In the space of eleven weeks in early 2026, FDA issued two warning letters to different OTC drug manufacturers, in different states, for the same underlying failure: a cleaning validation programme that could not be defended when an inspector looked closely at it.
Neither company had an exotic problem. Both had the kind of gap that exists quietly in a lot of quality systems until an inspection forces the question. Cleaning validation is one of the oldest requirements in pharmaceutical manufacturing, and it is still one of the most commonly cited.
Failure to clean, maintain, and, as appropriate for the nature of the drug, sanitize equipment and utensils at appropriate intervals to prevent contamination that would alter the safety, identity, strength, quality, or purity of the drug product (21 CFR 211.67(a)).
What the two 2026 letters found
FDA inspected Signature Formulations' Phoenix, Arizona facility from July 21 to 29, 2025. The firm had already issued a voluntary recall in December 2025 for children's toothpaste and mouthwash products due to potential contamination with exogenous hormones. The warning letter that followed cited a failure to clean and sanitize equipment at appropriate intervals, alongside gaps in finished-product testing and identity confirmation of each active ingredient before release.
Roughly two months later, FDA issued a separate warning letter to Chemco Corporation following an August 2025 inspection of its Miami Lakes, Florida facility. That letter described a more layered problem: investigators found visible residue on equipment that had already been logged as clean, no validated cleaning programme for equipment shared across multiple products, and inadequate identity testing of incoming components.
The Chemco letter did not treat the dirty equipment as an isolated housekeeping issue. FDA connected it to the absence of a validated cleaning programme for shared, non-dedicated equipment under 21 CFR 211.67, and to weak incoming-component identity testing under 21 CFR 211.84. Three separate observations became one cross-contamination narrative, and FDA asked for a retrospective risk assessment covering products already released.
What 21 CFR 211.67 actually requires
21 CFR 211.67 requires that equipment and utensils be cleaned, maintained, and, as appropriate, sanitized or sterilized at appropriate intervals to prevent contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond established requirements. Written procedures must assign responsibility, specify cleaning and maintenance schedules, and, where necessary, provide methods for disassembly and reassembly to allow thorough cleaning.
The regulation does not stop at writing a procedure. A cleaning process has to be shown to work, consistently, before it can be relied on. That is the distinction that separates a cleaning procedure from a validated cleaning programme, and it is the gap FDA found in both 2026 cases.
What a defensible cleaning validation programme actually contains
A validated cleaning programme is not a single study. It is a system with several parts that have to hold together:
- A grouping or worst-case rationale. Where equipment is shared across products, the firm has to identify which product and residue combination represents the hardest case to remove and the greatest risk if it carries over, and validate against that.
- Defined acceptance criteria. A maximum allowable carryover limit, calculated against dose, toxicity, and the next product manufactured, not an unsupported visual standard alone.
- A validated sampling and analytical method. Swab or rinse sampling with a method proven to recover residue at the levels being tested for, not assumed to work.
- A visual inspection standard that is actually defensible. Visually clean can be part of the acceptance criteria, but only alongside residue limits with a documented rationale, not as a substitute for them.
- Defined revalidation triggers. A change in product, cleaning agent, equipment, or batch size should trigger a documented evaluation of whether the existing validation still applies.
Both 2026 warning letters point to the same underlying pattern once you look past the specific facts: a cleaning process that was being performed, and even documented as complete, without evidence that it had ever been proven to reliably remove residue to a defined, justified limit.
Why "visually clean" keeps showing up in warning letters
Visual inspection is a legitimate and necessary part of a cleaning verification programme, but FDA has been consistent for over three decades, since its 1993 Guide to Inspections of Validation of Cleaning Processes, that visual inspection alone cannot establish that a cleaning process is validated. Residue can be present below the threshold a person can see. The Chemco letter is a direct illustration of what happens when that principle is ignored in the other direction: residue was visible, on equipment that had already been recorded as clean, which raises the question of whether the verification step happened at all.
Why shared equipment raises the stakes
Dedicated, single-product equipment simplifies cleaning validation considerably. Shared or non-dedicated equipment does not remove the requirement, it raises the bar. Every product that runs across the same equipment becomes part of the worst-case analysis, and every changeover between products becomes a point where an unvalidated assumption can turn into a cross-contamination event. FDA's request for a retrospective assessment in the Chemco letter reflects exactly this concern: once a shared-equipment cleaning programme is shown to be inadequate, the question is not only what happens going forward, but what may already have been released.
Cleaning validation is not a new or unusual requirement. It has existed in essentially its current form since the 1970s, and FDA's expectations for how to demonstrate it have been public since 1993. What both 2026 warning letters show is that the gap is rarely a lack of awareness that cleaning validation exists. It is a gap between having a cleaning procedure on paper and having evidence that the procedure has actually been validated, with defined acceptance criteria, a worst-case rationale, and a documented trigger for revalidation.
Key regulatory references
- FDA Warning Letter 320-26-60, Chemco Corporation, April 7, 2026
- FDA Warning Letter 320-26-38, Signature Formulations, LLC, January 21, 2026
- 21 CFR 211.67 — Equipment cleaning and maintenance
- 21 CFR 211.84 — Testing and approval or rejection of components, drug product containers, and closures
- FDA Guide to Inspections of Validation of Cleaning Processes, 1993
Our cleaning validation coursework covers this in full
Worst-case rationale, acceptance criteria, sampling method validation and revalidation triggers, built from 21 CFR 211.67 and FDA's cleaning validation guidance. Certificate on completion.