A Preparedness Sample Repository to Facilitate Rapid Diagnostic Test Development and Deployment

Introduction

Infectious disease outbreaks, even small or remote ones, may be a global threat and require a swift public health response. Accurate, accessible, and robust diagnostic tests are critical for patient management and public health response. However, when a new threat emerges, diagnostic tests may not exist and have to be developed rapidly, and then implemented by public health and clinical laboratories to support response efforts.

In the event that there are no suitable Food and Drug Administration (FDA) approved or cleared diagnostic tests, FDA has the authority to facilitate rapid deployment and use of tests under the expedited process of Emergency Use Authorization (EUA).1 If an emergency is declared by the United States (U.S.) Secretary of Health and Human Services, the FDA Commissioner may allow use of unapproved medical products or unapproved uses of approved medical products to aid in diagnosis of life-threatening diseases or conditions caused by infectious agents when there are no adequate, approved, and available alternatives. When reviewing an EUA, FDA relies on the totality of scientific evidence to determine that the product may be effective for the intended use in an emergency. For diagnostic tests, the scientific evidence includes validation of (limit of detection), inclusivity, exclusivity (near neighbors, pathogens with similar disease symptomology, endemic pathogens, etc.), and in silico analyses (if applicable). EUA tests may also require evidence of clinical performance using true positive and true negative samples alongside comparator methods (FDA cleared or other EUAs if available). These data, if not available before the emergency, must be generated by diagnostic test developers and included in the submission of a request for authorization.

Prior to implementing a legally distributed EUA test, clinical laboratories in the United States must satisfy regulatory requirements set forth by the Clinical Laboratory Improvement Amendment of 1988 (CLIA).2 For the use of an unmodified, FDA-cleared or approved test system (e.g., EUA test), laboratories must demonstrate that performance specifications (e.g., accuracy, precision, reportable range, reference range) obtained in their own laboratories are comparable to those established by the manufacturer. How these verification studies are performed is at the discretion of the laboratory director and often includes testing a variety of samples, including positive samples with an appropriate range of analyte concentrations, samples with interfering substances or related organisms, and negative samples. For use of EUA tests, the laboratories must only test the sample types (e.g., plasma or serum) that are approved or authorized by FDA when performing diagnostic testing, therefore, it's important to include those samples in their verification studies. Furthermore, the laboratory must also include negative and positive controls when performing testing on patient samples and comply with any additional local and state regulations that are applicable.

Access to samples and materials, which are accompanied by metadata including previous testing results and available through a nationally distributed repository, will improve diagnostic test development and the capacity of clinical and public health laboratories to respond to public health emergencies.