CDC Specs Limit Labs’ Ability to Test for COVID-19

As of today, it’s still difficult for suspected coronavirus patients to be tested for the disease. In Washington State, the epicenter of the disease in the U.S., the State Public Health Lab can test more than 200 samples (for 100 people) per day, with a 48-hour turnaround. The University of Washington virology lab is running about 800 specimens (for 400 people) per day.

Part of the blame for such limited testing availability could fall squarely on the Centers for Disease Control (CDC), which used highly restrictive language in its emergency use authorization for COVID-19 testing.

The CDC authorization “is like a recipe book of what you can and can’t do,” Joshua Trotta, a senior director of genetic sciences at Thermo Fisher Scientific, explained in a webcast.

That may be because it is taking an abundance of caution. (The CDC, however, had not commented before press time.) The emergency use authorization goes so far as to specify the PCR machine and software to be used. In this case, it specifies “the Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument with SDS version 1.4 software.” The CDC authorization also specifies using two 96-well plates.

“That’s absurdly restrictive,” said Justin Kinney, PhD., assistant professor, Cold Springs Harbor Laboratory. “This specific model of instrument is from 2012. It can only handle 96-well plates, not 384-well plates. Likewise, the software, SDS version 1.4, was released in 2011.”

Version 2.3 is the most current software.

Widespread availability is the rationale given for the choice of instrumentation and software, Trotta said. “qPRC has been out for 25 years and a lot of people already use this.”

But there’s more to the decision than mere availability.

The ‘DX” in the name is the giveaway,” said David Joyce, product development director at Thermo Fisher Scientific. “It’s a locked-down system and software version. It can be accredited for human diagnostics. It’s been validated in a clinical setting.”

“When designing a test for COVID-19, or any virus, researchers define the parameters very carefully and then go through the validation process,” Joyce said. “If different instruments are used, there could be different parameters that could cause false negatives. I’m sure we’re working on getting DX accreditation on additional instruments.”

The benefits could include the ability to bring data from labs around the world to a central point for analysis.

“There’s a lot of potential in the future to use connected technology to help in epidemiology,” Joyce said.

Once more tests and PCR instruments are validated, wide-spread testing will be easier, and the newest, most robust equipment and software may be applied to diagnosing what the World Health Organization on Wednesday designated as a global pandemic.

The CDC’s decision was a clear bid for accuracy. Yet, choosing not to allow the most up-to-date equipment creates a perceived, unnecessary bottleneck.

“The authorization reads as though it was written with too much emphasis on standardization,” Dr. Kinney said. “Quantitative PCRs can be run any place.”

And, he continues, specifying 96-well plates rather than 384-well plates further constricts testing throughput.

“Under the CDC authorization, you use only the top half of the plate. This means a clinician can run only about 10 samples at a time, versus the 22 that normally would run,” Dr. Kinney said. “With a 384-well-plate, a lab could run four times as many samples.”

The current COVID-19 test requires four primer/probe mixes and one human specimen control.

According to the CDC, “CDC’s (current) test kit is intended for use by laboratories designated by CDC as qualified, and in the United States, certified under the Clinical Laboratory Improvement Amendments (CLIA) to perform high complexity tests. The test kits also will be shipped to qualified international laboratories, such as World Health Organization (WHO) Global Influenza Surveillance Response System (GISRS) laboratories. The test will not be available in U.S. hospitals or other primary care settings. The kits will be distributed through the International Reagent Resource icon (IRR).”

More flexible versions of the COVID-19 diagnostic tests are being developed but, currently, are only available for research. For example, the CDC is developing a serology-based test, looking for antibodies in blood and tissue samples. Other labs around the world are engaging in similar efforts in an attempt to accurately – and quickly – diagnose this still-spreading contagion.