September 23, 2025

On September 23, 2025, the U.S. Food and Drug Administration finalized new guidance titled “Consideration of Enforcement Policies for In Vitro Diagnostic Tests During a Section 564 Declared Emergency”. This document outlines how and when the FDA will exercise enforcement discretion, effectively, when the Agency may choose not to enforce certain regulatory requirements, for in vitro diagnostics (IVDs) during emergencies declared under Section 564 of the Federal Food, Drug, and Cosmetic Act. The final guidance replaces an earlier draft guidance that was issued on 6 May 2024.

The guidance applies when there is a Section 564 declaration, which empowers FDA to issue Emergency Use Authorizations (EUAs) for medical products, including diagnostics, when specific statutory criteria are met.

Specifically, it addresses:

• Unapproved IVDs: tests not yet cleared, granted, approved, or authorized.
• Unapproved uses of approved or cleared IVDs: for example, using a test for sample types or in settings not covered by its cleared/approved labeling.

The document describes when the FDA would consider an enforcement policy (i.e., allowing use despite lack of full approval/authorization) for such tests, and also what factors it will evaluate for both initiating and terminating such policies.

The new guidance lays out several criteria the agency will weigh to decide whether to exercise enforcement discretion. Among them:

1. Public Health Need
   • How urgent is the need for more testing capacity?
   • Are current authorized or approved tests sufficient in supply, speed, access, etc.?
   • Size of the affected population; models may be used to estimate need.
2. Benefits vs. Risks
   • Potential improvement from earlier testing (accessible diagnostics, faster results) versus hazards like false negatives/positives.
   • Nature of the disease, severity, spread, asymptomatic cases, etc.
   • Capabilities of test manufacturers, their experience, reliability, and whether testing technology is complex or simple.
3. Availability of Alternatives
   • Whether there are other FDA-approved or EUA tests already available that could meet the need.
   • Whether alternate tests can be scaled up, and whether they perform acceptably.
4. Mitigations to Reduce Risk
   • Labeling practices that clearly disclose unapproved status.
   • Validations of test performance (e.g. clinical/analytical validation).
   • Confirmatory testing in settings where false results may have serious consequences.
   • Manufacturer track record; any prior EUAs or approvals.
5. Timing: When To Begin / When To End
   • The policy may be put in place when unmet need is high, supply limited, or when authorized tests cannot keep up.
   • It may end when authorized/approved tests become sufficiently available or when risks begin to outweigh benefits.

This guidance formalizes a structured, transparent framework for how FDA will handle unapproved or off-label IVD diagnostics during emergencies. During past emergencies like COVID-19 and the mpox outbreak, the FDA issued temporary enforcement policies to help increase testing availability.

With this document:

• Manufacturers have clearer expectations about what will be required (or excused) during a declared emergency.
• FDA lays out how it will proactively balance public health benefit with patient safety.
• The Agency commits to periodic review of any enforcement policy to ensure it remains appropriate given evolving circumstances.

• The guidance is nonbinding, meaning the guidance is meant as a recommendation, not a legal obligation. FDA still has discretion.

• Not all regulatory requirements may be relaxed under an enforcement policy; some obligations (e.g. certain reporting or safety requirements) might remain in effect.

• FDA intends this guidance to be used in consultation with stakeholders and may update or revise it as needed. Comments can be submitted via the regulations docket.

For diagnostic test developers and laboratories:

• If a new emergency is declared, those developing unapproved or off-label diagnostic tests should consider whether they can meet the mitigation, validation, and labeling expectations FDA has laid out.
• They might benefit from initiating EUA processes in parallel because enforcement discretion is intended to be temporary and conditional.
• Monitoring the availability of authorized tests will be critical, since gaining access to sufficient approved options may lead to the winding down of any enforcement policy.

From a regulatory policy perspective, this guidance strengthens preparedness by spelling out predefined triggers and decision points for when FDA will ease enforcement in emergencies, rather than relying solely on ad hoc policies.