FDA 483 to Jubilant : Data Integrity concerns and Investigation Lapses

USFDA inspected Jubilant Generics Limited facility in Roorkee, India, from January 25th to February 2nd, 2024. The USFDA 483 issued at the close of inspection by investigators Jaffrey P. Raimondi and Tamil Arasu cites deficiencies on cleaning validations, inadequate investigations, data integrity, process validation and controls. Summary of the four observations in the USFDA 483 are::

• Observation 1: Cleaning Validation and Verification Deficiencies, Inadequate Investigations

Investigations into unknown peaks in cleaning verification swab samples did not identify all peaks, no root cause was determined for the presence of drugs attributed to two of the unknown peaks identified. 

Additional samples collected during investigation from manufacturing equipment revealed two OOS results, yet no root cause was established for the OOS findings. Concerning deviation investigation was not documented in the cleaning verification report.

These lapses led the FDA auditors to conclude that the cleaning validation and verification processes were deficient and unreliable. 

• Observation 2: Data Integrity Shortcomings

Deficiencies reflecting breach of several elements of Data Integrity, ALCOA++ principles, and regulatory requirements for control of electronic records (21 CFR Part 11) were noted.

At least three investigation documents prepared outside the formal Electronic Document Management System (EDMS) were found among documents kept for shredding, with no reference in Track wise Deviation record or EDMS system. The shredder log was also found to deficient in that it fails to specify the type of documents destroyed (Attribution, Original)

All cleaning swab samples were not consistently logged in the equipment logbook. (Complete, Contemporaneous). The QC inward sample logbook contained entries marked as “Complies” without attribution to an analyst or a date of entry. (Attribution). There were no records to confirm that samples collected for microbiological testing were stored in a refrigerator till testing, compromising the chain of custody (Attribution, Complete).

A microbiology sample result reported as “Too Numerous to Count” (TNTC) was modified by a reviewer to be within specification limits without verifying the actual plate, reviewing only a zoomed-in photograph (Falsification, Compromising ALCOA principles – Original, Accurate)

Obsolete recipes in the compression machine were not removed in a timely manner, with some remaining for 10 months. Standalone analytical balances lacked audit trail capabilities, facilities for sequential weight printouts, or alternative controls like second-person verification (21 CFR Part 11, Control of electronic records)

• Observation 3: Inadequate Hold Time Studies

Hold time studies for compressed tablets did not represent current commercial batch sizes.

• Observation 4: Process Validation and Control Issues

Thickness and hardness specifications for tablets were changed based on a challenge study conducted on only one tablet strength. Effectiveness check of the new specifications was insufficient, covering only six batches and not all tablet strengths.

USFDA 483