Warning Letter to US Contract Manufacturer of OTC Drugs due to Cross-Contamination Risk

In July 2025, the FDA inspected a US contract manufacturer of OTC drugs. The Warning Letter specifically describes the lack of physical separation, inadequate cleaning of shared equipment, and deficiencies in the quality system. To make matters worse, the FDA had already pointed out similar deficiencies in 2018.

Lack of physical separation and high risk of cross-contamination

The FDA found that various OTC drugs were manufactured in a shared production environment and on shared equipment without sufficient structural or technical measures in place to prevent cross-contamination. Products containing potent active ingredients were processed on the same equipment before children's toothpaste and mouthwash, among other products, were manufactured.

During the inspection, the possibility of contamination with exogenous hormones was identified, which ultimately led to a voluntary recall of certain batches of children's toothpaste and mouthwash. The FDA noted that potential contamination of drugs with potent active ingredients may pose a risk to patient safety, especially in products for children.

In its statement, the manufacturer stated that it did not produce drugs. The FDA rejected this assessment and clarified that the manufactured products are classified as drugs under the FD&C Act and are therefore subject to GMP requirements. The FDA also explained that cross-contamination is typically not distributed homogeneously. Subsequent testing of individual retention samples is therefore not suitable for reliably assessing the actual extent of possible contamination. The agency clarified that purely retrospective sample testing does not allow for a reliable statement about the entire batch.

The statement submitted by the company was essentially limited to an announcement that exhaust air and other control systems would be examined. The FDA considered this to be insufficient, as no explanation was provided as to how effective separation of production processes or safe prevention of cross-contamination would be ensured in the future.

Inadequate cleaning and lack of effective cleaning validation

In addition to the lack of physical barriers, the FDA identified significant deficiencies in the maintenance, cleaning, and validation of cleaning procedures.

The equipment used was not dedicated and was used for several different products. The company was unable to demonstrate that its cleaning procedures were suitable for reliably removing residues and preventing cross-contamination. The existing cleaning validation was assessed by the FDA as inadequate. Although, according to the statement, the cleaning SOPs were updated and damaged equipment parts were replaced, the FDA objected that no comprehensive retrospective assessment of cleaning effectiveness was presented. In particular, the following were missing:

• A systematic worst-case scenario analysis (e.g., substances of particular toxicological relevance, high potency, poorly soluble substances, hard-to-reach cleaning areas, maximum dwell times before cleaning)
• A risk analysis of all products already manufactured and still on the market

Systemic deficiencies in the quality system

The FDA found that the Quality Unit (QU) was unable to perform its tasks properly. The FDA criticized the fact that finished medicinal products were released without complete chemical and microbiological testing. There was also a lack of identity testing of raw materials used, appropriate production and process controls, and proper investigation of deviations. An effective stability program was also not in place.

The FDA considered it critical that similar violations had already been criticized in an earlier Warning Letter. In the agency's view, the repeated deficiencies show that the corrective measures promised at that time were not implemented in a sustainable manner.

The detailed Warning Letter can be found on the FDA website.