Centaur Warning letter : Data Integrity, Document Control, Cleaning Deficiencies

Centaur Pharmaceuticals, India issued Warning letter by USFDA. The Warning letter dated 5 June 2023 was issued following the inspection at the Ambernath, Mumbai site (FEI 3003973520) in November 2022, for deviations in manufacture of active pharmaceutical ingredients (APIs).

USFDA Warning letter cites inadequate control over paper and electronic records, multiple cGMP documents with same control number, shredded cGMP documents, unlabelled HPLC vials, failure in equipment cleaning with residues, encrusted material, peelings in “Clean” equipment, inadequacy of response to FDA in identifying and addressing scope and extent of deficiencies

Observation 1:

Failure of Quality unit in ensuring cGMP compliance

A. Inadequate document control over paper and electronic records:

• Blank cGMP documents (Analytical worksheets, incident report forms, non-conformance reports, batch release copies, and pre-printed blank forms) with unrestricted access, Multiple copies of Blank Analytical Worksheet with same control number.
• CGMP documents (analytical worksheets, laboratory incident forms, and training records) were discarded and shredded without a review and traceability and description in shredder logbooks
• Inadequacy of response (to FDA) in identifying and addressing scope and extent of destruction of cGMP documents without adequate control and multiple cGMP documents with same control number.

B. Failure of Quality unit to appropriately test materials and report:

• Unlabelled vials of solutions in HPLC were processed, reliability of data and ability of Quality unit to ensure cGMP compliance is compromised
• Inadequacy of response (to FDA) in addressing scope of deficiency, root cause analysis, effectiveness of training programmes

Firm is asked to perform a comprehensive assessment and review of documentation system throughout the manufacturing and laboratory operations, material system (qualification, analysis, release), laboratory practices and analyst competencies, training programme effectiveness for QC and laboratory operations.

Observation 2:

Failure to clean equipment and utensils to prevent contamination and carry over:

• In equipment labelled “Clean” observed residues, encrusted material, peelings in discharge point.
• Inadequacy of response (to FDA), did not evaluate the potential risk of the peeling on all APIs the Firm manufacture.

Firm is asked to perform comprehensive, independent, retrospective assessment of cleaning effectiveness, cleaning program

USFDA Warning letter