Yiling Pharma Warning Letter: Equipment Duct Cleaning & Cross-Contamination Issues Flagged

The U.S. Food and Drug Administration (FDA) has issued a Warning Letter in June 2025 to Chinese drug manufacturer Yiling Pharmaceutical Ltd., (FEI 3011640199) citing serious deficiencies in equipment cleaning and inadequate cross-contamination prevention measures. The facility underwent inspection in October 2024, conducted by FDA investigator Patty P. Kaewussdangkul.

Key Findings from FDA Inspection

• Equipment Design & Maintenance Failures FDA observed that manufacturing equipment lacked proper design and maintenance to prevent backflow of bulk drug powder into air supply ducts. Residues were found inside the ducts, and swab samples revealed the presence of numerous drug substances, including highly potent drugs. Additionally, junctions on the equipment ducts had worn-out seals and were covered with tape.
• Deficiencies in Cleaning Procedures The firm’s Quality Unit (QU) failed to ensure appropriate cleaning protocols for equipment. Specifically, cleaning procedures did not include instructions for duct cleaning, disassembly, and visual inspection to confirm cleanliness. Furthermore, highly potent drugs were being manufactured on shared equipment, increasing the risk of cross-contamination.

FDA deemed the Firm’s proposed corrective actions inadequate:

• The proposed CAPA for testing of reserve samples for cross-contamination was limited only to residues of preceding drug substances, rather than a comprehensive evaluation of all drug substances processed in the shared equipment. Airflow over contaminated surfaces can cause cross-contamination, and contaminants do not distribute uniformly across drug batches. A comprehensive risk assessment with scientific rationale including analysis of adverse drug events, retrospective assessment of cleaning effectiveness including other manufacturing equipment should be performed. FDA has also asked the firm to appropriately segregate the production of high potent drug from other drug products. The CAPA plan should also cover an overall assessment of the Firm’s system for investigating deviations, discrepancies, complaints, out-of-specification results, and failures

Industry Implications & Key Takeaways

• The FDA has repeatedly flagged concerns regarding cleaning deficiencies in manufacturing equipment with air supply ducts, such as Fluid Bed Dryers (FBDs). Drug manufacturers must conduct a thorough evaluation of their cleaning procedures, ensuring Complete and thorough cleaning, including dismantling of hard-to-clean parts like air supply ducts and cleaning verification measures to ensure effectiveness.
• When equipment cleaning deficiencies are observed, testing reserve samples alone is insufficient to determine the extent of contamination. A scientific rationale is necessary to assess contamination nature and risk.
• Highly potent drugs, such as hormones, pose significant contamination risks if administered outside their therapeutic range. Such products may require dedicated equipment and segregation from other drug products to prevent hazardous drug exposure.

USFDA Warning letter to Yiling Pharmaceutical Ltd (June 2025)

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