Inadequate Dissolution Testing and Process Validation Trigger FDA Warning Letter

The The U.S. Food and Drug Administration (FDA) issued the Warning Letter, dated 14 March 2025, following an inspection at a drug manufacturing facility in Elmsford, New York, conducted in July and August 2024.

The letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) requirements for combination products.

The most important deficiencies noted by the FDA can be summarized as follows:

Inadequate controls to ensure sterility of drug products:

• No adequate procedures to ensure that sterile products meet appropriate quality attributes.
• No monitoring of pre-sterilization bioburden.
• Incomplete environmental monitoring in sterile manufacturing areas.
• Overreliance on final sterility testing without robust upstream controls.

Deficient dissolution testing:

• Lack of satisfactory conformance to the specifications for the rate of release of each active ingredient.
• Use of only a single dissolution time point without justification.
• Insufficient data to support extended-release claims.
• Lack of batch-specific dissolution profile testing.

Lack of process validation:

• Commercial batches released without validated processes.
• Batch records missing critical process parameters.
• Inadequate scientific rationale for manufacturing changes (e.g., scale-up).

Weak quality oversight:

• Quality Unit failed to oversee contract testing laboratories.
• Contract manufacturing organizations (CMOs) not properly qualified.
• Products received from CMOs without appropriate quality evaluation.

Due to the recurrence of similar issues during inspections in 2019 and 2021, the FDA recommends the involvement of a qualified CGMP consultant and warns of possible regulatory actions.

For further information, please see the complete Warning Letter to Advanced Pharmaceutical Technology published on the FDA's website.