FDA developments 2025–2026: five shifts in oversight, capacity and validation

1. Unannounced inspections at foreign manufacturing facilities

Back in 2025, the FDA announced a wider rollout of unannounced inspections at foreign manufacturing facilities, following an earlier pilot in India and China. The FDA explained that the gap in preparation time between domestic and foreign manufacturers had to be reduced.

According to the same press release, the FDA carries out around 12,000 domestic and 3,000 foreign inspections per year, across more than ninety countries. During those foreign inspections, which were announced in advance, the FDA found serious deficiencies "more than twice as often" as during domestic ones. FDA investigators have also been instructed to refuse travel accommodations from inspected firms, including lodging and taxi.

For sites supplying the U.S. market, this means document control, training records, deviation handling, complaint files and data integrity must be in order at any moment. A week of preparation is no longer in the picture.

2. Simultaneous reductions and hiring at the FDA

In the first half of 2025, HHS (the Department of Health and Human Services) and the FDA carried out substantial workforce reductions. An analysis in Medical Device and Diagnostic Industry (April 2026) cites several thousand FDA positions cut, with impact on CDRH and others. At the same time, Fierce Biotech reported on 21 November 2025 that the FDA would hire "more than 1,000 new employees" and start a new communications pilot for reviews. Citeline wrote in early January 2026 that more than four hundred of those new hires had already been onboarded.

The FDA is becoming more selective about where its capacity sits. Reviews and field investigations are being staffed. Some support functions are not. For our part of the industry, the part of the FDA you actually deal with stays at full strength, or gets stronger.

3. Faster approval trajectory for rare diseases and biosimilars

Two areas are clearly being prioritised. Rare diseases first. The FDA and NIH cite figures that make the scale clear: more than ten thousand rare diseases, affecting around 30 million Americans — roughly 1 in 10. With those numbers, rare-disease policy sits firmly on the central agenda.

Then biosimilars: in 2025, the FDA published initiatives to accelerate biosimilar development and approval, including proposed easing of certain testing requirements where the science allows (Reuters reported on this). The aim: lower consumer costs and more competition in biologics.

Where interpretation often goes wrong: the acceleration sits in procedural cycle time and in the communication between reviewers and sponsors. The scientific evidentiary bar does not change.

4. Rising warning letters from weak 483 responses

A quick analysis shows around 105 warning letters for human-drug quality issues in 2025, an increase of about 11% year over year.

The trigger is usually not the 483 observation itself, but an inadequate or late response to that 483. A response without a root-cause analysis, without a quantitative impact assessment and without a credible CAPA, etc., escalates quickly.

A new dimension since 2026: photographs. In the warning letter to Patcos Cosmetics (12 March 2026), the FDA for the first time included photographs to document "gross insanitary conditions," with an explicit CDER footnote. Whether this stays a one-off or becomes a standing pattern is still open, but the legal basis is in place through the June 2024 guidance on photography during inspections. An observation about "unsanitary conditions" says less than the photographs attached to this warning letter.

To view this warning letter, click this link.

5. Three-batch validation under the 2011 guidance

In dossiers and discussions we still regularly encounter the assumption that the "three-batch rule" for PPQ applies as before. Under the FDA Process Validation Guidance of 2011, that has not been the case for over a decade. The guidance replaces the "golden batch" approach with a lifecycle method based on risk analysis and scientific substantiation.

That the FDA still has to explain this regularly in 2025–2026 is partly down to slow industry adoption; the old number keeps showing up in dossiers and discussions. A few more recent developments have also put the risk-based approach back on the agenda. ICH Q9(R1), the revision of the Quality Risk Management framework that came into force in 2023, places risk-driven thinking more explicitly in the spotlight. ICH Q13 formalises continuous manufacturing, under continuous production, "three batches" is simply not a workable concept. And FDA leadership under Commissioner Makary has been more vocal since 2025 about science-based and risk-based regulation in public statements, workshops and inspection findings.

This works both ways in practice. For complex or variable processes, three batches can be statistically too few. For well-characterised, robust processes, a lower number can be defensible, provided the risk assessment, process knowledge and data support it.

Conclusion

These five developments show that the FDA is still going through major changes: leaner staffing, more focus on unannounced inspections, and now even photographs in warning letters. Keeping a close watch on these developments looks more relevant and urgent than in previous years. Changes are happening fast and are more disruptive than what we have seen at the U.S. FDA before.