Lupin announced resolution  of USFDA Warning letters to Goa and Pithampur Unit 2 with USFDA. Lupin has received correspondence from the US FDA that it has addressed the concerns raised in the Warning Letter for its facilities in Goa and Pithampur Unit-2, Indore issued in November 2017. The Warning letter had cited lapses in OOS investigation with repeat retests, lapses in hold time studies with small sample size of bulk for hold time studies, excessive hold times of commercial batches, similar lapses in multiple sites and asked Lupin to assess its global manufacturing operations for conformance.

Lupin had received Warning letter in November 2017, citing cGMP deficiencies at facilities in Goa and Pithampur (Unit 2), Indore India. (Warning Letter)

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.

Lupin statement on resolution of Warning letter