United States, January 7, 2025 — The FDA has officially released a comprehensive draft guidance titled “Validation of Certain In Vitro Diagnostic Devices for Emerging Pathogens During a Section 564 Declared Emergency“. This document marks a pivotal shift in how the Agency expects manufacturers to validate In Vitro Diagnostic (IVD) devices when time is of the essence during a public health crisis.
By drawing on lessons learned from COVID-19 and mpox, the FDA guidelines are providing a standardized “road map” to ensure that rapid innovation does not come at the expense of clinical accuracy. For manufacturers, this guidance represents the new baseline for securing Emergency Use Authorizations (EUAs).
VALIDATION OF CERTAIN IN VITRO DIAGNOSTIC DEVICES : A NEW BASELINE FOR CLINICAL DATA
One of the most significant updates is the clarification of clinical performance expectations. To demonstrate that a test is reliable, the FDA generally recommends a clinical performance evaluation using at least 30 positive and 30 negative specimens of the appropriate specimen type.
- The Comparator: Performance should be measured against a “highly sensitive comparator method,” typically a molecular method like RT-PCR.
- Success Metrics: For molecular tests, the Agency generally expects ≥ 95% Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA).
- Flexibility for Antigen Tests: While molecular tests have a high bar, the FDA may accept a PPA of ≥ 80% for antigen tests, provided certain mitigations like serial testing are in place.
EARLY-STAGE INNOVATION: VALIDATING WITHOUT PATIENT SAMPLES
The FDA acknowledges a major hurdle for developers: how do you validate a test when a virus has only just emerged and patient samples are not yet available?
In the initial stages of an outbreak, the guidance allows for the use of contrived (spiked) specimens. Manufacturers can create these by placing known concentrations of the pathogen into a negative human clinical matrix. However, this comes with a “post-market” catch: once the test is authorized, the FDA will typically require a follow-up clinical study using natural patient specimens as they become more accessible.
POINT-OF-CARE (POC) AND HOME USE: THE USABILITY REVOLUTION
The shift toward decentralized testing is a core focus of this guidance. If your device is intended for use in a kitchen or a bedside setting rather than a sterile lab, the validation requirements change drastically.
- The 7th Grade Rule: Instructions for Use (IFU) for home kits must be written for lay users at no higher than a 7th-grade reading level.
- Flex Studies: Manufacturers must conduct “Flex Studies” to see if the test still works under “out-of-specification” conditions. This includes testing the device after it has been dropped, exposed to extreme heat (up to 40°C), or read at the wrong time.
Human Factors: Usability studies must ensure that untrained users can complete the entire workflow from collection to result interpretation without professional assistance.
FUTURE-PROOFING VIA PREDETERMINED CHANGE CONTROL PLANS (PCCPS)
Perhaps the most innovative section for operational agility is the introduction of Predetermined Change Control Plans (PCCPs).
Historically, minor changes to a device required a new EUA submission. Under this guidance, a manufacturer can include a PCCP in their initial request. If the FDA authorizes the plan, the manufacturer can implement pre-defined modifications such as adding a new instrument or extending the shelf-life of reagents without needing a brand-new authorization. This allows the device to evolve at the speed of the outbreak.
NEXT STEPS FOR MANUFACTURERS
This guidance is currently in Validation of Certain In Vitro Diagnostic Devices Draft form and is distributed for comment purposes only.
What should you do now?
- Review the Templates: Download the “General IVD EUA Request Template” from the FDA website to align your current R&D with Agency thinking.
- Audit Your Software: Ensure your cybersecurity and software validation align with the latest FDA principles for mobile medical applications.
- Submit Comments: Stakeholders have 60 days from the publication date to submit suggestions to the FDA via regulations.gov.