FDA slashes number of analytical tests for IVDs used in public health emergencies
The US Food and Drug Administration (FDA) on Monday finalized guidance to assist manufacturers in validating in vitro diagnostic devices (IVDs) that test for emerging pathogens during public health emergencies. The guidance also provides recommendations on how this validation data should be submitted in a pre-Emergency Use Authorization (EUA) or an EUA request.
The guidance “describes general recommendations for the validation of IVDs for emerging pathogens to help test manufacturers better prepare for future outbreaks by clarifying FDA’s recommendations for test validation during an applicable declaration under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act),” FDA wrote in a Federal Register notice announcing the guidance. Alongside the guidance, FDA released a general template for IVD EUA and pre-EUA requests.
The final guidance updates a draft version released in January 2025. FDA said it reviewed the comments and revised the guidance to provide “consolidated and streamlined test validation recommendations applicable across diagnostic test types, adding language emphasizing flexibility in the validation recommendations and addressing challenges at different stages of an outbreak, and clarifying FDA’s focus on the most important and least burdensome information to collect and/or submit during a section 564 declared emergency.”
The final guidance, for example, reduces the number of analytical tests developers must conduct from 15 to five. These five tests include limit of detection (LoD), inclusivity, specimen stability, basic safety and software validation, and usability.
The guidance indicates that the recommendations in the guidance “are intended to be broadly applicable to potential future emerging pathogens.” FDA notes in the guidance that “outbreaks inherently come with uncertainty and that recommended validation approaches should be adjusted for certain situations.”
The guidance defines validation as demonstrating “that a finished device can consistently fulfill defined user needs and its intended use.” FDA states that the validation recommendations “provides for a lower level of evidence than the “effectiveness” standard that FDA uses for product approvals.”
The guidance provides recommendations for validation studies related to the initial outbreak. It outlines the study design, clinical data analysis, and protections for human subjects. Additionally, it addresses analytical validation testing for the five different test methods. The guidance also discusses specific considerations for certain types of tests, including multi-analyte panels, home specimen collection and use, and point-of-care (POC) tests.
In response to public comments from the Association for Molecular Pathology (AMP), the guidance grants more flexibility regarding clinical performance evaluations. The draft stated that “a clinical performance evaluation with at least 30 positive and 30 negative specimens of the appropriate specimen type should demonstrate the performance of the test compared to a highly sensitive comparator method, when available.”
The final guidance clarifies that “the number of samples and the design of the study, such as an appropriate comparator method, will depend on many factors including the target pathogen, type of test, availability of clinical specimens containing the pathogen, availability of appropriate comparator methods, the stage of the outbreak, and overall testing needs.”
However, FDA does recommend using at least 30 positive and 30 negative specimens for viral nucleic acid tests, particularly during an outbreak stage when clinical samples and comparators are generally available.
