Pitfalls of the Notification Pathway – “I’m Sciencing as Fast as I Can”

On August 25th, 2020 Hyman, Phelps & McNamara, P.C. released a blog post covering experiences and lessons learned from our interactions with FDA and what was at the time the new and unfamiliar EUA pathway (FDA, Testing, and COVID-19: A “Mid-Mortem”). In the six months since that post, we have seen new products hit the market for non-laboratory use, new technologies, and what I assume is attributable in some small part to my offerings to Jupiter, Son of Saturn, an effective vaccine.

Since the early days of the pandemic, FDA has made it possible for manufacturers to market and distribute certain diagnostic tests to high-complexity CLIA Labs prior to EUA authorization provided that the validation testing is complete at the time of marketing and an EUA is filed with 15 business days. The “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised) Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff” Issued on May 11, 2020 (the “FDA Testing Policy”).

FDA does not intend to object to a commercial manufacturer’s development and distribution of SARS-CoV-2 test kits for specimen testing for a reasonable period of time, where the test has been validated and while the manufacturer is preparing its EUA request, where the manufacturer gives notification of validation to FDA as described below, and where the manufacturer provides instructions for use of the test and posts data about the test’s performance characteristics on the manufacturer’s website.

On the surface, this statement sounds fantastic.  FDA appeared to understand that the pandemic is an all-hands-on-deck situation and is trying to find a middle ground to get tests on the market while manufacturers play catch-up compiling their EUA submission. But, in the words of the many great home shopping spokespeople, “But Wait! There’s More!”  The FDA Testing Policy states:

FDA believes that 15 business days is a reasonable period of time to prepare an EUA submission for a test that has already been validated. Soon after receiving the EUA request, FDA will perform a preliminary review to identify if there are any problems with the performance data. If a problem is identified, FDA intends to work with the manufacturer to address the problem (e.g., through labeling or bench testing). If the problem is significant and cannot be addressed in a timely manner, and the manufacturer has already distributed the device, FDA would expect the manufacturer to suspend distribution and conduct a recall of the test.

Per this policy, FDA is affording companies at least 3 weeks to compile completed data into a functional EUA submission and submit while also committing to a triage review with a tiered approach to deficiencies.  Hundreds of companies took advantage of this program and notified FDA of their intent to distribute test kits in accordance with FDA’s policy. This seemed too good to be true, and it most certainly was.

Many companies viewed the notification pathway as a way to stand out from the crowd by proactively signaling to FDA that their submission was complete and that their EUA should garner additional attention from the Agency. For many companies the notification pathway was only about visibility on FDA’s radar. In our experience, many manufacturers never availed themselves of the opportunity to distribute as nearly all potential customers were seeking out tests that had successfully obtained EUA authorization.

Weeks in the EUA queue turned into months with little to no action being taken by FDA for many EUAs on the notification list.  When companies finally received the reviewer introduction email, many were lifted from the morass of uncertainty and despair and filled with new hope for the future.  This life-reaffirming high would be snuffed out quickly by the all too common subsequent “Inadequate Validation” email.

This email would inform companies that they had not provided complete information to demonstrate that the studies performed are adequate to validate the test and support the claimed performance characteristics of the device.  The email would go on to list the deficiencies in the familiar fashion of a hold letter for a 510(K), De Novo, or PMA.  As you’ll recall, the FDA Testing Policy stated that, “If a problem is identified, FDA intends to work with the manufacturer to address the problem (e.g., through labeling or bench testing).” Most in industry expected that this meant FDA would allow time to address concerns via new labeling,  bench testing, or simply the submission of additional data.  The veritable chasm between industry’s expectations as to how this process would play out and the reality espoused by FDA can be found in the close of the “Inadequate Validation” letter, which typically, allowed a sponsor a mere 24 or 48 hours to respond:

[I]f the information you provide does not demonstrate that your device is adequately validated for its intended use and performing consistently, we may take steps as described in the guidance referenced above, including removing the test from the website listing of notifications, and may determine that the criteria for emergency use authorization have not been met. If such steps are taken and we make that determination, we would expect you to suspend distribution of your test, and we may request that you take additional actions to protect the public health as appropriate.

One can imagine the feeling of despair when after months of waiting for a reviewer to be assigned to your EUA submission FDA returns with questions but only provides you with 24 or 48 hours to respond with the rationale that the timeline was in the “interest of public health.” Once on the notification list FDA has no way of checking to see if devices were actually introduced into the market, therefore, FDA approaches each review as if they have allowed the company to exist in the marketplace unchecked for months.  It seems that FDA is content with the idea that by limiting response windows to one or two days they are fulfilling their mandate to promote and protect public health.  Many companies are at a loss, however, as they are not prepared for this over-correction by FDA and simply cannot operate within such arbitrary timelines with draconian enforcement.

We have to ask the question, “Is FDA intending for these companies to fail?” By now FDA should be well aware of industry’s plight.  Companies are waiting months only to scramble for 48-hours straight to try and deliver FDA the moon.  It behooves the Agency to publicly issue new instructions clarifying their expectations for companies on the notification list.

In comparison, for a company that has submitted an EUA without being added to the notification list, FDA may not even specify a deadline to respond to the review team’s questions.  Furthermore, we have not observed an acceleration in the review timeline for companies on the notification list. It appears that you have everything to lose by being added to the notification list with nothing to gain.

Prof. Hubert J. Farnsworth said it best “I’m sciencing as fast as I can.”  Only so much can be done in the span of 48 hours and many times FDA requests additional data or analysis. Bottom line: Companies should think twice before choosing to add their tests to the notification list.