It has been another busy week for FDA as the agency made moves to broaden COVID-19 testing to more Americans — including those who are not showing any symptoms of having the virus — while also cracking down on fraudulent tests and revoking a previously-authorized antibody test.
The agency posted template updates regarding the validation of molecular diagnostic tests for developers that intend their assay to be used for pooling patient samples or for screening asymptomatic individuals not suspected of having COVID-19. The agency also published a FAQs with information regarding tests for screening asymptomatic individuals.
FDA has authorized molecular diagnostic tests for anyone whose healthcare provider suspects of having the virus that causes COVID-19, whether they are symptomatic, pre-symptomatic, or asymptomatic. It has always been the healthcare provider's discretion to test patients who don't exhibit any of the symptoms if, for example, the individual has been in contact with someone else who has tested positive for the virus. However, FDA says that is not the same as using COVID-19 diagnostic tests as a broad screening tool.
The agency's updated templates for test developers explains FDA's expectations for how a test can be validated for screening of asymptomatic individuals, in an effort to make it easier to get tests authorized for this use. The point is so that organizations can conduct screening as part of a broader strategy to ensure the safety of employees, patients, students, and others.
What Is the Benefit of COVID-19 Sample Pooling?
FDA said that in order to preserve testing resources, many developers are interested in performing their COVID-19 testing using a technique of "pooling" samples, which allows a lab to mix several samples together in a batch or pooled sample and then process the pooled sample with a diagnostic test. For example, four samples may be tested together, using only the resources needed for a single test. If the pooled sample is negative, it can be deduced that all patients were negative. If the pooled sample comes back positive, then each sample needs to be tested individually to find out which was positive.
Because samples are pooled together, ultimately fewer tests are run overall, meaning fewer testing supplies are used, and results can be returned to patients more quickly in most cases, FDA said. The agency warned, however, that because samples are diluted, there is a greater likelihood of false negative results, particularly if not properly validated. The agency said this method works well when there is a low prevalence of cases, meaning more negative results are expected. Testing asymptomatic individuals means testing a greater volume of patients, and a low prevalence may be more likely in an asymptomatic population, particularly if the population is at low risk for contracting COVID-19, FDA said developers may be interested in using pooling techniques in tests for asymptomatic screening.
Cracking Down on COVID-19 Fraud
FDA also slapped three companies with warning letters this week for marketing adulterated and misbranded COVID-19 antibody tests. Generally, antibody tests, also called serological tests, detect antibodies to SARS-CoV-2, which can help identify individuals who have developed an adaptive immune response to the virus, as part of either an active infection or a prior infection. These tests may be important in the fight against this pandemic, the agency noted, as they may provide information on disease prevalence and the frequency of asymptomatic infection. Today’s warning letters are the first set of letters the agency has issued for marketing adulterated or misbranded COVID-19 test kits.
Warning letters were issued to: Medakit Ltd. of Sheung Wan, Hong Kong; Antibodiescheck.com and Yama Group; and Dr. Jason Korkus, DDS and Sonrisa Family Dental d/b/a My COVID19 Club of Chicago, Illinois.
“Providing regulatory flexibility during this public health emergency never meant we would allow fraud,” said Jeff Shuren, MD, director of FDA’s Center for Devices and Radiological Health. “When tests are marketed inappropriately, with inaccurate or misleading claims – such as the ability to perform the test completely at home, or that the test is authorized, cleared, or approved when it is not – they put the health of Americans at risk. Such conduct will not be tolerated by the FDA, and we will continue to monitor tests marketed in the U.S., taking appropriate action as warranted.”
Violations outlined in the warning letters include: offering test kits for sale in the United States directly to consumers for at-home use without marketing approval, clearance, or authorization from the FDA; misbranding products with labeling that falsely claims products are “FDA approved”; and labeling that bears the FDA logo.
FDA says consumers and healthcare professionals are encouraged to report suspected fraud to FDA's health fraud program, the Office of Criminal Investigations, or email FDA-COVID-19-Fraudulent-Products@fda.hhs.gov.
Chembio Loses COVID-19 Antibody Test Authorization
Performance/accuracy concerns prompted FDA to revoke the emergency use authorization of Chembio Diagnostic System's SARS-CoV-2 antibody test, which was among the first COVID-19 antibody tests authorized in the United States. FDA said it previously authorized the test based on information Chembio submitted at the time because the test's known and potential benefits outweighed its known and potential risks.
This week the agency said that as it has learned more regarding the capability for performance of SARS-CoV-2 antibody tests during the pandemic, and what performance is necessary for users to make well-informed decisions, FDA has developed general performance expectations for these tests, and Chembio's test didn't make the cut.
Data submitted by Chembio as well as an independent evaluation of the Chembio test showed that it generates a higher than expected rate of false results and higher than that reflected in the authorized labeling for the device. The agency said that the risk to public health from the false test results makes EUA revocation appropriate.
“Since the beginning of the COVID-19 public health emergency, the FDA has balanced the urgent need for access to diagnostic and antibody tests with providing a level of oversight that helps to ensure accurate tests are being deployed,” Shuren said. “By continuing to monitor authorized tests and emerging scientific evidence, we are able to make changes when appropriate – including taking action when a test’s benefits no longer outweigh its risks. Through these efforts, we are able to help assure that FDA-authorized tests meet the needs of the American public.”
Current Landscape of COVID-19 Testing in the United States
To date, FDA has authorized 140 tests under emergency use authorizations, which include 118 molecular tests, 21 antibody tests, and one antigen test.
The agency also continues to authorize more tests that are designed for at-home sample collection. Most recently, Fulgent Genetics received emergency use authorization for a COVID-19 diagnostic test. Fulgent said it will be offering the testing service through Picture Genetics, the company’s consumer-initiated genetic testing platform, beginning next week.
One molecular diagnostic company is cutting through the noise and reaching investors’ ears with a rapid COVID-19 test. Cue Health said last week it has raised a sizeable $100 million in a series C financing to help support the development and commercialization of its tests, which includes a molecular diagnostic for COVID-19. Speaking of which, Cue Health finished out the week on a high note with FDA authorizing the rapid, portable, point-of-care molecular test designed to detect the RNA of SARS-CoV-2. The test uses a nasal swab sample taken from the lower part of the nose and produces results in 25 minutes, Cue said.
Another significant recent development on the testing front is the addition of next-generation sequencing. FDA gave Illumina the greenlight to bring the first next-generation sequencing COVID-19 diagnostic test to the U.S. market, which is expected to become a key weapon in the battle against the virus. The test not only expands the United States' testing capabilities, but genetic sequencing information is expected to help scientists monitor if and how the virus mutates, which will be crucial as they continue to learn and fight the virus.
Abbott emerged as an early leader for COVID-19 testing, especially after bringing its ID NOW COVID-19 rapid test to the U.S. market. In May, however, the company went on the defensive after several independent research teams questioned the accuracy of the point-of-care molecular diagnostic test. One study in particular, out of NYU Langone Health, suggested that Abbott's test produced false negative results for almost half of the positive samples in a study of 101 patients. That study was criticized however because the patient samples were not collected at the point of care like the test was designed for. Instead, the researchers transported the samples to the hospital's laboratory within one or two hours and then tested using both Abbott's ID NOW machine and Cepheid's Xpert Xpress test. Abbott argued that outcomes of its ID NOW test depend on a number of factors including conformity to the way the test was designed to be run. ID NOW is intended to be used near the patient with a direct swab test method,"
FDA said on May 14 it was investigating concerns about the test, but the agency has not announced any updates or action related to those concerns.
Recently, Abbott published an interim analysis of an ongoing multi-site clinical study in urgent care clinics that indicates its ID NOW COVID-19 rapid test is showing strong agreement to lab-based molecular polymerase chain reaction (PCR) instruments. Abbott said the interim results are demonstrating ID NOW COVID-19 test performance is ≥94.7% in positive agreement (sensitivity) and ≥98.6% negative agreement (specificity) when compared to two different lab-based PCR reference methods.
Data from this, as well as two other Abbott-sponsored studies – The Everett Clinic in Washington and an ongoing study of hospitalized and nursing home patients – suggest ID NOW performs best in patients tested earlier post symptom onset, when they are most likely to go for care. In these studies, ID NOW was used as intended with variations in patient populations based on the number of days a patient was tested after first experiencing symptoms, Abbott said.