Recently, members of George Mason University faculty posed questions of concern about various aspects of the screening method the university used to screen the 3,200 Mason students before they came to campus to live in residence halls.
In response to faculty concerns, Mason President Gregory Washington asked me to evaluate our process and offer responses to the concerns expressed by the faculty members. I sincerely believe that the university has a moral and ethical obligation to protect our students, faculty, and staff and as such, I took my colleague’s concerns very seriously and have tried to provide objective answers to the questions that were posed.
Below are my detailed responses:
1. The Kallaco Test (Thermo Fisher TaqPath COVID-19 Combo Kit) was NOT EUA-approved by the FDA for home specimen collection. (Read the full FDA email here).
RESPONSE: This is true. Specimen collection was not addressed in the EUA.
2. The CDC has published guidelines for collecting COVID-19 samples.This CDC document explicitly states that oropharyngeal (OP) specimens (i.e., throat swabs) must be collected by health care providers to be acceptable. By contrast, the Kallaco-Thermo Fisher test kit required students to perform an oropharyngeal (OP) specimen collection (throat swab) at home, in violation of CDC guidelines. For the full guidelines visit bit.ly/3j59iYw.
RESPONSE: Successful collection of specimens is dependent on getting enough material from the collection site. Nasal or throat swabs need to abrade the tissue while minimizing irritation.
It should be noted that not all cells of the pharyngeal mucosa are likely to be infected by the virus and it is likely that infected patches, as well as noninfected areas are present in a patient. As such, it is conceivable that even properly trained personnel may miss an infected patch when swabbing.
The CDC does not have instructions for sample collection per se and states the specimens are acceptable when, depending on the specimen type, collection is carried out by a health care provider, or by the patient (self-collection), in a supervised onsite setting, or at home. Per the Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens for COVID-19, CDC states the following:
“For initial diagnostic testing for SARS-CoV-2, CDC recommends collecting and testing an upper respiratory specimen. The following are acceptable specimens (www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html):
A nasopharyngeal (NP) specimen collected by a health care provider; or
An oropharyngeal (OP) specimen collected by a health care provider; or
A nasal mid-turbinate swab collected by a health care provider or by a supervised onsite self-collection (using a flocked tapered swab); or
An anterior nares (nasal swab) specimen collected by a health care provider or by home or supervised onsite self-collection (using a flocked or spun polyester swab); or
Nasopharyngeal wash/aspirate or nasal wash/aspirate (NW) specimen collected by a healthcare provider.
3. On August 17, 2020, the FDA released an advisory titled “Risk of Inaccurate Results with Thermo Fisher Scientific TaqPath COVID-19 Combo Kit” (the now-infamous Kallaco test). This advisory was released to alert “clinical laboratory staff and health care providers of a risk of false results with Thermo Fisher Scientific TaqPath COVID-19 Combo Kit.” The full FDA advisory can be found here.
A. According to the FDA’s letter to clinical staff and health care providers, the following issues were identified:
“The first issue is related to inadequate vortexing and centrifugation of RT-PCR reaction plates. Thermo Fisher Scientific’s conclusion from investigations of customer complaints indicate that inadequate vortexing or centrifugation can lead to false positive results. Thermo Fisher Scientific has updated these instructions to reduce the risk of inaccurate results. The updated instructions related to vortexing and centrifugation are important for both laboratories performing testing according to the authorized instructions for use and laboratories who are performing validated modifications outside of the authorization” (https://www.fda.gov/medical-devices/letters-health-care-providers/risk-inaccurate-results-thermo-fisher-scientific-taqpath-covid-19-combo-kit-letter-clinical).
Vortexing mixes the contents of the PCR reaction plates. Opteo Laboratories was asked if they followed Thermo Fisher’s updated instructions. They responded that Opteo Laboratories performs vortexing of samples for 10 to 20 seconds, consistent with Thermo Fisher’s updated instructions.
Centrifugation is required to get all of the contents of the tube to the bottom of the wells after vortexing. Opteo Laboratories was asked if they followed Thermo Fisher’s updated instructions. They responded that Opteo Laboratories performs centrifugation for 2 minutes at 1,500 RPM, consistent with Thermo Fisher’s updated instructions.
B. The second issue identified by the FDA is “related to the assay Internal Positive Control (IPC) and requires laboratory staff to upgrade their software to reduce the risk of invalid, potential false negatives, or inconclusive tests and to decrease the potential need to retest” (https://www.fda.gov/medical-devices/letters-health-care-providers/risk-inaccurate-results-thermo-fisher-scientific-taqpath-covid-19-combo-kit-letter-clinical).
Al PCR reaction may be inhibited by a number of factors, including excess salt, detergents, sample components such as bile salts, and may be impacted by other issues, such as problems with nucleic acid extraction. As such, it is possible to get false negative results. To control for the presence of inhibitors, an internal positive control must be run. The internal positive control is extracted and amplified in the same tube as the pathogen whose presence is being tested by the PCR test (an external positive control, on the other hand, is used to ensure that the amplification reaction is working).
C. Third, the FDA recommends that test providers upgrade the Applied Biosystems COVID-19 Interpretive Software to version 1.3 or 2.3.
According to Opteo Laboratory, they use the Applied Biosystems COVID-19 Interpretive Software version 1.3 and the following was stated in Opteo’s EUA submission: “The data are analyzed by Applied Biosystems’s ExpressionSuiteTM Software 1.3 which uses updated algorithms with improved sensitivity for detection of low- copy samples as well as improved baselining algorithms for COVID19 assays.”
RESPONSE: Kallaco is not the testing entity and is the aggregator. Opteo Laboratory is the testing entity. Opteo focuses on genetic testing, as well as pathogen detection (opteolab.com).
5. We must alert students, faculty, staff, and families of these testing flaws and begin again with a new testing strategy. This is a public health imperative. We are asking the administration to take immediate action to remedy what could be inaccurate results from the Kallaco-Thermo Fisher test kit to ensure the health, safety and well-being of our campus community.
RESPONSE: Accurate tests are essential for the detection of any pathogen. Mason scientists are currently assessing and validating multiple state-of-the-art tests. The fact that the Thermo Fisher test was given an EUA by the FDA (https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#individual-molecular) suggests that it had met the agency’s criteria for robustness. According to the FDA, the subsequent findings and recommendations for remediation have not translated into an invalidation of the test—“The FDA is working with Thermo Fisher Scientific and our public health partners to resolve these issues. The FDA will continue to keep clinical laboratory staff, health care providers, manufacturers, and the public informed of new or additional information.”
6. Further, we have learned that VCU, William & Mary, Virginia State University, Hampden-Sydney College, and Randolph-Macon also have contracts with Kallaco. We therefore have a moral and ethical obligation to alert them of these testing issues. We urge you to join with us to demand an investigation into how we got here and to demand that GMU leaders immediately redress the failed Kallaco-Thermo Fisher COVID-19 testing process.
RESPONSE: Mason has been in contact with the senior leadership of other universities and have discussed the issues raised by Mason colleagues.
7. The FDA has issued an “Enforcement Policy for Viral Transport Media During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency” as well as FAQs on viral transport media. Not only is the correct labeling of media critically important, it is required. There is a reason for a label which states, “not for use in diagnostic procedures.”
RESPONSE: Kallaco personnel provided an explanation based on the logistics of procuring the tubes. Although understandable, the issue may remain of concern to students and faculty. Opteo Laboratories confirmed the contents of the collection tubes were the same, regardless of the label.
8. Kallaco did not exist until April 29 of this year. Students at VCU, William and Mary as well as Mason have looked into the company’s background. So has the GMU-AAUP. We have a lot more to say about Kallaco, but note that the sole source contract does not include any language about Opteo Laboratory. It does, however, include the following disclaimer: “THE COMPANY DISCLAIMS ALL LIABILITY REGARDING THE ACCURACY OF THIRD-PARTY DIAGNOSTIC SERVICES TO THE MAXIMUM EXTENT PERMITTED BY LAW.”
RESPONSE: This is true.
Kallaco notes in their online Q&A: kalla.co/updated-statement-from-kallaco
“Kallaco is a new company formed by individuals and partners with deep experience in healthcare investment and innovation….
Kallaco was created by U.S. healthcare executives who saw firsthand the need for a comprehensive technology platform that could also include integrated diagnostic testing. This vision was cemented as the COVID-19 pandemic hit Kallaco’s hometown of New Orleans, LA.”
As stated previously, Kallaco does not do the tests. Opteo Laboratory (CLIA Number: 19D2161808) performs the tests.
In closing, I want to reiterate my belief that we have an obligation to protect our students, faculty and staff. To achieve this goal, we must use the most advanced tests and must be ready to adopt new, robust and validated testing innovations as they become available. As such, Mason’s strategy should be and is one that actively seeks better testing modalities, and it is capable of pivoting to take advantage of new developments for the benefit of the Mason community. Better technologies will help us to increase the frequency of testing and the number of people that we test.
Ali Andalibi, PhD
College of Science