April 30, 2020
Interpretation and validation of antibody tests & false negative test results
On April 22, 2020, the FDA held its fourth town hall-style meeting where the in vitro diagnostics (IVD) community was invited to ask clarifying questions about the guidance on IVD testing released on March 16, 2020, allowing emergency use authorization (EUA) for qualifying diagnostic tests for SARS-CoV-2.
The key takeaways from the April 22, 2020, town hall meeting are listed below:
- The first home collection kit was authorized via EUA. It is authorized for use only with the LabCorp COVID-19 RT-PCR test. Several other applications for authorization have been submitted, but FDA is interested in seeing data showing that the samples can be accurately obtained by laypersons before considering authorization.
- The interagency effort to test the accuracy of serological tests for COVID-19 has begun and a number of kits have been received. Test kit developers interested in participating in this validation project should send an email to CDRH-OIR-POPS@fda.hhs.gov. Additional information is available on the FDA FAQ website.
- FDA also discussed the positive predictive value of testing when the prevalence of the disease is low. For example, even for tests with a high accuracy (95% sensitivity and 99% specificity), the positive predicative value is only 49% when the disease prevalence is 1%. Thus, a positive test result in this scenario would only be correct 49% of the time. A second positive test result from the same patient greatly increases the positive predictive value. FDA emphasized that since we do not yet know the COVID-19 disease prevalence, test results must be interpreted by a healthcare provider in the context of the patient's clinical history and test accuracy.
- An updated Instruction for Use (IFU) was published to clarify that only the direct swab approach should be used for a popular COVID-19 testing kit that was formerly used in conjunction with viral transport media (VTM). Labs wanting to validate testing not conducted at the point of care but hindered by the direct swab only instruction can contrive samples by pipetting known positive samples onto swabs with replicates for validation testing.
How Exponent Can Help
Exponent's multidisciplinary team of biotechnology, medical device, and pharmaceutical industry professionals develop safety information for products and processes that comply with all pertinent standards, regulations, and best practices. With expertise in risk communication and FDA assessments, Exponent can assist in FDA label preparation and pathway B or D submission for COVID-19 diagnostics. Our offerings also include reviewing diagnostic data to assess the completeness of the package for EUA or pathway D submission.