CN217449661U

CN217449661U - Continuous virus removal filtering equipment for drug virus safety evaluation verification

Info

Publication number: CN217449661U
Application number: CN202123431235.0U
Authority: CN
Inventors: 殷文静; 陆海燕; 薛亚芬; 张骑峰; 王小瑜; 蔡央
Original assignee: Liangchen Bio (suzhou) Corp
Current assignee: Liangchen Bio (suzhou) Corp
Priority date: 2021-12-30
Filing date: 2021-12-30
Publication date: 2022-09-20
Anticipated expiration: 2031-12-30

Abstract

The utility model relates to a remove virus filtration equipment in succession for medicine virus security appraisal is verified, it is including being linked together in proper order and being used for holding the material fluid reservoir of antibody sample, being used for filtering the filter assembly of antibody sample, being used for mixing the mixed subassembly of antibody sample and virus and being used for removing the virus subassembly that removes of virus, remove virus filtration equipment still include with mixed subassembly be linked together and can throw the material subassembly to the virus that lets in the virus in the mixed subassembly. The utility model discloses a filtering component and remove and connect the hybrid module between the viral subassembly, make instruction virus and antibody sample pass through hybrid module automatic mixing to improve the accuracy of medicine virus security evaluation verification experiment, made its continuous process in with the actual production keep unanimous.

Description

Continuous virus removal filtering equipment for drug virus safety evaluation verification

Technical Field

The utility model relates to the field of biotechnology, concretely relates to remove virus filtration equipment in succession for medicine virus security appraisal is verified.

Background

Along with the increasing of biological products prepared by expressing animal-derived tissues, cells, body fluids and recombinant eukaryotic cells, the used population is continuously expanded, and the problems of the risk of the animal-derived viruses infecting human beings, potential iatrogenic infection and the like are increasingly prominent. According to the requirements of drug registration management method, virus inactivation process verification data is required to be added to products extracted from tissues or body fluids of human and animals, animal-derived monoclonal antibodies and recombinant products expressed by eukaryotic cells. The virus inactivation/removal verification research should adopt a method of simulating a production process, and a virus inactivation/removal verification research scheme related to and reasonable to an actual production process should be designed as much as possible. The virus inactivation process comprises a low pH method, an S/D method, a nanofiltration method, a resin column adsorption method, a pasteurization method and the like. Among monoclonal antibody production processes, low pH and nanofiltration are the most common and effective virus inactivation/removal processes.

Nano-membrane filtration (NF) (nano-filtration for short) using nano-scale surface pore size (10) ^-9 m) a nanofiltration membrane, and the technical process of separating and purifying the component system by taking pressure difference or concentration difference as driving force has the characteristics of simple operation, short production period, good separation effect, strong pressure resistance and the like. In the actual production process of the antibody medicine, the antibody medicine is pretreated and then is directly subjected to nanofiltration treatment, and in the virus removal verification process of the antibody medicine, a sample enters a pressure tank, is collected by a prefiltration membrane and then needs to be added with an indicator virus, and then is added into the pressure tank again, and the sample is collected after a virus removal membrane is removed, so that subsequent detection is carried out. This step cannot be kept consistent with a continuous process in actual production. In particular, in the case where the filtration performance of the antibody sample itself is already poor, it is addedThe virus is easier to aggregate with the antibody in the operation process, and greatly interferes with the simulation experiment, so that the verification fails, and the virus safety evaluation in the clinical application stage of the antibody type biological medicine is hindered.

Disclosure of Invention

The utility model aims at providing a remove virus filtration equipment in succession that is used for medicine virus security evaluation to verify.

In order to achieve the above purpose, the utility model adopts the technical scheme that:

the continuous virus removing and filtering device comprises a liquid tank, a filtering component, a mixing component and a virus removing component, wherein the liquid tank is communicated in sequence and is used for containing an antibody sample, the filtering component is used for filtering the antibody sample, the mixing component is used for mixing the antibody sample and virus, the virus removing component is used for removing virus, and the virus removing and filtering device further comprises a virus feeding component which is communicated with the mixing component and can feed the virus into the mixing component.

Preferably, the mixing assembly comprises a sleeve and a mixing tube arranged in the sleeve, the mixing tube has a hollow structure and is in a spiral shape, and the mixing tube is respectively communicated with the filtering assembly and the virus removing assembly.

Preferably, the virus removing and filtering device further comprises a first connecting piece, the first connecting piece comprises a first interface, a second interface and a third interface which are mutually communicated, the first interface is connected with the filtering component, the second interface is connected with the mixing component, the third interface is connected with the virus feeding component, and the filtering component, the mixing component and the virus feeding component are respectively communicated through the first connecting piece.

Preferably, the virus feeding assembly comprises a first injector capable of being used for injecting the virus, a first pipeline for communicating the first injector with the mixing assembly, a second injector for sampling the mixed sample, and a second pipeline for communicating the second injector with the mixing assembly.

Further preferably, the first pipe and the second pipe are flexible pipes.

Still further preferably, the first pipe and the second pipe are silicone hoses.

Preferably, the virus feeding assembly further comprises a syringe pump which is respectively connected with the first syringe and the second syringe and can provide pushing force for the first syringe and pumping force for the second syringe.

Further preferably, the virus feeding assembly further comprises a third pipeline for communicating the first injector and the injection pump, and a fourth pipeline for communicating the second injector and the injection pump.

Still further preferably, the third pipe and the fourth pipe are flexible pipes.

Still further preferably, the third pipe and the fourth pipe are silica gel pipes.

Preferably, the virus removing and filtering device further comprises a second connecting piece, the second connecting piece comprises a fourth interface, a fifth interface and a sixth interface which are communicated with each other, the fourth interface is connected with the mixing component, the fifth interface is connected with the virus removing component, the sixth interface is communicated with the second pipeline, and the mixing component, the virus removing component and the second injector are respectively communicated through the second connecting piece.

Preferably, the filtration assembly comprises a first membrane filter and a second membrane filter in communication with each other.

More preferably, the first membrane filter has a membrane pore size of 0.1 to 0.45 μm.

Still more preferably, the second membrane filter has a membrane pore size of 0.1 to 0.45 μm.

Preferably, the virus removal assembly comprises a virus removal membrane filter.

Because of the application of the technical scheme, compared with the prior art, the utility model has the following advantages:

the utility model discloses a filtering component and remove and connect the hybrid module between the viral subassembly, make instruction virus and antibody sample pass through hybrid module automatic mixing to improve the accuracy of medicine virus security evaluation verification experiment, made its continuous process in with the actual production keep unanimous.

Drawings

Fig. 1 is a schematic partial sectional structure diagram of a continuous virus-removing filtering apparatus for evaluating and verifying the safety of drug viruses in an embodiment of the present invention;

FIG. 2 is an enlarged view of portion A of FIG. 1;

FIG. 3 is an enlarged view of portion B of FIG. 1;

FIG. 4 is an enlarged view of the portion C in FIG. 1;

in the above drawings: 1. a feed liquid tank; 21. a first membrane filter; 22. a second membrane filter; 23. a first valve; 24. a second valve; 31. a mixing tube; 32. a sleeve; 41. a virus removal membrane filter; 42. a third connecting member; 43. a third valve; 51. a first syringe; 52. a first conduit; 53. a second syringe; 54. a second conduit; 55. an injection pump; 56. a third pipeline; 57. a fourth conduit; 6. a first connecting member; 61. a first interface; 62. a second interface; 63. a third interface; 7. a second connecting member; 71. a fourth interface; 72. a fifth interface; 73. a sixth interface; 8. a container.

Detailed Description

The invention will be further described with reference to examples of embodiments shown in the drawings.

In the following, only certain exemplary embodiments are briefly described. As those skilled in the art will recognize, the described embodiments may be modified in various different ways, all without departing from the spirit or scope of the embodiments of the present invention. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

In the description of the present application, it is to be understood that the terms "up", "down", and the like indicate an orientation or positional relationship based on the orientation or positional relationship shown in fig. 1, for example, the liquid tank 1 is located at the "up" position, and the container 8 is located at the "down" position.

In the description of the embodiments of the present invention, it should be understood that the terms "first", "second" and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implying any indication of the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the embodiments of the present invention, "a plurality" means two or more unless specifically limited otherwise.

In the embodiments of the present invention, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "fixed" are to be construed broadly, e.g., as fixed or detachable connections or as an integral part; the connection can be mechanical connection, electrical connection or communication; either directly or indirectly through intervening media, either internally or in any other relationship. The specific meaning of the above terms in the embodiments of the present invention can be understood by those of ordinary skill in the art according to specific situations.

In embodiments of the invention, unless expressly stated or limited otherwise, the first feature "on" or "under" the second feature may comprise direct contact between the first and second features, or may comprise contact between the first and second features through another feature not in direct contact. Also, the first feature being "on," "above" and "over" the second feature includes the first feature being directly on and obliquely above the second feature, or merely indicating that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature includes the first feature being directly above and obliquely above the second feature, or simply meaning that the first feature is at a lesser level than the second feature.

The following disclosure provides many different embodiments or examples for implementing different configurations of embodiments of the invention. In order to simplify the disclosure of embodiments of the present invention, the components and arrangements of specific examples are described below. Of course, they are merely examples and are not intended to limit embodiments of the present invention. Furthermore, embodiments of the present invention may repeat reference numerals and/or reference letters in the various examples for purposes of simplicity and clarity and do not in themselves dictate a relationship between the various embodiments and/or arrangements discussed.

As shown in fig. 1, the virus removing and filtering device comprises a feed liquid tank 1, a filtering component, a mixing component and a virus component, wherein the feed liquid tank 1, the filtering component, the mixing component and the virus component are communicated in sequence. In this embodiment, the liquid tank 1, the filtering component, the mixing component and the virus component are sequentially arranged from top to bottom.

The virus filtering equipment also comprises a virus feeding component which is communicated with the mixing component and is used for introducing viruses into the mixing component. The virus dosing assembly comprises a first injector 51, a second injector 53, a first conduit 52, a second conduit 54, a third conduit 56, a fourth conduit 57, and a syringe pump 55. The injection pump 55 is connected with the first injector 51 through a third pipeline 56 to provide injection driving force for the first injector 51, the injection end of the first injector 51 is communicated with the inlet of the mixing assembly through the first pipeline 52, the first injector 51 contains viruses, the first injector 51 can inject the viruses into the mixing pipeline 31 under the driving of the injection pump 55, and the flow rate of the introduced viruses can be controlled by the injection pump 55. The syringe pump 55 is connected to the second syringe 53 via a fourth conduit 57, and the injection end of the second syringe 53 communicates with the outlet of the mixing assembly via a second conduit 54. The second injector 53 can suck the feed liquid at the outlet of the mixing component under the control of the injection pump 55, so as to detect the titer of the virus in the feed liquid before virus removal and filtration, and the pumping amount and the pumping speed of the second injection pump 55 can be controlled by the injection pump 55.

The first, second, third and

fourth conduits

52, 54, 56 and 57 are flexible conduits. Flexible tubing includes tubing that can be folded and bent, such as silicone tubing, rubber tubing, and the like. In this embodiment, the first tube 52, the second tube 54, the third tube 56 and the fourth tube 57 are silicone tubes.

The first injector 51 and the second injector 53 are commercially available injectors, and include a cylinder and a plunger core rod matching the cylinder.

The syringe pump 55 is a commercially available small flow syringe pump 55.

As shown in fig. 3 and 4, the virus filtration apparatus further comprises a first connector 6 and a second connector 7. The first connector 6 comprises a first connector 61, a second connector 62 and a third connector 63 which are communicated with each other, the first connector 61 is connected with an outlet of the filtering assembly, the second connector 62 is connected with an inlet of the mixing assembly, the third connector 63 is connected with the first pipeline 52, and the filtering assembly, the mixing assembly and the first injector 51 are respectively communicated through the first connector 6. The second connector 7 comprises a fourth port 71, a fifth port 72 and a sixth port 73 which are communicated with each other, the fourth port 71 is connected with the outlet of the mixing assembly, the fifth port 72 is connected with the inlet of the virus removing membrane, the sixth port 73 is connected with the second pipeline 54, and the mixing assembly, the second injector 53 and the virus removing assembly are respectively communicated through the second connector 7.

As shown in fig. 2, the mixing assembly includes a sleeve 32 and a mixing tube 31 disposed in the sleeve 32, the mixing tube 31 has a hollow structure and is spiral, and the mixing tube 31 is respectively communicated with the filtering assembly and the virus removing assembly. The spiral-shaped mixing tube 31 improves the uniformity of mixing of the antibody sample with the virus.

The feed liquid tank 1 is used for containing an antibody sample, the upper end of the feed liquid tank 1 is connected with a gas cylinder, and gas is introduced into the feed liquid tank 1 through the gas cylinder, so that feed liquid flows into the filter assembly from the bottom of the feed liquid tank 1. The gas may be air or an inert gas.

The filtering assembly comprises a second valve 24, a first membrane filter 21, a second membrane filter 22 and a first valve 23 which are connected in sequence. Both the first valve 23 and the second valve 24 can be opened or closed, and the opening degrees of the first valve 23 and the second valve 24 can be adjusted. The first membrane filter 21 has a membrane pore size of 0.1 to 0.45 μm or more and the second membrane filter 22 has a membrane pore size of 0.1 to 0.45 μm or less. The second membrane filter 22 has a membrane pore size of 0.1 to 0.45. mu.m, for example, 0.22 μm or 0.45. mu.m.

The virus assembly comprises a virus removal membrane filter 41, a third connection 42 and a third valve 43. The third connector 42 comprises a seventh port, an eighth port and a ninth port, the seventh port is communicated with the sixth port 73 through a pipeline, the eighth port is communicated with the container 8, and the ninth port is communicated with the inlet of the virus-removing membrane filter 41. A third valve 43 is connected to the outlet of the viral membrane filter 41, the third valve 43 can be opened or closed, and the opening degree of the third valve 43 can be adjusted.

The above embodiments are only for illustrating the technical concept and features of the present invention, and the purpose of the embodiments is to enable people skilled in the art to understand the contents of the present invention and to implement the present invention, which cannot limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered by the protection scope of the present invention.

Claims

1. A continuous virus removal filtering device for drug virus safety evaluation verification is characterized in that: the virus removing and filtering device comprises a liquid tank (1) which is communicated in sequence and is used for containing an antibody sample, a filtering component used for filtering the antibody sample, a mixing component used for mixing the antibody sample and virus, and a virus removing component used for removing virus, and the virus removing and filtering device also comprises a virus feeding component which is communicated with the mixing component and can introduce the virus into the mixing component.

2. The continuous virus removal filter device for verification of drug virus safety assessment according to claim 1, characterized in that: the mixing assembly comprises a sleeve (32) and a mixing pipe (31) arranged in the sleeve (32), the mixing pipe (31) is of a hollow structure and is in a spiral shape, and the mixing pipe (31) is communicated with the filtering assembly and the virus removing assembly respectively.

3. The continuous virus removal filter apparatus for drug and virus safety assessment validation of claim 1, wherein: the virus removing and filtering equipment further comprises a first connecting piece (6), the first connecting piece (6) comprises a first interface (61), a second interface (62) and a third interface (63) which are communicated with each other, the first interface (61) is connected with the filtering component, the second interface (62) is connected with the mixing component, the third interface (63) is connected with the virus feeding component, and the filtering component, the mixing component and the virus feeding component are communicated with each other through the first connecting piece (6).

4. The continuous virus removal filter device for verification of drug virus safety assessment according to claim 1, characterized in that: the virus feeding assembly comprises a first injector (51) capable of being used for injecting the virus, a first pipeline (52) used for communicating the first injector (51) with the mixing assembly, a second injector (53) used for sampling the mixed sample, and a second pipeline (54) used for communicating the second injector (53) with the mixing assembly.

5. The continuous virus removal filter device for verification of drug virus safety assessment according to claim 4, wherein: the first conduit (52) and the second conduit (54) are flexible conduits.

6. The continuous virus removal filter device for verification of drug virus safety assessment according to claim 4, wherein: the virus feeding assembly further comprises an injection pump (55) which is respectively connected with the first injector (51) and the second injector (53) and can provide pushing force for the first injector (51) and pumping force for the second injector (53).

7. The continuous virus removal filter device for verification of drug virus safety assessment according to claim 4, wherein: the virus removing and filtering device further comprises a second connecting piece (7), the second connecting piece (7) comprises a fourth interface (71), a fifth interface (72) and a sixth interface (73) which are communicated with each other, the fourth interface (71) is connected with the mixing assembly, the fifth interface (72) is connected with the virus removing assembly, the sixth interface (73) is communicated with the second pipeline (54), and the mixing assembly, the virus removing assembly and the second injector (53) are communicated with each other through the second connecting piece (7) respectively.

8. The continuous virus removal filter device for verification of drug virus safety assessment according to claim 1, characterized in that: the filtration assembly comprises a first membrane filter (21) and a second membrane filter (22) in communication with each other.

9. The continuous virus removal filter device for verification of drug virus safety assessment according to claim 8, wherein: the first membrane filter (21) has a membrane pore size of 0.1 to 0.45 [ mu ] m, and/or the second membrane filter (22) has a membrane pore size of 0.1 to 0.45 [ mu ] m.

10. The continuous virus removal filter device for verification of drug virus safety assessment according to claim 1, characterized in that: the virus removal assembly comprises a virus removal membrane filter (41).