FDA 483 - Cipla Limited - January 25, 2018

The FDA inspection of a pharmaceutical facility revealed several deficiencies, primarily concerning quality control, manufacturing processes, and documentation.

A significant repeat observation involved the failure to thoroughly review out-of-specification (OOS) results for an exhibit batch of redacted Capsules redacted mg, which failed in-process content testing. The OOS investigation (LC/OOS/OC/09/16/09, Amendment 02) was deemed scientifically unsound. Issues included incorrect statements about prior in-process testing, lack of data to support %RSD variation or demonstrate method accuracy and intermediate precision, and unsubstantiated root cause claims regarding sample handling/exposure. The investigation also lacked a CAPA plan and attributed the OOS to a method not amenable to in-process assessment, despite the company's intent to continue using it.

Batch production and control records for redacted Capsules redacted mg were deficient, lacking details on sampling plans and acceptance criteria for finished product rejection analysis, SOP references for reject analysis, documentation of defects per container, and % AQL defect calculations. Additionally, QA review of batch records and raw electronic data prior to batch approval and release was not documented.

Laboratory records were incomplete, with Standard Test Procedure STP-17-005238 lacking stability specifications for standard and sample solutions, and test data sheets not documenting preparation dates/times. Lab errors, such as a misaligned cannula in a dissolution test, were not always documented on test data sheets.