印度药企483震惊操作！！赤脚传递B级物料

本期文章将介绍第1条缺陷项，内容均与无菌生产操作相关，观察到的事例多达16条，详细翻译见下文：

OBSERVATION 1 缺陷项1

Procedures designed to prevent microbiological contamination of drug products supporting to be sterile are not established, written and followed.

Specifically, during setup, aseptic filling, transfer of equipment and components, and line disassembly/cleaning in the Grade A area of (b)(4) cap and bottle lines, (b)(4) and (b)(4) 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 (b)(4), 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 (b)(4) during the filling of (b)(4) (b)(4), Batch #(b)(4). These operators repeatedly performed (b)(4) interventions that included leaning over the filling line and open sterile bottles.

3.On filling line (b)(4) during the aseptic fling of (b)(4), Batch # (b)(4) 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 (b)(4). 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 (b)(4) 96 times in 24 minutes.

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

5. On October 12, 2023, on filling line (b)(4), during the aseptic filling of (b)(4) Batch (b)(4), an operator was observed reaching over and around the Grade A filling line (b)(4) holding the sterile (b)(4) used to cap bottles of aseptically filled (b)(4) drug products. The operator's gowned forearm and elbow was observed brushing up against the inside of the (b)(4) and the sterile (b)(4). This same operator was also observed bumping the inside of the (b)(4) with their non-sterile gown.

6. An operator, working on filling line (b)(4), (b)(4), Batch (b)(4) ,on 10/12/2023, was observed leaning over open sterile boules on the filling line and reaching over the (b)(4) (b)(4) 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 (b)(4) holding the filling and (b)(4). The blue cloth was observed brushing up against the filling and (b)(4).

一名操作员，在2023年12月10日，在XX药品的XX批次的XX灌装线上工作时，观察到他们俯身在灌装线上开放的无菌瓶上，并越过XX和XX，在那里他们的头部和躯干在A级灌装区域内，并在那里他们使用蓝色布擦拭放置灌装瓶的XX和XX的整个区域。观察到蓝布碰到了灌装线和XX。

7. Operators were observed taking bags of sterile components which were stacked up against the wall of the Grade B area outside of (b)(4) and placing them into the Grade A area without disinfecting then, then opening them and pouring their contents into one of the (b)(4) where the outer part of the plastic bap they were packed in touched the inside of the (b)(4) and the sterile component that was poured into that (b)(4). This was observed on October 12, 2023, during the aseptic filling of (b)(4) , Batch (b)(4) and on October 19, 2023, during the aseptic filing of (b)(4), Batch (b)(4).

观察到操作人员将无菌成分袋放在XX外的B级区域的墙壁上，并将其放置在A级区域而不进行消毒，然后打开它们并将袋内的物品倒入XX中的一个XX中，其中包装它们的塑料袋的外部接触XX的内部和倒入XX中的无菌成分。这是在2023年10月12日XX药品XX批次的无菌灌装期间和2023年10月19日XX药品XX批次的无菌灌装期间观察到的。

8. Operators were observed stopping the filling machine and wiping the bottle conveyer and surrounding area of the Grade A filling line on (b)(4) during the aseptic filling of (b)(4) Batch (b)(4), 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.

观察到操作人员在对XX药品XX批次进行无菌灌装时，暂停了灌装机，用双手擦拭XX上的A级灌装线的传瓶器和周围区域，同时手伸向打开的无菌未灌装瓶。然后，瓶子被允许留在生产线上，并继续进行灌装和轧盖。

9.An operator was observed using a non-sterile (b)(4) to stand up open, prefilled, fallen bottles on filling line (b)(4) during the aseptic filling of (b)(4) Batch (b)(4) and (b)(4), Batch # (b)(4). The bottles were permitted to remain on the line for filling, despite falling over where tie top of the bottle came in contact with the conveyer.

在XX药品XX批次和XX药品XX批次的无菌灌装过程中，观察到一名操作人员使用非无菌的XX在XX灌装线上站起来打开掉落的瓶子。瓶子被允许留在生产线上进行灌装，尽管瓶子顶部与传送带进行了接触。

10. During the setup of the aseptic filling line (b)(4), an operator was observed using his gloved hands to manipulate the (b)(4)" that hangs inside the bottle (b)(4) and comes in direct contact with the sterile bottles in which the aseptic (b)(4) is filled into.

在无菌灌装线XX的设置过程中，观察到一名操作人员戴着手套操作挂在XX瓶内的XX，直接与灌装无菌药品的无菌瓶接触。

11. An operator was observed reaching over the area near the filling (b)(4) and filling line on (b)(4) 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.

观察到一名操作员伸进XX和XX的灌装线附近的区域，以在灌装线上放置环境监测设备，观察到他的整个头部、躯干和右臂都在A级灌装区。

12.The (b)(4) enclosing the extended LAF Grade A area of (b)(4) was observed to have brown residue at the top where the (b)(4) connects to the HFPA filtration system. The (b)(4) (b)(4) surrounding the extended LAF Grade A area of (b)(4) was observed to be disconnected from where it was (b)(4) 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 (b)(4) intervention.

封闭扩展的LAF A级区域XX的XX被观察到在XX连接到HFPA过滤系统的顶部有棕色残留物。XX扩展的LAF A级区域周围的XX和XX被观察到与XX的位置断开，产生了一个间隙，允许从B级区域到扩展LAF的A级区域的自由空气通过。这是在XX干预期间观察到的。

13. Operators were observed reaching over open bottles with the non-sterile (b)(4) perform interventions at the incoming bottle (b)(4) to pick up fallen bottles, push jammed bottles, or change environmental monitoring plates during aseptic filling on (b)(4). Similar interventions were observed being performed on bottles following the placement of the sterile (b)(4) before the final cap was affixed.

观察到操作人员用非无菌的XX伸过打开的瓶子，在进瓶XX处进行干预，捡起掉落的瓶子，推开卡住的瓶子，或在XX无菌灌装期间更换环境监测培养皿。在最后盖上盖子之前，在放置无菌物品XX之后，观察到类似的干预措施在瓶子上进行。

14. On October 16, 2023, an operator working in the Grade B area, surrounding the aseptic filling line, (b)(4), was found not wearing a nose mask under their Grade B gowning. Per procedure KHIL/RD/PB/048, entitled, "Entry and Exit Procedure for (b)(4) Filling Area” September 21, 2022, operators are to don a nose mask prior to gowning (b)(4) Grade B area.

2023年10月16日，在无菌灌装线XX周围的B级区域工作的一名操作人员被发现在B级工作服下没有戴鼻口罩。根据标题为《XX灌装区进出程序》、生效日期为2022年9月21日的程序KHIL/RD/PB/048，操作人员在B级灌装区穿洁净服之前必须戴上鼻罩。

15.Per procedure KHIL/RB/PD049, entitled,“Entry and Exit Procedure for (b)(4) Manufacturing Area”, August 13, 2023, personnel are required to remove company uniform and don headgear, shirt, trouser, booties, hand gloves and footwear prior to entering the Grade of C area. Review of the CCTV footage from October 3 and 4, 2023, showed personnel working in the Grade C (b)(4) 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 (b)(4). The deputy manager of production confirmed that this is their standard practice.

根据2023年8月13日生效的程序KHIL/RB/PD049《XX生产区域的进出程序》，人员在进入C级区域之前必须脱下公司制服，戴上帽子、衬衫、裤子、靴子、手套和鞋子。回顾2023年10月3日和4日的闭路电视录像，显示人员在C级XX区域工作，在那里物料被传递到B级灌装区。操作人员没有穿规定的工作服和手套，并且赤脚工作，他们将物料转移到B级区域用于灌装线。生产副经理确认这是他们的标准做法。

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 brushing his hair while in the hood.

另外，这个房间有一个A级LAF罩，用于清洗小型灌装机零件。观察到一名操作员站在层流罩下，另一名操作员在层流罩内脱下帽子并梳理头发。

16.Upon arrival at the entrance to the Grade C area for (b)(4) on October 13, 2023, there were gloves in wet trays. Production personnel reported the gloves had been washed.

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