Special ultrafiltration device for biological medicine manufacturing

Abstract

The invention relates to the technical field of biological pharmacy, in particular to a special ultrafiltration device for biological medicine manufacturing, which comprises a biological medicine material storage tank, a first pressure pipeline, a first pressure pump, a first feed pipe, an ultrafilter cleaning liquid pipeline, a first ultrafilter, an ultrafilter waste liquid transmission pipeline, a second feed pipe, a waste liquid storage tank and a third feed pipe, the system comprises a first ultrafilter, a second ultrafilter, a fourth feeding pipe, a third ultrafilter, a biological medicine collection tank, a storage tank, a second medicine buffer tank, a first medicine buffer tank, a first transmission pipeline, a second transmission pipeline, a second pressure pipeline, a second pressure pump, a third pressure pump, a third pressure pipeline and an intelligent module. And the particle size of the final product is less than 2nm.

Description

Technical Field

[0001] The invention relates to the technical field of biopharmaceuticals, and in particular to a special ultrafiltration device for manufacturing biopharmaceuticals. Background Art

[0002] In the field of biopharmaceuticals, ultrafiltration technology is often used to separate and purify biomacromolecules, such as proteins and nucleic acids. However, traditional ultrafilters usually use simple filtration structures and fixed operating parameters, which cannot effectively cope with high-viscosity and high-concentration drugs. This results in a slow and inefficient ultrafiltration process, which not only prolongs the production cycle and increases production costs, but may also affect the quality and activity of drugs due to long-term processing.

[0003] Chinese Patent Publication No.: CN118949694B discloses an ultrafiltration system, including: a raw material tank, configured to store a raw material solution of a biological product; a replacement tank, configured to store a replacement solution; a cleaning tank, configured to store a cleaning solution; an ultrafiltration membrane package, configured to filter the raw material solution; a switching device, connected to the raw material tank, the replacement tank and the cleaning tank, and connected to the ultrafiltration membrane package fluid, configured to selectively switch or close the fluid connection relationship between the raw material tank, the replacement tank and the cleaning tank and the ultrafiltration membrane package; a fluid drive unit, which is arranged in series on the flow path between the ultrafiltration membrane package and the switching device. However, it is difficult for the ultrafiltration system to monitor and control the ultrafiltration process in real time, improve the ultrafiltration efficiency, and make the particle size of the final product less than 2nm. Summary of the invention

[0004] To this end, the present invention provides a special ultrafiltration device for the manufacture of biological drugs, which is used to overcome the problems of slow ultrafiltration process, low efficiency and large particle size of the final product in the prior art.

[0005] To achieve the above object, the present invention provides a special ultrafiltration device for manufacturing biological drugs, the device comprising:

[0006] A biopharmaceutical material storage tank, connected to the first feed pipe, for storing biopharmaceutical materials;

[0007] A first pressure pipeline, one end of which is connected to the first feed pipe, and one end of which is away from the first feed pipe is connected to the first pressure pump, for transmitting the transmission pressure of the first pressure pump to the first feed pipe;

[0008] A first pressure pump connected to the first pressure pipeline and used to provide transmission pressure;

[0009] A first feeding pipe, one end of which is connected to the biopharmaceutical material storage tank, the end of which is away from the biopharmaceutical material storage tank is connected to the first ultrafilter, and the end of which is close to the first ultrafilter is connected to the first pressure pipeline, for transmitting the biopharmaceutical material to the first ultrafilter;

[0010] An ultrafilter cleaning liquid pipeline, which is connected to the first ultrafilter, the second ultrafilter and the third ultrafilter one by one, and one end of which is far away from the first ultrafilter is connected to the storage tank, and is used to transfer the cleaning liquid in the storage tank to the first ultrafilter, the second ultrafilter and the third ultrafilter respectively;

[0011] A first ultrafilter, one end of which is connected to the first feed pipe, one end of which is close to the first feed pipe is connected to the ultrafilter cleaning liquid pipeline, one end of which is away from the ultrafilter cleaning liquid pipeline is connected to the ultrafilter waste liquid transmission pipeline, and one end of which is away from the first feed pipe is connected to the second feed pipe, for removing impurities in the biopharmaceutical material and preliminarily concentrating the target molecules to obtain a first biopharmaceutical material;

[0012] An ultrafilter waste liquid transmission pipeline, which is connected to the first ultrafilter, the second ultrafilter and the third ultrafilter one by one, and its end close to the second ultrafilter and the third ultrafilter is connected to the waste liquid storage tank, and its end away from the first ultrafilter is connected to the storage tank, and is used to transmit the waste liquid output by the first ultrafilter, the second ultrafilter and the third ultrafilter to the waste liquid storage tank;

[0013] A second feeding pipe, one end of which is connected to the first ultrafilter, the end of which is far from the first ultrafilter is connected to the second ultrafilter, the end of which is close to the first ultrafilter is connected to the second pressure pipeline, and the end of which is far from the second pressure pipeline is connected to the first transmission pipeline, for transmitting the first biological drug material in the first ultrafilter to the second ultrafilter;

[0014] A waste liquid storage tank, which is connected to the ultrafilter waste liquid transmission pipeline and is used to store the waste liquid output by the first ultrafilter, the second ultrafilter and the third ultrafilter;

[0015] A third feeding pipe, one end of which is connected to the second ultrafilter, the end of which is far from the second ultrafilter is connected to the third ultrafilter, the end of which is close to the second ultrafilter is connected to the third pressure pump, and the end of which is far from the third pressure pump is connected to the second transmission pipeline, for transmitting the second biological drug material in the second ultrafilter to the third ultrafilter;

[0016] A second ultrafilter, one end of which is connected to the second feed pipe, one end of which is close to the second feed pipe is connected to the ultrafilter cleaning liquid pipeline, one end of which is away from the ultrafilter cleaning liquid pipeline is connected to the ultrafilter waste liquid transmission pipeline, and one end of which is away from the second feed pipe is connected to the third feed pipe, for separating medium molecular weight impurities in the first biopharmaceutical material and performing secondary concentration on the first biopharmaceutical material to obtain a second biopharmaceutical material;

[0017] a fourth feed pipe, one end of which is connected to the third ultrafilter, and one end of which is away from the third ultrafilter is connected to the biopharmaceutical collection tank, and is used to transfer the third biopharmaceutical material in the third ultrafilter to the biopharmaceutical collection tank;

[0018] A third ultrafilter, one end of which is connected to the third feed pipe, one end of which is close to the third feed pipe is connected to the ultrafilter cleaning liquid pipeline, one end of which is away from the ultrafilter cleaning liquid pipeline is connected to the ultrafilter waste liquid transmission pipeline, and one end of which is away from the third feed pipe is connected to the fourth feed pipe, for removing small molecular impurities in the second biopharmaceutical material to obtain a third biopharmaceutical material;

[0019] A biopharmaceutical collection tank connected to the third ultrafilter and used for storing a third biopharmaceutical material;

[0020] A storage tank, one end of which is connected to the ultrafilter cleaning liquid pipeline, and the other end of which is connected to the ultrafilter waste liquid transmission pipeline, is used to store cleaning liquid and pure water, and a heating cooler is provided at the end storing pure water for heating and cooling the pure water;

[0021] A second drug buffer tank, connected to the second transmission pipeline, for storing the second biological drug material in the second ultrafilter;

[0022] A first drug buffer tank, connected to the first transmission pipeline, for storing the first biological drug material in the first ultrafilter;

[0023] A first transmission pipeline, one end of which is connected to the second feeding pipe, and one end of which is away from the second feeding pipe is connected to the first drug buffer tank, for transmitting the first biological drug material;

[0024] A second transmission pipeline, one end of which is connected to the fourth feeding pipe, and one end of which is away from the fourth feeding pipe is connected to the second drug buffer tank, for transmitting the second biological drug material;

[0025] a second pressure pump connected to the second pressure pipeline and used for providing transmission pressure;

[0026] a third pressure pump connected to the third pressure pipeline and used for providing transmission pressure;

[0027] The intelligent module is connected to the special ultrafiltration device for manufacturing biological medicines and is used for intelligently controlling the special ultrafiltration device for manufacturing biological medicines.

[0028] Furthermore, the intelligent module comprises:

[0029] A data acquisition unit, used to collect operating data of the dedicated ultrafiltration device for manufacturing biological drugs;

[0030] A membrane flux calculation unit, used to calculate the first real-time membrane flux, the second real-time membrane flux and the third real-time membrane flux according to the operation data;

[0031] A prediction and analysis unit, used for performing prediction and analysis on the first ultrafilter, the second ultrafilter and the third ultrafilter;

[0032] The intelligent ultrafiltration unit is used to control the first ultrafilter, the second ultrafilter, the third ultrafilter and the first pressure pump, the second pressure pump and the third pressure pump.

[0033] Further, the membrane flux calculation unit calculates the first real-time membrane flux Js1, the second real-time membrane flux Js2 and the third real-time membrane flux Js3, and sets the fluid volume of the first ultrafiltration membrane to be L1, the first effective area of ​​the membrane to be A1, and the first ultrafiltration time to be T1; the fluid volume of the second ultrafiltration membrane to be L2, the second effective area of ​​the membrane to be A2, and the second ultrafiltration time to be T2; the fluid volume of the third ultrafiltration membrane to be L3, the third effective area of ​​the membrane to be A3, and the third ultrafiltration time to be T3, and the calculation methods of the first real-time membrane flux Js1, the second real-time membrane flux Js2 and the third real-time membrane flux Js3 are respectively:

[0034] Further, the prediction and analysis unit is provided with an ultrafiltration prediction and analysis model, which sets the relationship between the membrane flux J1 of the first ultrafilter and the ultrafiltration pressure U1 of the first ultrafilter, the ultrafiltration drug feed flow rate V1 of the first ultrafilter and the first ultrafiltration temperature T1, the relationship between the membrane flux J2 of the second ultrafilter and the ultrafiltration pressure U2 of the second ultrafilter, the ultrafiltration drug feed flow rate V2 of the second ultrafilter and the second ultrafiltration temperature T2, and the relationship between the membrane flux J3 of the third ultrafilter and the ultrafiltration pressure U3 of the third ultrafilter, the ultrafiltration drug feed flow rate V3 of the third ultrafilter and the third ultrafiltration temperature T3, wherein:

[0035] The relationship between the membrane flux J1 of the first ultrafilter and the ultrafiltration pressure U1 of the first ultrafilter, the ultrafiltration drug feed flow rate V1 of the first ultrafilter and the first ultrafiltration temperature T1 is J1=a1*U1 2 +b1*V1+c1*T1+d1;

[0036] The relationship between the membrane flux J2 of the second ultrafilter and the ultrafiltration pressure U2 of the second ultrafilter, the ultrafiltration drug feed flow rate V2 of the second ultrafilter and the second ultrafiltration temperature T2 is J2 = a2*U2 2 +b2*V2+c2*T2+d2;

[0037] The relationship between the membrane flux J3 of the third ultrafilter and the ultrafiltration pressure U3 of the third ultrafilter, the ultrafiltration drug feed flow rate V3 of the third ultrafilter and the third ultrafiltration temperature T3 is J3 = a3*U3 2+b3*V3+c3*T3+d3;

[0038] a1, b1, c1, d1 are the fitting coefficients of the first ultrafilter, a2, b2, c2, d2 are the fitting coefficients of the second ultrafilter, and a3, b3, c3, d3 are the fitting coefficients of the third ultrafilter.

[0039] Furthermore, the ultrafiltration prediction and analysis model also compares the material viscosity N1 of the first ultrafilter, the material viscosity N2 of the second ultrafilter, and the material viscosity N3 of the third ultrafilter with the preset material viscosity N01 of the first ultrafilter, the material viscosity N02 of the second ultrafilter, and the material viscosity N03 of the third ultrafilter, respectively, and judges the viscosity of the material viscosity N1 of the first ultrafilter, the material viscosity N2 of the second ultrafilter, and the material viscosity N3 of the third ultrafilter and the effectiveness of the membrane flux J1 of the first ultrafilter, the membrane flux J2 of the second ultrafilter, and the membrane flux J3 of the third ultrafilter according to the comparison results, and adjusts the membrane flux J1 of the first ultrafilter, the membrane flux J2 of the second ultrafilter, and the membrane flux J3 of the third ultrafilter according to the judgment results.

[0040] Furthermore, the ultrafiltration prediction and analysis model also performs difference ratio calculations on the membrane flux J1 and the first real-time membrane flux Js1 of the first ultrafilter, the membrane flux J2 and the second real-time membrane flux Js2 of the second ultrafilter, and the membrane flux J3 and the third real-time membrane flux Js3 of the third ultrafilter, respectively, to obtain a first difference ratio, a second difference ratio and a third difference ratio, wherein:

[0041] The first difference ratio is Jc1,

[0042] The second difference ratio is Jc2,

[0043] The third difference ratio is Jc3,

[0044] Furthermore, the prediction and analysis unit compares the first difference ratio Jc1, the second difference ratio Jc2 and the third difference ratio Jc3 with the preset first difference ratio Jc01, the preset second difference ratio Jc02 and the preset third difference ratio Jc03 respectively, compares and judges the actual compliance status of each difference ratio according to the comparison results, and optimizes each fitting coefficient according to the judgment results.

[0045] Furthermore, the prediction and analysis unit obtains the difference j1 between the first ultrafilter membrane flux prediction value and the preset first ultrafilter membrane flux prediction value, the difference j2 between the second ultrafilter membrane flux prediction value and the preset second ultrafilter membrane flux prediction value, and the difference j3 between the third ultrafilter membrane flux prediction value and the preset third ultrafilter membrane flux prediction value according to the ultrafiltration prediction and analysis model, and compares them with the preset first difference j01, the preset second difference j02, and the preset third difference j03 respectively; based on the comparison results, the rationality of the first ultrafilter membrane flux prediction value, the second ultrafilter membrane flux prediction value, and the third ultrafilter membrane flux prediction value output by the ultrafiltration prediction and analysis model are judged respectively, and the material flow rate of each ultrafilter is monitored based on the judgment results.

[0046] Further, the intelligent ultrafiltration unit monitors the material flow rate of the first ultrafilter, the material flow rate of the second ultrafilter and the material flow rate of the third ultrafilter, obtains the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter, and obtains the material flow rate v3 of the third ultrafilter, and compares the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter, and the material flow rate v3 of the third ultrafilter with the preset material flow rate v01 of the first ultrafilter, the preset material flow rate v02 of the second ultrafilter, and the preset material flow rate v03 of the third ultrafilter, respectively, and judges the effectiveness of the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter, and the material flow rate v3 of the third ultrafilter according to the comparison results, and controls the first ultrafilter, the second ultrafilter, and the third ultrafilter according to the judgment results, wherein:

[0047] When v1=v01, the effective condition of the material flow rate v1 of the first ultrafilter is determined to be effective, and the first ultrafilter is not controlled;

[0048] When v2=v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be effective, and the second ultrafilter is not controlled;

[0049] When v3=v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be valid, and the third ultrafilter is not controlled;

[0050] When v1<v01, the validity of the material flow rate v1 of the first ultrafilter is determined to be invalid, and the first ultrafilter is controlled to increase the valve opening in the first ultrafilter;

[0051] When v2<v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be invalid, and the second ultrafilter is controlled to increase the valve opening in the second ultrafilter;

[0052] When v3<v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be invalid, and the third ultrafilter is controlled to increase the valve opening in the third ultrafilter;

[0053] When v1>v01, the effective condition of the material flow rate v1 of the first ultrafilter is determined to be invalid, and the first ultrafilter is controlled to reduce the valve opening in the first ultrafilter;

[0054] When v2>v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be invalid, and the second ultrafilter is controlled to reduce the valve opening in the second ultrafilter;

[0055] When v3>v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be invalid, and the third ultrafilter is controlled to reduce the valve opening in the third ultrafilter.

[0056] Furthermore, the intelligent ultrafiltration unit also compares the first ultrafilter ultrafiltration pressure u1, the second ultrafilter ultrafiltration pressure u2, and the third ultrafilter ultrafiltration pressure u3 with the preset first ultrafilter ultrafiltration pressure u01, the preset second ultrafilter ultrafiltration pressure u02, and the preset third ultrafilter ultrafiltration pressure u03, respectively, and judges the compliance of the first ultrafilter ultrafiltration pressure u1, the second ultrafilter ultrafiltration pressure u2, and the third ultrafilter ultrafiltration pressure u3 according to the comparison results, and controls the first pressure pump, the second pressure pump, and the third pressure pump according to the judgment results, wherein:

[0057] When u1=u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter meets the standard, and the first pressure pump is not controlled;

[0058] When u2=u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter meets the standard, and the second pressure pump is not controlled;

[0059] When u3=u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter meets the standard, and the third pressure pump is not controlled;

[0060] When u1<u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter does not meet the standard, and the first pressure pump is controlled to increase the transmission pressure provided by the first pressure pump;

[0061] When u2<u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter does not meet the standard, and the second pressure pump is controlled to increase the transmission pressure provided by the second pressure pump;

[0062] When u3<u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter does not meet the standard, and the third pressure pump is controlled to increase the transmission pressure provided by the third pressure pump;

[0063] When u1>u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter does not meet the standard, and the first pressure pump is controlled to reduce the transmission pressure provided by the first pressure pump;

[0064] When u2>u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter does not meet the standard, and the second pressure pump is controlled to reduce the transmission pressure provided by the second pressure pump;

[0065] When u3>u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter does not meet the standard, and the third pressure pump is controlled to reduce the transmission pressure provided by the third pressure pump.

[0066] Compared with the prior art, the beneficial effects of the present invention are that the device provides a stable material supply through a biopharmaceutical material storage tank, reduces manual intervention, and is convenient for large-scale production. The device ensures a stable transmission pressure of the material during the feeding process through a first pressure pipeline and a first pressure pump, and prevents a decrease in filtration efficiency due to pressure fluctuations. The device achieves efficient material transmission through a first feed pipe and a second feed pipe, reduces the risk of blockage, and ensures continuous operation. The device provides an automatic cleaning function through an ultrafilter cleaning liquid pipeline, extends the service life of the equipment, and ensures product purity. The device effectively removes impurities of different molecular weight ranges through a graded filtration design of a first ultrafilter, a second ultrafilter, and a third ultrafilter, and controls the particle size of the final product to be less than 2 nm, thereby improving the recovery rate and purity of the target molecule. The device centrally treats waste liquid through an ultrafilter waste liquid transmission pipeline, reduces environmental pollution, and is convenient for subsequent waste liquid resources. The device can safely store waste liquid through a waste liquid storage tank to prevent leakage. The device ensures a smooth transition of materials between ultrafilters at various stages through the third feed pipe and the fourth feed pipe to avoid losses. The device stores the final product through a biological drug collection tank to facilitate subsequent packaging or further processing. The device provides cleaning liquid and pure water through a storage tank. The heating and cooling functions can adjust the temperature as needed to adapt to different material properties. The device can balance the pressure difference between ultrafilters at various stages through the buffering effect of the second drug buffer tank and the first drug buffer tank to avoid overload and underpressure. The device optimizes the material transmission path through the first transmission pipeline and the second transmission pipeline to reduce energy consumption and loss. The device provides precise pressure control through the second pressure pump and the third pressure pump to support efficient transmission and filtration. The device realizes full-process automated control through an intelligent module to reduce human errors and improve production efficiency and product quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Figure 1 This is a schematic diagram of the structure of a dedicated ultrafiltration device for manufacturing biological drugs in this embodiment;

[0068] Figure 2Schematic diagram of the structure of the intelligent module of this embodiment. DETAILED DESCRIPTION

[0069] In order to make the objects and advantages of the present invention more clearly understood, the present invention is further described below in conjunction with embodiments; it should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0070] The preferred embodiments of the present invention are described below with reference to the accompanying drawings. It should be understood by those skilled in the art that these embodiments are only used to explain the technical principles of the present invention and are not intended to limit the protection scope of the present invention.

[0071] It should be noted that, in the description of the present invention, terms such as "up", "down", "left", "right", "inside" and "outside" indicating directions or positional relationships are based on the directions or positional relationships shown in the drawings. This is merely for the convenience of description and does not indicate or imply that the device or element must have a specific orientation, be constructed and operated in a specific orientation. Therefore, it cannot be understood as a limitation on the present invention.

[0072] In addition, it should be noted that in the description of the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0073] See also Figure 1 As shown, it is a structural schematic diagram of a dedicated ultrafiltration device for biopharmaceutical manufacturing in this embodiment, and the device includes:

[0074] A biopharmaceutical material storage tank 1, which is connected to the first feed pipe 4 and is used to store biopharmaceutical materials;

[0075] A first pressure pipe 2, one end of which is connected to the first feed pipe 4, and the other end of which is away from the first feed pipe 4 is connected to the first pressure pump 3, for transmitting the transmission pressure of the first pressure pump 3 to the first feed pipe 4;

[0076] A first pressure pump 3, which is connected to the first pressure pipeline 2 and is used to provide transmission pressure;

[0077] A first feeding pipe 4, one end of which is connected to the biopharmaceutical material storage tank 1, the end of which is away from the biopharmaceutical material storage tank 1 is connected to the first ultrafilter 6, and the end of which is close to the first ultrafilter 6 is connected to the first pressure pipe 2, for transmitting the biopharmaceutical material to the first ultrafilter 6;

[0078] The ultrafilter cleaning liquid pipeline 5 is connected to the first ultrafilter 6, the second ultrafilter 11 and the third ultrafilter 13 one by one, and one end thereof away from the first ultrafilter 6 is connected to the storage tank 15, and is used to transfer the cleaning liquid in the storage tank 15 to the first ultrafilter 6, the second ultrafilter 11 and the third ultrafilter 13 respectively;

[0079] A first ultrafilter 6, one end of which is connected to the first feed pipe 4, the end close to the first feed pipe 4 is connected to the ultrafilter cleaning liquid pipeline 5, the end away from the ultrafilter cleaning liquid pipeline 5 is connected to the ultrafilter waste liquid transmission pipeline 7, and the end away from the first feed pipe 4 is connected to the second feed pipe 8, for removing impurities in the biopharmaceutical material and preliminarily concentrating the target molecules to obtain the first biopharmaceutical material;

[0080] The ultrafilter waste liquid transmission pipeline 7 is connected to the first ultrafilter 6, the second ultrafilter 11 and the third ultrafilter 13 one by one, and the end thereof close to the second ultrafilter 11 and the third ultrafilter 13 is connected to the waste liquid storage tank 9, and the end thereof away from the first ultrafilter 6 is connected to the storage tank 15, and is used for transmitting the waste liquid outputted by the first ultrafilter 6, the second ultrafilter 11 and the third ultrafilter 13 to the waste liquid storage tank 9;

[0081] A second feeding pipe 8, one end of which is connected to the first ultrafilter 6, the end of which is away from the first ultrafilter 6 is connected to the second ultrafilter 11, the end of which is close to the first ultrafilter 6 is connected to the second pressure pipeline 27, and the end of which is away from the second pressure pipeline 27 is connected to the first transmission pipeline 18, for transmitting the first biological drug material in the first ultrafilter 6 to the second ultrafilter 11;

[0082] A waste liquid storage tank 9, which is connected to the ultrafilter waste liquid transmission pipeline 7 and is used to store the waste liquid output by the first ultrafilter 6, the second ultrafilter 11 and the third ultrafilter 13;

[0083] A third feeding pipe 10, one end of which is connected to the second ultrafilter 11, the end of which is away from the second ultrafilter 11 is connected to the third ultrafilter 13, the end of which is close to the second ultrafilter 11 is connected to the third pressure pump 30, and the end of which is away from the third pressure pump 30 is connected to the second transmission pipeline 19, for transmitting the second biological drug material in the second ultrafilter 11 to the third ultrafilter 13;

[0084] A second ultrafilter 11, one end of which is connected to the second feed pipe 8, the end close to the second feed pipe 8 is connected to the ultrafilter cleaning liquid pipeline 5, the end away from the ultrafilter cleaning liquid pipeline 5 is connected to the ultrafilter waste liquid transmission pipeline 7, and the end away from the second feed pipe 8 is connected to the third feed pipe 10, for separating medium molecular weight impurities in the first biopharmaceutical material and performing secondary concentration on the first biopharmaceutical material to obtain a second biopharmaceutical material;

[0085] A fourth feed pipe 12, one end of which is connected to the third ultrafilter 13, and one end of which is away from the third ultrafilter 13 is connected to the biopharmaceutical collection tank 14, for transferring the third biopharmaceutical material in the third ultrafilter 13 to the biopharmaceutical collection tank 14;

[0086] A third ultrafilter 13, one end of which is connected to the third feed pipe 10, one end of which is close to the third feed pipe 10 is connected to the ultrafilter cleaning liquid pipeline 5, one end of which is away from the ultrafilter cleaning liquid pipeline 5 is connected to the ultrafilter waste liquid transmission pipeline 7, and one end of which is away from the third feed pipe 10 is connected to the fourth feed pipe 12, and is used to remove small molecular impurities in the second biopharmaceutical material to obtain a third biopharmaceutical material;

[0087] A biopharmaceutical collection tank 14, which is connected to the third ultrafilter 13 and is used to store the third biopharmaceutical material;

[0088] A storage tank 15, one end of which is connected to the ultrafilter cleaning liquid pipeline 5, and the other end of which is connected to the ultrafilter waste liquid transmission pipeline 7, is used to store cleaning liquid and pure water, and a heating cooler is provided at one end for storing pure water, for heating and cooling the pure water;

[0089] A second drug buffer tank 16, which is connected to the second transmission pipeline 19 and is used to store the second biological drug material in the second ultrafilter;

[0090] A first drug buffer tank 17, which is connected to the first transmission pipeline 18 and is used to store the first biological drug material in the first ultrafilter;

[0091] A first transmission pipeline 18, one end of which is connected to the second feeding pipe 8, and the end of which is away from the second feeding pipe 8 is connected to the first drug buffer tank 17, for transmitting the first biological drug material;

[0092] A second transmission pipeline 19, one end of which is connected to the fourth feeding pipe 12, and the other end away from the fourth feeding pipe 12 is connected to the second drug buffer tank 16, for transmitting the second biological drug material;

[0093] A second pressure pump 20, connected to the second feed pipe 8, for providing transmission pressure;

[0094] A third pressure pump 21, which is connected to the third feed pipe 10 and is used to provide transmission pressure;

[0095] The intelligent module 22 is connected to the dedicated ultrafiltration device for biopharmaceutical manufacturing and is used to intelligently control the dedicated ultrafiltration device for biopharmaceutical manufacturing.

[0096] Specifically, the device is applied to the biopharmaceutical process, and the device drives the material in the biopharmaceutical material storage tank through the first pressure pump, transmits it to the first ultrafilter through the first feed pipe, and preliminarily filters the material through the first ultrafilter to remove large molecular impurities and preliminarily concentrate the target molecules to generate the first biopharmaceutical material. The waste liquid flows into the waste liquid storage tank through the ultrafilter waste liquid transmission pipeline, and the first biopharmaceutical material enters the second ultrafilter through the second feed pipe to remove medium molecular weight impurities and perform secondary concentration on the material to generate the second biopharmaceutical material. The second biopharmaceutical material enters the third ultrafilter through the third feed pipe to remove small molecular impurities, and finally generates the third biopharmaceutical material with a particle size less than 2nm. , the third biological drug material is transmitted to the biological drug collection tank for storage through the fourth feed pipe, and the ultrafilter cleaning liquid pipeline transmits the cleaning liquid in the storage tank to each ultrafilter respectively to ensure the cleanliness of the system. The waste liquid after cleaning is returned to the waste liquid storage tank through the ultrafilter waste liquid transmission pipeline. The intelligent module monitors and controls the entire ultrafiltration process in real time. In particular, the device provides a stable material supply through the biological drug material storage tank, reduces manual intervention, and is convenient for large-scale production. The device ensures a stable transmission pressure of the material during the feeding process through the first pressure pipeline and the first pressure pump to prevent the filtration efficiency from decreasing due to pressure fluctuations. The device realizes efficient transmission of materials through the first feed pipe and the second feed pipe, reducing The device reduces the risk of blockage and ensures continuous operation. The device provides an automatic cleaning function through the ultrafilter cleaning liquid pipeline, which prolongs the service life of the equipment and ensures the purity of the product. The device effectively removes impurities of different molecular weight ranges through the graded filtration design of the first ultrafilter, the second ultrafilter and the third ultrafilter, and controls the particle size of the final product to be less than 2nm, thereby improving the recovery rate and purity of the target molecule. The device centrally treats the waste liquid through the ultrafilter waste liquid transmission pipeline, reduces environmental pollution, and facilitates the subsequent resource utilization of waste liquid. The device safely stores the waste liquid through the waste liquid storage tank to prevent leakage. The device ensures the smooth transition of materials between the ultrafilters at each level through the third feed pipe and the fourth feed pipe to avoid losses. The device stores the final product through a biopharmaceutical collection tank to facilitate subsequent packaging or further processing. The device provides cleaning fluid and pure water through a storage tank. The heating and cooling functions can adjust the temperature as needed to adapt to different material properties. The device can balance the pressure difference between each level of ultrafilters through the buffering effect of the second drug buffer tank and the first drug buffer tank to avoid overload and underpressure. The device optimizes the material transmission path through the first transmission pipeline and the second transmission pipeline to reduce energy consumption and loss. The device provides precise pressure control through the second pressure pump and the third pressure pump to support efficient transmission and filtration. The device realizes full-process automated control through an intelligent module to reduce human errors and improve production efficiency and product quality.

[0097] The intelligent module monitors various parameters in the ultrafiltration process in real time, and automatically adjusts the operating parameters according to the preset algorithm to achieve accurate and timely control, thereby improving the stability and consistency of the ultrafiltration process. In addition, the present invention adopts a multi-stage filtration method, which can effectively process high-viscosity and high-concentration biological drugs, significantly improve the efficiency of ultrafiltration, and reduce the time of drug ultrafiltration.

[0098] See also Figure 2 As shown, it is a schematic diagram of the structure of the intelligent module of this embodiment, and the intelligent module includes:

[0099] A data acquisition unit, used to collect operating data of the dedicated ultrafiltration device for manufacturing biological drugs;

[0100] A membrane flux calculation unit, used for calculating the first real-time membrane flux, the second real-time membrane flux and the third real-time membrane flux according to the operation data, wherein the membrane flux calculation unit is connected to the data acquisition unit;

[0101] A prediction and analysis unit, used for performing prediction and analysis on the first ultrafilter, the second ultrafilter and the third ultrafilter, wherein the prediction and analysis unit is connected to the membrane flux calculation unit;

[0102] The intelligent ultrafiltration unit is used to control the first ultrafilter, the second ultrafilter and the third ultrafilter and the first pressure pump, the second pressure pump and the third pressure pump. The intelligent ultrafiltration unit is connected with the membrane flux calculation unit and the prediction analysis unit.

[0103] Specifically, the intelligent module is applied to the dedicated ultrafiltration device for the manufacture of biological drugs. The intelligent module monitors various parameters in the ultrafiltration process in real time through the intelligent ultrafiltration unit, and automatically adjusts the operating parameters according to the preset algorithm to achieve precise and timely control, thereby improving the stability and consistency of the ultrafiltration process.

[0104] Specifically, the data acquisition unit collects operating data of the special ultrafiltration device for the manufacture of biological drugs, wherein the operating data include: ultrafiltration pressure of the first ultrafilter, ultrafiltration pressure of the second ultrafilter, ultrafiltration pressure of the third ultrafilter, ultrafiltration drug feed flow rate of the first ultrafilter, ultrafiltration drug feed flow rate of the second ultrafilter, ultrafiltration drug feed flow rate of the third ultrafilter, ultrafiltration drug feed concentration of the first ultrafilter, ultrafiltration drug feed concentration of the second ultrafilter, ultrafiltration drug feed concentration of the third ultrafilter, ultrafiltration drug feed viscosity of the first ultrafilter, ultrafiltration drug feed viscosity of the second ultrafilter, ultrafiltration drug feed viscosity of the third ultrafilter, volume of fluid passing through the membrane of the first ultrafilter, volume of fluid passing through the membrane of the second ultrafilter, volume of fluid passing through the membrane of the third ultrafilter, first effective area of ​​the membrane, second effective area of ​​the membrane, third effective area of ​​the membrane, ultrafiltration material temperature, drug purity, ultrafiltration time and membrane usage time.

[0105] Specifically, this embodiment does not limit the method for collecting the operating data. Relevant technical personnel in the field can freely set it according to actual needs, and only need to meet the needs of collecting the operating data. For example, it can be set to collect the operating data through a sensor matrix. The ultrafiltration pressure of the first ultrafilter refers to the pressure applied when the biological pharmaceutical material in the first ultrafilter passes through the ultrafiltration membrane. The ultrafiltration pressure of the second ultrafilter refers to the pressure applied when the first biological pharmaceutical material in the second ultrafilter passes through the ultrafiltration membrane. The ultrafiltration pressure of the third ultrafilter refers to the pressure applied when the second biological pharmaceutical material in the third ultrafilter passes through the ultrafiltration membrane. The ultrafiltration drug feed flow rate of the first ultrafilter refers to the pressure per unit time. The volume of biological pharmaceutical material entering the first ultrafilter per unit time, the ultrafiltration drug feed flow rate of the second ultrafilter refers to the volume of the first biological pharmaceutical material entering the second ultrafilter per unit time, the ultrafiltration drug feed flow rate of the third ultrafilter refers to the volume of the second biological pharmaceutical material entering the third ultrafilter per unit time, the ultrafiltration drug feed concentration of the first ultrafilter refers to the content of the target molecule in the biological pharmaceutical material entering the first ultrafilter, the ultrafiltration drug feed concentration of the second ultrafilter refers to the content of the target molecule in the first biological pharmaceutical material entering the second ultrafilter, the ultrafiltration drug feed concentration of the third ultrafilter refers to the content of the target molecule in the second biological pharmaceutical material entering the third ultrafilter, and the The viscosity of the ultrafiltration drug feed of the first ultrafilter refers to the viscosity of the biological drug material entering the first ultrafilter, the viscosity of the ultrafiltration drug feed of the second ultrafilter refers to the viscosity of the first biological drug material entering the second ultrafilter, the viscosity of the ultrafiltration drug feed of the third ultrafilter refers to the viscosity of the second biological drug material entering the third ultrafilter, the volume of fluid passing through the membrane of the first ultrafilter refers to the volume of liquid passing through and discharged from the ultrafiltration membrane of the first ultrafilter per unit time, the volume of fluid passing through the membrane of the second ultrafilter refers to the volume of liquid passing through and discharged from the ultrafiltration membrane of the second ultrafilter per unit time, and the volume of fluid passing through the membrane of the third ultrafilter refers to the volume of liquid passing through and discharged from the ultrafiltration membrane of the third ultrafilter per unit time. The volume of liquid that passes through and discharges the filter membrane, the first effective area of ​​the membrane refers to the surface area of ​​the ultrafiltration membrane actually involved in the filtration in the first ultrafilter, the second effective area of ​​the membrane refers to the surface area of ​​the ultrafiltration membrane actually involved in the filtration in the second ultrafilter, the third effective area of ​​the membrane refers to the surface area of ​​the ultrafiltration membrane actually involved in the filtration in the third ultrafilter, the ultrafiltration material temperature refers to the ambient temperature of the biological drug material during the ultrafiltration process, the drug purity refers to the content ratio of the target molecule in the finally collected biological drug, the ultrafiltration time refers to the time required for the entire ultrafiltration process, including the filtration and cleaning time at each level, and the service life of the membrane refers to the cumulative running time of the ultrafiltration membrane from installation to replacement.

[0106] Specifically, the membrane flux calculation unit calculates the first real-time membrane flux Js1, the second real-time membrane flux Js2 and the third real-time membrane flux Js3, and sets the fluid volume of the first ultrafiltration membrane to be L1, the first effective area of ​​the membrane to be A1, and the first ultrafiltration time to be T1; the fluid volume of the second ultrafiltration membrane to be L2, the second effective area of ​​the membrane to be A2, and the second ultrafiltration time to be T2; the fluid volume of the third ultrafiltration membrane to be L3, the third effective area of ​​the membrane to be A3, and the third ultrafiltration time to be T3, and the calculation methods of the first real-time membrane flux Js1, the second real-time membrane flux Js2 and the third real-time membrane flux Js3 are respectively:

[0107] The prediction and analysis unit is provided with an ultrafiltration prediction and analysis model, which sets the relationship between the membrane flux J1 of the first ultrafilter and the ultrafiltration pressure U1 of the first ultrafilter, the ultrafiltration drug feed flow rate V1 of the first ultrafilter and the first ultrafiltration temperature T1, the relationship between the membrane flux J2 of the second ultrafilter and the ultrafiltration pressure U2 of the second ultrafilter, the ultrafiltration drug feed flow rate V2 of the second ultrafilter and the second ultrafiltration temperature T2, and the relationship between the membrane flux J3 of the third ultrafilter and the ultrafiltration pressure U3 of the third ultrafilter, the ultrafiltration drug feed flow rate V3 of the third ultrafilter and the third ultrafiltration temperature T3, wherein:

[0108] The relationship between the membrane flux J1 of the first ultrafilter and the ultrafiltration pressure U1 of the first ultrafilter, the ultrafiltration drug feed flow rate V1 of the first ultrafilter and the first ultrafiltration temperature T1 is J1=a1*U1 2 +b1*V1+c1*T1+d1;

[0109] The relationship between the membrane flux J2 of the second ultrafilter and the ultrafiltration pressure U2 of the second ultrafilter, the ultrafiltration drug feed flow rate V2 of the second ultrafilter and the second ultrafiltration temperature T2 is J2 = a2*U2 2 +b2*V2+c2*T2+d2;

[0110] The relationship between the membrane flux J3 of the third ultrafilter and the ultrafiltration pressure U3 of the third ultrafilter, the ultrafiltration drug feed flow rate V3 of the third ultrafilter and the third ultrafiltration temperature T3 is J3 = a3*U3 2 +b3*V3+c3*T3+d3;

[0111] a1, b1, c1, d1 are the fitting coefficients of the first ultrafilter, a2, b2, c2, d2 are the fitting coefficients of the second ultrafilter, and a3, b3, c3, d3 are the fitting coefficients of the third ultrafilter;

[0112] The ultrafiltration prediction and analysis model also compares the material viscosity N1 of the first ultrafilter, the material viscosity N2 of the second ultrafilter, and the material viscosity N3 of the third ultrafilter with the preset material viscosity N01 of the first ultrafilter, the material viscosity N02 of the second ultrafilter, and the material viscosity N03 of the third ultrafilter, and judges the viscosity of the material viscosity N1 of the first ultrafilter, the material viscosity N2 of the second ultrafilter, and the material viscosity N3 of the third ultrafilter and the effective conditions of the membrane flux J1 of the first ultrafilter, the membrane flux J2 of the second ultrafilter, and the membrane flux J3 of the third ultrafilter according to the comparison results, and adjusts the membrane flux J1 of the first ultrafilter, the membrane flux J2 of the second ultrafilter, and the membrane flux J3 of the third ultrafilter according to the judgment results, wherein:

[0113] When N1≤N01, it is determined that the viscosity of the material viscosity N1 of the first ultrafilter is low, the membrane flux J1 of the first ultrafilter is effective, and the membrane flux J1 of the first ultrafilter is not adjusted;

[0114] When N2≤N02, it is determined that the viscosity of the material viscosity N2 of the second ultrafilter is low, the membrane flux J2 of the second ultrafilter is effective, and the membrane flux J2 of the second ultrafilter is not adjusted;

[0115] When N3≤N03, it is determined that the viscosity of the material viscosity N3 of the third ultrafilter is low, the membrane flux J3 of the third ultrafilter is effective, and the membrane flux J3 of the third ultrafilter is not adjusted;

[0116] When N1>N01, the viscosity of the material viscosity N1 of the first ultrafilter is determined to be high, and the membrane flux J1 of the first ultrafilter is invalid. The membrane flux J1 of the first ultrafilter is adjusted, and the membrane flux of the first ultrafilter after adjustment is set to J1. 、 ,

[0117] When N2>N02, the viscosity of the material viscosity N2 of the second ultrafilter is determined to be high, and the membrane flux J2 of the second ultrafilter is invalid. The membrane flux J2 of the second ultrafilter is adjusted, and the membrane flux of the second ultrafilter after adjustment is set to J2. 、 ,

[0118] When N3>N03, the viscosity of the material viscosity N3 of the third ultrafilter is determined to be high, and the membrane flux J3 of the third ultrafilter is invalid. The membrane flux J3 of the third ultrafilter is adjusted, and the membrane flux of the third ultrafilter after adjustment is set to J1. 、 ,

[0119] The ultrafiltration prediction and analysis model also calculates the difference ratio of the membrane flux J1 and the first real-time membrane flux Js1 of the first ultrafilter, the membrane flux J2 and the second real-time membrane flux Js2 of the second ultrafilter, and the membrane flux J3 and the third real-time membrane flux Js3 of the third ultrafilter, respectively, to obtain the first difference ratio, the second difference ratio and the third difference ratio, wherein:

[0120] The first difference ratio is Jc1,

[0121] The second difference ratio is Jc2,

[0122] The third difference ratio is Jc3,

[0123] The prediction and analysis unit compares the first difference ratio Jc1, the second difference ratio Jc2 and the third difference ratio Jc3 with the preset first difference ratio Jc01, the preset second difference ratio Jc02 and the preset third difference ratio Jc03 respectively, compares and judges the actual compliance of each difference ratio according to the comparison results, and optimizes each fitting coefficient according to the judgment results, wherein:

[0124] When Jc1≤Jc01, it is determined that the actual compliance of the first difference ratio Jc1 is compliance, and the fitting coefficient of the first ultrafilter is not optimized;

[0125] When Jc2≤Jc02, it is determined that the actual compliance of the second difference ratio Jc2 is compliance, and the fitting coefficient of the second ultrafilter is not optimized;

[0126] When Jc3≤Jc03, it is determined that the actual compliance of the third difference ratio Jc3 is compliance, and the fitting coefficient of the third ultrafilter is not optimized;

[0127] When Jc1>Jc01, it is determined that the actual compliance of the first difference ratio Jc1 is not up to standard, and the fitting coefficient of the first ultrafilter is optimized;

[0128] When Jc2>Jc02, it is determined that the actual compliance of the second difference ratio Jc2 is not up to standard, and the fitting coefficient of the second ultrafilter is optimized;

[0129] When Jc3>Jc03, it is determined that the actual compliance of the third difference ratio Jc3 is not up to standard, and the fitting coefficient of the third ultrafilter is optimized;

[0130] The prediction and analysis unit obtains the difference j1 between the first ultrafilter membrane flux prediction value and the preset first ultrafilter membrane flux prediction value, the difference j2 between the second ultrafilter membrane flux prediction value and the preset second ultrafilter membrane flux prediction value, and the difference j3 between the third ultrafilter membrane flux prediction value and the preset third ultrafilter membrane flux prediction value according to the ultrafiltration prediction and analysis model, and compares them with the preset first difference j01, the preset second difference j02, and the preset third difference j03 respectively, and judges the rationality of the first ultrafilter membrane flux prediction value, the second ultrafilter membrane flux prediction value, and the third ultrafilter membrane flux prediction value output by the ultrafiltration prediction and analysis model according to the comparison results, and monitors the material flow rate of each ultrafilter according to the judgment results, wherein:

[0131] When j1∈j01, the reasonableness of the predicted value of the first ultrafilter membrane flux output by the ultrafiltration prediction analysis model is determined to be reasonable, and the material flow rate of the first ultrafilter is not monitored;

[0132] When j2∈j02, the reasonableness of the predicted value of the membrane flux of the second ultrafilter output by the ultrafiltration prediction analysis model is determined to be reasonable, and the material flow rate of the second ultrafilter is not monitored;

[0133] When j3∈j03, the reasonableness of the predicted value of the membrane flux of the third ultrafilter output by the ultrafiltration prediction analysis model is determined to be reasonable, and the material flow rate of the third ultrafilter is not monitored;

[0134] when When the first ultrafilter membrane flux prediction value output by the ultrafiltration prediction analysis model is determined to be unreasonable, the material flow rate of the first ultrafilter is monitored;

[0135] when When the second ultrafilter membrane flux prediction value output by the ultrafiltration prediction analysis model is determined to be unreasonable, the material flow rate of the second ultrafilter is monitored;

[0136] when When the third ultrafilter membrane flux prediction value output by the ultrafiltration prediction analysis model is determined to be unreasonable, the material flow rate of the third ultrafilter is monitored;

[0137] The intelligent ultrafiltration unit monitors the material flow rate of the first ultrafilter, the material flow rate of the second ultrafilter and the material flow rate of the third ultrafilter to obtain the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter and the material flow rate v3 of the third ultrafilter, and compares the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter and the material flow rate v3 of the third ultrafilter with the preset material flow rate v01 of the first ultrafilter, the preset material flow rate v02 of the second ultrafilter and the preset material flow rate v03 of the third ultrafilter, and judges the effectiveness of the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter and the material flow rate v3 of the third ultrafilter according to the comparison results, and controls the first ultrafilter, the second ultrafilter and the third ultrafilter according to the judgment results, wherein:

[0138] When v1=v01, the effective condition of the material flow rate v1 of the first ultrafilter is determined to be effective, and the first ultrafilter is not controlled;

[0139] When v2=v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be effective, and the second ultrafilter is not controlled;

[0140] When v3=v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be valid, and the third ultrafilter is not controlled;

[0141] When v1<v01, the validity of the material flow rate v1 of the first ultrafilter is determined to be invalid, and the first ultrafilter is controlled to increase the valve opening in the first ultrafilter;

[0142] When v2<v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be invalid, and the second ultrafilter is controlled to increase the valve opening in the second ultrafilter;

[0143] When v3<v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be invalid, and the third ultrafilter is controlled to increase the valve opening in the third ultrafilter;

[0144] When v1>v01, the effective condition of the material flow rate v1 of the first ultrafilter is determined to be invalid, and the first ultrafilter is controlled to reduce the valve opening in the first ultrafilter;

[0145] When v2>v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be invalid, and the second ultrafilter is controlled to reduce the valve opening in the second ultrafilter;

[0146] When v3>v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be invalid, and the third ultrafilter is controlled to reduce the valve opening in the third ultrafilter;

[0147] The intelligent ultrafiltration unit also compares the first ultrafilter ultrafiltration pressure u1, the second ultrafilter ultrafiltration pressure u2, and the third ultrafilter ultrafiltration pressure u3 with the preset first ultrafilter ultrafiltration pressure u01, the preset second ultrafilter ultrafiltration pressure u02, and the preset third ultrafilter ultrafiltration pressure u03, respectively, and judges the compliance of the first ultrafilter ultrafiltration pressure u1, the second ultrafilter ultrafiltration pressure u2, and the third ultrafilter ultrafiltration pressure u3 according to the comparison results, and controls the first pressure pump, the second pressure pump, and the third pressure pump according to the judgment results, wherein:

[0148] When u1=u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter meets the standard, and the first pressure pump is not controlled;

[0149] When u2=u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter meets the standard, and the second pressure pump is not controlled;

[0150] When u3=u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter meets the standard, and the third pressure pump is not controlled;

[0151] When u1<u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter does not meet the standard, and the first pressure pump is controlled to increase the transmission pressure provided by the first pressure pump;

[0152] When u2<u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter does not meet the standard, and the second pressure pump is controlled to increase the transmission pressure provided by the second pressure pump;

[0153] When u3<u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter does not meet the standard, and the third pressure pump is controlled to increase the transmission pressure provided by the third pressure pump;

[0154] When u1>u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter does not meet the standard, and the first pressure pump is controlled to reduce the transmission pressure provided by the first pressure pump;

[0155] When u2>u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter does not meet the standard, and the second pressure pump is controlled to reduce the transmission pressure provided by the second pressure pump;

[0156] When u3>u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter does not meet the standard, and the third pressure pump is controlled to reduce the transmission pressure provided by the third pressure pump;

[0157] The intelligent ultrafiltration unit compares the ultrafiltration material temperature C with the preset ultrafiltration material temperature C0, judges whether the ultrafiltration material temperature meets the standard according to the comparison result, and controls the heating and cooling device in the storage tank according to the judgment result, wherein:

[0158] When C=C0, it is determined that the temperature of the ultrafiltration material meets the standard, and the heating and cooling device in the storage tank is not controlled;

[0159] When C<C0, it is determined that the temperature of the ultrafiltration material does not meet the standard, the heating cooler in the storage tank is turned on, and the pure water in the storage tank is heated;

[0160] When C1>C0, it is determined that the temperature of the ultrafiltration material does not meet the standard, the heating cooler in the storage tank is turned on, and the pure water in the storage tank is refrigerated.

[0161] Specifically, the first real-time membrane flux Js1 refers to the ratio of the volume of fluid passing through the membrane per unit time to the effective area of ​​the membrane in the first ultrafilter, the second real-time membrane flux Js2 refers to the ratio of the volume of fluid passing through the membrane per unit time to the effective area of ​​the membrane in the second ultrafilter, the third real-time membrane flux Js3 refers to the ratio of the volume of fluid passing through the membrane per unit time to the effective area of ​​the membrane in the third ultrafilter, the fitting coefficient of the first ultrafilter refers to the coefficient of the relationship between the membrane flux J1 of the first ultrafilter and the ultrafiltration pressure U1, the feed flow rate V1 and the temperature T1, the fitting coefficient of the second ultrafilter refers to the coefficient of the relationship between the membrane flux J2 of the second ultrafilter and the ultrafiltration pressure U2, the feed flow rate V2 and the temperature T2, the third The fitting coefficient of the ultrafilter refers to the coefficient of the relationship between the membrane flux J3 of the third ultrafilter and the ultrafiltration pressure U3, the feed flow rate V3 and the temperature T3. The preset material viscosity N01 of the first ultrafilter refers to the ideal viscosity value of the material in the first ultrafilter, the material viscosity N02 of the second ultrafilter refers to the ideal viscosity value of the material in the second ultrafilter, and the material viscosity N03 of the third ultrafilter refers to the ideal viscosity value of the material in the third ultrafilter. The first difference ratio refers to the difference ratio between the membrane flux J1 of the first ultrafilter and the real-time membrane flux Js1, the second difference ratio refers to the difference ratio between the membrane flux J2 of the second ultrafilter and the real-time membrane flux Js2, and the third difference ratio refers to the difference ratio between the membrane flux J3 of the third ultrafilter and the real-time membrane flux Js 3, the preset first difference ratio Jc01 refers to the standard deviation ratio of the first ultrafilter, the preset second difference ratio Jc02 refers to the standard deviation ratio of the second ultrafilter, the preset third difference ratio Jc03 refers to the standard deviation ratio of the third ultrafilter, the difference j1 refers to the difference between the membrane flux prediction value of the first ultrafilter and the preset membrane flux prediction value, the difference j2 refers to the difference between the membrane flux prediction value of the second ultrafilter and the preset membrane flux prediction value, the difference j3 refers to the difference between the membrane flux prediction value of the third ultrafilter and the preset membrane flux prediction value, the preset first difference j01 refers to the standard deviation value of the first ultrafilter, the preset second difference j02 refers to the standard deviation value of the second ultrafilter, The preset third difference j03 refers to the standard deviation value of the third ultrafilter, the preset material flow rate v01 of the first ultrafilter refers to the ideal flow rate value of the material in the first ultrafilter, the preset material flow rate v02 of the second ultrafilter refers to the ideal flow rate value of the material in the second ultrafilter, the preset material flow rate v03 of the third ultrafilter refers to the ideal flow rate value of the material in the third ultrafilter, the preset first ultrafilter ultrafiltration pressure u01 refers to the ideal ultrafiltration pressure value of the first ultrafilter, the preset second ultrafiltration pressure u02 refers to the ideal ultrafiltration pressure value of the second ultrafilter, the preset third ultrafiltration pressure u03 refers to the ideal ultrafiltration pressure value of the third ultrafilter, and the preset ultrafiltration material temperature C0 refers to the ideal temperature value of the ultrafiltration material.

[0162] Specifically, the intelligent ultrafiltration unit synchronously calculates the real-time membrane flux of the three ultrafilters, and dynamically correlates the pressure, flow rate, and temperature parameters with the prediction model to form a closed-loop feedback system, automatically adjusting the membrane flux set value to ensure the best filtration efficiency under complex working conditions. At the same time, a three-level pressure control strategy is adopted in conjunction with dynamic adjustment of the valve opening to effectively avoid membrane damage caused by overpressure operation, and intelligent temperature compensation stabilizes the membrane working environment in the optimal range, thereby extending the service life of the membrane component and reducing maintenance costs.

[0163] So far, the technical solutions of the present invention have been described in conjunction with the preferred embodiments shown in the accompanying drawings. However, it is easy for those skilled in the art to understand that the protection scope of the present invention is obviously not limited to these specific embodiments. Without departing from the principle of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will fall within the protection scope of the present invention.

Claims

1. A special ultrafiltration device for the manufacture of biopharmaceuticals, characterized in that: The device comprises: A biopharmaceutical material storage tank, connected to the first feed pipe, for storing biopharmaceutical materials; A first pressure pipeline, one end of which is connected to the first feed pipe, and one end of which is away from the first feed pipe is connected to the first pressure pump, for transmitting the transmission pressure of the first pressure pump to the first feed pipe; A first pressure pump connected to the first pressure pipeline and used to provide transmission pressure; A first feeding pipe, one end of which is connected to the biopharmaceutical material storage tank, the end of which is away from the biopharmaceutical material storage tank is connected to the first ultrafilter, and the end of which is close to the first ultrafilter is connected to the first pressure pipeline, for transmitting the biopharmaceutical material to the first ultrafilter; An ultrafilter cleaning liquid pipeline, which is connected to the first ultrafilter, the second ultrafilter and the third ultrafilter one by one, and one end of which is far away from the first ultrafilter is connected to the storage tank, and is used to transfer the cleaning liquid in the storage tank to the first ultrafilter, the second ultrafilter and the third ultrafilter respectively; A first ultrafilter, one end of which is connected to the first feed pipe, one end of which is close to the first feed pipe is connected to the ultrafilter cleaning liquid pipeline, one end of which is away from the ultrafilter cleaning liquid pipeline is connected to the ultrafilter waste liquid transmission pipeline, and one end of which is away from the first feed pipe is connected to the second feed pipe, for removing impurities in the biopharmaceutical material and preliminarily concentrating the target molecules to obtain a first biopharmaceutical material; An ultrafilter waste liquid transmission pipeline, which is connected to the first ultrafilter, the second ultrafilter and the third ultrafilter one by one, and its end close to the second ultrafilter and the third ultrafilter is connected to the waste liquid storage tank, and its end away from the first ultrafilter is connected to the storage tank, and is used to transmit the waste liquid output by the first ultrafilter, the second ultrafilter and the third ultrafilter to the waste liquid storage tank; A second feeding pipe, one end of which is connected to the first ultrafilter, the end of which is far from the first ultrafilter is connected to the second ultrafilter, the end of which is close to the first ultrafilter is connected to the second pressure pipeline, and the end of which is far from the second pressure pipeline is connected to the first transmission pipeline, for transmitting the first biological drug material in the first ultrafilter to the second ultrafilter; A waste liquid storage tank, which is connected to the ultrafilter waste liquid transmission pipeline and is used to store the waste liquid output by the first ultrafilter, the second ultrafilter and the third ultrafilter; A third feeding pipe, one end of which is connected to the second ultrafilter, the end of which is far from the second ultrafilter is connected to the third ultrafilter, the end of which is close to the second ultrafilter is connected to the third pressure pump, and the end of which is far from the third pressure pump is connected to the second transmission pipeline, for transmitting the second biological drug material in the second ultrafilter to the third ultrafilter; A second ultrafilter, one end of which is connected to the second feed pipe, one end of which is close to the second feed pipe is connected to the ultrafilter cleaning liquid pipeline, one end of which is away from the ultrafilter cleaning liquid pipeline is connected to the ultrafilter waste liquid transmission pipeline, and one end of which is away from the second feed pipe is connected to the third feed pipe, for separating medium molecular weight impurities in the first biopharmaceutical material and performing secondary concentration on the first biopharmaceutical material to obtain a second biopharmaceutical material; a fourth feed pipe, one end of which is connected to the third ultrafilter, and one end of which is away from the third ultrafilter is connected to the biopharmaceutical collection tank, and is used to transfer the third biopharmaceutical material in the third ultrafilter to the biopharmaceutical collection tank; A third ultrafilter, one end of which is connected to the third feed pipe, one end of which is close to the third feed pipe is connected to the ultrafilter cleaning liquid pipeline, one end of which is away from the ultrafilter cleaning liquid pipeline is connected to the ultrafilter waste liquid transmission pipeline, and one end of which is away from the third feed pipe is connected to the fourth feed pipe, for removing small molecular impurities in the second biopharmaceutical material to obtain a third biopharmaceutical material; A biopharmaceutical collection tank connected to the third ultrafilter and used for storing a third biopharmaceutical material; A storage tank, one end of which is connected to the ultrafilter cleaning liquid pipeline, and the other end of which is connected to the ultrafilter waste liquid transmission pipeline, is used to store cleaning liquid and pure water, and a heating cooler is provided at the end storing pure water for heating and cooling the pure water; A second drug buffer tank, connected to the second transmission pipeline, for storing the second biological drug material in the second ultrafilter; A first drug buffer tank, connected to the first transmission pipeline, for storing the first biological drug material in the first ultrafilter; A first transmission pipeline, one end of which is connected to the second feeding pipe, and one end of which is away from the second feeding pipe is connected to the first drug buffer tank, for transmitting the first biological drug material; A second transmission pipeline, one end of which is connected to the fourth feeding pipe, and one end of which is away from the fourth feeding pipe is connected to the second drug buffer tank, for transmitting the second biological drug material; a second pressure pump connected to the second pressure pipeline and used for providing transmission pressure; a third pressure pump connected to the third pressure pipeline and used for providing transmission pressure; The intelligent module is connected to the special ultrafiltration device for manufacturing biological medicines and is used for intelligently controlling the special ultrafiltration device for manufacturing biological medicines.

2. The dedicated ultrafiltration device for biopharmaceutical manufacturing according to claim 1, characterized in that: The smart module comprises: A data acquisition unit, used to collect operating data of the dedicated ultrafiltration device for manufacturing biological drugs; A membrane flux calculation unit, used to calculate the first real-time membrane flux, the second real-time membrane flux and the third real-time membrane flux according to the operation data; A prediction and analysis unit, used for performing prediction and analysis on the first ultrafilter, the second ultrafilter and the third ultrafilter; The intelligent ultrafiltration unit is used to control the first ultrafilter, the second ultrafilter, the third ultrafilter and the first pressure pump, the second pressure pump and the third pressure pump.

3. The dedicated ultrafiltration device for biopharmaceutical manufacturing according to claim 2, characterized in that: The membrane flux calculation unit calculates the first real-time membrane flux Js1, the second real-time membrane flux Js2 and the third real-time membrane flux Js3, and sets the fluid volume of the first ultrafiltration membrane to be L1, the first effective area of ​​the membrane to be A1, and the first ultrafiltration time to be T1; the fluid volume of the second ultrafiltration membrane to be L2, the second effective area of ​​the membrane to be A2, and the second ultrafiltration time to be T2; the fluid volume of the third ultrafiltration membrane to be L3, the third effective area of ​​the membrane to be A3, and the third ultrafiltration time to be T3, and the calculation methods of the first real-time membrane flux Js1, the second real-time membrane flux Js2 and the third real-time membrane flux Js3 are respectively:

4. The dedicated ultrafiltration device for biopharmaceutical manufacturing according to claim 2, characterized in that: The prediction and analysis unit is provided with an ultrafiltration prediction and analysis model, which sets the relationship between the membrane flux J1 of the first ultrafilter and the ultrafiltration pressure U1 of the first ultrafilter, the ultrafiltration drug feed flow rate V1 of the first ultrafilter and the first ultrafiltration temperature T1, the relationship between the membrane flux J2 of the second ultrafilter and the ultrafiltration pressure U2 of the second ultrafilter, the ultrafiltration drug feed flow rate V2 of the second ultrafilter and the second ultrafiltration temperature T2, and the relationship between the membrane flux J3 of the third ultrafilter and the ultrafiltration pressure U3 of the third ultrafilter, the ultrafiltration drug feed flow rate V3 of the third ultrafilter and the third ultrafiltration temperature T3, wherein: The relationship between the membrane flux J1 of the first ultrafilter and the ultrafiltration pressure U1 of the first ultrafilter, the ultrafiltration drug feed flow rate V1 of the first ultrafilter and the first ultrafiltration temperature T1 is J1=a1*U1 2 +b1*V1+c1*T1+d1; The relationship between the membrane flux J2 of the second ultrafilter and the ultrafiltration pressure U2 of the second ultrafilter, the ultrafiltration drug feed flow rate V2 of the second ultrafilter and the second ultrafiltration temperature T2 is J2 = a2*U2 2 +b2*V2+c2*T2+d2; The relationship between the membrane flux J3 of the third ultrafilter and the ultrafiltration pressure U3 of the third ultrafilter, the ultrafiltration drug feed flow rate V3 of the third ultrafilter and the third ultrafiltration temperature T3 is J3 = a3*U3 2 +b3*V3+c3*T3+d3; a1, b1, c1, d1 are the fitting coefficients of the first ultrafilter, a2, b2, c2, d2 are the fitting coefficients of the second ultrafilter, and a3, b3, c3, d3 are the fitting coefficients of the third ultrafilter.

5. The dedicated ultrafiltration device for biopharmaceutical production according to claim 4, characterized in that: The ultrafiltration prediction and analysis model also compares the material viscosity N1 of the first ultrafilter, the material viscosity N2 of the second ultrafilter, and the material viscosity N3 of the third ultrafilter with the preset material viscosity N01 of the first ultrafilter, the material viscosity N02 of the second ultrafilter, and the material viscosity N03 of the third ultrafilter, respectively, and judges the viscosity of the material viscosity N1 of the first ultrafilter, the material viscosity N2 of the second ultrafilter, and the material viscosity N3 of the third ultrafilter and the effectiveness of the membrane flux J1 of the first ultrafilter, the membrane flux J2 of the second ultrafilter, and the membrane flux J3 of the third ultrafilter according to the comparison results, and adjusts the membrane flux J1 of the first ultrafilter, the membrane flux J2 of the second ultrafilter, and the membrane flux J3 of the third ultrafilter according to the judgment results.

6. The dedicated ultrafiltration device for biopharmaceutical production according to claim 5, characterized in that: The ultrafiltration prediction and analysis model also calculates the difference ratio of the membrane flux J1 and the first real-time membrane flux Js1 of the first ultrafilter, the membrane flux J2 and the second real-time membrane flux Js2 of the second ultrafilter, and the membrane flux J3 and the third real-time membrane flux Js3 of the third ultrafilter, respectively, to obtain the first difference ratio, the second difference ratio and the third difference ratio, wherein: The first difference ratio is Jc1, The second difference ratio is Jc2, The third difference ratio is Jc3, 7. The dedicated ultrafiltration device for biopharmaceutical production according to claim 6, characterized in that: The prediction and analysis unit compares the first difference ratio Jc1, the second difference ratio Jc2 and the third difference ratio Jc3 with the preset first difference ratio Jc01, the preset second difference ratio Jc02 and the preset third difference ratio Jc03 respectively, compares and judges the actual compliance status of each difference ratio according to the comparison results, and optimizes each fitting coefficient according to the judgment results.

8. The dedicated ultrafiltration device for biopharmaceutical production according to claim 7, characterized in that: The prediction and analysis unit obtains the difference j1 between the first ultrafilter membrane flux prediction value and the preset first ultrafilter membrane flux prediction value, the difference j2 between the second ultrafilter membrane flux prediction value and the preset second ultrafilter membrane flux prediction value, and the difference j3 between the third ultrafilter membrane flux prediction value and the preset third ultrafilter membrane flux prediction value according to the ultrafiltration prediction and analysis model, and compares them with the preset first difference j01, the preset second difference j02, and the preset third difference j03 respectively; based on the comparison results, the rationality of the first ultrafilter membrane flux prediction value, the second ultrafilter membrane flux prediction value, and the third ultrafilter membrane flux prediction value output by the ultrafiltration prediction and analysis model are judged, and the material flow rate of each ultrafilter is monitored based on the judgment results.

9. The dedicated ultrafiltration device for biopharmaceutical manufacturing according to claim 2, characterized in that: The intelligent ultrafiltration unit monitors the material flow rate of the first ultrafilter, the material flow rate of the second ultrafilter and the material flow rate of the third ultrafilter, obtains the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter, and obtains the material flow rate v3 of the third ultrafilter, and compares the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter, and the material flow rate v3 of the third ultrafilter with the preset material flow rate v01 of the first ultrafilter, the preset material flow rate v02 of the second ultrafilter, and the preset material flow rate v03 of the third ultrafilter, respectively, and judges the effectiveness of the material flow rate v1 of the first ultrafilter, the material flow rate v2 of the second ultrafilter, and the material flow rate v3 of the third ultrafilter according to the comparison results, and controls the first ultrafilter, the second ultrafilter, and the third ultrafilter according to the judgment results, wherein: When v1=v01, the effective condition of the material flow rate v1 of the first ultrafilter is determined to be effective, and the first ultrafilter is not controlled; When v2=v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be effective, and the second ultrafilter is not controlled; When v3=v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be valid, and the third ultrafilter is not controlled; When v1<v01, the validity of the material flow rate v1 of the first ultrafilter is determined to be invalid, and the first ultrafilter is controlled to increase the valve opening in the first ultrafilter; When v2<v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be invalid, and the second ultrafilter is controlled to increase the valve opening in the second ultrafilter; When v3<v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be invalid, and the third ultrafilter is controlled to increase the valve opening in the third ultrafilter; When v1>v01, the effective condition of the material flow rate v1 of the first ultrafilter is determined to be invalid, and the first ultrafilter is controlled to reduce the valve opening in the first ultrafilter; When v2>v02, the effective condition of the material flow rate v2 of the second ultrafilter is determined to be invalid, and the second ultrafilter is controlled to reduce the valve opening in the second ultrafilter; When v3>v03, the validity of the material flow rate v3 of the third ultrafilter is determined to be invalid, and the third ultrafilter is controlled to reduce the valve opening in the third ultrafilter.

10. The dedicated ultrafiltration device for biopharmaceutical production according to claim 9, characterized in that: The intelligent ultrafiltration unit also compares the first ultrafilter ultrafiltration pressure u1, the second ultrafilter ultrafiltration pressure u2, and the third ultrafilter ultrafiltration pressure u3 with the preset first ultrafilter ultrafiltration pressure u01, the preset second ultrafilter ultrafiltration pressure u02, and the preset third ultrafilter ultrafiltration pressure u03, respectively, and judges the compliance of the first ultrafilter ultrafiltration pressure u1, the second ultrafilter ultrafiltration pressure u2, and the third ultrafilter ultrafiltration pressure u3 according to the comparison results, and controls the first pressure pump, the second pressure pump, and the third pressure pump according to the judgment results, wherein: When u1=u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter meets the standard, and the first pressure pump is not controlled; When u2=u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter meets the standard, and the second pressure pump is not controlled; When u3=u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter meets the standard, and the third pressure pump is not controlled; When u1<u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter does not meet the standard, and the first pressure pump is controlled to increase the transmission pressure provided by the first pressure pump; When u2<u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter does not meet the standard, and the second pressure pump is controlled to increase the transmission pressure provided by the second pressure pump; When u3<u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter does not meet the standard, and the third pressure pump is controlled to increase the transmission pressure provided by the third pressure pump; When u1>u01, it is determined that the ultrafiltration pressure u1 of the first ultrafilter does not meet the standard, and the first pressure pump is controlled to reduce the transmission pressure provided by the first pressure pump; When u2>u02, it is determined that the ultrafiltration pressure u2 of the second ultrafilter does not meet the standard, and the second pressure pump is controlled to reduce the transmission pressure provided by the second pressure pump; When u3>u03, it is determined that the ultrafiltration pressure u3 of the third ultrafilter does not meet the standard, and the third pressure pump is controlled to reduce the transmission pressure provided by the third pressure pump.

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