Potential False Results with Roche Molecular Systems’ SARS-CoV-2 Assay

On Friday, March 12th FDA posted a letter to healthcare providers about performance concerns regarding the Roche Molecular Systems, Inc. cobas SARS-CoV-2 & Influenza Test for use on cobas Liat System.  This public letter appears to be the culmination of a dialogue between Roche and FDA.  Roche’s root cause analysis investigation has identified two potential causes for the false positives:

• Roche identified that the assay tubes may sporadically leak, causing an obstructed optical path in the Liat analyzer, producing abnormal PCR growth curves. This could lead to invalid or erroneous positive results, particularly for the Flu B test. If a tube leak occurs, later testing runs may have an increased likelihood of false positive Flu B results.

• Roche determined that abnormal PCR cycling in the reaction tubes may also produce abnormal PCR growth curves, leading to erroneous results. The issue is sporadic and may be caused by multiple factors happening at the same time, such as hardware positioning, volume movement, and curve interpretation. This issue may cause false positive results for multiple analytes (Influenza A, Influenza B and/or SARS-CoV-2) in a single testing run.

In response, FDA recommended three actions by users:

1. Monitor for unexpected clusters of positive Flu B results, as this may indicate the cobas Liat System has experienced a tube leak.
2. Repeat tests when two or three analytes are positive. Different results on the repeat test may indicate abnormal PCR cycling.
3. Stop using the cobas Liat System and contact Roche if you suspect either of these two issues has occurred.

This letter is not the first FDA has posted for Clinical Laboratory and Point-of-Care staff.  It is actually the fourth one since October 2020 and the eighth such notice flagging in‑vitro diagnostic performance issues or concerns during the pandemic.

These notices have hit each of the three major classes of in-vitro diagnostic products used for the nation’s pandemic response, PCR, Serology, and Antigen Tests.  Here are three relatively recent examples:

PCR

• Genetic Variants of SARS-CoV-2 May Lead to False Negative Results with Molecular Tests for Detection of SARS-CoV-2 – Letter to Clinical Laboratory Staff and Health Care Providers (Posted 01/08/2021)

Antigen

• Potential for False Positive Results with Antigen Tests for Rapid Detection of SARS-CoV-2 – Letter to Clinical Laboratory Staff and Health Care Providers (Posted 11/03/2020)

Serology

• Important Information on the Use of Serological (Antibody) Tests for COVID-19 – Letter to Health Care Providers (Posted 04/17/2020)

The full list of FDA’s “Letters to Health Care Providers” can be found here.

As we proceed through this pandemic, it is becoming more critical that manufacturers be as vigilant as ever with post-market surveillance to flag performance issues early in order to be able to investigate and identify potential root causes.  Prompt investigation and correction is always preferable to pulling a test that works out of the marketplace.  It is in no one’s best interest to lose testing capacity and we hope that FDA is affording companies of all sizes the same opportunity that Roche has been given to investigate and correct rather than be forced to pull an assay from distribution.