CN117529446A - Carrier liquid sterile split charging system and application thereof - Google Patents
Carrier liquid sterile split charging system and application thereof Download PDFInfo
- Publication number
- CN117529446A CN117529446A CN202380012308.5A CN202380012308A CN117529446A CN 117529446 A CN117529446 A CN 117529446A CN 202380012308 A CN202380012308 A CN 202380012308A CN 117529446 A CN117529446 A CN 117529446A
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- Prior art keywords
- sterile
- carrier liquid
- filling
- isolator
- assembly
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- 239000007788 liquid Substances 0.000 title claims abstract description 63
- 238000011049 filling Methods 0.000 claims abstract description 55
- 238000004806 packaging method and process Methods 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 13
- 239000012530 fluid Substances 0.000 claims description 15
- 230000002572 peristaltic effect Effects 0.000 claims description 15
- 238000003860 storage Methods 0.000 claims description 14
- 238000012546 transfer Methods 0.000 claims description 14
- 239000013598 vector Substances 0.000 claims description 10
- 230000001954 sterilising effect Effects 0.000 claims description 9
- 238000012806 monitoring device Methods 0.000 claims description 7
- 238000004659 sterilization and disinfection Methods 0.000 claims description 7
- 238000011144 upstream manufacturing Methods 0.000 claims description 7
- 241000700605 Viruses Species 0.000 claims description 6
- 239000013603 viral vector Substances 0.000 claims description 6
- 210000001124 body fluid Anatomy 0.000 claims description 3
- 239000010839 body fluid Substances 0.000 claims description 3
- 238000003466 welding Methods 0.000 claims description 3
- 239000013600 plasmid vector Substances 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 239000013589 supplement Substances 0.000 claims 1
- 241000701161 unidentified adenovirus Species 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 13
- 238000009455 aseptic packaging Methods 0.000 abstract description 3
- 230000036512 infertility Effects 0.000 abstract 1
- 230000002068 genetic effect Effects 0.000 description 5
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 210000004507 artificial chromosome Anatomy 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000009963 fulling Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 241001524679 Escherichia virus M13 Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012859 sterile filling Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B67—OPENING, CLOSING OR CLEANING BOTTLES, JARS OR SIMILAR CONTAINERS; LIQUID HANDLING
- B67C—CLEANING, FILLING WITH LIQUIDS OR SEMILIQUIDS, OR EMPTYING, OF BOTTLES, JARS, CANS, CASKS, BARRELS, OR SIMILAR CONTAINERS, NOT OTHERWISE PROVIDED FOR; FUNNELS
- B67C7/00—Concurrent cleaning, filling, and closing of bottles; Processes or devices for at least two of these operations
Landscapes
- Basic Packing Technique (AREA)
Abstract
A carrier liquid sterile packaging system and a method for performing sterile packaging by using the same. The carrier liquid sterile packaging system comprises a disposable filling unit and a sterile isolator. The aseptic packaging method has the advantages of simple operation, high production efficiency, difficult pollution, sterility, guarantee, accurate sample adding and quantitative, effective increase of production efficiency, product quality guarantee and the like.
Description
Technical Field
The application belongs to the field of aseptic packaging, and in particular relates to a carrier liquid aseptic packaging system and application thereof.
Background
After the production of the biological product, the biological product is affected by objective environments such as light, temperature, air, moisture, microorganisms and the like, and gradually deteriorates. The prepared biological product is reasonably subpackaged and packaged, so that the influence of various external factors on the product quality can be prevented.
The production of virus carrier liquid has the characteristics of small production batch, low storage temperature, high requirement on packaging containers and the like, so that the packaging and capping treatment is also required after the product is obtained. At present, a traditional manual split charging mode is generally adopted, the used package is usually manual, and the traditional manual split charging mode has certain defects: the operation is complex, the pollution is easy, and the production speed is slower; the product loading is not accurate enough, and errors of missing and repeated split charging are easy to occur; the sealability is greatly affected by individual operation differences.
Although improvements based on conventional methods have been described in the prior art, CN110745761a, for example, discloses a sterile isolator provided with an electric dispenser and an electric cap-screwing device. However, when using the separator for packaging the product, the container containing the product needs to be sterilized together with all packaging tools, the sterilization time is long, and the quality of the product is affected by the gas.
Detailed Description
While the present application will hereinafter disclose various aspects and embodiments, it will be apparent to those skilled in the art that various equivalent changes and modifications can be made therein without departing from the spirit and scope of the subject matter of the present application. The various aspects and embodiments disclosed herein are for illustration only and are not intended to limit the application, the actual scope of which is subject to the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. All references, patents, patent applications cited in this application are incorporated herein by reference in their entirety.
Definition of the definition
The english language of the term "rapid transfer interface" or "rapid transfer port" used in this application is generally called Rapid Transfer Port, abbreviated RTP, which is a two-gate transmission system consisting of two main components, an alpha valve (flag) and a beta assembly (or beta valve). Wherein the alpha valve is typically mounted on a side wall of a closed environment and the beta assembly is movable and connected to a container, bag or process assembly.
The term "beta bag" as used in this application is sterile and is primarily used to transport sterile filling needles located therein to the filling unit of a sterile isolator for filling during the filling process without contamination.
The term "Sartorius sterile rapid transfer system" as used herein, which is commonly known as Sartorius aseptic rapid transfer system in english and simply referred to as SART system, is a type of rapid transfer interface (RTP) that allows the isolator to remain intact and to perform a sterile transfer of a liquid (e.g., a carrier fluid). In some embodiments, the SART system is comprised of an external interface, an internal interface, and a disposable connection device.
The term "peristaltic pump" as used in this application is composed of a drive, a pump head and a hose that pumps fluid by alternately squeezing and releasing the flexible delivery hose of the pump.
The term "vector" in this application refers to a vehicle into which a genetic element can be operatively inserted and which allows the genetic element to be expressed, for example, in the production of a protein, RNA or DNA encoded by the genetic element, or in the replication of the genetic element. Vectors may be used to transform, transduce or transfect host cells such that the genetic elements carried thereby are expressed within the host cells. For example, the carrier comprises: plasmids, phagemids, cosmids (cosmid), artificial chromosomes such as Yeast Artificial Chromosome (YAC), bacterial Artificial Chromosome (BAC) or P1-derived artificial chromosome (PAC), phages such as lambda phage or M13 phage, animal viruses, and the like. In certain embodiments of the present application, the vector is a viral vector, such as a lentiviral vector (LVV) or an adenoviral vector (AVV). In certain embodiments, the vector is a plasmid vector.
Aseptic sub-packaging system for carrier liquid
In one aspect, the present application provides a carrier liquid sterile packaging system comprising a disposable filling unit and a sterile isolator connected by a rapid transfer interface (Rapid Transfer Port, RTP).
Disposable filling unit
The disposable filling unit is sequentially provided with a liquid storage device (1), a buffer device (2) and a beta bag (3), and is connected in series through a pipeline; the end (43) of the pipeline is provided with a filling needle (5), the end pipeline (43) and the filling needle (5) are nested in the beta bag (3), and the beta bag (3) is in a fully-closed state; the beta bag (3) has attached thereto a beta assembly (31) of the RTP, the line end (43) entering the sterile isolator through RTP when filling is performed.
In certain embodiments, a reservoir (1), a buffer (2), and a beta pocket (3) described herein are connected in series by a pipeline. Liquid enters the liquid storage device (1) through the sample injection pipeline (41), the liquid storage device (1) is connected with the buffer device (2) in series through the connecting pipeline (42), and the liquid of the buffer device (2) flows out through the tail end pipeline (43). Wherein the sample introduction pipe (41), the connecting pipe (42) and the end pipe (43) are respectively provided with a pipe clamp to control the opening/closing of the pipes.
The reservoir means in this application may be in a form conventional in the art, such as a reservoir bag, a reservoir tank or a tank. In certain embodiments, the fluid storage device is a fluid storage bag.
In certain embodiments, the buffer device is provided with a liquid level control system (12). The liquid level control system can effectively maintain the liquid level in the buffer unit and improve the filling precision. The liquid level control system described herein may be a liquid level control system conventional in the art, such as a commercially available liquid level controller, an infinite liquid level control system, or the like. In some embodiments, the liquid level control system automatically controls (e.g., controls a peristaltic pump) the liquid replenishment by giving a signal to the weighing of the buffer device, so as to ensure that the liquid level in the buffer device is maintained at a constant value, and reduce manual liquid replenishment operations for personnel.
The cushioning means in this application may be of conventional form in the art, such as a cushioning bag, a cushioning tank or a cushioning box, for adjusting the filling pressure to avoid affecting the filling accuracy. In certain embodiments, the cushioning device is a cushioning bag.
In the present application, the connection (44) between the end and the beta bag is welded, glued or otherwise sealed to achieve the fully closed state. In certain embodiments, the ends are joined to the junction of the beta pocket by welding.
In certain embodiments, the beta pocket is a sterile beta pocket, e.g., a disposable sterile beta pocket.
In certain embodiments, the beta bag (3) has a beta component of the RTP attached, such as beta valve (31), and the tubing end (43) enters the sterile isolator through the RTP consisting of beta valve (31) when filling.
In certain embodiments, the reservoir and the buffer are connected by a sterile connector (45).
In some embodiments, a first peristaltic pump (131) is further provided in the disposable filling unit, the first peristaltic pump (131) being located downstream of the reservoir means and upstream of the buffer means in the connection sequence.
In some embodiments, the disposable filling unit is further provided with a pipeline bubble monitoring device (14), wherein the pipeline bubble monitoring device is positioned downstream of the liquid storage device and upstream of the buffer device according to the connection sequence; when a peristaltic pump is arranged in the disposable filling unit, the pipeline bubble monitoring device is positioned at the downstream of the peristaltic pump.
In certain embodiments, the RTP is a Sartorius sterile rapid transfer (Sartorius aseptic rapid transfer, SART) system.
Sterile isolator
In certain embodiments, the sterile isolator is provided with an alpha valve of the RTP, a filling assembly, a plugging assembly and a capping assembly;
the alpha valve (6) is located on the inner wall of the sterile isolator.
The filling assembly in the present application may be a conventional filling assembly in the art. In certain embodiments, the filling assembly is an automatic filling device (7).
The stoppering assembly described in this application may be a conventional stoppering assembly in the art. In certain embodiments, the tucking assembly is an automatic tucking attachment (8).
The roll cover assembly described herein may be a conventional roll cover assembly in the art. In certain embodiments, the capping assembly is an automatic capping device (9).
In some embodiments, a conveyor belt is further arranged below the filling assembly, the plugging assembly and the capping assembly in the sterile isolator for conveying sub-packaging bottles (11) which are not filled or are filled with carrier liquid.
In certain embodiments, a second peristaltic pump (132) is also provided upstream of the filling needle when filling is performed.
The split-charging bottles in the present application may be split-charging bottles conventional in the art. In certain embodiments, the split-fill bottle is a sterile split-fill bottle.
Method for aseptic split loading of body fluids
In another aspect, the present application provides a method of aseptic loading of body fluids comprising dispensing using the carrier fluid aseptic dispensing system described herein.
In certain embodiments, the method comprises the steps of:
1) Sterilizing the aseptic isolator;
2) Introducing virus carrier liquid into the sterile isolator through an RTP interface by a disposable filling unit;
3) The carrier liquid entering the aseptic isolator is split-packed into split-packed bottles through a filling assembly;
4) Plugging the split charging bottle by using a plugging assembly;
5) The split charging bottle is capped using a roll capping assembly.
In certain embodiments, the sterilization in step 1) is VHP sterilization.
In certain embodiments, step 2) comprises pouring the viral vector fluid into the reservoir and connecting the sterile connector (45).
In certain embodiments, step 2) comprises communicating an alpha valve (6) of the RTP with a beta valve (31).
In certain embodiments, said step 3) comprises monitoring the liquid level in the buffer device (2). In certain embodiments, the first peristaltic pump (131) is controlled by a fluid level control system.
In certain embodiments, the filled sub-bottles (11) are filled using an automatic filling device (7).
In certain embodiments, the automated stoppering device (8) is used to stopple the partial-filled bottles (11) containing the carrier fluid;
in certain embodiments, the capped sub-filled bottles (11) are capped using an automatic capping device (9).
In certain embodiments, the method comprises transporting the split-bottles (11) from the automatic filling device (7) to the automatic plugging device (8) and the automatic capping device (9) in sequence by a conveyor belt.
Use the aseptic partial shipment system of carrier liquid of this application to pass through the RTP interface and let in aseptic isolator after use automatic partial shipment equipment to carry out aseptic partial shipment with virus carrier liquid partial shipment to the partial shipment container in, use the stopper equipment to add the stopper one by one to the partial shipment container, roll and cover equipment and to cover the partial shipment bottle one by one, the whole process all goes on in aseptic environment, easy operation, production efficiency is high, difficult pollution, aseptic has guarantee, and the application of sample ration is accurate, effectively increase production efficiency, guarantee product quality. The RTP interface is arranged, the product is imported from the interface, articles in the isolator can be sterilized in advance, the preparation time before product split charging is reduced, real-time split charging can be realized, the storage time of virus vectors at room temperature is reduced, and the quality of the product is effectively ensured.
In addition, the liquid storage device and the buffer device are arranged outside the sterile isolator, and the container filled with the product does not need to be subjected to VHP sterilization together with all the split charging tools, so that the production preparation time can be saved, and the buffer device is prevented from adsorbing H in the isolator 2 O 2 Thereby affecting the quality of the product.
Drawings
Fig. 1 is a schematic view of a disposable filling unit.
Fig. 2 is a schematic view of a sterile isolator.
FIG. 3 is a schematic diagram of a carrier fluid aseptic dispensing system.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
Example 1: sterile split charging system for constructing carrier liquid
The carrier liquid sterile packaging system consists of a disposable filling unit and a sterile isolator.
(1) Disposable filling unit
According to the connection sequence or the step of mass production, a liquid storage bag (1), a first peristaltic pump (131), a pipeline bubble monitoring device (14), a buffer bag (2) and a sterile beta bag (3) are sequentially arranged along a pipeline (see fig. 1 and 3).
Wherein, the buffer bag is provided with a liquid level control system (12) to maintain the liquid level in the buffer bag at a required level, thereby ensuring the filling precision. The beta bag (3) is sleeved outside the tail end pipeline (43) and the filling needle (5), and the part (44) where the bag body is contacted with the tail end of the pipeline is connected in a welding mode so as to ensure that the beta bag is in a fully-closed state; a beta valve (31) of a rapid transfer interface (RTP) is attached to the beta bag.
(2) Sterile isolator
The method comprises the steps of production according to a connection sequence or scale, wherein an alpha valve (6) (positioned on the inner wall of an isolator), an automatic filling device (7), an automatic plugging device (8) and an automatic capping device (9) of a quick transmission interface are sequentially arranged. A conveyor belt (10) is also provided directly below the means for filling, plugging and capping for conveying the partial bottles (11) that have not yet been filled or that have been filled with carrier liquid (see fig. 2).
Example 2: sub-packaging was performed using the carrier liquid sterile sub-packaging system constructed in example 1
Step 1: performing VHP sterilization treatment on the sterile isolator under the condition that the production auxiliary tool is in place;
step 2: introducing carrier liquid into the sterile isolator through an RTP interface (15) by a disposable filling unit;
the end of the tubing in the disposable filling unit enters the sterile isolator through RTP (15) and optionally a peristaltic pump (132) is mounted on the tubing (43) upstream of the filling needle (5);
step 3: the carrier liquid entering the aseptic isolator is split-packed into aseptic split-packed bottles (11) through an automatic filling device (7);
step 4: the automatic plugging device (8) is used for plugging the split charging bottle (11) filled with the carrier liquid;
step 5: and (3) capping the plugged split charging bottles (11) by using an automatic capping device (9).
Claims (20)
1. The carrier liquid sterile packaging system is characterized by comprising a disposable filling unit and a sterile isolator, wherein the disposable filling unit and the sterile isolator are connected through a rapid transfer interface (RTP);
the disposable filling unit is sequentially provided with a liquid storage device, a buffer device and a beta bag, and is connected in series through a pipeline; the tail end of the pipeline is provided with a filling needle, the tail end is nested in the beta bag, and the beta bag is in a fully-closed state; the beta bag has the beta component of the RTP attached and the tubing end enters the sterile isolator through RTP when filling.
2. The carrier liquid sterile packaging system as claimed in claim 1, wherein a liquid level control system is provided on the buffer device; the liquid level control system preferably controls the liquid supplement by weighing the buffer device to give a signal.
3. The carrier fluid aseptic dispensing system of claim 1 or 2, wherein the terminal ends are connected to the beta bag by welding.
4. The carrier liquid sterile packaging system according to any one of the preceding claims, wherein the beta bag is a sterile beta bag, such as a disposable sterile beta bag.
5. The carrier liquid sterile dispensing system of any one of the preceding claims, wherein the reservoir means and the buffer means are connected by a sterile connector.
6. A carrier liquid sterile packaging system according to any one of the preceding claims, further comprising a peristaltic pump in the disposable filling unit, said peristaltic pump being located downstream of the reservoir means and upstream of the buffer means in connection order.
7. The carrier liquid sterile packaging system according to any one of the preceding claims, further comprising a line bubble monitoring device in the disposable filling unit, said line bubble monitoring device being located downstream of the liquid storage device and upstream of the buffer device in connection order;
when a peristaltic pump is arranged in the disposable filling unit, the pipeline bubble monitoring device is positioned at the downstream of the peristaltic pump.
8. The carrier fluid sterile dispensing system of any one of the preceding claims, wherein the RTP is a Sartorius sterile rapid transfer (SART) system.
9. A carrier liquid sterile dispensing system according to any one of the preceding claims wherein the liquid storage means is in the form of a liquid storage bag or tank.
10. A carrier liquid sterile dispensing system according to any one of the preceding claims wherein the buffer means is in the form of a buffer bag or a buffer bin.
11. The carrier liquid sterile packaging system according to any one of the preceding claims, wherein the sterile isolator is provided with an alpha valve of the RTP, a filling assembly, a plugging assembly and a capping assembly;
the alpha valve is located on an inner wall of the sterile isolator.
12. The carrier fluid aseptic dispensing system of claim 11, wherein the filling assembly is an automatic filling device;
and/or, the plugging component is an automatic plugging device;
and/or, the capping assembly is an automatic capping device.
13. The carrier fluid aseptic dispensing system of claim 11 or 12, wherein a conveyor belt is disposed in the aseptic isolator below the filling assembly, the capping assembly, and the capping assembly for conveying the dispensing bottles that have not been filled or that have been filled with carrier fluid.
14. The carrier liquid sterile dispensing system according to any one of claims 11-13, wherein a peristaltic pump is provided upstream of the filling needle when filling is performed.
15. The carrier liquid sterile packaging system as claimed in claim 13 or 14, wherein the packaging bottles are sterile packaging bottles.
16. The sterile packaging system for a viral vector solution according to any one of the preceding claims, wherein the vector is a viral vector or a plasmid vector.
17. The sterile packaging system for a viral vector solution according to claim 16, wherein the viral vector is an adenovirus vector or a lentiviral vector.
18. A method of aseptic loading of body fluids comprising dispensing using the carrier fluid aseptic dispensing system of any one of claims 1-17.
19. The method of claim 18, wherein the method comprises the steps of:
1) Sterilizing the aseptic isolator;
2) Introducing virus carrier liquid into the sterile isolator through an RTP interface by a disposable filling unit;
3) The carrier liquid entering the aseptic isolator is split-packed into split-packed bottles through a filling assembly;
4) Plugging the split charging bottle by using a plugging assembly;
5) The split charging bottle is capped by using a capping assembly.
20. The method of claim 19, wherein the sterilization in step 1) is VHP sterilization.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210858404 | 2022-07-20 | ||
CN2022108584049 | 2022-07-20 | ||
PCT/CN2023/108342 WO2024017323A1 (en) | 2022-07-20 | 2023-07-20 | Vector liquid aseptic dispensing system and application thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117529446A true CN117529446A (en) | 2024-02-06 |
Family
ID=89617180
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN202380012308.5A Pending CN117529446A (en) | 2022-07-20 | 2023-07-20 | Carrier liquid sterile split charging system and application thereof |
Country Status (2)
Country | Link |
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CN (1) | CN117529446A (en) |
WO (1) | WO2024017323A1 (en) |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN204660323U (en) * | 2015-05-15 | 2015-09-23 | 奥星衡迅生命科技(上海)有限公司 | Disposable sterilized liquid shifts airtight bag |
CN207391404U (en) * | 2017-10-23 | 2018-05-22 | 刘嘉臻 | The sterile quantitative liquid sub-packaging system of portable type |
CN210000912U (en) * | 2019-04-04 | 2020-01-31 | 颇尔奥星包装科技(北京)有限责任公司 | Disposable aseptic liquid filling bag |
EP3972789B1 (en) * | 2019-08-26 | 2024-05-22 | EMD Millipore Corporation | Fluid transfer system for isolators |
CN210437438U (en) * | 2019-09-06 | 2020-05-01 | 科济生物医药(上海)有限公司 | A partial shipment device for cell suspension |
CN110745761A (en) * | 2019-11-06 | 2020-02-04 | 无锡生基医药科技有限公司 | Aseptic subpackaging method and subpackaging system for lentiviral vector liquid |
CN211393828U (en) * | 2019-11-06 | 2020-09-01 | 无锡生基医药科技有限公司 | Aseptic partial shipment system of lentiviral vector |
CN211766446U (en) * | 2019-12-19 | 2020-10-27 | 珠海西格膜生物技术有限公司 | Disposable sterile liquid storage split charging device |
AU2021217829A1 (en) * | 2020-02-06 | 2022-08-18 | Cutiss Ag | Cell isolation device and method |
DE102020124826A1 (en) * | 2020-09-23 | 2022-03-24 | Syntegon Technology Gmbh | Beta component of a transfer system for a sterile isolation area, sterile isolation area, aseptic filling system and a method for operating such a filling system |
CN215798398U (en) * | 2021-08-26 | 2022-02-11 | 青岛科创质量检测有限公司 | Sterile filling system suitable for microorganism choosing method |
CN216916386U (en) * | 2022-01-28 | 2022-07-08 | 上海优替济生生物医药有限公司 | Whole aseptic filling system |
-
2023
- 2023-07-20 WO PCT/CN2023/108342 patent/WO2024017323A1/en active Application Filing
- 2023-07-20 CN CN202380012308.5A patent/CN117529446A/en active Pending
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WO2024017323A1 (en) | 2024-01-25 |
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