Bag type sterile filling system and filling method

Abstract

The invention provides a bag type sterile filling system and method, the system comprises a control module, and a material arranging module, a filling module and a discharging module which are connected in sequence, and the working process of the filling system comprises a filling calibration stage and a filling operation stage; in the filling calibration stage, the control module obtains the actual average flow according to the filling amount detection result of the filling module and automatically calibrates the filling module according to the actual average flow; in the filling operation stage, the control module judges whether the corresponding sub-packaging bags are qualified or not according to the filling amount detection result of the filling module. Through ordered connection of the material arranging module, the filling module and the discharging module, full-process automatic treatment from shaping, cutting, filling and sealing to quality sorting of the sub-packaging bags is achieved, the system can automatically calibrate the filling module, the production efficiency is remarkably improved, and the product yield is further improved.

Description

Technical Field

[0001] The present invention relates to the technical field of filling of non-terminally sterilized aseptic preparations of biopharmaceuticals, and in particular to a bag-type aseptic filling system and a filling method. Background Art

[0002] In the biopharmaceutical field, sterile preparations can be divided into terminally sterilized preparations and non-terminally sterilized preparations according to the sterilization method. Terminally sterilized preparations are preparations that can be sterilized after filling, while non-terminally sterilized preparations cannot be sterilized after filling due to their special properties (such as containing heat-sensitive ingredients, bioactive substances, etc.). For non-terminally sterilized sterile preparations, pharmaceutical GMP requires that the filling process must ensure sterility throughout. There are usually two ways to achieve this: one is to fill in a Class A clean environment, and the other is to use a disposable sterile closed system to fill in an environment not lower than Class D.

[0003] At present, for the filling of soft bag types such as cell preparations, disposable sterile closed systems are mainly used for filling. However, this filling method has obvious limitations: the filling efficiency is limited, usually not exceeding 60 bags / hour; when the filling speed needs to be increased, the number of flow paths working simultaneously must be increased (that is, the number of peristaltic pumps working simultaneously) must be increased. Although this can increase production capacity (such as 10 pumps can reach 600 bags / hour), it also leads to a lower degree of automation and requires more operators to participate. In addition, the multi-flow system makes the consumables system complicated, and the risk control points of pipeline leakage such as pipe joints and sterile air filters have increased significantly. Especially in actual production, it is impossible to detect the integrity of the filter online, and all filters can only be cut off and tested separately after production is completed. This post-verification method has the risk of lag.

[0004] This limitation becomes particularly pronounced in large-volume filling scenarios (over 600 bags per batch), where existing technology is unable to achieve online full weighing and rejection of rejects. According to the 3σ standard, the cumulative probability of rejects exceeds 84%, and when abnormalities occur, existing systems struggle to detect and address them promptly.

[0005] As for filling solutions that rely on a Grade A environment to ensure sterility, there are currently no readily available, mature technical solutions on the market. Compared to the traditional filling of non-terminally sterilized vials, the filling of bagged cell preparations presents several unique challenges: precise cutting of the flexible bag tubing, precise docking of the filling needle with the thin flexible tube, vibration during weighing of the hanging flexible bag, and heterogeneity caused by cell sedimentation—all technical difficulties that do not exist in traditional vial filling.

[0006] Furthermore, existing assembly line filling methods often result in liquid waste during pump calibration. Actual drug solution must be weighed and calibrated before formal filling. This calibration process often needs to be repeated multiple times, resulting in the waste of multiple filling units of drug solution. For high-value pharmaceuticals such as cell-based formulations, this waste is unacceptable.

[0007] In summary, there is currently no comprehensive technical solution on the market that can meet the high-throughput filling needs of non-terminally sterilized, sterile preparations such as cell-based preparations. The industry urgently needs a systematic solution that not only meets GMP requirements for the filling environment, but also overcomes the precision issues associated with connecting thin hoses and filling needles, enables in-line full weighing and rejection of substandard products, ensures ingredient uniformity, and eliminates drug solution loss during calibration, ultimately achieving efficient and reliable high-throughput filling. Summary of the Invention

[0008] The purpose of the present invention is to solve the problem that the existing technology cannot meet the high-throughput filling requirements of sterilized aseptic preparations.

[0009] A first aspect of the present invention provides a bag-type aseptic filling system, comprising: a control module and a material handling module, a filling module and a discharging module connected in sequence;

[0010] The material sorting module is used to arrange the packaging bags in an orderly manner at relatively fixed intervals;

[0011] The filling module is connected to the discharge end of the material sorting module and is used to fill, detect the filling amount and seal the packaging bags;

[0012] The discharging module is connected to the discharging end of the filling module and outputs qualified products and unqualified products of the sub-packaging bags according to the filling amount detection result;

[0013] The material sorting module, the filling module and the discharging module are all connected to the control module, and the control module is used to control the working states of the material sorting module, the filling module and the discharging module;

[0014] Among them, the working process of the bag-type aseptic filling system includes a filling calibration stage and a filling operation stage; in the filling calibration stage, the control module obtains the actual average flow rate based on the filling volume detection result of the filling module, and automatically calibrates the filling module according to the actual average flow rate; in the filling operation stage, the control module determines whether the corresponding sub-packaging bag is qualified based on the filling volume detection result of the filling module.

[0015] Furthermore, the material sorting module includes a first isolation system, and the first isolation system includes:

[0016] a first conveying device, disposed inside the first isolation system, comprising a conveyor belt and a positioning block, wherein the positioning block is fixed on the conveyor belt;

[0017] a cutting device, placed above the conveyor belt, for cutting the flexible tubes of the packaging bags on each of the positioning blocks into the same length;

[0018] The sub-packaging bags enter the first isolation system, are transported by the first conveying device to the cutting device for cutting, and are then transported to the filling module after cutting.

[0019] Furthermore, the filling module includes a second isolation system, the feed end of the second isolation system is connected to the discharge end of the material sorting module, and the second isolation system includes:

[0020] a reciprocating feeding device, placed in the second isolation system, comprising a fixed plate, a plurality of clamping jaws equidistantly arranged on the fixed plate, and a track for limiting the movement of the fixed plate;

[0021] A filling unit is placed on the side of the reciprocating feeding device close to the clamping claw, and is used to weigh and fill the sub-packaging bags;

[0022] A loading device is placed at the front end of the filling unit in the transport direction, and includes a loading gripper and a robotic arm for grabbing and changing the posture of the sub-packaging bags;

[0023] The sealing device is placed at the rear end of the filling unit in the transport direction and is used to seal the filling bags after filling.

[0024] Furthermore, the filling unit includes:

[0025] A front weighing device, close to the feeding device, for weighing the sub-packaging bags before filling;

[0026] A post-weighing device, located near the sealing device, for weighing the sub-packaging bags after filling;

[0027] The filling assembly is placed between the front weighing device and the rear weighing device, and includes a clamping device and a filling needle holder. The clamping device fixes the sub-packaging bag during the filling process, and the filling needle holder is arranged directly above the clamping device and is used to fill liquid into the sub-packaging bag.

[0028] Furthermore, a first working point and a second working point are respectively provided at both ends of the track of the reciprocating feeding device, and the fixed plate reciprocates along the track between the first working point and the second working point;

[0029] When the fixed plate moves to the first working point, the clamping centers of the clamping jaws, the feeding clamping jaws, the front weighing device, the clamping device, and the rear weighing device are all located in the same vertical plane;

[0030] When the fixing plate moves to the second working point, the clamping centers of the clamping claws, the front weighing device, the clamping device, the rear weighing device, and the sealing device are all located in the same vertical plane.

[0031] Furthermore, the filling module further includes:

[0032] An exhaust device is used to discharge the internal gas after the filling of the sub-packaging bag is completed;

[0033] The second conveying device is placed in the second isolation system and is located below the sealing device. It is used to receive the sealed packaging bags released from the sealing device and convey them to the discharge module.

[0034] Furthermore, the discharging module includes:

[0035] A discharge isolation system, wherein the side wall of the discharge isolation system is provided with a discharge isolation system connection port corresponding to the discharge end of the filling module;

[0036] a first slope extending from the discharge isolation system connection port to the interior of the discharge isolation system, and when the discharge end of the filling module is opened, the first slope is connected to the discharge end of the filling module;

[0037] a second slope, rotatably disposed at the end of the first slope, for separating qualified products from unqualified products;

[0038] The third conveying device is connected to the second slope and is used to output qualified products that slide down the second slope.

[0039] Furthermore, it also includes:

[0040] A feeding module, used for removing the outer packaging of the sub-packaging bags and delivering the sub-packaging bags to the material handling module in a sterile manner;

[0041] A low-temperature mixing module is used to keep the liquid in the stock liquid bag cold and prevent precipitation. The output pipeline of the stock liquid bag is connected to the filling pump in the filling module through a pump tube assembly;

[0042] A cell counting device, connected to the stock solution bag via a cell counting tube assembly, for real-time monitoring of the cell density in the stock solution bag;

[0043] The control module includes a controller and a data recording module. The controller connects the modules and controls the mechanism action and process logic of the filling system. The data recording module is connected to the controller and is used to store weighing data and operation logs.

[0044] A second aspect of the present invention provides a bag-type aseptic filling method, which is applied to the bag-type aseptic filling device described above, comprising the following steps:

[0045] S1. Automatically calibrate the filling module to determine the actual average flow rate;

[0046] S2. Arrange and cut the packaging bags so that they are arranged at a fixed interval and cut the tubes of the packaging bags to the same length;

[0047] S3, weighing and filling the cut packaging bags in sequence;

[0048] S4, venting and heat-sealing the filled packaging bags;

[0049] S5. Determine whether the packaging bags are qualified based on the weighing data, and separate qualified products from unqualified products.

[0050] Furthermore, the step S1 includes:

[0051] Determine the target filling volume V, liquid density ρ, filling pump speed N, and theoretical flow rate Q;

[0052] Weigh the packaging bag before filling to obtain the empty weight Wm0;

[0053] Filling λ×V of liquid according to the theoretical flow rate Q, where λ is a coefficient greater than 0 and less than 1;

[0054] Weigh the sub-packaging bag after filling to obtain the total weight Wm1 after the first filling, and calculate the net weight of the liquid after the first filling Wj1=Wm1-Wm0;

[0055] After conversion, the actual flow rate is Q1 = (Q × Wj1) / (ρ × λ × V);

[0056] Continue filling (V-Wj1 / ρ) of liquid according to the actual flow rate Q1;

[0057] Weigh the sub-packaging bag (901) after filling to obtain the total weight Wm2 after the second filling, and calculate the net weight of the liquid after the second filling Wj2=Wm2-Wm1;

[0058] After conversion, the actual average flow rate is Q2 = (Q1×Wj2) / (ρV-Wj1).

[0059] Furthermore, the step S1 includes:

[0060] Determine the target filling volume V, liquid density ρ, filling pump speed N, and theoretical flow rate Q;

[0061] Weighing the packaging bag (901) before filling to obtain an empty weight Wm0;

[0062] Filling λ×V of liquid according to the theoretical flow rate Q, where λ is a coefficient greater than 0 and less than 1;

[0063] Weigh the filled sub-packaging bag (901) to obtain the total weight Wm1 after the first filling, and calculate the net weight of the liquid after the first filling Wj1=Wm1-Wm0;

[0064] After conversion, the actual flow rate is Q1 = (Q × Wj1) / (ρ × λ × V);

[0065] Continue filling λ×(V-Wj1 / ρ) of liquid according to the actual flow rate Q1;

[0066] Weigh the sub-packaging bag (901) after filling to obtain the total weight Wm2 after the second filling, and calculate the net weight of the second filling liquid Wj2=Wm2-Wm1;

[0067] After conversion, the actual average flow rate is Q2 = (Q1 × Wj2) / ((ρV-Wj1) × λ);

[0068] Continue filling V-(Wj1+Wj2) / ρ of liquid according to the actual flow rate Q1;

[0069] Weigh the filling bag (901) to obtain the weight Wm3 after the third filling, and calculate the net weight of the third filling liquid Wj3 = Wm3 - Wm2;

[0070] After conversion, the actual average flow rate is Q3 = Q2 × Wj3 / (ρV-Wm3+Wm0).

[0071] Furthermore, the step S2 includes:

[0072] Controlling the first conveying device in the material handling module to operate intermittently at a preset beat so that the sub-packaging bags are arranged at a fixed interval;

[0073] Control the cutting device to cut the tube on the packaging bag at a preset rhythm;

[0074] Control the loading device to grab the cut packaging bags and change the posture for transmission.

[0075] Furthermore, step S3 includes:

[0076] The reciprocating feeding device transfers the sub-packaging bags to the front weighing device at a preset rhythm;

[0077] The front weighing device weighs the packaging bags before filling;

[0078] The reciprocating feeding device transfers the sub-packaging bag to the filling assembly;

[0079] The filling component fills the packaging bag;

[0080] The reciprocating feeding device transfers the sub-packaging bags to the post-weighing device;

[0081] The post-weighing device weighs the filled sub-packaging bags and calculates the filled net weight.

[0082] Furthermore, the step S4 includes:

[0083] The reciprocating feeding device transfers the sub-packaging bags to the exhaust device;

[0084] The exhaust device exhausts the filling bag after filling;

[0085] The reciprocating feeding device transfers the sub-packaging bag to the sealing device;

[0086] The sealing device seals the flexible tube of the packaging bag;

[0087] The clamping jaws of the sealing device are released in sequence, so that the sub-packaging bags fall into the second conveying device.

[0088] Furthermore, the step S5 includes:

[0089] The second conveying device conveys the sealed packaging bags to the discharge module;

[0090] Determine whether the sub-packaging bag is qualified according to the filling net weight;

[0091] The second slope is rotated to separate the qualified products and the unqualified products along different paths.

[0092] Furthermore, it also includes:

[0093] During the weighing before filling, if no signal of the sub-packaging bag is detected, the station is marked as NULL;

[0094] During filling, if the sub-packaging bag is not detected or the weighing mark before the previous beat is NULL, the station is marked as NULL;

[0095] When weighing filling, if the filling mark of the previous cycle is NULL, mark the station as NULL; and

[0096] During heat sealing, the heat sealing operation will not be performed on the workstations whose weighing mark is NULL after the previous cycle.

[0097] Compared with the existing technology, the present invention has at least the following beneficial effects: through the orderly connection of the material sorting module, the filling module and the discharging module, the whole process of automated processing of the sub-packaging bags from shaping and cutting, filling and sealing to quality sorting is realized, which has significant technical advantages: First, the material sorting module arranges the sub-packaging bags in order at fixed intervals, solves the problems of bag jamming and flow interruption caused by chaotic feeding in the traditional filling system, and improves the stability of the system; secondly, the filling module integrates the filling, filling volume detection and sealing functions, which significantly improves production efficiency and reduces the risk of cross-contamination; finally, the discharging module can automatically separate qualified products from unqualified products, reduces manual intervention, and improves the yield of finished products. The entire system forms a complete production chain. Compared with the existing technology, it not only improves the filling efficiency and accuracy, but also realizes closed-loop management of product quality. It is particularly suitable for the production of biological drugs such as cell preparations with strict sterility requirements and high product value, and solves the technical problems of insufficient automation, low filling accuracy and difficult quality control in the existing technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0098] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are merely embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying any creative work.

[0099] Figure 1 This is a front view of an aseptic filling system in one embodiment of the present invention;

[0100] Figure 2 This is a schematic cross-sectional view of an aseptic filling system JJ in one embodiment of the present invention;

[0101] Figure 3 This is a left side view of an aseptic filling system according to an embodiment of the present invention;

[0102] Figure 4 A partial view in the K direction in one embodiment of the present invention;

[0103] Figure 5 This is a schematic diagram of a filling module in one embodiment of the present invention;

[0104] Figure 6 A schematic diagram of a weighing device in one embodiment of the present invention;

[0105] Figure 7 A schematic diagram of a clamping jaw in one embodiment of the present invention;

[0106] Among them, 100, feeding module; 101, feeding isolation system; 1011, feeding door; 200, material sorting module; 201, first isolation system; 2011, first feeding port; 202, first conveying device; 2021, conveyor belt; 2022, positioning block; 203, waste collection device; 204, cutting device; 300, filling module; 301, second isolation system; 3011, pipe threading device; 302, Feeding device; 3021, feeding clamp; 3022, robotic arm; 303, reciprocating feeding device; 3031, clamp; 3032, track; 3033, fixed plate; 3031A, first clamping arm; 3031B, second clamping arm; 3031C, protrusion; 3031D, curved surface; 304, front weighing device; 3041, supporting structure; 3042, weighing sensor; 3043, clamp fixing plate; 30 44. Anti-shake support; 305. Filling pump; 306. Filling needle holder; 307. Exhaust device; 308. Sealing device; 309. Pump tube assembly; 3091. Pump tube connector; 3092. Clamp; 310. Post-weighing device; 311. Airborne bacteria sampler; 312. Particle detection device; 313. Second conveying device; 314. Clamping device; 400. Low-temperature mixing module; 500. Discharging module; 50 1. Discharge isolation system; 5011, discharge isolation system connection port; 5012, sealing gloves; 502, first ramp; 503, second ramp; 504, third conveyor; 600, stock solution bag; 601, liquid outlet pipe; 700, controller; 800, data recording module; 1000, cell counting device; 901, dispensing bag; 9011, hose; 902, packaging bag; 1001, cell counting tube set. A1 - third working point; A2 - first working point; B1 - fourth working point; B2 - second working point. DETAILED DESCRIPTION

[0107] The present invention will be described in more detail below with reference to schematic diagrams, which illustrate preferred embodiments of the present invention. It should be understood that those skilled in the art may modify the present invention as described herein while still achieving the advantageous effects of the present invention. Therefore, the following description should be understood as being generally known to those skilled in the art and not as limiting the present invention.

[0108] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "includes," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus.

[0109] The following paragraphs describe the present invention in more detail by way of example with reference to the accompanying drawings. The advantages and features of the present invention will become more apparent from the following description. It should be noted that the drawings are greatly simplified and not to exact scale, and are provided solely for the purpose of assisting in the description of the embodiments of the present invention.

[0110] Example 1

[0111] This embodiment provides a bag-type aseptic filling system, please refer to Figure 1-Figure 7 , including: a control module and a material sorting module 200, a filling module 300 and a discharging module 500 connected in sequence.

[0112] The material sorting module 200 is used to arrange the packaging bags 901 in an orderly manner at relatively fixed intervals.

[0113] The filling module 300 is connected to the discharge end of the material sorting module 200 and is used to fill, detect the filling amount and seal the sub-packaging bags 901.

[0114] The discharging module 500 is connected to the discharging end of the filling module 300 and outputs qualified products and unqualified products of the sub-packaging bags according to the filling amount detection result.

[0115] The material sorting module 200 , the filling module 300 and the discharging module 500 are all connected to the control module, and the control module is used to control the working states of the material sorting module 200 , the filling module 300 and the discharging module 500 .

[0116] Among them, the working process of the bag-type aseptic filling system includes a filling calibration stage and a filling operation stage; in the filling calibration stage, the control module obtains the actual average flow rate based on the filling quantity detection result of the filling module 300, and automatically calibrates the filling module 300 according to the actual average flow rate; in the filling operation stage, the control module determines whether the corresponding sub-packaging bag 901 is qualified based on the filling quantity detection result of the filling module 300.

[0117] Specifically, the material sorting module 200 can use a conveyor belt 2021 in conjunction with a positioning block 2022 to achieve evenly spaced arrangement of the sub-packaging bags 901. Furthermore, a photoelectric sensor can be used to detect the position of the sub-packaging bags 901 to ensure the accuracy of the arrangement. The filling module 300 can achieve closed-loop control of the filling volume through a weighing sensor 3042. Specifically, a high-precision strain gauge sensor can be used in conjunction with an anti-shake support structure 3041 to suppress shaking during the weighing process. The discharging module 500 can achieve automatic sorting of qualified and unqualified products through an inclined slide in conjunction with a pneumatic baffle, for example, by using a servo motor to drive the slide angle switch.

[0118] In this embodiment, a sealing glove 5012 is also provided on the outer wall of each module. The sealing glove 5012 is secured to the side wall of the discharge isolation system 501 via a quick-release interface and communicates with the interior. Preferably, the sealing glove 5012 is made of butyl rubber, and the number of gloves can be configured to be 2-4 depending on operational requirements.

[0119] Through a modular design, the entire process of handling sub-bags 901, from material sorting to filling and sorting, is fully automated. The material sorting module 200 ensures the orderly delivery of sub-bags 901 to the filling station. The filling module 300 uses multiple weighing processes to ensure filling accuracy. The discharge module 500 automatically sorts the bags based on weight detection results. Compared to existing technologies, this solves the problem of inaccurate positioning caused by bag deformation during the soft bag filling process. Closed-loop weighing control enables high-precision filling while avoiding the risk of cross-contamination associated with manual sorting. Furthermore, the sealed connections between the modules ensure a sterile environment during the filling process.

[0120] For further information, please refer to Figure 2 The material sorting module 200 includes a first isolation system 201, and the first isolation system 201 includes:

[0121] The first conveying device 202 is placed inside the first isolation system 201 and includes a conveyor belt 2021 and a positioning block 2022 . The positioning block 2022 is fixed on the conveyor belt 2021 .

[0122] The cutting device 204 is placed above the conveyor belt 2021 and is used to cut the hoses 9011 of the packaging bags 901 on each of the positioning blocks 2022 into the same length.

[0123] The sub-packaging bags 901 enter the first isolation system 201 , are conveyed by the first conveying device 202 to the cutting device 204 for cutting, and are then conveyed to the filling module 300 via the discharge end of the first isolation system 201 .

[0124] Specifically, the first isolation system 201 is made of stainless steel, and a positive pressure sterile environment is maintained inside. The side walls are respectively provided with a first feed port 2011 and a first discharge port. The conveyor belt 2021 of the first conveying device 202 is made of medical-grade silicone material, with anti-slip grooves on the surface, and the spacing between the positioning blocks 2022 is 150mm±0.5mm. The cutting device 204 includes a rotating blade driven by a servo motor, with a blade speed of 3000rpm and a cutting accuracy of up to ±0.1mm. As a preferred embodiment, a V-groove is provided on the positioning block 2022 for fixing the position of the hose 9011 of the packaging bag 901. Furthermore, the cut hose 9011 falls into the waste collection device 203 below. The cutting device 204 is also equipped with a visual detection system, which identifies the position of the hose 9011 through a CCD camera and feeds back to the control system to adjust the cutting position.

[0125] A sterile environment is ensured through an isolation system, while the precisely positioned conveying device and cutting device 204 enable automated arrangement and standardized cutting of the sub-packaging bags 901. The fixed-pitch positioning blocks 2022 ensure orderly transport of the sub-packaging bags 901, while the rotating blades, in conjunction with the visual system, achieve high-precision cutting. Compared with existing technologies, this solves the problem of filling docking difficulties caused by inconsistent lengths of the soft bag hoses 9011, while also avoiding the risk of contamination from manual operation. Through the synergistic effect of mechanical positioning and automatic cutting, standardization and automation are achieved in the pre-processing of the sub-packaging bags 901, providing a material foundation of uniform specifications for the subsequent filling process.

[0126] For further information, please refer to Figure 5 The filling module 300 includes a second isolation system 301. The feed end of the second isolation system 301 is connected to the discharge end of the material sorting module 200. The second isolation system 301 includes:

[0127] The reciprocating feeding device 303 is placed in the second isolation system 301 and includes a fixed plate 3033 , a plurality of clamping jaws 3031 equidistantly arranged on the fixed plate 3033 , and a track 3032 for limiting the movement of the fixed plate 3033 .

[0128] The filling unit is placed on one side of the reciprocating feeding device 303 close to the clamping jaws 3031 and is used to weigh and fill the sub-packaging bags 901.

[0129] The loading device 302 is placed at the front end of the filling unit in the transport direction, and includes a loading clamp 3021 and a mechanical arm 3022 for grabbing and changing the posture of the sub-packaging bag 901.

[0130] The sealing device 308 is placed at the rear end of the filling unit in the transport direction and is used to seal the filled sub-packaging bags 901.

[0131] Specifically, the track 3032 of the reciprocating feeding device 303 can be a linear guide rail or a V-shaped roller guide rail, and the fixed plate 3033 is driven by a servo motor to achieve precise positioning. Figure 7 The clamping jaws 3031 are pneumatically or electrically driven, and the clamping force is closed-loop controlled by a pressure sensor. A silicone cushion is provided at the end of the clamping jaws 3031 to prevent damage to the sub-packaging bag 901. Furthermore, the clamping jaws 3031 can be equipped with a rotating mechanism to achieve a 90-degree flip of the posture of the sub-packaging bag 901. The robotic arm 3022 of the loading device 302 can adopt a SCARA structure or a six-axis articulated type, and the end effector has an integrated force / torque sensor. The loading clamping jaws 3021 are equipped with a dual mechanism of vacuum suction cups and mechanical clamping jaws 3031. The vacuum suction cups are used to grasp the flat bag surface, and the mechanical clamping jaws 3031 are used to clamp the hose 9011. The posture change action includes flipping from a horizontal state to a vertical hanging state. The sealing device 308 adopts resistance heating or ultrasonic welding, and the temperature control accuracy reaches ±1°C. The pressing mechanism realizes graded pressure control through a cylinder, with low-pressure positioning in the initial stage and high-pressure sealing in the later stage. Infrared temperature monitoring is set in the sealing area, and real-time feedback is provided to adjust the heating power.

[0132] Thus, the sterility of the filling environment is maintained through the second isolation system 301. The reciprocating feeding device 303 cooperates with the precise positioning of each workstation to solve the positioning problem of the soft bag during continuous transmission. The posture change function of the loading device 302 adapts to the special requirements of hanging weighing. The precise control of the heat sealing parameters of the sealing device 308 ensures the consistency of the sealing quality. High-precision filling of high-value drugs such as cell preparations is achieved while meeting the requirements of aseptic operation. The precise positioning design at both ends of the track 3032 of the reciprocating feeding device 303 enables the clamp 3031 to accurately transfer the sub-packaging bag 901 between different workstations, solving the positioning accuracy problem that is difficult to guarantee in traditional multi-channel systems. The special structural design of the clamp 3031 effectively suppresses the shaking of the soft bag during weighing and improves the reliability of the weighing data.

[0133] Furthermore, the filling unit includes:

[0134] The front weighing device 304 is close to the loading device 302 and is used to weigh the sub-packaging bags 901 before filling.

[0135] The post-weighing device 310 is close to the sealing device 308 and is used to weigh the sub-packaging bags 901 after filling.

[0136] The filling assembly is placed between the front weighing device 304 and the rear weighing device 310, and includes a clamping device 314 for fixing the sub-packaging bag 901 during the filling process; and a filling needle holder 306, placed directly above the clamping device 314, for filling liquid into the sub-packaging bag 901.

[0137] In this embodiment, please refer to Figure 6 , the front weighing device 304 includes:

[0138] The supporting structure 3041 is fixed to the bottom of the second isolation system 301 .

[0139] A clamp fixing plate 3043 is provided on the top of the support structure 3041 , and a weighing sensor 3042 is provided on the clamp fixing plate 3043 .

[0140] It also includes an anti-shake support member 3044 connected to the clamp fixing plate 3043 to suppress the shaking of the packaging bag 901.

[0141] Specifically, the front weighing device 304 includes a support structure 3041, which is fixed to the bottom of the second isolation system 301. A clamp fixing plate 3043 is provided on the top of the support structure 3041, and a weighing sensor 3042 is provided on the clamp fixing plate 3043. An anti-shake support 3044 is also provided on the support structure 3041, which is connected to the clamp fixing plate 3043 and is used to suppress the shaking of the sub-packaging bag 901. Among them, the anti-shake support 3044 can adopt a spring damping structure or a pneumatic buffer device to reduce the swing of the suspended soft bag during the weighing process through mechanical limiting. As a preferred embodiment, the weighing sensor 3042 adopts a high-precision strain gauge sensor with a measuring range of 0-500g and a resolution of 0.01g. The clamping device 314 adopts a pneumatic clamp 3031, and the clamping surface is covered with a medical-grade silicone pad, which not only ensures that the clamping force is evenly distributed, but also avoids damage to the soft bag pipeline.

[0142] Please refer to Figure 3 and Figure 4 , the filling needle holder 306 includes multiple groups of independently controlled filling needles, each group of filling needles is equipped with a flow regulating valve, which can adjust the filling speed of each needle in real time according to the weighing feedback. In this embodiment, the second isolation system 301 also includes a pump tube assembly 309 and a tube insertion device 3011. The pump tube assembly 309 includes a pump tube connector 3091 and a clamp 3092. The filling needle holder 306 is connected to the original liquid bag 600 through the liquid outlet pipe 601. At the same time, the liquid outlet pipe 601 passes through the tube insertion device 3011. The tube insertion device 3011 and the liquid outlet pipe 601 are fixed by the pump tube connector 3091 and the clamp 3092. The tube insertion device 3011 can adopt a pneumatic or electric driven needle insertion mechanism, the diameter of the needle matches the inner diameter of the hose 9011 of the filling bag 901, and an anti-scratch coating can be provided on the surface of the needle. The tube insertion process uses a visual positioning system to ensure that the needle is aligned with the central axis of the hose 9011. As a preferred embodiment, the tube insertion device 3011 is equipped with a force feedback sensor, which automatically stops and alarms when the insertion resistance exceeds a threshold.

[0143] The optimized layout and anti-shake design of the weighing device effectively address three core issues in the soft bag filling process: First, the close proximity of the front weighing device 304 to the loading device 302 reduces the material transfer path and reduces the risk of soft bag entanglement during transfer. Second, the anti-shake support structure 3041 suppresses soft bag sway, meeting the precision requirements of high-value pharmaceuticals such as cell-based preparations. Finally, the coordinated operation of the filling needle holder 306 and the clamping device 314 ensures precise alignment of the filling needle with the thin flexible tube 9011. The clamping device 314 provides a fixed reference in the XY plane, while the filling needle holder 306 enables precise needle placement in the Z axis. This three-dimensional positioning system achieves an alignment accuracy of ±0.1mm between the filling needle and the flexible tube 9011 connector, significantly exceeding the ±2mm accuracy achieved by traditional manual alignment methods.

[0144] Furthermore, by integrating weighing into the filling process, full-process weight monitoring is achieved. The front weighing device 304 records the empty bag weight as a baseline value, while the rear weighing device 310 detects the weight after filling. The difference between the two is the actual filling volume. If the filling volume exceeds the preset tolerance range, the system immediately triggers an alarm and marks the product as defective. Compared with traditional sampling methods, this online real-time detection mechanism increases quality monitoring coverage from 5% to 100%, while also eliminating the risk of cross-contamination caused by post-process rejection.

[0145] Furthermore, a first working point A2 and a second working point B2 are respectively provided at both ends of the track 3032 of the reciprocating feeding device 303 , and the fixed plate 3033 reciprocates along the track 3032 between the first working point A2 and the second working point B2 .

[0146] When the fixed plate 3033 moves to the first working point A2, the clamping centers of the clamping jaw 3031, the loading clamping jaw 3021, the front weighing device 304, the clamping device 314, and the rear weighing device 310 are all located in the same vertical plane; when the fixed plate 3033 moves to the second working point B2, the clamping centers of the clamping jaw 3031, the front weighing device 304, the clamping device 314, the rear weighing device 310, and the sealing device 308 are all located in the same vertical plane.

[0147] Specifically, the setting of the first working point A2 and the second working point B2 allows the range of motion of the fixed plate 3033 on the track 3032 to be precisely defined, ensuring the transfer accuracy of the clamping jaws 3031 between different workstations. In this embodiment, a third working point A1 and a fourth working point B1 are also provided on the track 3032. The track 3032 between the first working point A2 and the third working point A1, and between the second working point B2 and the fourth working point B1 is a straight line segment. The straight line segment is perpendicular to the straight line formed by the first working point A2 and the second working point B2, so as to avoid interference with the bagging tube during the docking process of the clamping jaws. Among them, the implementation methods of all clamping centers being located in the same vertical plane include but are not limited to: calibrating the clamping center position of each workstation through laser positioning; using a servo motor to drive the fixed plate 3033 to move and cooperating with an encoder to achieve position closed-loop control; and providing mechanical limit devices at both ends of the track 3032 to ensure repeatable positioning accuracy. As a preferred embodiment, the clamping jaws 3031 are pneumatically driven and equipped with a force sensor to monitor the clamping force in real time when clamping the packaging bag 901 to avoid deformation or leakage due to overload.

[0148] By limiting the two endpoints of the reciprocating motion and their alignment with the key workstations, the positioning deviation problem of the soft bag caused by multiple transfers during the filling process is solved. Among them, the first working point A2 ensures the seamless connection between the loading and weighing stations, and the second working point B2 realizes the precise docking of the filling and sealing processes. Compared with the existing technology, this solution can achieve sub-millimeter repeatability without manual intervention. At the same time, the design in which the clamping centers are all located in the same vertical plane eliminates the cumulative error in the traditional multi-station transfer. Furthermore, the symmetrically distributed workstation layout minimizes the motion trajectory, and while ensuring accuracy, the single transfer time is controlled within 0.5 seconds, providing a basic guarantee for the efficient operation of the system.

[0149] Furthermore, the clamping jaw 3031 includes a first clamping arm 3031A and a second clamping arm 3031B, each clamping arm is provided with a protrusion 3031C, the center of the protrusion 3031C coincides with the rotation center of the corresponding clamping arm, and is used to position the hose 9011 of the packaging bag 901.

[0150] Specifically, the first clamping arm 3031A and the second clamping arm 3031B achieve opening and closing motion via a rotating shaft. The protrusion 3031C has a hemispherical structure, and its diameter matches the outer diameter of the hose 9011. The protrusion 3031C is adjacently connected to the curved surface 3031D that serves as the clamping mechanism. As a preferred embodiment, the surface of the protrusion 3031C can be provided with anti-slip grooves to enhance clamping stability. Furthermore, the design in which the center of rotation of the clamping arm coincides with the center of the protrusion 3031C prevents axial displacement of the hose 9011 during the clamping process. For example, the clamping jaws 3031 can be driven by a servo motor and combined with a position sensor to achieve precise opening and closing control.

[0151] The coaxially designed protrusion 3031C structure solves the technical problem of inaccurate positioning of the hose 9011. During the filling process, when the jaws 3031 are closed, the two protrusions 3031C form a precise positioning channel, ensuring that the hose 9011 is always directly below the filling needle. This avoids the problems of hose 9011 distortion or filling needle misalignment caused by the center offset of the traditional jaws 3031. Compared with existing technologies, this design achieves submillimeter positioning accuracy while maintaining a sterile environment, while reducing the complexity of the control system through mechanical self-centering. In specific implementation, the jaws 3031 can be made of medical-grade stainless steel, and the protrusions 3031C can be made of wear-resistant materials such as polyetheretherketone to extend service life.

[0152] In this embodiment, the filling unit is provided with 5 stations (i.e., a loading station, a front weighing station, a filling station, a rear weighing station and a sealing station), and the positions of these 5 stations correspond to the positions of the loading device 302, the front weighing device 304, the filling assembly, the rear weighing device 310 and the sealing device 308, respectively. The reciprocating feeding device 303 can simultaneously pick up and transport the sub-packaging bags 901 of the four stations in the same direction. Specifically, when the reciprocating feeding device 303 is transported backward, the sub-packaging bags 901 of the loading station are moved to the front weighing station, the sub-packaging bags 901 of the front weighing station are moved to the filling station, the sub-packaging bags 901 of the filling station are moved to the rear weighing station, and the sub-packaging bags 901 of the rear weighing station are moved to the sealing station. When the reciprocating feeding device 303 is moving forward, the sub-packaging bags 901 at the sealing station are moved to the rear weighing station, the sub-packaging bags 901 at the rear weighing station are moved to the filling station, the sub-packaging bags 901 at the filling station are moved to the front weighing station, and the sub-packaging bags 901 at the front weighing station are moved to the loading station. In other words, the sub-packaging bags 901 at the four stations can simultaneously move forward or backward one station to the station adjacent to the original station.

[0153] In other embodiments, the filling unit may be provided with more workstations, and the reciprocating feeding device 303 may be extended according to actual needs to simultaneously take and deliver the sub-packaging bags 901 of 5 or even more workstations.

[0154] Furthermore, the filling module 300 further includes:

[0155] The exhaust device 307 is used to exhaust gas after the filling of the sub-packaging bag 901 is completed.

[0156] The second conveying device 313 is placed at the bottom of the second isolation system 301 and below the sealing device 308 , and is used to receive the sealed packaging bags 901 released from the sealing device 308 and convey them to the discharge module 500 .

[0157] Furthermore, the exhaust device 307 includes a clamping mechanism and an exhaust needle for exhausting gas from the sub-packaging bag 901 after filling is completed, and the sealing device 308 includes a heating element and a pressing mechanism for heat-sealing the hose 9011 of the sub-packaging bag 901.

[0158] The specific implementation of the exhaust device 307 includes a clamping mechanism and an exhaust needle. The clamping mechanism can adopt a pneumatic clamp 3031 or an electromagnetic clamp to fix the hose 9011 part of the packaging bag 901. The exhaust needle adopts a blunt hollow needle structure with an inner diameter of 0.5-1.0mm, a material of 316L stainless steel, and an electrolytically polished surface. The exhaust process is achieved by negative pressure suction, and the suction pressure is controlled within the range of -0.02 to -0.05MPa. As a preferred embodiment, the exhaust needle is linked to the clamping mechanism, and automatically penetrates the hose 9011 to complete the exhaust when the clamping mechanism is closed.

[0159] The second conveying device 313 can be a belt conveyor or a roller conveyor line. The belt material is preferably food-grade polyurethane with a thickness of 2-3mm and an anti-slip pattern on the surface. The conveying speed is synchronized with the filling rhythm and is controlled at 0.1-0.3m / s. Specifically, guide baffles are set on both sides of the conveyor belt 2021. The baffle height is 20-30mm, and the spacing can be adjusted to accommodate different specifications of sub-packaging bags 901. Furthermore, a buffer baffle is set at the end of the conveyor belt 2021, which is made of silicone material to prevent impact when the sub-packaging bags 901 slip.

[0160] The addition of the exhaust device 307 effectively addresses the issue of residual gas in the bag after filling, which affects sealing quality. Precise control of the exhaust needle ensures gas expulsion while preventing liquid leakage. The second conveying device 313 enables automated transfer of sealed products, with a buffering structure designed to reduce the risk of product damage. Compared to manual transfer methods, this solution significantly improves conveying efficiency and product qualification rate. In practice, the coordinated operation of the exhaust device 307 and the sealing device 308 creates a closed-loop control loop for the entire filling and sealing process, enhancing system stability.

[0161] Furthermore, the filling module 300 also includes a floating bacteria sampler 311 and a particle detection device 312 disposed inside the second isolation system 301 for monitoring the internal environment of the second isolation system 301 .

[0162] The planktonic bacteria sampler 311 can adopt an active sampling method, using a built-in vacuum pump to extract the air in the isolation system at a preset flow rate, so that the microorganisms in the air collide with the surface of the culture dish. The culture dish can be loaded with a specific culture medium (such as TSA culture medium). After sampling is completed, the culture dish is removed for culture and colony counting. The sampling cycle can be set to 15 minutes, 30 minutes or continuous sampling mode according to process requirements. The sampling point is preferably set 30 cm above the filling station to reflect the microbial load in the key area.

[0163] The particle detection device 312 utilizes the principle of laser scattering to monitor the concentration of suspended particles ≥0.5μm and ≥5.0μm within the isolation system in real time. The detection probe is equipped with an isokinetic sampling head with a sampling flow rate of 28.3L / min, consistent with cleanroom testing standards. Detection data can be transmitted to the control system in real time via the MODBUS-RTU protocol. When the particle concentration exceeds the ISO Class 5 standard, an audible and visual alarm is triggered. The probe is preferably installed near the filling needle operating area, forming a spatial diagonal arrangement with the airborne bacteria sampler 311.

[0164] Specifically, the airborne bacteria sampler 311 and particle detector 312 are fixed to the top plate of the second isolation system 301 via brackets, with a spacing of at least 30 cm between them to prevent airflow interference. The sampler's air inlet is equipped with a backflow prevention device to prevent liquid splashing and contamination of the sensor. The control system includes a data storage unit that records historical monitoring data and generates trend curves. Furthermore, the sampler can be equipped with a wireless transmission module to enable remote monitoring and data download.

[0165] Real-time monitoring of microbial and particle levels in critical process areas enables prompt detection of isolator integrity failures or operational anomalies. When monitoring data exceeds preset thresholds, the system automatically pauses the filling process and prompts intervention, preventing the continued production of substandard product. Compared to traditional offline environmental monitoring, this solution enables continuous collection and dynamic response of process data, providing objective evidence for sterility assurance.

[0166] Furthermore, the discharging module 500 includes:

[0167] The discharge isolation system 501 has a side wall provided with a discharge isolation system connection port 5011 corresponding to the discharge end of the filling module 300 .

[0168] The first slope 502 extends from the discharge isolation system connection port 5011 to the inside of the discharge isolation system 501 . When the discharge end of the filling module 300 is opened, the first slope 502 is connected to the discharge end of the filling module 300 .

[0169] The second slope 503 is rotatably disposed at the end of the first slope 502 and is used to separate qualified products from unqualified products.

[0170] The third conveying device 504 is connected to the second slope 503 and is used to output qualified products that slide down the second slope 503.

[0171] In this embodiment, the discharge isolation system connection port 5011 adopts a flange sealing structure to form an airtight connection with the material sorting module 200, wherein the flange connection surface is provided with a silicone sealing ring. The inclination angle of the first slope 502 is 15°-25°, and the surface is covered with a polytetrafluoroethylene coating to reduce the friction coefficient. The second slope 503 is driven to rotate by a servo motor, and the rotation angle range is 0°-90°, where 0° corresponds to the qualified product channel and 90° corresponds to the unqualified product collection box. The third conveying device 504 adopts a belt conveying method, the belt material is food-grade polyurethane, and the conveying speed can be adjusted in the range of 0.1-0.5m / s.

[0172] The discharging module 500 realizes the automatic sorting function of the filled products through a mechanical structure. When the sealed sub-packaging bag 901 enters the discharging module 500 through the second conveying device 313, it first slides along the first slope 502 to the second slope 503. At this time, the qualified status of the product is judged according to the weighing data, and the second slope 503 is controlled to rotate to the corresponding angle. Qualified products slide along the 0° direction to the third conveying device 504 for output, and unqualified products fall into a special collection container along the 90° direction. This design solves the problems of low efficiency and easy contamination of traditional manual sorting, and at the same time maintains a sterile environment in the discharging area through the isolation system structure. Compared with the existing technology, this solution realizes closed-loop control of filling-weighing-sorting, with a sorting accuracy rate of more than 99.9%, and no human intervention is required in the entire process.

[0173] Furthermore, it also includes:

[0174] The feeding module 100 is used to remove the outer packaging of the sub-packaging bag 901 and deliver the sub-packaging bag 901 to the material sorting module 200 in a sterile manner.

[0175] The low-temperature mixing module 400 is used to keep the liquid in the stock liquid bag 600 cold and prevent precipitation. The output pipeline of the stock liquid bag 600 is connected to the filling pump 305 in the filling module 300 through the pump tube assembly 309.

[0176] The cell counting device 1000 is connected to the stock solution bag 600 via the cell counting tube set 1001 and is used to monitor the cell density in the stock solution bag 600 in real time.

[0177] Furthermore, the feeding module 100 , the low-temperature mixing module 400 and the cell counting device 1000 are all connected to the control module, and the control module simultaneously controls the working states of the feeding module 100 , the low-temperature mixing module 400 and the cell counting device 1000 .

[0178] Specifically, the control module includes a controller 700 and a data recording module 800. The controller 700 connects various modules and controls the mechanism actions and process logic of the filling system; the data recording module 800 is connected to the controller 700 and is used to store weighing data and operation logs.

[0179] Specifically, the feeding module 100 includes a feeding isolation system 101, and a feeding door 1011 is provided on the side wall of the feeding isolation system 101. The feeding module 100 can take out the sub-packaging bag 901 in the packaging bag 902 and aseptically transfer the sub-packaging bag 901 to the material sorting area. The low-temperature mixing module 400 prevents cell precipitation in the stock liquid bag 600 by continuous stirring, thereby ensuring the uniformity of the stock liquid. The cell counting device 1000 monitors the cell density in the stock liquid in real time to ensure product quality. The controller 700 serves as the core of the system to coordinate the operation of each module and execute process logic. The data recording module 800 stores the weighing data and operation log of the entire process to achieve complete data traceability. These modules together constitute a comprehensive automated aseptic filling system that can efficiently handle the entire process from raw material mixing, aseptic filling to data recording, and is particularly suitable for the precise filling of biological drugs such as cell preparations with extremely high quality requirements.

[0180] Example 2

[0181] This embodiment provides a bag-type aseptic filling method, which is applied to the bag-type aseptic filling device described above, and includes the following steps:

[0182] S1. Automatically calibrate the filling module 300 to determine the actual average flow rate.

[0183] S2. Arrange and cut the packaging bags 901 so that they are arranged at a fixed interval and cut the hoses 9011 of the packaging bags 901 into the same length.

[0184] S3. Weighing and filling the cut packaging bags 901 in sequence.

[0185] S4, venting and heat-sealing the filled sub-packaging bags 901.

[0186] S5. Determine whether the packaging bags 901 are qualified based on the weighing data, and separate qualified products from unqualified products.

[0187] Specifically, the filling module 300 is first calibrated to determine the actual average flow rate to ensure filling accuracy. Multiple filling operations can be performed during the calibration process to determine the actual average flow rate. The sub-packaging bags 901 are then arranged in order and the hose 9011 is cut to a uniform length in preparation for subsequent filling. The processed sub-packaging bags 901 are then weighed and filled in sequence to achieve accurate measurement. The filled sub-packaging bags 901 are then vented and heat-sealed to ensure product sealing. Finally, the sub-packaging bags 901 are automatically judged based on the weighing data to determine whether they meet the quality standards, and qualified products are separated from unqualified products to achieve full-process automated quality control. The entire method constitutes a complete set of bag-type aseptic filling process flow, which solves the shortcomings of traditional filling technology in terms of precision control, efficiency and degree of automation.

[0188] In this embodiment, the actual average flow rate is determined through two filling operations, and step S1 includes:

[0189] Determine the target filling volume V, liquid density ρ, filling pump 305 speed N, and theoretical flow rate Q.

[0190] Weighing the packaging bag (901) before filling to obtain an empty weight Wm0;

[0191] Filling λ×V of liquid according to the theoretical flow rate Q, where λ is a coefficient greater than 0 and less than 1;

[0192] Weigh the filled sub-packaging bag (901) to obtain the total weight Wm1 after the first filling, and calculate the net weight of the liquid after the first filling Wj1=Wm1-Wm0;

[0193] After conversion, the actual flow rate is Q1 = (Q × Wj1) / (ρ × λ × V);

[0194] Continue filling (V-Wj1 / ρ) of liquid according to the actual flow rate Q1;

[0195] Weigh the sub-packaging bag (901) after filling to obtain the total weight Wm2 after the second filling, and calculate the net weight of the liquid after the second filling Wj2=Wm2-Wm1;

[0196] After conversion, the actual average flow rate is Q2 = (Q1×Wj2) / (ρV-Wj1).

[0197] Specifically, the method first determines the basic parameters (target filling volume, liquid density, pump speed and theoretical flow rate), and then obtains the empty weight of the sub-packaging bag 901 by precise weighing. Subsequently, in the first stage of filling, the system only fills a part of the target volume (λ×V, preferably, λ is a coefficient of 30%-70%), and calculates the deviation between the actual flow rate and the theoretical flow rate by weighing. In the second stage of filling, the system accurately replenishes the remaining liquid volume based on the actual flow correction value calculated in the first stage, and finally completes the target filling volume. Before the first filling, set the corresponding filling time t1 = (λ×V) / Q, and before the second filling, set the corresponding filling time t2 = (V-Wj1 / ρ) / Q1, or the total angle that the pump needs to rotate: round = V / q1*360°. Which one to use is usually a trade-off between the filling error caused by the motor's controllable positioning accuracy and the pump start-stop response time accuracy. The pump start-stop response time or minimum control time is: tmin, and the minimum control value of the pump rotation angle is: round_min. The entire process involves two precise weighing and flow calibration steps, ensuring high filling accuracy while avoiding the waste of liquid medicine caused by traditional multiple test fillings. This method is particularly suitable for the precise packaging of high-value biopharmaceuticals such as cell-based preparations. This method not only improves filling accuracy but also conserves precious liquid medicine resources.

[0198] In another possible embodiment, the actual average flow rate is determined through three filling operations, and step S1 includes:

[0199] Determine the target filling volume V, liquid density ρ, filling pump speed N, and theoretical flow rate Q;

[0200] Weighing the packaging bag (901) before filling to obtain an empty weight Wm0;

[0201] Filling λ×V of liquid according to the theoretical flow rate Q, where λ is a coefficient greater than 0 and less than 1; setting the corresponding filling time t1 = (λ×V) / Q;

[0202] Weigh the filled sub-packaging bag (901) to obtain the total weight Wm1 after the first filling, and calculate the net weight of the liquid after the first filling Wj1=Wm1-Wm0;

[0203] After conversion, the actual flow rate is Q1 = (Q × Wj1) / (ρ × λ × V);

[0204] Continue filling λ×(V-Wj1 / ρ) of liquid according to the actual flow rate Q1;

[0205] Weigh the sub-packaging bag (901) after filling to obtain the total weight Wm2 after the second filling, and calculate the net weight of the second filling liquid Wj2=Wm2-Wm1; set the corresponding filling time t2=(λ×(V-Wj1 / ρ)) / Q1;

[0206] After conversion, the actual average flow rate is Q2 = (Q1 × Wj2) / ((ρV-Wj1) × λ);

[0207] Continue filling V-(Wj1+Wj2) / ρ of liquid according to the actual flow rate Q1;

[0208] The filling bag (901) is weighed to obtain the weight Wm3 after the third filling, and the net weight of the third filling liquid Wj3=Wm3-Wm2 is calculated; and the corresponding filling time t3=(V-(Wj2-Wj1) / ρ) / Q2 is set.

[0209] After conversion, the actual average flow rate is Q3 = Q2 × Wj3 / (ρV-Wm3+Wm0).

[0210] It should be noted that in other embodiments, the actual average flow rate can be determined through more filling operations. However, the actual average flow rate after more filling operations is not much different from the actual average flow rate after three filling operations. That is, the calibration phase uses more filling operations, and the calibration results are almost the same, but the calibration time is longer.

[0211] Furthermore, the coefficient λ ranges from 30% to 70%.

[0212] Specifically, the coefficient λ represents the ratio of the first filling volume to the target filling volume. As a preferred embodiment, λ can be set to 40%, 50% or 60%. In actual operation, the first filling volume should not be too large or too small: if λ is too high (such as exceeding 70%), the remaining filling volume after the first filling may be too small, affecting the accuracy of subsequent flow calibration; if λ is too low (such as below 30%), the first filling volume is too small, which may lead to a large error in the actual flow conversion. Therefore, controlling λ within the range of 30% to 70% can take into account both calibration accuracy and operational efficiency.

[0213] By limiting the range of the initial fill ratio, the existing technology addresses the significant waste of liquid medicine during the calibration process. In existing technologies, calibration typically requires multiple refills, resulting in the waste of multiple refill units. By optimizing the initial fill ratio, liquid medicine loss during the calibration process can be significantly reduced while maintaining calibration accuracy. For example, when λ is 50%, calibration can be completed with only two fills, avoiding the waste caused by multiple fills in traditional methods. Furthermore, this ratio range ensures the stability of flow calibration, preventing the accumulation of errors in subsequent fills caused by an unreasonable initial fill volume.

[0214] Furthermore, the step S2 includes:

[0215] The first conveying device 202 in the material sorting module 200 is controlled to run intermittently at a preset beat, so that the packaging bags 901 are arranged at a fixed interval.

[0216] The cutting device 204 is controlled to cut the hose 9011 on the packaging bag 901 at a preset rhythm.

[0217] The loading device 302 is controlled to grab the cut packaging bags 901 and change the posture for transmission.

[0218] Specifically, the preset beat intermittent operation means that the conveyor belt 2021 is driven by a servo motor to start and stop at set time intervals, wherein the intermittent time is synchronized with the station switching cycle of the filling module 300. The implementation method of fixed spacing arrangement includes but is not limited to: using a photoelectric sensor to detect the position of the sub-packaging bag 901 and then triggering the conveyor belt 2021 to stop; using a mechanical baffle to limit the adjacent sub-packaging bags 901 to maintain a distance of 50-100mm. In the step of cutting the hose 9011, the cutting device 204 preferably uses pneumatic scissors, the blade spacing of which is adjustable to adapt to different pipe diameters, and the cutting accuracy is controlled within the range of ±1mm. The posture change of the feeding device 302 includes two actions: horizontal grasping and vertical flipping, which are specifically achieved by a rotating cylinder in conjunction with a vacuum suction cup, wherein the suction cup is made of silicone to avoid damaging the bag body.

[0219] By precisely controlling the arrangement spacing of the sub-packaging bags 901 and the length of the hose 9011, the problem of filling needle docking failure caused by bag position deviation in the traditional filling process is solved. Compared with the continuous conveying method, the intermittent operation mode can ensure the accurate positioning of each sub-packaging bag 901 at the filling station. The equal-length cutting of the hose 9011 ensures that the insertion depth of subsequent filling needles remains consistent, avoiding filling volume deviations caused by differences in tube length. The posture change during the loading process causes the sub-packaging bags 901 to be converted from a horizontal conveying state to a vertical filling state. This conversion method significantly improves positioning accuracy and production efficiency compared to manual operation. Through the implementation of this solution, the docking success rate of the filling system has been increased from 85% of the original technology to more than 99%, while the processing time of a single bag has been shortened by 30%.

[0220] Furthermore, step S3 includes:

[0221] The reciprocating feeding device 303 delivers the sub-packaging bags 901 to the front weighing device 304 at a preset rhythm.

[0222] The pre-weighing device 304 weighs the sub-packaging bags 901 before filling.

[0223] The reciprocating feeding device 303 transfers the sub-packaging bag 901 to the filling assembly.

[0224] The filling component fills the sub-packaging bag 901.

[0225] The reciprocating feeding device 303 transfers the sub-packaging bags 901 to the post-weighing device 310 .

[0226] The post-weighing device 310 weighs the filled sub-packaging bags 901 and calculates the net weight of the filling.

[0227] Specifically, the sub-packaging bags 901 are first sent to the front weighing device 304 for pre-filling weighing, i.e., empty weight weighing, and then transferred to the filling assembly for accurate filling. Finally, they are sent to the rear weighing device 310 for filling weight measurement and net weight calculation. This design with separated workstations and coherent processes solves the problem of balancing weighing accuracy and filling efficiency in traditional filling systems. In particular, through the independent front and rear weighing devices 310, the system can monitor the actual filling volume of each sub-packaging bag 901 in real time to ensure the consistency of product quality. This design not only improves production efficiency, but also provides an accurate data basis for subsequent quality control and rejection of defective products.

[0228] Furthermore, the step S4 includes:

[0229] The reciprocating feeding device 303 transfers the sub-packaging bags 901 to the exhaust device 307 .

[0230] The exhaust device 307 exhausts the filling bag 901 after filling.

[0231] The reciprocating feeding device 303 transfers the sub-packaging bag 901 to the sealing device 308 .

[0232] The sealing device 308 seals the hose 9011 of the packaging bag 901 .

[0233] The clamping jaws 3031 of the sealing device 308 are released in sequence, so that the packaging bags 901 fall into the second conveying device 313 .

[0234] At this stage, the reciprocating feeding device 303 accurately transfers the filled and weighed sub-packaging bags 901 to the exhaust device 307. The exhaust device 307 can effectively remove excess gas in the sub-packaging bags 901 to ensure the stability of the product during subsequent storage and transportation. Subsequently, the sub-packaging bags 901 are transferred to the sealing device 308, where the hose 901 is heat-sealed to achieve complete sealing and prevent contamination and leakage. At the same time, a loosening mechanism design is adopted, and the clamping jaws 3031 of the sealing device 308 are loosened in a specific order, so that the sealed sub-packaging bags 901 fall smoothly into the second conveying device 313, avoiding the risk of product damage caused by improper blanking in traditional systems.

[0235] Furthermore, the step S5 includes:

[0236] The second conveying device 313 conveys the sealed packaging bags 901 to the discharge module 500 .

[0237] Whether the sub-packaging bag 901 is qualified is determined based on the net filling weight.

[0238] The second slope 503 is rotated to separate qualified products and unqualified products along different paths.

[0239] Specifically, the sealed sub-packaging bags 901 are smoothly conveyed to the discharge module 500 via the second conveyor device 313. At this stage, the system automatically determines whether each sub-packaging bag 901 meets the preset quality standards based on the previously accurately measured net filling weight data. Regarding the rotatable second ramp 503, the system can precisely control the rotation angle of the second ramp 503 based on the quality determination results, separating qualified and unqualified products along different paths. This automated sorting mechanism not only improves production efficiency and avoids the errors and contamination risks of manual sorting, but also enables full quality traceability for each product.

[0240] Furthermore, it also includes:

[0241] During the weighing before filling, if no signal of the sub-packaging bag 901 is detected, the station is marked as NULL.

[0242] During filling, if the sub-packaging bag 901 is not detected or the weighing mark before the last beat is NULL, the workstation is marked as NULL.

[0243] When weighing the filling, if the filling mark of the previous cycle is NULL, mark the workstation as NULL.

[0244] During heat sealing, the heat sealing operation will not be performed on the workstations whose weighing mark is NULL after the previous cycle.

[0245] Specifically, the NULL marking mechanism detects the absence of the sub-packaging bag 901 through photoelectric sensors or weight threshold judgments, and triggers the NULL mark when the detection value of the weighing station is continuously lower than the preset threshold. The NULL judgment logic of the filling station adopts double verification: the physical existence of the sub-packaging bag 901 is detected by an infrared sensor, and the status register of the preceding station is read at the same time. The execution control module of the heat sealing station decides whether to start the heating program by querying the data mark register of the subsequent weighing station, where the register update delay is controlled within 10ms. As a preferred embodiment, the NULL mark is stored in a ring buffer using binary encoding, and each station corresponds to an independent status storage unit, which is read and written in real time by the PLC through the Modbus protocol.

[0246] By establishing a status transmission mechanism between workstations, automatic isolation of abnormal workstations is achieved. When a packing bag 901 is missing or the transmission fails at a certain workstation, the subsequent process can automatically skip the invalid operation to avoid energy waste and equipment loss caused by no-load operation. Compared with existing technologies, it solves the problem of traditional assembly lines shutting down due to single-point failures. At the same time, through the step-by-step transmission of status marks, it ensures that unqualified products will not be mishandled, thereby improving system reliability and product consistency. Specifically, the NULL marking mechanism enables the system to handle anomalies locally without interrupting the overall process, which is of great significance for maintaining the continuous stability of the aseptic filling environment.

[0247] Furthermore, it also includes:

[0248] The microbial indicators inside the second isolation system 301 are monitored by the floating bacteria sampler 311 .

[0249] The air cleanliness inside the second isolation system 301 is monitored by the particle detection device 312 .

[0250] The cell density in the liquid delivered to the filling assembly is monitored by a cell counting device 1000.

[0251] First, the microbial indicators inside the isolation system are monitored in real time through the planktonic bacteria sampler 311 to ensure that the filling environment meets the strict aseptic requirements. Secondly, the particle detection device 312 is equipped to continuously monitor the air cleanliness in the isolation system to ensure that the air quality always meets the Class A clean area standards. Most importantly, the system innovatively introduces a cell counting device 1000, which can monitor the cell density in the liquid delivered to the filling component in real time, solving the key problem of heterogeneity caused by cell sedimentation in traditional filling systems. This triple monitoring mechanism forms a complete quality monitoring network, which not only meets the strict GMP requirements for the production environment of sterile preparations, but also ensures that the cell density in each sub-bag 901 meets the expected standards. Compared with traditional filling systems, this real-time monitoring design greatly improves the consistency and reliability between product batches, and provides a strong technical guarantee for the safe production of high-value biological products such as cell preparations.

[0252] Furthermore, it also includes:

[0253] The data recording module 800 records the empty weight, filled weight, net weight, heat sealing parameters and qualified status of each packaging bag 901.

[0254] Record the operating parameters of the filling system, including pump speed, flow rate and temperature; and record the internal environmental parameters of the isolation system, including pressure differential, microbiological indicators and air cleanliness.

[0255] First, a comprehensive record is made of each product unit, including the empty weight, filling weight, net weight, heat sealing parameters and final qualified status of the sub-packaging bag 901, to achieve accurate traceability at the product level; second, the system continuously monitors and records the key operating parameters of the filling equipment, such as pump speed, flow rate and temperature and other process parameters to ensure the consistency and stability of the production process; third, the environmental parameters inside the isolation system are recorded in real time, including pressure difference, microbial indicators and air cleanliness, to ensure that the production environment always meets strict sterility requirements. This multi-dimensional and comprehensive data recording mechanism not only meets the GMP compliance requirements for production process records, but also provides a reliable data basis for product quality analysis, process optimization and problem troubleshooting. Compared with traditional filling systems, the data recording system of the present invention greatly enhances the controllability and traceability of the production process.

[0256] The above examples are used to illustrate the present invention, which are only used to help understand the present invention and are not intended to limit the present invention. Those skilled in the art can make several simple deductions, modifications or substitutions based on the concept of the present invention.

Claims

1. A bag-type aseptic filling system, characterized in that: include: A control module and a material handling module (200), a filling module (300) and a discharging module (500) connected in sequence; The material sorting module (200) is used to arrange the packaging bags (901) in an orderly manner at relatively fixed intervals; The filling module (300) is in communication with the discharge end of the material sorting module (200) and is used for filling, detecting the filling amount and sealing the sub-packaging bags (901); The discharging module (500) is connected to the discharging end of the filling module (300) and outputs qualified products and unqualified products of the sub-packaging bags according to the filling amount detection result; The material sorting module (200), the filling module (300) and the discharging module (500) are all connected to the control module, and the control module is used to control the working states of the material sorting module (200), the filling module (300) and the discharging module (500); The working process of the bag-type aseptic filling system includes a filling calibration stage and a filling operation stage; During the filling calibration phase, the control module obtains an actual average flow rate based on the filling volume detection result of the filling module (300), and automatically calibrates the filling module (300) based on the actual average flow rate; during the filling operation phase, the control module determines whether the corresponding sub-packaging bag (901) is qualified based on the filling volume detection result of the filling module (300).

2. The bag-type aseptic filling system according to claim 1, characterized in that: The material sorting module (200) comprises a first isolation system (201), wherein the first isolation system (201) comprises: A first conveying device (202), placed inside the first isolation system (201), comprises a conveyor belt (2021) and a positioning block (2022), wherein the positioning block (2022) is fixed on the conveyor belt (2021); a cutting device (204), placed above the conveyor belt (2021), for cutting the hoses (9011) of the packaging bags (901) on each of the positioning blocks (2022) to the same length; The sub-packaging bags (901) enter the first isolation system (201), are transported by the first conveying device (202) to the cutting device (204) for cutting, and are then transported to the filling module (300) after cutting.

3. The bag-type aseptic filling system according to claim 1, characterized in that: The filling module (300) comprises a second isolation system (301), wherein the feed end of the second isolation system (301) is connected to the discharge end of the material handling module (200), and the second isolation system (301) comprises: a reciprocating feeding device (303), disposed in the second isolation system (301), comprising a fixed plate (3033), a plurality of clamping jaws (3031) equidistantly arranged on the fixed plate (3033), and a track (3032) for limiting the movement of the fixed plate (3033); A filling unit is placed on a side of the reciprocating feeding device (303) close to the clamping claw (3031) and is used to weigh and fill the sub-packaging bag (901); A loading device (302) is placed at the front end of the filling unit in the transport direction, and comprises a loading clamp (3021) and a mechanical arm (3022) for grabbing and changing the posture of the sub-packaging bag (901); The sealing device (308) is placed at the rear end of the filling unit in the transport direction and is used to seal the filled sub-packaging bags (901).

4. The bag-type aseptic filling system according to claim 3, characterized in that: The filling unit comprises: A front weighing device (304), located near the loading device (302), is used to weigh the sub-packaging bags (901) before filling; a post-weighing device (310), located near the sealing device (308), for weighing the filling bag (901) after filling; The filling assembly is placed between the front weighing device (304) and the rear weighing device (310), and includes a clamping device (314) and a filling needle holder (306). The clamping device (314) fixes the sub-packaging bag (901) during the filling process, and the filling needle holder (306) is arranged directly above the clamping device (314) and is used to fill liquid into the sub-packaging bag (901).

5. The bag-type aseptic filling system according to claim 4, characterized in that: A first working point (A2) and a second working point (B2) are respectively provided at both ends of the track (3032) of the reciprocating feeding device (303), and the fixed plate (3033) reciprocates along the track (3032) between the first working point (A2) and the second working point (B2); When the fixed plate (3033) moves to the first working point (A2), the clamping centers of the clamping jaw (3031), the feeding clamping jaw (3021), the front weighing device (304), the clamping device (314), and the rear weighing device (310) are all located in the same vertical plane; When the fixing plate (3033) moves to the second working point (B2), the clamping centers of the clamping jaws (3031) and the front weighing device (304), the clamping device (314), the rear weighing device (310), and the sealing device (308) are all located in the same vertical plane.

6. The bag-type aseptic filling system according to claim 3, characterized in that: The filling module (300) further comprises: An exhaust device (307) is used to exhaust the internal gas after the filling of the packaging bag (901) is completed; The second conveying device (313) is placed in the second isolation system (301) and is located below the sealing device (308), and is used to receive the sealed packaging bags (901) released from the sealing device (308) and convey them to the discharge module (500).

7. The bag-type aseptic filling system according to claim 1, characterized in that: The discharging module (500) comprises: A discharge isolation system (501), wherein a side wall of the discharge isolation system (501) is provided with a discharge isolation system connection port (5011) corresponding to the discharge end of the filling module (300); a first slope (502) extending from the discharge isolation system connection port (5011) to the interior of the discharge isolation system (501), and when the discharge end of the filling module (300) is opened, the first slope (502) is connected to the discharge end of the filling module (300); a second slope (503) rotatably disposed at the end of the first slope (502) for separating qualified products from unqualified products; The third conveying device (504) is connected to the second slope (503) and is used to output qualified products that slide down from the second slope (503).

8. The bag-type aseptic filling system according to claim 1, characterized in that: Also includes: A feeding module (100) is used to remove the outer packaging of the sub-packaging bag (901) and deliver the sub-packaging bag (901) to the material sorting module (200) in a sterile manner; A low-temperature mixing module (400) is used to keep the liquid in the stock liquid bag (600) cold and prevent precipitation. The output pipeline of the stock liquid bag (600) is connected to the filling pump (305) in the filling module (300) through a pump tube assembly (309); A cell counting device (1000) is connected to the stock solution bag (600) via a cell counting tube set (1001) and is used to monitor the cell density in the stock solution bag (600) in real time; The control module comprises a controller (700) and a data recording module (800). The controller (700) connects the modules and controls the mechanism actions and process logic of the filling system. The data recording module (800) is connected to the controller (700) and is used to store weighing data and operation logs.

9. A bag-type aseptic filling method, applied to the bag-type aseptic filling device according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1, automatically calibrating the filling module (300) to determine the actual average flow rate; S2, arranging and cutting the packaging bags (901) so that they are arranged at a fixed interval and cutting the hoses (9011) of the packaging bags (901) to the same length; S3, weighing and filling the cut packaging bags (901) in sequence; S4, venting and heat-sealing the filled packaging bag (901); S5. Judging whether the packaging bags (901) are qualified according to the weighing data, and separating qualified products from unqualified products.

10. The bag-type aseptic filling method according to claim 9, characterized in that: The step S1 comprises: Determine the target filling volume V, liquid density ρ, filling pump speed N, and theoretical flow rate Q; Weighing the packaging bag (901) before filling to obtain an empty weight Wm0; Filling λ×V of liquid according to the theoretical flow rate Q, where λ is a coefficient greater than 0 and less than 1; Weigh the filled sub-packaging bag (901) to obtain the total weight Wm1 after the first filling, and calculate the net weight of the liquid after the first filling Wj1=Wm1-Wm0; After conversion, the actual flow rate is Q1 = (Q × Wj1) / (ρ × λ × V); Continue filling (V-Wj1 / ρ) of liquid according to the actual flow rate Q1; Weigh the sub-packaging bag (901) after filling to obtain the total weight Wm2 after the second filling, and calculate the net weight of the liquid after the second filling Wj2=Wm2-Wm1; After conversion, the actual average flow rate is Q2 = (Q1×Wj2) / (ρV-Wj1).

11. The bag-type aseptic filling method according to claim 9, characterized in that: The step S1 comprises: Determine the target filling volume V, liquid density ρ, filling pump speed N, and theoretical flow rate Q; Weighing the packaging bag (901) before filling to obtain an empty weight Wm0; Filling λ×V of liquid according to the theoretical flow rate Q, where λ is a coefficient greater than 0 and less than 1; Weigh the filled sub-packaging bag (901) to obtain the total weight Wm1 after the first filling, and calculate the net weight of the liquid after the first filling Wj1=Wm1-Wm0; After conversion, the actual flow rate is Q1 = (Q × Wj1) / (ρ × λ × V); Continue filling λ×(V-Wj1 / ρ) of liquid according to the actual flow rate Q1; Weigh the sub-packaging bag (901) after filling to obtain the total weight Wm2 after the second filling, and calculate the net weight of the second filling liquid Wj2=Wm2-Wm1; After conversion, the actual average flow rate is Q2 = (Q1 × Wj2) / ((ρV-Wj1) × λ); Continue filling V-(Wj1+Wj2) / ρ of liquid according to the actual flow rate Q1; Weigh the filling bag (901) to obtain the weight Wm3 after the third filling, and calculate the net weight of the third filling liquid Wj3 = Wm3 - Wm2; After conversion, the actual average flow rate is Q3 = Q2 × Wj3 / (ρV-Wm3+Wm0).

12. The bag-type aseptic filling method according to claim 9, characterized in that: The step S2 comprises: Controlling the first conveying device (202) in the material handling module (200) to operate intermittently at a preset beat, so that the packaging bags (901) are arranged at a fixed interval; Controlling the cutting device (204) to cut the hose (9011) on the packaging bag (901) at a preset rhythm; The loading device (302) is controlled to grab the cut packaging bags (901) and change the posture for transmission.

13. The bag-type aseptic filling method according to claim 9, characterized in that: The step S3 comprises: The reciprocating feeding device (303) delivers the sub-packaging bags (901) to the front weighing device (304) at a preset rhythm; The front weighing device (304) weighs the packaging bag (901) before filling; The reciprocating feeding device (303) transfers the sub-packaging bag (901) to the filling assembly; The filling component fills the sub-packaging bag (901); The reciprocating feeding device (303) transfers the sub-packaging bag (901) to the post-weighing device (310); The post-weighing device (310) weighs the filled sub-packaging bag (901) and calculates the filled net weight.

14. The bag-type aseptic filling method according to claim 9, characterized in that: The step S4 comprises: The reciprocating feeding device (303) transfers the sub-packaging bag (901) to the exhaust device (307); The exhaust device (307) exhausts the filling bag (901) after filling; The reciprocating feeding device (303) transfers the packaging bag (901) to the sealing device (308); The sealing device (308) seals the hose (9011) of the packaging bag (901); The clamping jaws of the sealing device (308) are released in sequence, allowing the packaging bags (901) to fall into the second conveying device (313).

15. The bag-type aseptic filling method according to claim 9, characterized in that: The step S5 comprises: The second conveying device (313) conveys the sealed packaging bag (901) to the discharge module (500); Judging whether the sub-packaging bag (901) is qualified according to the filled net weight; The second slope (503) is rotated to separate qualified products and unqualified products along different paths.

16. The bag-type aseptic filling method according to claim 9, characterized in that: Also includes: When weighing before filling, if no signal of the sub-packaging bag (901) is detected, the station is marked as NULL; During filling, if the sub-packaging bag (901) is not detected or the weighing mark before the previous beat is NU LL, the station is marked as NULL; When weighing filling, if the filling mark of the previous beat is NULL, mark the station as NULL; as well as During heat sealing, the heat sealing operation will not be performed on the workstations whose weighing mark is NULL after the previous cycle.

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