FDA 483 - Akorn Operating Company LLC - August 30, 2018

The FDA inspected Akorn Inc., a sterile drug manufacturer in Somerset, NJ, from July 23 to August 30, 2018. The inspection, conducted under Current Good Manufacturing Practices (cGMP) regulations, identified significant deficiencies across quality, laboratory, and production systems. Key issues included a systemic failure to thoroughly investigate unexplained discrepancies and out-of-specification (OOS) results. For instance, stability failures for Azelastine Ophthalmic Solution batches were observed to have modified or recalculated results, with affected products remaining on the market until recalled. Investigations into OOS results for other products like Ciprofloxacin were inadequate, and widespread use of 'trial injections' in laboratories raised data integrity concerns, a repeat observation from a previous inspection. Many OOS results were invalidated without adequate scientific support.

Further observations noted that investigations did not extend to all potentially impacted batches, particularly regarding metal shavings in packaging and container integrity issues for sterile products. The quality control unit experienced extensive delays in closing investigations and reviewing critical laboratory data, attributed to resource limitations. Computerized systems lacked sufficient controls to prevent unauthorized data changes or deletions, and data backups were not consistently performed. Instrument calibration procedures were deficient, and laboratory records lacked complete reviewer sign-offs.

Critically, the inspection revealed poor aseptic processing techniques in sterile filling areas, including product leaks, improper operator interventions without sanitization, and inadequate handling of contaminated materials. Non-routine mechanical repairs during filling operations were also not adequately validated within the aseptic media fill program. Akorn Inc. is now required to provide a comprehensive response detailing corrective and preventative actions to address these serious deviations and ensure full compliance with cGMP regulations, thereby safeguarding the quality and safety of its sterile drug products.