WO2024017323A1 - 一种载体液无菌分装系统及其应用 - Google Patents

一种载体液无菌分装系统及其应用 Download PDF

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Publication number
WO2024017323A1
WO2024017323A1 PCT/CN2023/108342 CN2023108342W WO2024017323A1 WO 2024017323 A1 WO2024017323 A1 WO 2024017323A1 CN 2023108342 W CN2023108342 W CN 2023108342W WO 2024017323 A1 WO2024017323 A1 WO 2024017323A1
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Prior art keywords
dispensing system
carrier liquid
aseptic
filling
bag
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PCT/CN2023/108342
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English (en)
French (fr)
Inventor
徐丙良
徐鹏
吴守亮
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浙江健新原力制药有限公司
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Application filed by 浙江健新原力制药有限公司 filed Critical 浙江健新原力制药有限公司
Priority to CN202380012308.5A priority Critical patent/CN117529446A/zh
Publication of WO2024017323A1 publication Critical patent/WO2024017323A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B67—OPENING, CLOSING OR CLEANING BOTTLES, JARS OR SIMILAR CONTAINERS; LIQUID HANDLING
    • B67C—CLEANING, FILLING WITH LIQUIDS OR SEMILIQUIDS, OR EMPTYING, OF BOTTLES, JARS, CANS, CASKS, BARRELS, OR SIMILAR CONTAINERS, NOT OTHERWISE PROVIDED FOR; FUNNELS
    • B67C7/00—Concurrent cleaning, filling, and closing of bottles; Processes or devices for at least two of these operations

Definitions

  • This application belongs to the field of aseptic dispensing, and specifically relates to a carrier liquid aseptic dispensing system and its application.
  • the production of viral vector liquid has the characteristics of small production batch, low storage temperature, and high requirements for packaging containers. Therefore, after obtaining the product, it needs to be packaged and capped.
  • the traditional manual packaging method is generally used, and the packaging used is usually manual.
  • the traditional manual packaging method has certain defects: it is complex to operate, easy to contaminate, and the production speed is slow; the product filling volume is not precise enough, and leakage is prone to occur. and repeated packaging errors; sealing performance is greatly affected by individual operating differences.
  • CN110745761A discloses a sterile isolator provided with an electric dispenser and an electric capper.
  • the container containing the product needs to be sterilized together with all the packaging tools. The sterilization time is long and the gas will affect the quality of the product.
  • rapid transfer interface or "rapid transfer port” used in this application is the full English name of Rapid Transfer Port, or RTP for short. It is a two-door transmission system consisting of two main components: ⁇ valve (flange) and ⁇ valve. assembly (or beta valve). Among them, the alpha valve is usually installed on the side wall of the closed environment, and the beta assembly is removable and connected to the container, bag or process component.
  • ⁇ bag as used in this application is sterile and is mainly used to transfer the sterilized filling needle located therein to the filling unit of the sterile isolator without contamination during the filling process. Filling.
  • SART system Sartorius aseptic rapid transfer system
  • RTP rapid transfer interface
  • the SART system consists of an external interface, an internal interface, and a disposable connection device.
  • peripheral pump as used in this application consists of a driver, a pump head and a hose that pumps fluid by alternately squeezing and releasing the elastic delivery hose of the pump.
  • vector in this application refers to a vehicle into which a genetic element can be operatively inserted and expressed, for example, to produce a protein, RNA or DNA encoded by the genetic element, or to replicate the genetic element. genetic elements. Vectors can be used to transform, transduce or transfect host cells so that the genetic elements they carry can be expressed in the host cells.
  • vectors include: plasmids, phagemids, cosmids, artificial chromosomes such as yeast artificial chromosomes (YAC), bacterial artificial chromosomes (BAC) or P1-derived artificial chromosomes (PAC), phages such as lambda phage Or M13 bacteriophage, as well as animal viruses, etc.
  • the vector is a viral vector, such as a lentiviral vector (LVV) or an adenoviral vector (AVV).
  • the vector is a plasmid vector.
  • the present application provides a carrier liquid aseptic dispensing system, which includes a disposable filling unit and a sterile isolator, and the disposable filling unit and the sterile isolator pass through a rapid transfer interface ( Rapid Transfer Port,RTP) connection.
  • a rapid transfer interface Rapid Transfer Port,RTP
  • the disposable filling unit described herein is provided with a liquid storage device (1), a buffer device (2) and a beta bag (3) in sequence, and are connected in series through pipelines; the end (43) of the pipeline is provided with a filling needle (5), and the end pipeline (43) together with the filling needle (5) are nested in the ⁇ bag (3), and the ⁇ bag (3) is in a fully closed state; the ⁇ bag (3) ) has the beta assembly (31) attached to the RTP, and when filling, the end of the line (43) enters the sterile isolator through the RTP.
  • the liquid storage device (1), buffer device (2) and beta bag (3) described herein are connected in series through pipelines.
  • the liquid enters the liquid storage device (1) through the sampling pipe (41).
  • the liquid storage device (1) and the buffer device (2) are connected in series through the connecting pipe (42).
  • the liquid in the buffer device (2) passes through the terminal pipe (42). 43) Outflow.
  • the sampling pipeline (41), the connecting pipeline (42) and the end pipeline (43) are respectively provided with pipe clamps to control the opening/closing of the pipelines.
  • the liquid storage device in this application may be in a conventional form in the art, such as a liquid storage bag, a liquid storage tank or a liquid storage tank.
  • the liquid storage device is a liquid storage bag.
  • the buffer device is provided with a liquid level control system (12).
  • the liquid level control system can effectively maintain the liquid level in the buffer unit and improve filling accuracy.
  • the liquid level control system in this application may be a conventional liquid level control system in the field, such as a commercially available liquid level controller, an infinite liquid level control system, etc.
  • the liquid level control system automatically controls (for example, controls a peristaltic pump) fluid replenishment by giving a signal to the weighing of the buffer device to ensure that the liquid level in the buffer device is maintained at a level. Fixed value to reduce manual rehydration operations.
  • the buffer device in this application can be in the conventional form in the art, such as a buffer bag, a buffer tank or a buffer box, to adjust the filling pressure to avoid affecting the filling accuracy.
  • the cushioning device is a cushioning bag.
  • connection point (44) between the end and the ⁇ bag is welded, glued or otherwise sealed to achieve the fully enclosed state.
  • the connection between the end and the ⁇ bag is connected by welding.
  • the beta bag is a sterile beta bag, such as a disposable sterile beta bag.
  • the beta bag (3) is attached with a beta component of the RTP, such as a beta valve (31).
  • a beta component of the RTP such as a beta valve (31).
  • the fluid storage device and the buffer device are connected by a sterile connector (45).
  • the disposable filling unit is also provided with a first peristaltic pump (131).
  • the first peristaltic pump (131) is located downstream of the liquid storage device, and the buffer upstream of the device.
  • the disposable filling unit is also provided with a pipeline bubble monitoring device (14), which is located downstream of the liquid storage device according to the connection sequence, and the buffer device upstream; when a peristaltic pump is provided in the disposable filling unit, the pipeline bubble monitoring device is located downstream of the peristaltic pump.
  • a pipeline bubble monitoring device 14
  • the RTP is a Sartorius aseptic rapid transfer (SART) system.
  • the sterile isolator is provided with the alpha valve, filling component, stopper component and capping component of the RTP;
  • the ⁇ valve (6) is located on the inner wall of the sterile isolator.
  • the filling component in this application may be a conventional filling component in this field.
  • the filling assembly is an automatic filling device (7).
  • the stopper component in this application may be a conventional stopper component in this field.
  • the stoppering assembly is an automatic stoppering device (8).
  • the capping assembly in this application may be a conventional capping assembly in this field.
  • the capping assembly is an automatic capping device (9).
  • the aseptic isolator is further provided with a conveyor belt below the filling assembly, the stoppering assembly and the capping assembly to convey unfilled or filled products.
  • Dispensing bottle (11) with carrier liquid Dispensing bottle (11) with carrier liquid.
  • a second peristaltic pump (132) is provided upstream of the filling needle.
  • the dispensing bottle in this application may be a conventional dispensing bottle in this field.
  • the dispenser bottle is a sterile dispenser bottle.
  • the present application provides a method for aseptic dispensing of a carrier fluid, which includes using the carrier fluid aseptic dispensing system described in the present application for dispensing.
  • the method includes the following steps:
  • the sterilization described in step 1) is VHP sterilization.
  • step 2) includes infusing the viral vector liquid into the liquid storage device and connecting the sterile connector (45).
  • step 2) includes connecting the alpha valve (6) of the RTP to the beta valve (31).
  • said step 3) includes monitoring the liquid level in the buffer device (2).
  • the first peristaltic pump (131) is controlled by a liquid level control system.
  • an automatic filling device (7) is used to fill the corked bottle (11). Pack.
  • an automatic stoppering device (8) is used to stopper the dispensing bottle (11) containing the carrier liquid;
  • an automatic capping device (9) is used to cap the corked dispensing bottle (11).
  • the method includes sequentially transporting the divided bottles (11) from the automatic filling device (7) to the automatic corking device (8) and the automatic capping device (9) via a conveyor belt.
  • the carrier liquid aseptic dispensing system of the present application uses the carrier liquid aseptic dispensing system of the present application to pass the virus carrier liquid into the sterile isolator through the RTP interface, and then use the automatic dispensing equipment to perform aseptic dispensing.
  • the virus carrier liquid is dispensed into the dispensing container, and then the stopper is used
  • the equipment plugs the dispensing containers one by one, and the capping equipment seals the dispensing bottles one by one.
  • the whole process is carried out in a sterile environment. It is easy to operate, has high production efficiency, is not easy to contaminate, has guaranteed sterility, and can add quantitative samples. Accurate, effectively increase production efficiency and ensure product quality.
  • the RTP interface is set up, and products are imported from the interface.
  • the items in the isolator can be sterilized in advance, reducing the preparation time before product packaging. It can realize real-time packaging, reduce the storage time of virus vectors at room temperature, and effectively ensure the quality of the product
  • liquid storage device and buffer device are outside the sterile isolator. There is no need to sterilize the container containing the product together with all the dispensing tools. This can not only save production preparation time, but also avoid the buffer device in the isolator. The adsorption of H 2 O 2 will have an impact on the quality of the product.
  • Figure 1 is a schematic diagram of a disposable filling unit.
  • Figure 2 is a schematic diagram of a sterile isolator.
  • Figure 3 is a schematic diagram of the carrier liquid aseptic dispensing system.
  • Example 1 Constructing a carrier liquid aseptic dispensing system
  • the carrier liquid aseptic dispensing system consists of a disposable filling unit and a sterile isolator.
  • liquid storage bag (1) there are a liquid storage bag (1), a first peristaltic pump (131), a pipeline bubble monitoring device (14), a buffer bag (2) and a sterile ⁇ bag ( 3) (See Figure 1 and Figure 3).
  • the buffer bag is provided with a liquid level control system (12) to maintain the liquid level in the buffer bag at a required level to ensure filling accuracy.
  • the ⁇ bag (3) is placed outside the end pipe (43) and the filling needle (5).
  • the contact point (44) between the bag body and the end of the pipe is connected by welding to ensure that the ⁇ bag is fully closed; ⁇ A rapid transfer port (RTP) beta valve (31) is attached to the bag.
  • RTP rapid transfer port
  • the ⁇ valve (6) of the rapid transfer interface located on the inner wall of the isolator
  • the automatic filling device (7) located on the inner wall of the isolator
  • the automatic plugging device (8) and the automatic capping device ( 9).
  • a conveyor belt (10) directly below the device for filling, stoppering and capping which is used to transport the filling bottles (11) that have not yet been filled or have been filled with carrier liquid (see Figure 2).
  • Example 2 Use the carrier liquid aseptic dispensing system constructed in Example 1 for dispensing
  • Step 1 With the production auxiliary tools in place, perform VHP sterilization on the sterile isolator;
  • Step 2 Introduce the carrier liquid into the sterile isolator through the RTP interface (15) through the disposable filling unit;
  • the end of the pipeline enters the sterile isolator through the RTP (15), and optionally a peristaltic pump (132) is installed on the pipeline (43) upstream of the filling needle (5). );
  • Step 3 The carrier liquid entering the sterile isolator is divided into sterile filling bottles (11) through the automatic filling device (7);
  • Step 4 Use the automatic stoppering device (8) to stopper the sub-bottle (11) containing the carrier liquid;
  • Step 5 Use the automatic capping device (9) to cap the corked bottle (11).

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  • Basic Packing Technique (AREA)

Abstract

一种载体液无菌分装系统以及使用其进行无菌分装的方法。载体液无菌分装系统包括一次性灌装单元和无菌隔离器。使用其进行无菌分装具有操作简易、生产效率高、不易污染、无菌有保障、且加样定量准确，有效增加生产效率，保证产品质量等优势。

Description

一种载体液无菌分装系统及其应用 技术领域
本申请属于无菌分装领域，具体涉及一种载体液无菌分装系统及其应用。
背景技术
生物制品生产之后，受客观环境如光线、温度、空气、水分以及微生物等因素的影响，将逐渐变质。对制备得到的生物制品进行合理的分装和包装可防止各种外界因素对产品质量的影响。
病毒载体液的生产具有生产批量小、储存温度低、对包装容器的要求高等特点，因此获得产品后还需要进行分装、轧盖处理。目前一般采用传统手工分装的方式，所用的包装通常是手动，传统手工分装方式存在一定的缺陷：操作复杂，易污染，且生产速度较慢；对产品装量不够精密，易出现漏装及重复分装的差错；密封性受个体操作差异影响大。
尽管现有技术中已有基于传统方法进行改进的记载，例如CN110745761A公开了设有电动分液器以及电动旋盖器的无菌隔离器。然而在使用该隔离器对产品进行分装时需要将装有产品的容器连同所有的分装工具一起进行灭菌，灭菌时间长且气体会对产品的质量产生影响。
发明详述
尽管本申请将在以下公开多个方面和实施方式，但是在不违背本申请主题精神和范围的前提下，本领域技术人员显然可以对其进行各种等同改变和修改。本申请公开的多个方面和实施方式仅用于举例说明，其并非旨在限制本申请，本申请的实际保护范围以权利要求为准。除非另外指出，本文中使用的所有技术和科学术语均具有与本申请所属领域中的普通技术人员通常所理解的相同的含义。本申请中引用的所有参考文献、专利、专利申请均通过整体引用并入本文。
定义
本申请中使用的术语“快速传递接口”或者“快速传输端口”的英文全称为Rapid Transfer Port、简称为RTP，其是一种双门传输系统，由两个主要部件α阀(flange)和β组件(或β阀)组成。其中，α阀通常安装在密闭式环境的侧壁上，β组件是可移动的，并连接到容器、袋或工艺组件上。
本申请中使用的术语“β袋”为无菌状态，主要用于在灌装过程中将位于其中的、灭过菌的灌装针无污染地转运到无菌隔离器的灌装单元中进行灌装。
本申请中使用的术语“Sartorius无菌快速转移系统”，其英文全称为Sartorius aseptic rapid transfer system、简称为SART系统，为快速传递接口(RTP)的一种，可使隔离器保持完整，对液体(如载体液)进行无菌转移。在一些实施方式中，SART系统由一个外接口，一个内接口，和一个一次性的连接装置组成。
本申请中使用的术语“蠕动泵”是由驱动器、泵头和软管组成，其通过对泵的弹性输送软管交替进行挤压和释放来泵送流体。
本申请中的术语“载体”是指可将遗传元件操作性地插入其中并使该遗传元件获得表达的一种运载工具，例如生产由该遗传元件编码的蛋白质、RNA或DNA，或者复制所述遗传元件。载体可用于转化、转导或转染宿主细胞，使其携带的遗传元件在宿主细胞内得以表达。举例来说，载体包括：质粒、噬菌粒、柯斯质粒(cosmid)、人工染色体如酵母人工染色体(YAC)、细菌人工染色体(BAC)或P1衍生的人工染色体(PAC)、噬菌体如λ噬菌体或M13噬菌体，以及动物病毒等。本申请的某些实施方式中，所述载体为病毒载体，例如慢病毒载体(LVV)或者腺病毒载体(AVV)。在某些实施方式中，所述载体为质粒载体。
载体液无菌分装系统
在一个方面，本申请提供了一种载体液无菌分装系统，其包括一次性灌装单元和无菌隔离器，所述一次性灌装单元和所述无菌隔离器通过快速传递接口(Rapid Transfer Port,RTP)连接。
一次性灌装单元
本文所述一次性灌装单元依次设有储液装置(1)、缓冲装置(2)以及β袋(3)，并通过管路串联；所述管路的末端(43)设有灌装针(5)，且所述末端管路(43)连同灌装针(5)嵌套于所述β袋(3)中，所述β袋(3)为全封闭状态；所述β袋(3)附接有所述RTP的β组件(31)，当进行灌装时，所述管路末端(43)通过RTP进入所述无菌隔离器。
在某些实施方式中，本文所述的储液装置(1)、缓冲装置(2)以及β袋(3)通过管路串联。液体通过进样管路(41)进入储液装置(1)，储液装置(1)与缓冲装置(2)通过连接管路(42)串联，缓冲装置(2)的液体经末端管路(43)流出。其中进样管路(41)、连接管路(42)和末端管路(43)分别设置有管夹以控制管路的开/闭。
本申请中的所述储液装置可为本领域常规的形式，例如储液袋、储液罐或者储液箱。在某些实施方式中，所述储液装置为储液袋。
在某些实施方式中，所述缓冲装置上设有液位控制系统(12)。所述液位控制系统可有效维持所述缓冲单元中的液位，提高灌装精度。本申请中的所述液位控制系统可为本领域常规的液位控制系统，例如市售可得的液位控制器、无限液位控制系统等。在某些实施方式中，所述液位控制系统通过对所述缓冲装置的称重给出信号，来自动控制(例如控制蠕动泵)补液，以保证所述缓冲装置内的液位维持在一个定值，减少人员手动补液操作。
本申请中的所述缓冲装置可为本领域中的常规形式，例如缓冲袋、缓冲罐或者缓冲箱，用以调整灌装压力避免影响灌装精度。在某些实施方式中，所述缓冲装置为缓冲袋。
本申请中，所述末端与所述β袋的连接处(44)采用焊接、胶黏或者其他封口方式以实现所述全封闭的状态。在某些实施方式中，所述末端与所述β袋的连接处连用焊接的方式连接。
在某些实施方式中，所述β袋为无菌β袋，例如一次性无菌β袋。
在某些实施方式中，所述β袋(3)附接有所述RTP的β组件，如β阀(31)当进行灌装时，所述管路末端(43)通过由β阀(31)组成的RTP进入所述无菌隔离器。
在某些实施方式中，所述储液装置和所述缓冲装置通过无菌连接器(45)连接。
在某些实施方式中，所述一次性灌装单元中还设有第一蠕动泵(131)，按照连接顺序所述第一蠕动泵(131)位于所述储液装置的下游，所述缓冲装置的上游。
在某些实施方式中，所述一次性灌装单元中还设有管路气泡监测装置(14)，按照连接顺序所述管路气泡监测装置位于所述储液装置的下游，所述缓冲装置的上游；当所述一次性灌装单元中设有蠕动泵时，所述管路气泡监测装置位于所述蠕动泵的下游。
在某些实施方式中，所述RTP为Sartorius无菌快速转移(Sartorius aseptic rapid transfer,SART)系统。
无菌隔离器
在某些实施方式中，所述的无菌隔离器中设有所述RTP的α阀、灌装组件、加塞组件以及轧盖组件；
所述α阀(6)位于所述无菌隔离器的内壁。
本申请中的所述灌装组件可为本领域常规的灌装组件。在某些实施方式中，所述灌装组件为自动灌装装置(7)。
本申请中的所述加塞组件可为本领域常规的加塞组件。在某些实施方式中，所述加塞组件为自动加塞装置(8)。
本申请中的所述轧盖组件可为本领域常规的轧盖组件。在某些实施方式中，所述轧盖组件为自动轧盖装置(9)。
在某些实施方式中，所述的无菌隔离器中于所述灌装组件、所述加塞组件以及所述轧盖组件的下方还设有输送带，用以传送尚未灌装或者已灌装有载体液的分装瓶(11)。
在某些实施方式中，在进行灌装时，所述灌装针的上游还设有第二蠕动泵(132)。
本申请中的所述分装瓶可为本领域中常规的分装瓶。在某些实施方式中，所述分装瓶为无菌分装瓶。
无菌分装载体液的方法
另一方面，本申请提供一种无菌分装载体液的方法，其包括使用本申请所述的载体液无菌分装系统进行分装。
在某些实施方式中，所述方法包括如下步骤：
1)将无菌隔离器进行灭菌处理；
2)将病毒载体液经一次性灌装单元通过RTP接口导入无菌隔离器；
3)进入无菌隔离器的载体液通过灌装组件分装至分装瓶；
4)使用加塞组件对分装瓶进行加塞；
5)使用轧盖组件对分装瓶进行封盖。
在某些实施方式中，步骤1)中所述灭菌为VHP灭菌。
在某些实施方式中，所述步骤2)包括将病毒载体液灌注到储液装置，并连接无菌连接器(45)。
在某些实施方式中，所述步骤2)包括将RTP的α阀(6)与β阀(31)连通。
在某些实施方式中，所述步骤3)包括监测缓冲装置(2)中的液位。在某些实施方式中，通过液位控制系统控制第一蠕动泵(131)。
在某些实施方式中，使用自动灌装装置(7)对加塞后的分装瓶(11)进行灌 装。
在某些实施方式中，使用自动加塞装置(8)对装有载体液的分装瓶(11)进行加塞；
在某些实施方式中，使用自动轧盖装置(9)对加塞后的分装瓶(11)进行封盖。
在某些实施方式中，所述方法包括通过输送带将分装瓶(11)依次从自动灌装装置(7)输送到自动加塞装置(8)以及自动轧盖装置(9)。
使用本申请的载体液无菌分装系统将病毒载体液通过RTP接口通入无菌隔离器后使用自动分装设备进行无菌分装将病毒载体液分装至分装容器中，再使用加塞设备逐一对分装容器进行加塞，轧盖设备逐一对分装瓶进行封盖，整个过程均在无菌环境中进行，操作简易、生产效率高、不易污染、无菌有保障、且加样定量准确，有效增加生产效率，保证产品质量。其中设置的RTP接口，产品从接口导入，隔离器中物品可提前灭菌，减少产品分装前的准备时间，可以实现实时分装，减少病毒载体在室温下的存放时间，有效保证产品的质量。
此外，储液装置和缓冲装置在无菌隔离器外面，无需将装有产品的容器连同所有的分装工具一起进行VHP灭菌，既能节约生产准备时间，又避免了缓冲装置在隔离器中吸附H2O2进而对产品的质量产生影响。
附图说明
图1为一次性灌装单元的示意图。
图2为无菌隔离器的示意图。
图3为载体液无菌分装系统的示意图。
具体实施方式
下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法，按照常规方法和条件，或按照商品说明书选择。
实施例1：构建载体液无菌分装系统
载体液无菌分装系统由一次性灌装单元和无菌隔离器组成。
(1)一次性灌装单元
按照连接顺序或者规模生产的步骤，沿管路依次设有储液袋(1)、第一蠕动泵(131)、管路气泡监测装置(14)、缓冲袋(2)以及无菌β袋(3)(见图1、图3)。
其中缓冲袋上设有液位控制系统(12)以维持缓冲袋中的液位在所需的水平，保证灌装的精度。β袋(3)套在末端管路(43)和灌装针(5)的外面，袋体与管路末端接触的地方(44)采用焊接方式连接，以确保β袋是全封闭状态；β袋上附接有快速传递接口(RTP)的β阀(31)。
(2)无菌隔离器
按照连接顺序或者规模生产的步骤，其中依次设有快速传递接口的α阀(6)(位于隔离器的内壁)、自动灌装装置(7)、自动加塞装置(8)和自动轧盖装置(9)。在用于灌装、加塞以及压盖的装置的正下方还设有输送带(10)，用以传送尚未灌装或者已灌装有载体液的分装瓶(11)(见图2)。
实施例2：使用实施例1构建的载体液无菌分装系统进行分装
步骤1：在生产辅助工具已就位的情况下，将无菌隔离器进行VHP灭菌处理；
步骤2：将载体液经一次性灌装单元通过RTP接口(15)导入无菌隔离器；
在一次性灌装单元中管路的末端通过RTP(15)进入无菌隔离器，并且可选择地在所述灌装针(5)的上游，于管路(43)上安装蠕动泵(132)；
步骤3：进入无菌隔离器的载体液通过自动灌装装置(7)被分装至无菌分装瓶(11)；
步骤4：使用自动加塞装置(8)对装有载体液的分装瓶(11)进行加塞；
步骤5：使用自动轧盖装置(9)对加塞后的分装瓶(11)进行封盖。

Claims (20)

  1. 一种载体液无菌分装系统，其特征在于，其包括一次性灌装单元和无菌隔离器，所述一次性灌装单元和所述无菌隔离器通过快速传递接口(RTP)连接；
    所述一次性灌装单元依次设有储液装置、缓冲装置以及β袋，并通过管路串联；所述管路的末端设有灌装针，且所述末端嵌套于所述β袋中，所述β袋为全封闭状态；所述β袋附接有所述RTP的β组件，当进行灌装时，所述管路末端通过RTP进入所述无菌隔离器。
  2. 如权利要求1所述的载体液无菌分装系统，其特征在于，所述缓冲装置上设有液位控制系统；所述液位控制系统优选通过对所述缓冲装置进行称重以给出信号、控制补液。
  3. 如权利要求1或2所述的载体液无菌分装系统，其特征在于，所述末端与所述β袋采用焊接方式进行连接。
  4. 如前述权利要求中任一项所述的载体液无菌分装系统，其特征在于，所述β袋为无菌β袋，例如一次性无菌β袋。
  5. 如前述权利要求中任一项所述的载体液无菌分装系统，其特征在于，所述储液装置和所述缓冲装置通过无菌连接器连接。
  6. 如前述权利要求中任一项所述的载体液无菌分装系统，其特征在于，所述一次性灌装单元中还设有蠕动泵，按照连接顺序所述蠕动泵位于所述储液装置的下游，所述缓冲装置的上游。
  7. 如前述权利要求中任一项所述的载体液无菌分装系统，其特征在于，所述一次性灌装单元中还设有管路气泡监测装置，按照连接顺序所述管路气泡监测装置位于所述储液装置的下游，所述缓冲装置的上游；
    当所述一次性灌装单元中设有蠕动泵时，所述管路气泡监测装置位于所述蠕动泵的下游。
  8. 如前述权利要求中任一项所述的载体液无菌分装系统，其特征在于，所述RTP为Sartorius无菌快速转移(SART)系统。
  9. 如前述权利要求中任一项所述的载体液无菌分装系统，其特征在于，所述储液装置为储液袋或者储液箱的形式。
  10. 如前述权利要求中任一项所述的载体液无菌分装系统，其特征在于，所述缓冲装置为缓冲袋或者缓冲箱的形式。
  11. 如前述项权利要求中任一项所述的载体液无菌分装系统，其特征在于，所述的无菌隔离器中设有所述RTP的α阀、灌装组件、加塞组件以及轧盖组件；
    所述α阀位于所述无菌隔离器的内壁。
  12. 如权利要求11所述的载体液无菌分装系统，其特征在于，所述灌装组件为自动灌装装置；
    和/或，所述加塞组件为自动加塞装置；
    和/或，所述轧盖组件为自动轧盖装置。
  13. 如权利要求11或12所述的载体液无菌分装系统，其特征在于，所述的无菌隔离器中于所述灌装组件、所述加塞组件以及所述轧盖组件的下方还设有输送带，用以传送尚未灌装或者已灌装有载体液的分装瓶。
  14. 如权利要求11-13任一项所述的载体液无菌分装系统，其特征在于，在进行灌装时，所述灌装针的上游设有蠕动泵。
  15. 如权利要求13或14所述的载体液无菌分装系统，其特征在于，所述分装瓶为无菌分装瓶。
  16. 如前述权利要求中任一项所述的病毒载体液无菌分装系统，其特征在于，所述载体为病毒载体或质粒载体。
  17. 如权利要求16所述的病毒载体液无菌分装系统，其特征在于，所述病毒载体为腺病毒载体或者慢病毒载体。
  18. 一种无菌分装载体液的方法，其包括使用如权利要求1-17任一项所述的载体液无菌分装系统进行分装。
  19. 如权利要求18所述的方法，其特征在于，所述方法包括如下步骤：
    1)将无菌隔离器进行灭菌处理；
    2)将病毒载体液经一次性灌装单元通过RTP接口导入无菌隔离器；
    3)进入无菌隔离器的载体液通过灌装组件分装至分装瓶；
    4)使用加塞组件对分装瓶进行加塞；
    5)使用轧盖组件对分装瓶进行安装封盖。
  20. 如权利要求19所述的方法，其特征在于，步骤1)中所述灭菌为VHP灭菌。
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