阅读说明：本技术 一种阵列式反应器使用方法 (Application method of array reactor ) 是由 陈皓 杨开琳 于 2020-12-03 设计创作，主要内容包括：本发明涉及生物药品生产技术领域,尤其为一种阵列式反应器使用方法,其具体操作步骤如下：S1：反应器F1、F2、F3、F4、F5、F6、F7、F8在新批次启动前,完成耗材安装与生产试剂补充,本发明通过设计实现了个性化生物药品基于反应器体系的分布式、并行化、智能化生产,可有效服务临床多病人、多轮次病患的并发式需求,大大降低辅助设备,特别是检测设备、反应器控制软件的重复投入,有效降低生产过程中的直接成本,相比较传统反应器,大大降低对空间面积的需求,研发过程中,大大加速药品的对比、对照试验,加速成药过程,可有效增加数据的累计,便于大型数据集的深度价值挖掘,操作方便,功能丰富,且实用性较高,具有一定的推广价值。(The invention relates to the technical field of biological medicine production, in particular to a use method of an array type reactor, which comprises the following specific operation steps: s1: the reactors F1, F2, F3, F4, F5, F6, F7 and F8 complete consumable installation and production reagent supplement before starting a new batch, the invention realizes the distributed, parallel and intelligent production of personalized biological medicines based on a reactor system through design, can effectively serve the concurrent requirements of clinical multiple patients and multiple rounds of patients, greatly reduces the repeated investment of auxiliary equipment, particularly detection equipment and reactor control software, effectively reduces the direct cost in the production process, greatly reduces the requirements on space area compared with the traditional reactor, greatly accelerates the comparison and contrast tests of medicines in the research and development process, accelerates the medicine forming process, can effectively increase the data accumulation, is convenient for the deep value mining of a large-scale data set, is convenient to operate, has rich functions, has higher practicability and has certain popularization value.)

1. The application method of the array reactor comprises the following specific operation steps:

s1: the reactors F1, F2, F3, F4, F5, F6, F7 and F8 complete consumable installation and production reagent supplement before a new batch is started;

s2: reactors F1, F2, F3, F4, F5, F6, F7 and F8 enter the interior of the array system quick positioning unit D in sequence to complete quick positioning and installation;

s3: then adding production seed samples into reactors F1, F2, F3, F4, F5, F6, F7 and F8, and formally starting production;

s4: carrying sampling consumables H by using a robot unit J to automatically move to automatic sampling units at the back of each reactor to carry out full-automatic sampling;

s5: then the robot unit J transfers the sample to a full-automatic analysis module Q for biochemical index analysis;

s6: calculating and planning a process by using a comprehensive control management system K to adjust parameters;

s7: after finishing production, confirming the standard;

s8: reactors F1, F2, F3, F4, F5, F6, F7 and F8 are sequentially withdrawn from the interior of the array system quick positioning unit D, and separation and disassembly are completed;

s9: independent off-line product harvesting was performed for reactors F1, F2, F3, F4, F5, F6, F7, F8.

2. The method of using an array reactor of claim 1, wherein: the automatic sampling unit in the S4 is connected with reactors F1, F2, F3, F4, F5, F6, F7 and F8 through fully-closed pipelines.

3. The method of using an array reactor of claim 1, wherein: the automatic sampling unit in S4 includes: the automatic cleaning sampling probe comprises a self-cleaning sampling probe Z1, a full-automatic cleaning unit or a liquid seal disinfection unit Z2 for the outer surface of the sampling probe, and a sampling process waste liquid collection unit Z3.

4. The method of using an array reactor of claim 1, wherein: the full-automatic analysis module Q in S5 includes: the device comprises a sample filling unit, a detection liquid refrigerating unit, a biochemical indicator, a cell imager, a cell counter and a flow cytometer.

5. The method of using an array reactor of claim 1, wherein: the steps S4-S6 are operated periodically until the batch is finished.

6. The method of using an array reactor of claim 1, wherein: reactors F1, F2, F3, F4, F5, F6, F7 and F8 in the S1 respectively comprise a reactor circulating unit X1 and a liquid storage unit X2.

Technical Field

The invention relates to the technical field of biological medicine production, in particular to a use method of an array type reactor.

Background

In the process of rapid development of biopharmaceutical production, reactors of various types and specifications have become the main means of biopharmaceutical production, especially large-scale production. Currently mainstream antibody drugs such as PD1, and various types of vaccines, are usually produced using hundreds, thousands, or even tens of thousands of liters reactors. The traditional reactor is a production mode with higher efficiency in the traditional standardized medicine production.

However, the rapid change of the production mode of the biological medicines requires further optimized upgrade of the application mode of the reactor:

1. the sample sources of novel biological medicines such as cell medicines and the like are from different donors, efficient amplification production needs to be carried out based on different sample sources, the humanized cell sources have an amplification upper limit (such as T cells, the amplification upper limit is within 1000 times), the samples from the donor sources generally have a reactor system of several liters and can meet the production requirement, the traditional reactor volume of hundreds of liters and thousands of liters loses the significance under the production environment, and the small-batch, multi-batch and personalized production can better meet the actual production requirement;

2. the continuous perfusion reactor greatly improves the production density and efficiency of the medicine, greatly reduces the volume of the reactor compared with the traditional reactor, and makes the production of a plurality of reactors on the same site possible. In the traditional production mode, the same production facility generally only produces single-class standardized medicines, but the rapid development of novel medicines needs the same production facility to complete the production of medicines of different types and different adaptation populations;

3. in the traditional reactor, each reactor needs to be matched with a complete auxiliary system, the cost is high, and the utilization efficiency can be further improved; in order to meet the requirement of efficient multi-batch production of personalized biopharmaceuticals, there is a need for an array reactor using method that improves on the above problems.

Disclosure of Invention

The present invention is directed to a method for using an array reactor to solve the above problems.

In order to achieve the purpose, the invention provides the following technical scheme:

the application method of the array reactor comprises the following specific operation steps:

s1: the reactors F1, F2, F3, F4, F5, F6, F7 and F8 complete consumable installation and production reagent supplement before a new batch is started;

s2: reactors F1, F2, F3, F4, F5, F6, F7 and F8 enter the interior of the array system quick positioning unit D in sequence to complete quick positioning and installation;

s3: then adding production seed samples into reactors F1, F2, F3, F4, F5, F6, F7 and F8, and formally starting production;

s4: carrying sampling consumables H by using a robot unit J to automatically move to automatic sampling units at the back of each reactor to carry out full-automatic sampling;

s5: then the robot unit J transfers the sample to a full-automatic analysis module Q for biochemical index analysis;

s6: calculating and planning a process by using a comprehensive control management system K to adjust parameters;

s7: after finishing production, confirming the standard;

s8: reactors F1, F2, F3, F4, F5, F6, F7 and F8 are sequentially withdrawn from the interior of the array system quick positioning unit D, and separation and disassembly are completed;

s9: independent off-line product harvesting was performed for reactors F1, F2, F3, F4, F5, F6, F7, F8.

Preferably, the automatic sampling unit in the S4 is connected with reactors F1, F2, F3, F4, F5, F6, F7 and F8 through fully-closed pipelines.

Preferably, the automatic sampling unit in S4 includes: the automatic cleaning sampling probe comprises a self-cleaning sampling probe Z1, a full-automatic cleaning unit or a liquid seal disinfection unit Z2 for the outer surface of the sampling probe, and a sampling process waste liquid collection unit Z3.

Preferably, the full-automatic analysis module Q in S5 includes: the device comprises a sample filling unit, a detection liquid refrigerating unit, a biochemical indicator, a cell imager, a cell counter and a flow cytometer.

Preferably, the steps S4-S6 are performed periodically until the batch is finished.

Preferably, each of the reactors F1, F2, F3, F4, F5, F6, F7 and F8 in the S1 comprises a reactor circulation unit X1 and a liquid storage unit X2.

Compared with the prior art, the invention has the beneficial effects that:

in the invention, through the design of the array type reactor, the automatic sampling unit and the full-automatic analysis module Q, the distributed, parallel and intelligent production of personalized biological medicines based on a reactor system can be realized, the concurrent requirements of clinical multiple patients and multiple rounds of patients can be effectively served, the repeated investment of auxiliary equipment, particularly detection equipment and reactor control software is greatly reduced, the direct cost in the production process is effectively reduced, compared with the traditional reactor, the requirements on space area are greatly reduced, the comparison and contrast tests of medicines are greatly accelerated in the research and development process, the medicine forming process is accelerated, the data accumulation can be effectively increased, and the deep value mining of a large-scale data set is facilitated.

Drawings

FIG. 1 is a schematic diagram of a reactor unit according to the present invention;

FIG. 2 is a general layout of a reactor array system according to the present invention;

FIG. 3 is a schematic diagram of a fully automatic sampling unit according to the present invention;

FIG. 4 is a top view of the overall layout of the reactor array system of the present invention;

FIG. 5 is a schematic view of a fully automatic detection unit according to the present invention;

FIG. 6 is a schematic diagram of an integrated information system according to the present invention;

FIG. 7 is a schematic view of a reactor quick positioning unit according to the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments, and all other embodiments obtained by a person of ordinary skill in the art without any creative work based on the embodiments of the present invention belong to the protection scope of the present invention.

Referring to fig. 1-7, the present invention provides a technical solution:

the application method of the array reactor comprises the following specific operation steps:

s1: the reactors F1, F2, F3, F4, F5, F6, F7 and F8 complete consumable installation and production reagent supplement before a new batch is started;

s2: reactors F1, F2, F3, F4, F5, F6, F7 and F8 enter the interior of the array system quick positioning unit D in sequence to complete quick positioning and installation;

s3: then adding production seed samples into reactors F1, F2, F3, F4, F5, F6, F7 and F8, and formally starting production;

s4: carrying sampling consumables H by using a robot unit J to automatically move to automatic sampling units at the back of each reactor to carry out full-automatic sampling;

s5: then the robot unit J transfers the sample to a full-automatic analysis module Q for biochemical index analysis;

s6: calculating and planning a process by using a comprehensive control management system K to adjust parameters;

s7: after finishing production, confirming the standard;

s8: reactors F1, F2, F3, F4, F5, F6, F7 and F8 are sequentially withdrawn from the interior of the array system quick positioning unit D, and separation and disassembly are completed;

s9: independent off-line product harvesting was performed for reactors F1, F2, F3, F4, F5, F6, F7, F8.

Further, the automatic sampling unit in the S4 is connected with reactors F1, F2, F3, F4, F5, F6, F7 and F8 through fully-closed pipelines.

Further, the automatic sampling unit in S4 includes: the automatic cleaning sampling probe comprises a self-cleaning sampling probe Z1, a full-automatic cleaning unit or a liquid seal disinfection unit Z2 for the outer surface of the sampling probe, and a sampling process waste liquid collection unit Z3.

Further, the fully automatic analysis module Q in S5 includes: the device comprises a sample filling unit, a detection liquid refrigerating unit, a biochemical indicator, a cell imager, a cell counter and a flow cytometer.

Further, the steps S4-S6 are performed periodically until the batch is finished.

Further, each of the reactors F1, F2, F3, F4, F5, F6, F7, and F8 in S1 includes a reactor circulation unit X1 and a liquid storage unit X2.

The specific implementation case is as follows:

step 1, firstly, consumable installation and production reagent supplement are carried out on reactors F1, F2, F3, F4, F5, F6, F7 and F8, wherein each of the reactors F1, F2, F3, F4, F5, F6, F7 and F8 comprises a reactor circulation unit X1 and a liquid storage unit X2;

step 2, reactor fixation: as shown in the overall layout diagram of the reactor array system in fig. 2, reactors F1, F2, F3, F4, F5, F6, F7 and F8 are sequentially installed into the fast positioning unit D of the array system to complete fast positioning installation;

step 3, adding production seed samples into reactors F1, F2, F3, F4, F5, F6, F7 and F8 in sequence, and formally starting production;

step 4, sampling: as shown in the schematic diagram of the fully automatic sampling unit in fig. 3, the fully automatic sampling unit is connected with reactors F1, F2, F3, F4, F5, F6, F7 and F8 through fully closed pipelines, and comprises: the automatic cleaning and disinfecting device comprises a self-cleaning sampling needle Z1, a full-automatic cleaning unit or a liquid seal disinfecting unit Z2 on the outer surface of the sampling needle and a sampling process waste liquid collecting unit Z3, a robot unit J is used for automatically conveying sampling consumables H to automatic sampling units at the back of each reactor, the self-cleaning sampling needle Z1 is used for sampling, the full-automatic cleaning unit or the liquid seal disinfecting unit Z2 on the outer surface of the sampling needle is used for cleaning and disinfecting, and the sampling process waste liquid collecting unit Z3 is used for collecting waste liquid in a centralized manner;

and 5, analyzing: as shown in fig. 5, the full-automatic detection unit is schematically illustrated, the robot unit J is used to transfer the sample to the full-automatic analysis module Q for analysis of biochemical indexes, and the full-automatic analysis module Q includes: the device comprises a sample filling unit, a detection liquid refrigerating unit, a biochemical indicator, a cell imager, a cell counter and a flow cytometer;

and 6, adjusting: as shown in the schematic diagram of the integrated novel system in fig. 6, the integrated control management system K is used to calculate and plan a process for parameter adjustment, and steps 4-6 are performed periodically until the batch production is completed;

step 7, after the production is finished, the standard is confirmed;

step 8, disassembling the reactor: as shown in the schematic diagram of the reactor quick positioning unit in fig. 7, the reactors F1, F2, F3, F4, F5, F6, F7, and F8 are sequentially withdrawn from the interior of the array system quick positioning unit D to complete separation and disassembly;

and 9, finally carrying out independent off-line product harvesting on reactors F1, F2, F3, F4, F5, F6, F7 and F8 in sequence.

The process achieves the following advantages by design:

1) the distributed, parallel and intelligent production of the personalized biological medicines based on the reactor system is realized, and the concurrent requirements of clinical multiple patients and multiple rounds of patients can be effectively met;

2) the repeated investment of auxiliary equipment, particularly detection equipment and reactor control software is greatly reduced, and the direct cost in the production process is effectively reduced;

3) compared with the traditional reactor, the reactor greatly reduces the requirement on the space area;

4) in the research and development process, the contrast and contrast tests of the medicine are greatly accelerated, and the medicine forming process is accelerated;

5) the accumulation of data can be effectively increased, and the deep value mining of a large data set is facilitated.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.