FDA Warning Letter: From Inadequate Investigations and Laboratory Controls to Supplier Qualification and Process Validation.

The U.S. Food and Drug Administration (FDA) issued a Warning Letter to a drug manufacturing facility in Santa Fe Springs, California, on 25 September 2025, following an inspection conducted in March 2025.

The agency identified significant violations of Current Good Manufacturing Practice (CGMP) regulations. The FDA further concluded that the firm’s over-the-counter (OTC) drug products are adulterated and that one product was also unapproved and misbranded.

Inadequate Investigations and CAPA

The company’s Quality Unit (QU) failed to properly investigate out-of-specification (OOS) results, identify root causes, and implement corrective and preventive actions (CAPA):

• No thorough review of discrepancies in APIs, microbial results, or stability failures.
• Incomplete or scientifically unjustified investigations. 
• Lack of retrospective review of prior manufacturing and laboratory deviations.

The FDA demanded a complete, independent assessment of investigation and CAPA systems, including enhanced QU oversight and training.

Deficient Laboratory Controls

Laboratory practices were found to be scientifically unsound:

• Sampling and testing procedures were inadequate or missing.
• Microbiological test methods lacked verification and suitability testing.
• Samples were often taken “by memory,” and finished product testing was incomplete.

The FDA ordered a full independent evaluation of laboratory systems, testing methods, and personnel competency, as well as retesting of retain samples from distributed lots still within expiry.

Missing Identity Testing for High-Risk Raw Materials

The firm did not perform required identity testing for glycerin and propylene glycol, components at risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination.

• No identity testing for glycerin and propylene glycol using USP methods.
• Sole reliance on suppliers’ Certificates of Analysis (CoA) without verification.
• No established system to confirm supplier reliability.

The FDA reminded the firm that failure to test for DEG/EG has caused fatal poisoning incidents globally. The company must now test all retains and conduct a full risk assessment for distributed batches.

Lack of Process Validation and Water System Control

The firm had not validated its manufacturing processes or water system used in drug production and equipment cleaning.

• No process performance qualification data.
• No program to monitor batch-to-batch variability.
• Uncontrolled and potentially contaminated water system.

FDA emphasized that process validation and water monitoring are critical to maintaining product consistency and patient safety.

Ineffective Quality Unit and Quality Systems

The FDA found the overall quality system deficient:

• No clear QU responsibilities or authority for release, change control, or annual product reviews.
• No validated cleaning or maintenance programs.
• No stability testing program to establish expiry dates.

The agency recommended a full overhaul of the firm’s Quality Management System and urged the engagement of a qualified CGMP consultant under 21 CFR 211.34.

Conclusion

The company must respond within 15 working days, outlining corrective actions and timelines. The agency may re-inspect the facility to verify the effectiveness of implemented measures before reassessing its compliance status.

For further information, please see the Warning letter to Creative Essences, Inc. on the FDA's website.