One need only peruse issues of IVD Technology magazine from the last decade to appreciate the tremendous development and advancement of biotechnology-based IVDs. Although regulators such as FDA have instituted forward-leaning policies and programs such as FDA’s Critical Path Initiative to facilitate medical product development, implementation of these programs has been uneven. One area badly in need of more focused and enlightened regulation is point-of-care test (POCT) IVDs; in particular, physician office laboratory (POL)–type IVDs. The promise of POCT devices is that test results can be obtained quickly so that appropriate medical care can be administered to patients without delay. With the emergence of portable test instrument technologies, realization of the benefits of POCT can now occur in a wide range of settings that are in close proximity to the patient. The challenge to manufacturers, of course, is to develop POCT IVDs that are at least as high quality and reliable as their clinical laboratory counterparts. This aspect is understandably the salient focus of the FDA premarket review process.
Unlike other types of IVDs, POL devices often must undergo a two-tiered regulatory scheme that can impose additional barriers and disincentives to the manufacturers. Many POL IVDs must satisfy not only FDA regulatory requirements, but, for marketing purposes, CLIA waiver requirements as well. Typically a POL IVD that can be shown to perform as well as its clinical laboratory counterpart when evaluated in a POL setting is usually acceptable to FDA and is cleared or approved as being safe and effective for use in this setting. However, since many POLs wish to avoid being subject to full-blown CLIA requirements, their decision to use an FDA-cleared POL IVD is often contingent on the device being CLIA waived. Consequently, many sponsors of FDA-cleared POL IVDs must return to FDA and seek a CLIA waiver for their device, which consumes considerably more time and cost. Moreover, unlike the FDA premarket review (typically the 510(k) process), through which the overwhelming majority of new IVDs of all types are cleared (and FDA rejection is the exception), the premise of the CLIA waiver review process is that the waived device should be an exception and the waiver not routinely granted. In effect, an FDA-cleared POL IVD may not be readily available if CLIA waiver is not also granted.
Although FDA has done a credible job of providing waiver guidance to the IVD industry, the threshold for demonstrating POL IVD accuracy and reliability to obtain CLIA waiver often significantly exceeds FDA 510(k) requirements, thus leading to a highly uncertain waiver review end point. Unfortunately, a safe and effective POL IVD as determined by FDA through the 510(k) process may not be usable given the CLIA waiver burden. Although FDA’s premarket submission review and CLIA waiver processes focus on different aspects of test validation and use, there is clear linkage regarding their particular effect on the commercial usability of POL IVDs.
One of the primary concerns leading to CLIA in 1988 was the poor quality of testing evidenced in POLs. To address this concern, CLIA required that any facility, including POLs, performing clinical testing would be subject to the same testing standards unless the facility obtained a Certificate of Waiver, which meant that the facility could only deploy waived tests. Thus, in order for a test to be used in a waived CLIA facility, the test would need to “employ methodologies that are so simple and accurate as to render the likelihood of erroneous results negligible; or pose no reasonable risk of harm to the patient if the test is performed incorrectly.” Although FDA has granted waiver for a variety of POL IVDs, it is still exceedingly difficult for a new POL IVD that has obtained 510(k) clearance to also obtain CLIA waiver despite the POL IVD sponsor’s attempt to design “simple and accurate” tests.
CMS surveys over the last two decades have shown that the quality of testing in POLs, even when the tests being used are waived, is still at best uneven. If, as Congress intended, the quality of testing performed in a POL environment were comparable to testing performed in other testing environments, then why would any test have to be waived in order for it to be used in most POLs? Admittedly, however, if the waived category were eliminated, then POLs would be forced to comply with current CLIA requirements for non-waived tests—which arguably would be highly resisted by most POLs. Clearly, resolution of this situation is difficult and may require Congress to act by amending CLIA. Nevertheless, the process of enabling access to new POL IVDs would be much less burdensome if a single FDA clearance would suffice.
Thomas M. Tsakeris is president of Devices and Diagnostics Consulting Group. He can be reached at firstname.lastname@example.org.