What The FDA Is Finding in API Facilities

The U.S. Food and Drug Administration (FDA) has been steadily increasing its oversight of global active pharmaceutical ingredient (API) manufacturers. Recent warning letters issued in early 2025 to firms paint a consistent picture of recurring compliance failures, and they reveal exactly where the FDA is focusing its attention.

Across four facilities, inspectors documented a pattern of weak quality systems, poor contamination controls, and lapses in data integrity.

These findings underscore that the FDA's expectations are aligned with ICH Q7, and that firms supplying APIs to the U.S. market cannot afford to cut corners.

Operators in Cleanroom Garments.

Quality Unit Failures Remain Central

One of the most striking commonalities is the failure of the quality unit (QU) to exercise adequate authority.

• Macsen Drugs released API lots that had been exposed to fire, smoke, and unstable storage conditions, despite internal records showing degradation.

• Mentha & Allied Products allowed torn batch records, incomplete documentation, and uncontrolled data backups, practices that cast doubt on the reliability of every batch on the market.

• Jagsonpal Pharmaceuticals relied on an unregistered contract manufacturer without ensuring process validation or method verification had been completed, even while listing itself as the manufacturer on import records.

In each case, the QU failed to serve as the final safeguard for product quality.

The FDA's message is clear: a weak QU is a systemic red flag, and firms must empower their quality leaders with authority and resources to stop distribution when risks are present.

Facility & Equipment: Sanitation Still a Core Issue

Basic facility conditions also continue to draw the FDA's attention.

• At Aspen Biopharma, investigators found open manufacturing areas with exposure to the external environment and no segregation for highly toxic APIs.

• At Mentha & Allied, the washroom and gowning areas were heavily soiled, with dirty lockers, reused gloves stored in drawers, and "cleaned" equipment still carrying visible residues.

These are not minor housekeeping issues, they directly raise the risk of contamination and cross-contamination.

The FDA has repeatedly stressed that facility design, preventive maintenance, and equipment upkeep are not optional, but foundational.

Cleaning and Contamination Risks

Cleaning validation (or the lack thereof) stood out as another trend.

• Aspen Biopharma had equipment labelled as "clean" that still contained residues, with no cleaning validation studies in place.

• Mentha & Allied failed to scientifically justify cleaning methods, with poor sampling practices and missing documentation.

• Macsen Drugs attempted to justify that APIs stored during a facility fire were still accountable, despite clear risk of contamination and degradation.

Together, these cases reinforce that contamination control must be proactive, validated, and documented. In the FDA's eyes, reliance on assumptions or post-hoc rationalisations is not enough.

Data Integrity & Documentation: Persistent Red Flags

Data integrity problems continue to appear in nearly every inspection.

• Aspen Biopharma admitted to backdating QC documents and failing to maintain original records, ultimately triggering a nationwide recall and an import alert.

• Mentha & Allied showed torn records, uncontrolled forms, and a corrupted hard drive containing months of chromatographic data.

The FDA has published extensive guidance on data integrity, but these cases highlight how fragile compliance remains without strong documentation culture. Firms that cannot produce original, contemporaneous records will face enforcement.

Stability & Process Validation

Another consistent theme was the failure to generate reliable stability data and adequately validate processes.

• Macsen Drugs relied on stability chambers with repeated power failures and no dataloggers, leaving expiry assignments unsupported.

• Aspen Biopharma lacked a documented stability program and shipped APIs without assurance of shelf life.

• Mentha & Allied failed to verify analytical methods and skipped required USP tests.

• Jagsonpal Pharmaceuticals could not demonstrate process validation for products made by its CMO, leaving the FDA without confidence in batch-to-batch consistency.

Without validated processes and robust stability programs, API manufacturers cannot prove that their products meet specifications through their lifecycle, a fundamental expectation under cGMP.

Oversight of Contract Manufacturing

The Jagsonpal case highlights another key enforcement trend: sponsor accountability.

The FDA considers CMOs an extension of the manufacturer, and firms cannot distance themselves from deficiencies by pointing to third parties.

Quality agreements are not a shield; companies that place their names on import records must ensure their partners are compliant and registered.

The Bigger Picture

When viewed together, these warning letters send a clear message: the FDA is not just auditing checklists, it is evaluating whether API manufacturers operate with a culture of quality.

The recurring failures, weak QU authority, poor cleaning, unreliable data, and unstable processes, all point to organisations that react to problems rather than prevent them.

For firms supplying APIs to the U.S. market, the lesson is straightforward:

• Empower the quality unit.

  
  

• Maintain facilities and equipment in a state of control.

  
  

• Validate cleaning and processes.

  
  

• Protect data integrity.

  
  

• Ensure contract manufacturers are held to the same standard as internal sites.

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