Specifically, during setup, aseptic filling, transfer of equipment and components, and line disassembly/cleaning in the Grade A area of *** cap and bottle lines, *** and *** used to aseptically fill U.S. marketed drug products, the following instances of improper aseptic processing technique were observed:

(1) On October 12, 2023, and October 17, 2023, operators working in the grade A area of ***, performing line set up, aseptic filling and equipment transfer and cleaning, were not wearing goggles resulting in skin exposure to the Grade A area.

(2) Operators working in the Grade A area on October 12, 2023, were observed to have exposed skin on their nose throughout the entire aseptic filling process on *** during the filling of *** Batch ***. These operators repeatedly performed *** interventions that included leaning over the filling line and open sterile bottles.

(3) On filling line *** during the aseptic filling of *** Batch *** an operator was observed standing outside of the filling line in the extended Grade A LAF scooping sterile empty bottles from an open non-sterile bag into a shoot, extending outside of the filling line, that feeds into the bottle ***. On October 19, 2023, this operator was observed bent over a bag of sterile bottles, reaching his gloved hand into the bag holding the sterile bottles, taking scoops of bottles out and placing them into the *** 96 times in 24 minutes.

(4) On October 19, 2023, an operator was observed performing continuous interventions in the *** using the non-sterile *** and ***, for 10 minutes and 15 minutes consecutively on *** during the aseptic filling of ***, Batch *** The were also observed placing a partially filled bag of extra caps onto the filling line between the *** and the cap *** where the bag extended upward blocking/interfering with first pass air to the surrounding area.

(5) On October 12, 2023, on filling line *** during the aseptic filling of *** Batch ***, an operator was observed reaching over and around the Grade A filling line *** holding the sterile *** used to cap bottles of aseptically filled *** drug products. The operator’s gowned forearm and elbow was observed blushing up against the inside of the *** and the sterile ***. This same operator was also observed bumping the inside of the *** with their non-sterile gown.

(6) An operator, working on filling line ***, ***, Batch ***, on 10/12/2023, was observed leaning over open sterile bottles on the filling line and reaching over the ***, *** where their head and torso were inside the Grade A filling area, and where they used a blue cloth to wipe the entire area of the *** holding the filling and ***. The blue cloth was observed brushing up against the filling and ***.

(7) Operators were observed taking bags of sterile components which were stacked up against the wall of the Grade B area outside of *** and placing them into the Grade A area without disinfecting them, then opening them and pouring their contents into one of the *** where the outer pan of the plastic bag they were packed in touched the inside of the *** and the sterile component that was poured into ***. This was observed on October 12, 2023,
during the aseptic filling of ***, Batch *** and on October 19, 2023, during the aseptic filling of ***, Batch ***.

(8) Operators were observed stopping the filling machine and wiping the bottle conveyer and surrounding area of the Grade A filling line on *** during the aseptic filling of *** Batch ***, using both hands, while reaching over open sterile unfilled bottles. The bottles were then permitted to remain on the line and progress through filling and capping.

(9) An operator was observed using a non-sterile *** to stand up open, refilled, fallen bottles on filling line *** during the aseptic filling of *** Batch *** and ***, Batch ***. The bottles were permitted to remain on the line for filling despite falling over where the top of the bottle came in contact with the conveyer.

(10) During the setup of the aseptic filling line, ***, an operator was observed using his gloved hands to manipulate the ***” that hangs inside the bottle *** and comes in direct contact with the sterile bottles in which the aseptic *** is filled into.

(11) An operator was observed reaching over the area near the filling *** and filling line on *** to place an environmental monitoring stand on the line, their entire head, torso and right arm were observed to be in the Grade A filling area.

(12) The *** enclosing the extended LAF Grade A area of *** was observed to have brown residue at the top where the *** connects to the HEPA filtration system. The *** surrounding the extended LAF Grade A area of *** was observed to be disconnected from where it was *** creating a gap allowing free air passage from the Grade B area to the Grade A area of the extended LAF. This was observed during an *** intervention.

(13) Operators were observed reaching over open bottles with the non-sterile *** to perform interventions at the incoming bottle *** to pick up fallen bottles, push jammed bottles, or change environmental monitoring plates during aseptic filling on ***. Similar interventions were observed being performed on bottles following the placement of the sterile *** before the final cap was affixed.

(14) On October 16, 2023, an operator working in the Grade B area, surrounding the aseptic filling line, ***, was found not wearing a nose mask under their Grade B gowning. Per procedure KHWRB/PD/048, entitled, “Entry and Exit Procedure for *** filling Area”, September 21, 2022, operators are to don a nose mask prior to gowning *** Grade B area.

(15) Per procedure KHIL/RB/PD/049, entitled, “Entry and Exit Procedure for *** Manufacturing Area”, August 13, 2023, personnel are required to remove company uniform and don headgear, shift, trouser, booties, hand gloves and footwear prior to entering the Grade C area. Review of the CCTV footage from October 3 and 4th, 2023, showed personnel working in the Grade C *** area where materials are passed into the Grade B filling area. Operators did not wear the specified gowning, gloves, and were working barefoot as they transferred materials into the Grade B area for filling line ***. The deputy manager of production confirmed that this is their standard practice.

Additionally, this room has a Grade A LAF hood for washing small filling machine parts. An operator was observed standing in the hood and another operator was observed taking his hat off and blushing his hair while in the hood.

(16) Upon arrival at the entrance to the Grade C area *** on October 13, 2023, there were gloves in wet trays. Production personnel reported the gloves had been washed.