FDA Cites Serious CGMP Deficiencies at Stream2Sea

The U.S. Food and Drug Administration (FDA) issued a Warning Letter to Stream2Sea, LLC, after inspecting its manufacturing facility in Bowling Green, Florida, from July 9 to 15, 2025. The Warning Letter describes significant violations of current Good Manufacturing Practice (CGMP) requirements for finished pharmaceuticals.

The Warning Letter focuses on three principal areas:

• Testing and release of finished products: The FDA found that the company did not perform adequate analytical and microbiological testing on each batch of its over-the-counter (OTC) drugs before distribution. In one example, a bulk batch underwent further manufacturing about two months after initial sampling, but the resulting finished batch was not tested. The FDA also reported that a batch was released before the quality unit had documented its approval.
• Control of incoming materials: Stream2Sea did not test each incoming component lot for identity, including lots of active pharmaceutical ingredients (APIs). It also relied on supplier certificates of analysis (COAs) without adequately qualifying suppliers or periodically verifying the reliability of their test results. The FDA noted that the company had not provided procedures demonstrating how these controls would be implemented.
• Cleaning and maintenance of equipment: The agency found that cleaning procedures for non-dedicated equipment had not been adequately validated to demonstrate the removal of API residues and cleaning agents or to control potential microbial contamination. The equipment was shared between OTC drug products and cosmetics, and documentation did not consistently specify the cleaning performed or the agent used.

FDA requests assessments and detailed corrective-action plans

The FDA reviewed Stream2Sea’s response to the inspection findings and acknowledged its stated plans, including additional testing and revisions to cleaning procedures. However, the agency considered the response inadequate because it lacked sufficient procedures, technical details and evidence to show how the proposed measures would address the underlying problems.

For finished products, the FDA requested an independent assessment of the laboratory system, covering procedures, analytical methods, equipment, documentation and analyst competencies. It also asked for a remediation plan and a clear list of chemical and microbiological specifications and test methods used before each batch is released.

For incoming materials, the agency requested a comprehensive review of the material-control system, including supplier qualification, expiration or retest dates and controls to prevent unsuitable materials from being used. Stream2Sea is also expected to describe how it will test component lots for identity, strength, quality and purity. If it plans to rely on supplier COAs for some tests, it must explain how the reliability of those results will be established and periodically revalidated.

Focus on cleaning validation and cross-contamination risks

The FDA asked Stream2Sea to strengthen its cleaning validation programme, including an assessment of worst-case conditions. This should consider, among other factors, products with higher toxicity or potency, low solubility in cleaning solvents, difficult-to-clean characteristics, hard-to-reach equipment locations and maximum hold times before cleaning.

The agency also requested updated procedures for verifying and validating cleaning processes, products and equipment. In addition, it called for an independent retrospective assessment of cleaning effectiveness across shared manufacturing equipment. That review should identify potential residues and equipment-cleaning weaknesses, and assess whether cross-contaminated products may have been released for distribution.

The complete warning letter is available on the FDA website.