A) Product contact equipment including *** stopper drums, *** were sterilized without outer wrapping and transferred from Grade A cart to Inside of the RABS without cover in Workshop *** Filling Room ***. There were no physical separations between Grade A areas (Outside the RABS and ***) and Grade B area (the rest of the room). Airflow visualization study did not include the transitions between Grade A and Grade B.

B) During observation of filling process of production batch *** injection USP ***mg *** ml batch number *** manufactured for US market per your firm, we observed a routine intervention of adding stoppers to the filling line performed, which we observed with staff time of 3:58 pm and stop time of 4:03 pm; however, upon review of your batch record, we observed the start and stop time recorded by your firm to be 4:00 pm to 4:01 pm (16:00 — 16:01), which was significantly different than our observed documented intervention time. Upon further review of procedure PO-1 01 007, titled “Operating Procedure for Filling Post”, effective date 11/30/2023, procedures with respect to when an intervention starts and stops is not clearly defined.

C) There is no assurance that your process simulation studies (media fills) performed in your *** “General Parenteral workshops are representative of the current commercial manufacturing operations. The validation plans for your media fill studies do not appear to adequately incorporate the nature and frequency of interventions incorporating worst-case activities and conditions with respect to operator interventions, such as start and stop time of interventions performed and the total time for interventions performed during media fill and commercial batches.

D)Production operator requalification procedures with respect to performing routine and non-routine interventions are inadequate. During our review of (6) six media fill studies across all *** manufacturing workshops, we observed operators who performed the bulk of interventions, operators who performed several interventions, and operators who performed no interventions during media fill studies, who were all considered to be requalified as a result of the media fill study participation. As a result, there is no assurance that all production operators participating in commercial manufacturing operations are adequately qualified to perform interventions during aseptic operations.