The latest U.S. FDA town hall for testing for the COVID-19 included a few updates on serological testing, but perhaps the most important take-away was when Tim Stenzel, director of the Office of In Vitro Diagnostics and Radiology, advised attendees that performance expectations regarding next-generation sequence (NGS) testing for the SARS-CoV-2 virus will closely resemble those of conventional molecular testing.

Stenzel said that the information from the National Cancer Institute’s review of serology tests is forwarded to the instructions for use for those tests more or less immediately. The agency has also removed more than 30 serology tests from the EAU list.

Next-generation sequencing technology, as applied to the SARS-CoV-2 virus, “is coming forward, and that is going to be a tremendous help in this battle,” Stenzel said. The FDA is urging developers of NGS systems to make available any sequencing information they obtain so others can use that information to keep track of mutations. This is particularly of interest when a mutation occurs at primer binding sites.

Broadly speaking, the FDA’s recommendations for NGS testing will be very similar to the current recommendations for other molecular testing technologies, usually polymerase chain reaction approaches, and Stenzel said the performance of NGS systems should be validated using actual patient samples. The performance of the NGS test should be at least 95% relative to another molecular test, and Stenzel said the molecular test template “is a really great place to start” for any parties interested in developing an NGS system for the virus. He said the agency will update the molecular templates for NGS testing as soon as it has enough data to do so.

Some transport media proving problematic

Toby Lowe, associate director for programs and performance at the Center for Devices and Radiological Health, said that certain types of transport media that are not compatible with certain testing platforms, noting that some materials interact with bleach to create cyanide gas. She said the Primestore molecular transport medium by Longhorn Vaccines and Diagnostics LLC, of Bethesda, Md., should not be used with two versions of the Panther system by Hologic Inc., of Marlborough, Mass., given that those systems use a disinfection step that entails the use of bleach.

Lowe said the FDA has become aware of instances in which transport media are being distributed without appropriate labeling, which creates confusion in labs regarding which media they are using and the ingredients used in those media. The agency is working with labs to make them aware of this predicament and with the manufacturers of the transport media to correct the situation with amendments to product labels.

In regard to a question about a pathway for serological test 510(k)s, Stenzel said a de novo filing would likely be a prerequisite for many novel tests, but added that the Q-sub process is available for developers to review their proposals with the agency. The FDA recommends that developers invoke pre-submission process, Stenzel said, adding that although this is not mandatory, pre-submission interactions can give developers a better understanding of the FDA’s views of questions such as post-infection time points for testing live subjects during test validation.

Stenzel said the agency’s current policy for any test developer eyeing the market for testing of asymptomatics is that the developer should go through the EUA program if the label makes claims directed toward asymptomatic use. If the test is already under an EUA for use in symptomatic patients and a prescriber has ordered the test, “we think it’s okay for the lab to process” the sample and report the results.

With regard to sample pooling, “we are looking at the situation very closely,” Stenzel said, adding that recommendations pertaining to pooling should emerge in the near future. These recommendations will provide more granularity, but Stenzel advised, “the bottom line we’re interested in is accurate information.” This holds true even for pooling undertaken for testing in workplace and other large-scale settings, and he said the FDA wants the developer to ensure that low-positive samples are not missed in any given sample pooling scheme.

New update for test supply substitutions

The FDA provided a June 3 update for its testing FAQ page that provides a new web resource for labs that are performing COVID-19 tests that have already been authorized in the EUA program. This resource lists validated supply alternatives that labs can use to allow them to sustain testing activities when supplies are unavailable for some components of a test.

Among the topics covered in the resource are specimen collection swabs, and media, and substitution options for open mix-and-match tests. The file is highlighted in blue near the top of the FAQ page, and is titled, “Testing Supply Substitution Strategies” and the FDA noted that the resource is available as a slide show file. Users can download the file to their computers.

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