” to a device already on the market.

As is true for PMAs, there are no well-defined performance standards for 510(k) reviews, nor does the FDA clearly define the requirements for substantial equivalence. However, the agency has issued guidance documents that indicate the standards by which it will review a variety of types of diagnostics. It has also accepted the laboratory test standards set by other organizations, such as the Clinical Laboratory Standards Institute. None of these standards, nor the 510(k) or PMA review process itself, considers the clinical safety and effectiveness of the diagnostic.

SOURCES: Gutman, 2000; Hackett and Gutman, 2005; IOM, 2005; FDA, 2006a.