Warning letter to Australian API manufacturer Antaria: Laboratory compliance issues

USFDA Warning letter to Australian API manufacturer cites basic laboratory compliance issues – Inadequate OOS investigations, failure to follow USP monograph methods, laboratory records do not capture all relevant test details to establish traceability and validity of data and failure to place batches for stability annually. Antaria Pty facility at Queensland Australia was inspected by USFDA during 1—17 November 2023 and Warning letter issued on 22 March 2024

Observation 1.

Antaria Pty failed to adequately investigate, establish root cause and corrective actions (CAPA) on numerous OOS results, including for assay and loss on ignition (LOI) tests of API lots; API lots with OOS results were released.

Antaria response to FDA attributed staff turnover, poor training, lack of competency for the lapses. Antaria proposed to revise the OOS procedure, review historical LOI to establish root cause and train staff. However Antaria responses were found lacking as it did not holistically review all investigations, root causes, corrective actions for adequacy, failed to inform customers who has received the OOS API lots and did not perform a retrospective assessment of retainer samples.

FDA has asked Antaria to perform an independent review of all invalidated OOS, determine whether the investigations conclusively or inconclusively demonstrative causative laboratory error. Where laboratory root cause is conclusively established, identify all other similar laboratory methods vulnerable to similar root cause and take up remediation. For all OOS results with inconclusive or no root cause Antaria should perform thorough production investigation, identify potential manufacturing root causes and remediation. FDA has also asked Antaria to perform a thorough independent review of overall system for failure investigations (OOS, Deviations, Complaints) and detailed remediation plan.

Observation 2.

Antaria failed to test API lots for assay and LOI as per USP monograph procedures, and there was no data to show the test methods employed were equivalent to USP monograph. FDA has asked Antaria to perform an independent assessment of all laboratory practices, test methods and procedures and provide remediation plan.

Observation 3

Laboratory records do not capture complete information pertaining to the tests – sample preparations, dilutions, mobile phase and reagents, instruments used. Antaria’s response was found inadequate as it failed to address overall lack of traceability and validity of previous analytical data,

Observation 4

Antaria failed to place at least one batch of API lot every year for stability, in the years 2019, 2020 and 2021. FDA has asked Antaria to perform a comprehensive assessment of its stability programme covering stability indicative methods, stability studies in marketed containers with lots placed in stability in each year to assure validity of shelf life claim and remediation plans.

USFDA Warning letter