FDA has been clearing over-the-counter (OTC) in vitro diagnostic (IVD) tests nearly since the beginning of its premarket regulation of devices.  The first OTC IVD cleared by FDA was a qualitative dipstick urine glucose test in 1977, followed shortly thereafter by the first OTC pregnancy test clearance in 1978.  In the intervening decades, FDA has cleared approximately 1,200 OTC IVDs.  Though there has been a large number of OTC IVD clearances and decades of experience reviewing OTC IVDs, the bulk of OTC IVD clearances fall in just a few categories, such as pregnancy tests, drugs of abuse tests, and glucose monitoring devices.  FDA has cleared very few novel OTC IVDs.  In fact, in FDA’s entire history of OTC IVD regulation, according to FDA’s OTC IVD database, there has only been four de novo authorizations for OTC IVDs, of which three were granted to 23andMe for home collection of samples tested at a central laboratory, not home testing itself.

FDA has repeatedly voiced its support of OTC and home testing, particularly in the context of the COVID‑19 pandemic in which the value of home diagnostic testing has been undeniable.  Regarding COVID-19, Tim Stenzel, Director of CDRH’s Office of In Vitro Diagnostics, has stated that “in-home testing and home collections is a top priority” (June 2020 FDA Virtual Town Hall); “obviously home over-the-counter tests including rapid antigen tests are a high priority” (February 2021 FDA Virtual Town Hall).  FDA hailed its authorization of the Lucira OTC home test for influenza and COVID-19 as “underscor[ing] the Agency’s continued commitment to increase availability of accurate and reliable at-home diagnostic tests” (April 2023 FDA Update to CDC).

Ironically, Lucira filed for bankruptcy earlier this year; its CEO cited a “protracted [FDA] authorization cycle time” as a factor in the firm’s failure.  FDA, in turn, filed its own statement “to address misinformation” (see FDA’s statement here).  This type of public spat does not instill confidence in companies developing or investing in OTC IVDs.  Notably, FDA did not grant marketing authorization of an OTC COVID test until June 6, 2023, when Cue Health finally received de novo authorization.

Most recently, Jeff Shuren, CDRH Director, gave a speech at the 2023 Food and Drug Law Institute (FDLI) annual conference in which he identified facilitating “availability of and access to existing and novel home-use medical technologies” as a strategic priority for 2022-2023 to advance health equity.  He also identified “Next-Generation Home-based Testing Technologies, including new IVDs, Digital Lateral Flow Readers, and Reporting Technologies” as an opportunity to “extend care from the hospital and clinic into the home setting.”

Despite CDRH’s professed support for and “prioritization” of OTC home diagnostics, IVD sponsors of OTC home tests often run into strong resistance from CDRH in attempting to get such tests cleared.  This is particularly true if the test does not fall into one of the few established categories (e.g., pregnancy, glucose, drugs of abuse).

There are several factors that increase the difficulty of obtaining an OTC home clearance or authorization for an IVD, as opposed to a test that is done in a clinic following a physician order.

To obtain clearance of an OTC home IVD, a sponsor must provide the usual suite of analytical and clinical validation that would be required for any IVD, demonstrating adequate repeatability, stability, sensitivity, specificity, and so on.

On top of this standard IVD validation testing, a sponsor must perform its clinical validation in the hands of the intended user (i.e., lay users).  Additionally, the sponsor must demonstrate that the user can determine that they are an appropriate candidate for the test based on the labeling (e.g., have the relevant symptoms or fall within the correct demographics); correctly follow instructions to self-collect an adequate specimen; perform the test correctly according to instructions; interpret the results correctly; and understand the significance of the results and appropriate next steps (e.g., seeking treatment).  This usually requires human factors or usability testing and labeling comprehension testing.

However, even if an IVD sponsor is willing and able to provide robust data addressing all of these topics, in our experience, CDRH is nevertheless concerned about whether the test, by the nature of its intended use, is appropriate for consumers.  CDRH may express concerns that patients will not understand when the test is appropriate for them, that they will misinterpret or overly rely on results, or that they will forego or delay visits to a doctor.  Some of the concerns expressed by FDA today about home testing derive from paternalistic views that were debunked years ago in the context of HIV home testing.  See Steven R. Salbu, HIV Home Testing and the FDA: The Case for Regulatory Restraint, 46 Hastings L.J. 403 (1995).  FDA also expects that the performance in the hands of consumers will essentially match the results when the test is performed in the laboratory.

The stringency of these requirements makes it less appealing for IVD sponsors to undertake the burdensome testing necessary for an OTC home test because, even if adequate data are collected, CDRH can – and in our experience, does – still raise roadblocks preventing clearance.  This makes seeking clearance of an OTC home test a risky business endeavor.  As a result, novel IVD manufacturers are more likely to start with clearance of a prescription test intended for use in clinical settings with the thought that one day in the future, after several years of clinical experience demonstrating safe use, they may return to FDA to seek clearance of an OTC version.  However, even years of experience with the test in a lab setting does not mean that the OTC version will receive a favorable reception.

Companies are also experiencing significant regulatory obstacles with another related category: home collection devices.  Home tests of course require the use of devices that allow consumers to collect samples at home.  Home collection devices can also be used to obtain samples that are sent to central laboratories for processing.

Home collection devices are – or, at least were – typically cleared separately from the assays with which they are used.  Early in FDA’s clearance of home collection devices, the clearances were not specific to any analyte or clinical application.  A device such as the widely-used Vacutainer would be cleared for use with blood, without trying to limit the diagnostic uses of the blood.  However, in recent years, particularly for blood collection devices, FDA has required that collection device clearances be restricted to specific clinical applications.  Therefore, instead of a general tool-type indication for collection of a sample matrix (e.g., saliva, capillary blood), separate clearances are often required for each application (e.g., HbA1c, diagnosis of a particular virus, etc.).  As a thought experiment, consider what the state of the U.S. health care system would today be if each collection device had to be cleared for each clinical use separately.  (FDA has indicated that after a manufacturer has shown that a collection device is suitable for numerous different tests it could then have generic labeling, but that is obviously a monumental task.)

As a result, not only does each assay require analytical and clinical validation and clearance, but the home collection device paired with the assay may also require separate clearances and clinical validation for each application.  This is particularly true for home collection devices, where CDRH requires more data to demonstrate the ability of a lay user to collect an adequate sample for each individual test.

This approach to regulation of collection devices is overly burdensome and it discourages innovation.  Collection device manufacturers that develop innovative collection device designs, intended to make it easy for a lay user to collect an adequate sample of the correct volume and quality, are often thwarted when they approach the Agency seeking clearance.  Once manufacturers learn of the requirement to seek a new clearance for every new clinical application, the FDA process becomes even more daunting and the financial returns less attractive.  This is especially true for collection device manufacturers that do not also manufacture diagnostic tests; seeking clearance would require the manufacturer to anticipate the clinical applications for which their IVD manufacturer customers may want to use their collection device, or partner with kit manufacturers early in the process.

Requiring home collection devices to be cleared analyte by analyte should not be necessary in most situations.  Collection devices are designed to collect a specimen in a particular volume and with a particular storage method (e.g., dried blood, in viral transport media).  As with other devices with tool-type indications, manufacturers of home collection devices should be able to obtain tool-type indications for collection of specimens within certain parameters, outlined in labeling (we know, however, that CDRH has moved away from tool-type indications for all sorts of devices, see our prior post regarding surgical robots here).  Then, IVDs, including OTC home tests, can be validated for use with the home collection device if it collects an appropriate specimen with the requisite volume.  The sample matrix and type are already validated through analytical and clinical validation of the assay; it is unnecessary and duplicative to require separate analyte and application-specific validation for the collection device itself.  While there may be some particular analytes where extra testing is warranted due to unique concerns about a collection device, that should not be the default position.

In Dr. Shuren’s recent statements at the Food and Drug Law Institute’s Annual Conference, he declared that home access to healthcare, including diagnostics, was a priority.  The paucity of different types of OTC tests and the struggles of home collection devices belies, at least so far, this pronouncement.  If FDA is serious about making access to OTC home diagnostics a priority, it needs to provide clear, comprehensible, specific, and reasonable guidance to industry about the necessary validation testing.  If these guidelines are satisfied, regardless of the novelty of the intended use for the IVD, CDRH should be willing to clear the IVD.  Additionally, it needs to rethink the currently burdensome approach to clearance of home collection devices, to pave the way for clearance of innovative collection devices designed to make it easier for a lay user to self-collect adequate samples.

In considering OTC IVDs and home collection devices, FDA needs to give more weight to the benefits of these products.  COVID illustrated the significant public health value of at-home tests.  They can increase access to health care, and advancing access is itself an FDA goal.  They can also improve health equity, another FDA goal.  And they can reduce costs, which is a significant public health benefit.  Indeed, FDA acknowledges all of these benefits in its recent request for comment on “Increasing Patient Access to At-Home Use Medical Technologies,” including IVDs.  FDA is accepting comments on this topic, including questions like “How can the FDA support the development of medical technologies, including digital health technologies and diagnostics, for use in non-clinical care settings, such as at home?” through August 30, 2023.  A link to FDA’s announcement and the public docket can be found here and here, respectively.