During aseptic filling operations, procedure HO-CQA-SOP-2*** “Clean Room Practices and Aseptic Behavior” and line specific intervention procedures were not followed:

(A) During set-up and aseptic filling of *** Injection batch *** (US market) on January 20, 2024, the following was observed…

(a) An operator performed an *** intervention at approximately ***  for *** tubing adjustment (Intervention C43). The operator was supposed to perform the intervention from *** so they did not need to reach over the fill line, but instead *** which required them to lean over the conveyor. The operator did not first sanitize their hands before entering the filling barrier. The operator leaned over open vials that were still present on the line at the time of the intervention. Not all exposed vials were removed. This intervention was not documented and performing this intervention from *** has not been evaluated in smoke studies or media fills.

(b) An intervention was observed at the stoppering *** that required an *** intervention at approximately 10:14 to clear broken vials. The operator used a forceps brought from the Grade B area into Grade A to clear vials without first sanitizing it. Then the operator directly used their hand on sterile parts of the stoppering *** and on the conveyor. This intervention was not recorded in the batch record. It had not been previously covered in a smoke study or media fill. No personnel monitoring finger dabs were collected at the end of the intervention.

(c) An *** intervention was performed at approximately 10: 17 that included putting a zip tie on the tubing connected to the ***. The operator performed the intervention while reaching over the exposed ***. This intervention was inaccurately recorded in the intervention record as C46 (*** adjustment), which does not include installing zip ties and does not require the operator to work directly above the ***.

(d) During interventions at the vial *** to remove broken or fallen vials, the operator used the RABS *** directly over open Vials that were not subsequently removed. The RABS *** are removed *** for *** but otherwise remain on the line where they are sanitized, but not sterilized. The intervention record under reported the number of times this intervention occurred.
When glass breakage occurred and generated glass particulate during this intervention, the operator did not remove surrounding vials that could have been contaminated with glass particles. Glass breakage was observed during interventions at approximately ***. There were no entries in the intervention record of any glass breakage during filling of the batch.

(e) An operator reached the RABS *** over stoppers and the sterile stopper bowl at approximately 13:34. This intervention (C31) was not recorded in the intervention record.

(f) Following set-up and before the staff of filling, an operator performed an *** intervention (C16) to adjust the filling machine at approximately *** working directly above the exposed ***. The operator unnecessarily left the barrier *** of the *** open when going to a different part of the filling room.

(g) Liquid was observed below the conveyor near the vial *** area. The operators did not take action to address the liquid, determine the source, or document the occurrence in the batch record.

(2) During set-up and aseptic filling of *** batch *** (US market) on January 21-22, 2024, the following was observed:

(a) An operator reached a RABS ** during interventions at approximately 8:10 and 8:26. The RABS *** are removed *** for *** but otherwise remain on the line where they are sanitized, but not sterilized. The exposed *** were not removed. This intervention was not established in the smoke studies or media fill.

(b) An operator performed an intervention (C 11) by reaching the RABS *** directly over sterile stoppers and the sterile stopper bowl to clear stopper jams. This occurred approximately 16 times during the batch, but was only documented in the intervention record 3 times.

(c) During installation of the stopper bowl, the hands of the operator were directly over the sterile stopper bowl.

(3) During set-up and aseptic filling of *** Injection batch *** (US market) on January 21-22, 2024, the following was observed:

(a) During an *** intervention (C38) to remove fallen vials at approximately *** on January 24, 2024, an operator reached over open vials that were not subsequently removed. This intervention was not documented in the intervention record.

(b) During set-up activities, the operator had their hands, forearms and head in the Grade A area and directly above the exposed sterile ***.

(c) During interventions (C3) at the vial *** the operator extended the RABS *** over open vials that were not subsequently removed.

(d) During interventions at the stopper bowl (C54), the operator used the RABS *** over exposed sterile stoppers and the surfaces of the stopper bowl.

(4) During set-up and aseptic filling of *** Injectable Suspension *** Vial batch *** (US market) on January 17-18, 2024, the following was observed:

(a) During an *** intervention (C39) to clear jammed stoppers on the stopper track, the operator reached over exposed stoppers and the sterile surfaces of the stopper track with their hand and arm. A second operator using a RABS *** reached over open, filled vials and moved their hand rapidly near open vials.

(b) During interventions (Cl) to remove jammed and fallen vials in the incoming vial area, the operator reached the RABS *** over open vials. Exposed vials were not removed. These interventions were not documented in the intervention record.

(c) During an intervention to adjust the stopper holder (C32), an operator took a wipe, which had been used to wipe a tool in the Grade B area and was on a cart in the Grade B area, and passed it into the Grade A area. It was then used to wipe the conveyor near open vials.

(d) During installation of the stopper bowl, the operator repeatedly touched the sterile contact surfaces of the stopper track that move the stoppers to the fill line.

(5) During aseptic filling of *** Injection batch *** (Canada market) on January 18, 2024, the following was observed:

(a) During an intervention to remove a jammed vial at approximately 8:13, the operator forcefully struck a vial with the forceps, causing it to break. No vials in the area were removed and there was no documentation of the intervention or glass breakage. The RABS *** were observed directly over other open vials that were not removed during this intervention.

(b) During an intervention (Cl 7) for adjustment of *** near the stoppering station, the operator placed a black *** which is sanitized, but not sterilized, on the sterile stoppering ***. This Intervention was not documented.

(c) Liquid was observed below the conveyor near the vial *** area. The operators did not take action to address the liquid, determine the source, or document the occurrence in the batch record.

(6) During machine setup on Line ***prior to aseptic filling of batch *** solution ***mL, an operator performed an *** intervention to install the Stopper *** in the Grade A area. The operator was using their hands to uncover the *** bowl and then placed their hands directly inside the *** they were observed touching the inside walls and base of the ***. The inside of this *** comes in direct contact with sterilized *** stoppers used to aseptically filled vials.