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Warning letters, 483s, Recalls, Import Alerts, Audit observations
Warning letters, 483s, Recalls, Import Alerts, Audit observations
Lupin has received correspondence from the US FDA that Lupin has addressed the concerns raised in the Warning Letter for its facilities in Goa and Indore (Pithampur Unit-2). Lupin had received Warning letter in November 2017 for cGMP deficiencies at facilities in Goa and Indore citing lapses in OOS investigation with repeat retests, lapses in hold time studies. In the warning letter USFDA asked Lupin to assess its global manufacturing operations for conformance as it has observed similar CGMP issues at multiple sites in the company’s network.
The Goa plant was cited for:
Lapses in OOS investigation-An API batch, OOS for Assay, was retested multiple times before a final retest result was acceptable, the initial OOS result invalidated considering it as an outlier; An OOS for test of Content uniformity was invalidated despite repeat test giving similar results and, manufacturing investigation was not performed though a conclusive root cause was not established for the OOS.
Lapses in hold time studies for solid dosage forms – small sample sizes were used for hold time studies and lacked meaningful information on effects of lengthy bulk holding conditions; bulk intermediate for several batches were held for excessive hold time, yet the finished product batches were released and rarely placed in stability.
Lupin was asked to perform independent assessment, review all invalidated OOS results, all test methods, actual hold times of all batches released to US and holding times of all stages of all OOS batches, systems and procedures for handling of OOS and investigations.
The Indore plant was cited for similar lapses of excessive hold times of bulk, small sample sizes used for hold time studies, invalidating almost all OOS reported between January 1, 2015, to December 31, 2016, not performing manufacturing investigations when root cause was not conclusive.
FDA cited similar deficiencies in other sites in Lupin network and asked Lupin to assess its global manufacturing operations to ensure the systems, processes and products confirm to requirements at all sites.
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