Will We Ever Have Widespread OTC COVID Testing in America?

February 23, 2022By Jeffrey K. Shapiro & Richard A. Lewis, Senior Regulatory Device & Biologics Expert

Last November, we explained FDA’s role in blocking over-the-counter (OTC) rapid antigen tests from the American market.  We identified as the main culprit FDA’s requirement that these tests achieve 80% sensitivity (positive percent agreement or PPA) even when a required percentage of low positive patients are included.  FDA has never publicly justified this 80% minimum, which until last October was an even stricter 90% minimum.  For reasons we explained in our prior post, this requirement is not a good fit with rapid antigen tests.

At the time, the Biden administration was standing up a new program at the National Institutes of Health (NIH) to help companies break through FDA’s brick wall.  The program is known as the Independent Test Assessment Program (ITAP).  We speculated that this program might simply be a public relations move.

Three months later, there is good news and bad news.  The good news is that the NIH’s program is real and has been offering helpful assistance to manufacturers seeking to obtain Emergency Use Authorization (EUA) approval from FDA for OTC rapid antigen tests.  The NIH is in regular contact with FDA to ensure they understand the agency’s latest requirements.  The NIH screens manufacturers to ensure they have reputable tests already in use in other countries with good supporting test data.  The NIH also only accepts manufacturers into the program if they can demonstrate the ability to provide high volumes (e.g., 20 million / month or more) of tests to the American market.

For those accepted, the NIH provides a comprehensive team of project management and scientific experts to help the manufacturer prepare a viable EUA application.  The silent killer of EUA applications is the disconnect between what FDA wants and the publicly available EUA templates.  Having a direct line to FDA through the ITAP program gives companies a clearer understanding about their prospects for authorization.  Additionally, the NIH assists with all the analytical and clinical testing, using protocols already vetted with FDA.  This testing is done by testing labs and clinical research organizations (CROs).  Because FDA trusts the NIH, the EUA review is likely to be prioritized and conducted quickly.  FDA will even accept a modular submission and review it on a rolling basis as the data comes in.  The upshot is potential for a rapid review and approval, provided the data are satisfactory.

The bad news is that NIH-assisted manufacturers are running into the same FDA brick wall as everyone else.  To our knowledge, five clinical studies conducted by NIH have failed to hit 80% sensitivity.  We understand NIH shared the details of these data with FDA.  Yet, recent FDA town halls with test developers suggest that FDA is not budging on performance.

Since the start of the pandemic, FDA has authorized a total of 17 OTC rapid antigen tests.  These 17 tests self-evidently have not been able to satisfy demand.  Subsequent to the rise of the omicron variant in the United States toward the end of 2021, FDA has only authorized a single OTC rapid antigen test, and that EUA was likely based on a study without a significant number of omicron patients.  Therefore, at present, it does not appear that the American market has any OTC rapid antigen tests optimized for the omicron variant.  The few tests FDA approved before the appearance of the omicron variant have not had their labeling updated to reflect their ability to detect omicron in a prospective clinical study.  We are moving backward, not forward in terms of having widespread OTC testing capability that is pertinent to current circumstances.

We understand that NIH is now going to try to obtain approval for tests labeled for serial use.  An example of serial use would be taking a test on a Monday and followed by a test on Wednesday.  In trial design, this type of intended use provides two opportunities to identify an individual as positive.  Although FDA still requires that a test labeled for serial use achieve a minimum 80% sensitivity, that is statistically more likely if the calculation is based on two tests rather than just one.

This option has been available all along but apparently has not proven attractive for most manufacturers.  While we have seen FDA grant serial screening claims to antigen tests, we have not seen FDA authorize an antigen test that required serial testing to meet the minimum performance requirement.  One of the reasons why it may not be common for manufacturers go out of their way to validate their devices for serial screening is that the complexity of the study to support this indication greatly expands the time, cost, and risk of failure.  If serial testing is required to bring a product to market it will likely shut out smaller manufacturers that have the potential to supplement the national testing supply after they ramp up production post-authorization.

It appears that we are at an impasse.  Unlike the rest of the world, this country has a shortage of OTC rapid antigen tests.  FDA has issued EUAs for very few, primarily due to the 80% sensitivity requirement.  What should be done?  Perhaps our legislators can intervene.  For one thing, they should require FDA to provide a detailed scientific justification for its 80% sensitivity requirement.  To date, FDA has failed to publicly explain its reasoning and justification for either the original 90% requirement or the more recent 80% requirement.

It might also be worthwhile for Congress to hold hearings, with medical and public health experts testifying, to come to a decision about the tradeoff between lowering the sensitivity threshold versus enabling widespread availability of OTC rapid tests.  A good case can be made that FDA has made the perfect the enemy of the good.  In the meantime, if the status quo continues, it is doubtful that Americans will ever have access to the widespread OTC testing that other countries are widely utilizing.

Categories: COVID19 |  Medical Devices