Specifically,

(A) Requalification of the *** Sterilization Process for *** Loads *** Bottle Formats) in the *** Model ***, Equipment ID# E-0832-W, performed 11/11/2022 failed to meet the minimum requirement of *** on ***.*** reported a value of 120.05 during the qualification. The acceptance criteria states the minimum temperatures from all *** during sterilization phase must be ***.

Additionally, *** failed its pre- and post- calibration check and was used during the requalification.

Although the requalification occurred 11/11/2022, to date, the final report has not been approved by the quality unit.

This *** is used to sterilize human and animal drug products inside *** bottles, prior to these products being aseptically filled. Between 11/11/2022 and now, there have been approximately *** batches of drug product sterilized with this equipment.

(B) Operators were observed blocking first pass air on 11/01/2023 while filling the following drug products:

• Tacrolimus 0.02% in Com Oil, Ophthalmic Solution, 15 mL lot #***
• Cyclosporine 2%/Tacrolimus 0.2% in Com Oil, Ophthalmic Solution, 15 mL lot# ***

(C) Airflow – visualization studies are inadequate for the following reason:

1. The generated smoke was not robust enough to show the flow of air.
2. Smoke was not always observed to be directly above the area where the activity was occurring during video “*** Process APR2023″. Smoke appeared to be in the back comer of the BSC while operator activities were occurring in the center of the BSC.
3. Unidirectional airflow was interrupted with eddy currents detected at timepoint *** during video “*** Dynamic Basic APR2023″.
4. While smoke studies were performed for *** among the ISO-5 hoods, the entire filling process including setup and filling operations have not been evaluated within each hood under dynamic conditions as part of qualification.