FDA 483 - Hikma Injectables USA Inc - June 25, 2024

The FDA Form 483 details observations from an inspection of a facility manufacturing sterile drug products, including Phenylephrine HCL 1 mg per 10 ml (100 mcg/ml) in 0.9% Sodium Chloride Injection.

Several deficiencies were noted in aseptic processing areas. The design of syringe filling lines and enclosures fails to maintain first-pass HEPA-filtered laminar airflow over critical areas, such as open syringes and tamper-evident caps within ISO 5 classified filling enclosures. Airflow visualization studies revealed objectionable patterns, including turbulence and upward circulating air, which firm management accepted without corrective actions. Additionally, a divider/safety guard obstructs first-pass HEPA-filtered air over critical components.

Environmental monitoring is deficient as active air sampling for airborne viable monitoring is not performed in the ISO 5 classified syringe filling and capping zone during sterile filling operations.

Compounding finished drug product samples for quality control testing are not representative of each sub-assembly when a sub-assembly batch process is followed, contrary to SOPDTN15106. For example, for Phenylephrine HCL 1 mg per 10 ml (100 mcg/ml) in 0.9% Sodium Chloride Injection Lot #, there was no record demonstrating that samples tested were representative of each sub-assembly.

Finally, laboratory controls are inadequate. The firm does not fully follow SOPDTN15087, Growth Promotion Test, to