Process development assistance system and process development assistance method

Abstract

To provide a process development assistance system capable of creating a small-scale experimental condition based on a culture condition specific to a large-scale experiment even when experimental data on a large scale is insufficient.SOLUTION: A process development assistance system S according to the present invention comprises: a calculation unit 41 that, on the basis of experimental data that includes information relating to the amount of change in a plurality of parameters obtained by subjecting a culture target to a culture experiment in a first-scale culture facility under a first culture condition, and second-scale facility information that includes information on at least the shape of a second-scale culture facility that is larger than the first-scale culture facility, simulates the case where the culture target is cultured in the second-scale culture facility under a second culture condition, and outputs condition range information indicating the relationship between the second culture condition and the plurality of parameters on the basis of a result of the simulation; and a planning unit 42 that, on the basis of these, outputs a culture condition for the culture experiment in the first-scale culture facility.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a process development support system and a process development support method. [Background technology]

[0002] In the context of SDGs, climate change issues, and the realization of carbon neutrality, there is a demand for both sustainable economic growth and the resolution of social issues. In the field of manufacturing, as the need for alternatives to petroleum products increases, biomanufacturing (production of materials using microorganisms, etc.) that makes the most of biological functions through smart cell technology and other advances is attracting attention.

[0003] The starting point for the industrialization of biomanufacturing is the development of microorganisms that make the most of the biological functions of the organisms themselves, such as by making them smart cells. After that, it will be necessary to develop a process to determine the culture conditions and scale-up technology to industrialize the cultivation in culture tanks exceeding several thousand liters.

[0004] In particular, in process development, after microorganisms capable of producing a substance are selected, small-scale experiments at the level of a few mL to a few liters are carried out to determine the culture conditions for production. Here, it is necessary to determine the requirements for the culture medium, oxygen supply, and culture environment for production. For this reason, optimal culture conditions are derived by combining multiple conditions and ranges of controllable parameter items.

[0005] However, since the number of combinations is enormous, in consideration of time and cost, culture conditions are generally explored within a very limited range of combinations based on experience. Therefore, in some cases, a computer is used to efficiently search for optimal culture conditions for a large number of combinations. Related prior art includes the technique described in Patent Document 1.

[0006] Patent Document 1 discloses a "cell culture process exploration method having a process condition generating step of generating a plurality of process conditions for culturing cells, a culture result predicting step of acquiring a predicted cell culture result for each of the plurality of process conditions generated in the process condition generating step, and an optimized process condition acquiring step of finding optimal process conditions from the culture prediction result acquired in the culture result predicting step."

[0007] In addition, the productivity of the culture conditions obtained in the small-scale experiment is confirmed in a large-scale culture tank with a capacity of several hundred or several thousand liters. In particular, in this scale-up, it is common to maintain the geometric shape similar and to maintain the operating factors constant by calculating the input power and other factors in a chemical engineering manner. However, this examination alone may not be enough to fully utilize the performance of the microorganism, and productivity may decrease. Therefore, in reality, engineers respond by tuning and fitting the oxygen supply and stirring speed control intuitively based on their past experience. However, this takes time and effort, and there are often cases where the cause cannot be identified. Furthermore, since productivity decreases without the cause being identified, there is a need to go back to the small-scale experiment to verify it again, which not only increases the number of experiments on a large scale, but also takes a considerable amount of time.

[0008] Furthermore, in culture conditions obtained by combining a limited range of conditions on a small scale, even if similar conditions are used, the conditions of the culture tank are different and the environmental conditions vary as the scale increases, so that the conditions on a large scale are not reflected, and productivity may be impaired. In response to this, technologies have been developed to improve the efficiency of the cycle of feedback between small-scale and large-scale results.

[0009] In addition, Patent Document 2 discloses a computer-implemented method for designing a first-scale experiment for an organism to generate first-scale performance data for use in predicting the performance of the organism at a larger second scale, the method comprising: a. determining first-scale screening conditions based at least in part on the contribution of second-scale conditions to performance parameters of a first strain of the organism at the second scale, where the first-scale screening conditions include one or more surrogates for second-scale conditions that cannot be reproduced at the first scale; b. determining first-scale screening parameters based at least in part on computer modeling of the metabolism of the organism at the second scale; and c. designing an experiment for experimentally screening a second strain of the organism under the first-scale screening conditions based at least in part on the first-scale screening parameters. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] International Publication No. 2021 / 166824 [Patent Document 2] Special Publication No. 2022-531464 Summary of the Invention [Problem to be solved by the invention]

[0011] With only data on culture conditions determined in small-scale experiments at the level of a few mL to a few L, there are uncertain conditions that cannot be reproduced or unexpected constraints in the large-scale culture tanks that are subsequently scaled up to hundreds or thousands of L or more. If these conditions are not taken into consideration, productivity cannot be obtained on a large scale, and a great deal of time and effort is required to reconsider the small-scale experiments. Therefore, in order to efficiently develop a process that scales up, it is desirable to conduct culture experiments while taking into account conditions specific to large scales that are different from small scales. However, in order to conduct experiments to try various culture conditions on a large scale, it takes a great deal of time and money for process development, and dedicated equipment is required. Therefore, it has been difficult to secure sufficient experimental data on a large scale.

[0012] Therefore, in order to make the study of scale-up more efficient, a system is desired that can create small-scale experimental conditions that take into account the specific culture conditions at a large scale, such as being able to compare the difference in behavior of the same parameter at a small scale and a large scale even when there is a lack of large-scale experimental data. Patent Documents 1 and 2 do not take the above-mentioned problems into consideration.

[0013] The present invention has been made in view of the above-mentioned circumstances, and an object of the present invention is to provide a process development support system and a process development support method that are capable of creating small-scale experimental conditions that take into account specific large-scale culture conditions even when large-scale experimental data is insufficient. [Means for solving the problem]

[0014] The process development support system of the present invention, which has solved the above-mentioned problem, comprises a memory unit that stores experimental data including information on the amount of change in multiple parameters indicating the state in a first-scale culture equipment when a culture experiment is conducted on a culture target under first culture conditions in the first-scale culture equipment, and second-scale equipment information, which is information on equipment conditions including at least shape information on a second-scale culture equipment that is larger than the first-scale culture equipment; a calculation unit that performs a simulation on the amount of change in parameters that are the same as the multiple parameters when the culture target is cultured under second culture conditions in the second-scale culture equipment based on the experimental data and the second-scale equipment information, and outputs condition range information, which is information on the relationship between the second culture conditions and the multiple parameters, based on the results of the simulation; and a planning unit that outputs the culture conditions for a culture experiment in the first-scale culture equipment based on the experimental data and the condition range information. Effect of the Invention

[0015] The present invention can provide a process development support system and a process development support method that can create small-scale experimental conditions that take into account specific large-scale culture conditions even when large-scale experimental data is insufficient. Problems, configurations and effects other than those described above will become apparent from the following description of the embodiments. [Brief description of the drawings]

[0016] [Figure 1] 1 is a configuration diagram of a process development support system according to an embodiment of the present invention. [Figure 2A] FIG. 1 is an explanatory diagram illustrating an example of the principle of a small-scale experiment condition searching program. [Figure 2B] FIG. 11 is an explanatory diagram for explaining another example of the principle of the small-scale experiment condition searching program. [Figure 2C] FIG. 11 is an explanatory diagram for explaining another example of the principle of the small-scale experiment condition searching program. [Figure 2D]FIG. 11 is an explanatory diagram for explaining another example of the principle of the small-scale experiment condition searching program. [Figure 2E] FIG. 13 is an explanatory diagram for explaining the recommendation of a more preferable first scale experiment range. [Diagram 3] FIG. 2 is an explanatory diagram for explaining a solution concept in the process development support system according to the embodiment. [Figure 4] FIG. 13 is an explanatory diagram illustrating an example in which the calculation unit outputs information about an apparatus that meets the first-scale experiment recommendation conditions. [Diagram 5] FIG. 13 is an explanatory diagram illustrating an example in which the calculation unit outputs information about an apparatus that meets the second-scale experiment recommendation conditions. [Figure 6] 13 is a flowchart illustrating an example of a culture equipment matching program. [Figure 7] 1 is a flowchart illustrating the contents of a process development support method according to the present embodiment. [Figure 8] 1 is a flowchart illustrating a specific example of a process development support method according to the present embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. In the following description, the same components are denoted by the same terms and reference numerals, and duplicate descriptions may be omitted.

[0018] In the following embodiment, an example in which the process development support system S according to the present embodiment is applied to process development for scaling up a culture process performed on a small scale (referred to as a first scale) and culturing on a large scale (referred to as a second scale) will be mainly described, but the embodiment of the process development support system S according to the present embodiment is not limited to this example. For example, the process development support system S according to the present embodiment is applicable to cases in which the culture target is not limited to a specific organism, but is also applicable to cases in which microorganisms, cellular fungi, etc. are cultured. The first scale is at least smaller in capacity than the second scale to be scaled up. The capacity is not particularly limited, but if the purpose is to obtain culture conditions in an experiment, the first scale may be a laboratory-level scale. The first scale is preferably a level of several mL to several tens of L because it is easy to handle and to carry out multiple experiments. In addition, the equipment specifications of the first scale are preferably close to those of the second scale, but are not necessarily the same, and may be a commonly used culture tank and equipment. On the other hand, the second scale may be a bench, pilot, or production scale. The second scale may be, for example, a scale of several tens of L to several tens of thousands of L. In this embodiment, the first scale and the second scale do not indicate a capacity of a certain fixed value, but indicate a capacity within a range having a predetermined width.

[0019] FIG. 1 is a configuration diagram of a process development support system S according to this embodiment. The process development support system S according to this embodiment is embodied as a management server 1, for example. The management server 1 is a computer having a communication interface 2, a storage unit 3, a control unit 4, a memory 5, an input unit 6, and an output device 7. The communication interface 2 communicates with other servers other than the management server 1, user terminals, and culture equipment.

[0020] The storage unit 3 stores various information such as experimental data, equipment information, condition range information, experimental design information, past information, first equipment information, second equipment information, matching database (DB), etc. The storage unit 3 also stores various programs such as a simulation program, a small-scale experimental condition search program, and a culture equipment matching program, which will be described later. The control unit 4 is, for example, a CPU (Central Processing Unit), and realizes various functions by reading and executing programs stored in the storage unit 3. In this embodiment, the various functions include a calculation unit 41 and a planning unit 42, which will be described later. In this embodiment, the various functions also include an extraction unit 43 and a proposal output unit 44, which will be described later.

[0021] It should be noted that the programs and the various functions do not necessarily have to correspond one-to-one. A process of reading and executing one program may correspond to two or more different functions, or a process of reading and executing two or more programs may correspond to one function. Therefore, in this embodiment, a calculation unit 41, a planning unit 42, an extraction unit 43, a proposal output unit 44, etc. are shown as configurations corresponding to the functions realized by the control unit 4, but each function is realized by reading and executing one or more programs from among a simulation program, a small-scale experiment condition search program, and a culture equipment matching program. In addition, the classification of functions or programs in this embodiment is an example, and is not limited to this example.

[0022] The memory 5 is a random access memory, a read-only memory, or the like. The input unit 6 is a keyboard, a pointing device, or the like. The output device 7 is a display, a printer, or the like. The input unit 6 and the output device 7 are direct input / output interfaces for the management server 1 .

[0023] The specific roles of the storage unit 3, the calculation unit 41, and the planning unit 42 in this embodiment are as follows.

[0024] The memory unit 3 stores the experimental data and the second-scale equipment information. The experimental data is obtained by culturing a culture subject in a first-scale culture facility. The experimental data includes information regarding the amount of change in a plurality of parameters that indicate a state in the first-scale culture facility when a culture experiment is performed on the culture target under first culture conditions in the first-scale culture facility. Note that the first culture conditions refer to the culture conditions when the culture target is cultured in the first-scale culture facility.

[0025] The experimental data may include information on the organism to be cultured, information on the culture environment including control information for the culture equipment, and information on the product produced by the organism to be cultured. Representative examples of items included in the information on the organism to be cultured include the type of organism, its characteristics, the number of passages, seeding density, etc. These items can be used as culture conditions when culturing the organism to be cultured in the first-scale culture facility.

[0026] Representative examples of items included in the information on the culture environment, including the control information of the culture equipment, include aeration volume, agitation speed, pressure, bubble information, temperature, pH, dissolved oxygen (DO) concentration and dissolved carbon dioxide (DCO2) concentration, medium concentration and additive information, and liquid volume. The set values ​​of these items can be used as culture conditions when culturing the culture subject in the first-scale culture equipment. In addition, information on the actual values ​​of these items obtained in experiments can be used as information on the amount of change in multiple parameters that indicate the state inside the first-scale culture equipment.

[0027] Representative examples of items included in the information on the product produced by the culture target organism include the results of the cultured product, the amounts of various metabolic components, etc. These items can also be used as information on the amount of change in multiple parameters that indicate the state inside the first-scale culture facility. However, the parameter items used as the experimental data are not limited to these.

[0028] The equipment information is information on equipment conditions including at least shape information on the culture equipment. The equipment information includes at least second-scale equipment information. The second-scale equipment information is information on equipment conditions including at least shape information on second-scale culture equipment that is larger than the first-scale culture equipment.

[0029] The culture equipment includes, in addition to the culture tank, equipment for supplying the culture medium, an aeration device for supplying air and oxygen, an agitator for stirring the inside of the tank, and various control devices for controlling the pH and oxygen concentration. The equipment conditions including at least shape information regarding the culture equipment include, for example, the capacity of the culture tank and its aspect ratio, the tank diameter to blade diameter ratio, the shape of the stirring blade, and other incidental equipment information. The equipment information may be information on a drawing that comprehensively includes the above information.

[0030] The matching DB stores information on candidates for culture tanks or culture devices that correspond to second-scale culture facilities. Information on the candidates for culture tanks or culture devices in the matching DB, such as specifications, names, manufacturers, providers, bases, locations, costs for use, usage history, usage status, peripheral equipment, etc., is stored. In addition, the information on specifications includes the chassis for culture, products, tank capacity, equipment specifications, etc., for the culture tank or culture device.

[0031] The past information is information for identifying the type and range of parameters that affect the degree to which the culture result satisfies a predetermined standard. The past information is, for example, information on past performance data of the culture process at the first scale or the second scale. Based on the performance data, the type and range of parameters that affect the degree to which the culture result satisfies a predetermined standard can be extracted. The extraction can be performed by analyzing and evaluating the relationship between each parameter and an index of the culture result using a method such as machine learning or a statistical method. Existing clustering analysis techniques may also be used. The past information may be information on literature related to the culture process in addition to the performance data of the culture process. The past information may store information on important parameters that are already obtained as knowledge and that may be importantly involved in the purpose of the culture or the process of developing the culture process, or information indicating a specific range of the parameters. The past information may be information acquired from an external server using the communication interface 2. Further information and programs are described below.

[0032] The items stored in the storage unit 3 are not limited to the various information and data described above. For example, the storage unit 3 can accumulate information on the first-scale culture equipment, culture experiment data in the second-scale culture equipment obtained after the process development support system S according to this embodiment is implemented, and the like. In this embodiment, the necessary data may be stored in the storage unit 3 of the management server 1, or may be stored in a distributed manner in a plurality of servers connected via a network.

[0033] The calculation unit 41 performs a simulation on the amount of change in parameters that are the same as the above-mentioned multiple parameters when the culture target is cultured under the second culture conditions in the second-scale culture equipment based on the first-scale experimental data and the second-scale equipment information. Then, the calculation unit 41 outputs condition range information, which is information indicating the relationship between the second culture conditions and the multiple parameters, based on the results of the simulation. The second culture conditions refer to the culture conditions when the culture target is cultured in the second-scale culture equipment.

[0034] The condition range information is information created by a simulation program, that is, the calculation unit 41. The condition range information is information indicating the relationship between the culture conditions (second culture conditions) and various parameters that may affect the culture in the second-scale culture equipment. The condition range information may be information indicating the behavior of various parameters that may affect the culture when the second culture conditions are changed in the second-scale culture equipment. The condition range information may be information indicating the range of values ​​that various parameters can take in the second-scale culture equipment. Here, the second culture condition may be any experimental condition that can be simulated in the simulation. Examples of the culture conditions include initial conditions such as viscosity and various concentrations, temperature setting values, pH setting values, rotation speed, and aeration, as well as operating conditions. Examples of the various parameters that may affect the culture include flow rate distribution in the culture tank, shear stress distribution, temperature change amount, pH change amount, oxygen supply rate, DO concentration, DCO2 concentration, heat transfer, mass transfer, and gas dispersion.

[0035] The condition range information may also include information on values ​​that the various parameters can take for each culture condition. With this information, information on the degree of influence of the culture conditions on changes in the various parameters can be calculated. The degree of influence of the culture conditions on changes in the various parameters may be specified as a plurality of evaluation levels. In this case, the greater the influence on the various parameters when the culture conditions are changed, the greater the degree of influence is specified. As an example, the magnitude of the influence of the culture conditions on changes in the various parameters is quantitatively calculated based on information on the rate at which the various parameters change when the culture conditions are changed by a predetermined rate. The degree of influence of the culture conditions on changes in the various parameters may be a value calculated for each type of the various parameters.

[0036] The planning unit 42 outputs the culture conditions (experimental planning information) of the culture experiment in the first-scale culture facility based on the experimental data and the condition range information. The culture conditions output here can be the first culture conditions of the next culture experiment in the first-scale culture facility.

[0037] The experimental design information is information created by the small-scale experimental condition search program, i.e., the planning unit 42. The experimental design information is information about an experimental plan in a first-scale culture facility that is necessary in the process development for culturing a culture target in a second-scale culture facility. The experimental design information can assist in creating an experimental plan in a first-scale culture facility. The experimental design information may be in any format that matches the culture system, process system, and management form. The experimental design information may be, for example, information indicating the range of values ​​to be set for parameters that can be set in the first-scale culture facility. The experimental design information may also include information about the culture conditions, experimental procedure, and experimental method of a specific culture experiment.

[0038] The planning unit 42 can also output information for recommending the culture equipment to be used on the first scale. In this case, information related to the experimental procedure and the experimental method related to the culture equipment to be used on the first scale may also be output. Furthermore, the planning unit 42 may output information regarding candidates for culture equipment to be used as second-scale culture equipment after scale-up.

[0039] The simulation program is a program for simulating the behavior of various parameters (called secondary parameters) when culturing is performed in the second-scale culturing equipment, based on predetermined culture conditions and information on the second-scale culturing equipment (called primary parameters). The simulation program can be executed by the calculation unit 41. For example, a commonly used fluid dynamics (CFD) simulation can be used as the simulation program.

[0040] For the simulation to estimate the parameter change amount of the second culture condition from the first scale experimental data and the second scale equipment information, for example, chemical engineering calculations and fluid analysis can be used. Examples of primary parameters include operating conditions such as the stirring speed, aeration amount, and volume, and equipment setting conditions such as the shape of the stirring blade and the aspect ratio of the tank. Examples of secondary parameters calculated based on these include gas-liquid volumes such as shear stress, DO concentration, and DCO2 concentration, speed, energy, mixing time, product and substrate concentration distribution, flow rate distribution, Kolmogorov scale, foaming, carbon dioxide partial pressure (pCO2), and pH distribution, and it is desirable for the simulation results to show the state of these distributions. The behavior of the aforementioned secondary parameters can be simulated by using commonly used fluid analysis techniques based on the information of the aforementioned primary parameters. From these, the relationship of the parameters to the culture conditions can be shown, and the condition range information of each parameter can be extracted, acquired, and output. A simulation using a simulation program shows, for example, that the distribution of DO concentration in the second scale culture equipment is 1 to 5 mg / L.

[0041] The small-scale experimental condition search program is a program for creating experimental plan information for a first-scale culture facility required in the process development for culturing a culture target in a second-scale culture facility based on the results of a simulation by the simulation program. The small-scale experimental condition search program can be executed by the planning unit 42. An example of the principle of the small-scale experimental condition search program will be described later.

[0042] The small-scale experimental condition search program analyzes the difference between the behavior of a plurality of parameters that may affect the culture result in the first-scale culture facility and the behavior of a second-scale culture facility based on the condition range information. The small-scale experimental condition search program also extracts important parameters that should be noted when scaling up the target process based on the analysis results. The small-scale experimental condition search program may also create recommendation information regarding the experiment plan using information on the extracted important parameters. An important parameter is a parameter or a specific range of the parameter that may be important in the culture purpose or the process development of the culture process.

[0043] The small-scale experimental condition search program outputs the conditions if the parameters can be directly set in the first-scale culture equipment. The small-scale experimental condition search program can also output culture conditions (new first culture conditions) by converting them into parameters to be considered in the first scale, for example, by chemical engineering calculations. The small-scale experimental condition search program particularly outputs the ranges for changing the setting values ​​of multiple operating condition items.

[0044] The small-scale experimental condition search program can output information on items not significantly reflected in the experimental data, items not considered, and important parameters to be considered in the second-scale culture equipment based on the condition range information, from the first-scale experimental data and the acquired condition range information. The small-scale experimental condition search program can also use clustering analysis, etc., when extracting important parameters, etc. Clustering analysis is preferably performed, for example, on new experimental data obtained by performing a culture experiment under the newly output culture conditions (first culture conditions) of the culture experiment in the first-scale culture equipment. Clustering analysis is preferably performed repeatedly each time new experimental data is obtained. By performing clustering analysis in this manner, the accuracy of the experimental plan information for the first-scale culture equipment can be improved.

[0045] In addition, the small-scale experiment condition search program not only outputs the culture conditions for the culture experiment to be considered in the first-scale culture equipment and sets the range of conditions, but also proposes and recommends the conditions of the culture equipment to obtain those conditions. For example, if there is a concentration distribution of the substrate, it is possible to propose equipment that can reproduce the concentration distribution. Furthermore, this also includes proposals for the shape of the stirring blades.

[0046] The small-scale experimental condition search program can further propose and recommend the conditions of the second-scale culture equipment required to minimize items with a large distribution and parameters with a high influence when the important parameters and condition range information are taken into consideration. For example, the small-scale experimental condition search program can propose and recommend the shape of the culture tank, the stirring blades used in the culture tank, the stirring conditions, the diffuser conditions for the bubble diameter, etc. The small-scale experiment condition search program can further propose information on recommended culture equipment (first-scale culture equipment) from culture equipment information stored in the memory unit 3. When recommending equipment, it is preferable to show the installation location, operating status, and usage history in addition to the equipment information and specifications.

[0047] Next, an example of the principle of the small-scale experiment condition search program will be described with reference to Figures 2A to D. Figures 2A to D are explanatory diagrams for explaining an example of the principle of the small-scale experiment condition search program. The small-scale experiment condition search program extracts important parameters as described above. The important parameters are parameters that may play an important role in the purpose of the culture or the process development of the culture, or a specific range of the parameters. There are several extraction methods for identifying the important parameters, and some of the methods will be described below as an example of the principle of the small-scale experimental condition search program, but the methods are not limited to the following methods.

[0048] [1] Extraction by scale difference As shown in FIG. 2A, when there is a range in which the analysis distribution range (second-scale analysis distribution range 2A1) of analyzed parameters X and Y in the second-scale culture equipment of a certain parameter candidate is not included in the range of experimental conditions of the initial first-scale culture equipment (initial first-scale experimental range 2A2), the planning unit 42 can extract the parameter in which the range exists or the parameter in the range as an important parameter. Alternatively, when the ratio of the range not included in the range of experimental conditions of the initial first-scale culture equipment among the analysis distribution range in the second-scale culture equipment is larger than a predetermined threshold, the corresponding parameter may be extracted as an important parameter. In this way, a parameter in which the second-scale analysis distribution range 2A1 is significantly different from the initial first-scale experimental range 2A2 can be recognized as an important parameter in the development of a culture process. Note that the predetermined threshold may be arbitrarily selected for each parameter. The initial first-scale experimental range 2A2 and the second-scale analysis distribution range 2A1 are also the first-scale experimental recommended ranges.

[0049] Also, the influence of each parameter on the culture process development may be evaluated. Here, the influence on the culture process development may be calculated based on information on the ratio of the range of the second scale analysis distribution range 2A1 that is not included in the initial first scale experimental range 2A2. As an example, the influence may be a relative value of the change width of the range of the second scale analysis distribution range 2A1 that is not included in the initial first scale experimental range 2A2 when the change width of the initial first scale experimental range 2A2 is set to 1. In this case, the larger the relative value, the larger the influence on the culture process development is evaluated to be. This allows a parameter whose second scale analysis distribution range 2A1 is significantly different from the initial first scale experimental range 2A2 to be recognized as having a large influence on the culture process development.

[0050] [2] Extraction from a hardware perspective As shown in FIG. 2B, when the planning unit 42 finds a condition (a range 2B2 difficult to control at the second scale) in which the first-scale input experimental condition 2B1 cannot be realized at the second-scale culture equipment under the experimental condition (first-scale input experimental condition 2B1) input for the first-scale culture equipment as a result of analyzing the parameters X and Y of a certain analyzed parameter candidate at the second scale, the planning unit 42 can extract a parameter in the range 2B2 or a parameter in the range 2B2 as an important parameter. Alternatively, when the ratio of the range of the first-scale input experimental condition 2B1 that cannot be realized at the second-scale culture equipment is greater than a predetermined threshold, the parameter may be extracted as an important parameter. In this way, a parameter that has a large overlap between the initial first-scale experimental range and the range that cannot be used at the second scale can be recognized as an important parameter in the development of the culture process. In this case, the planning unit 42 can also specify the first-scale recommended experimental range (second-scale analysis distribution range 2B3) by excluding the range 2B2 that is difficult to control at the second scale.

[0051] The planning unit 42 may also be configured to evaluate the degree of influence of each parameter on the culture process development. Here, the degree of influence on the culture process development may be calculated based on information on the proportion of the range of the first-scale Input experimental condition 2B1 that cannot be realized by the second-scale culture equipment. In this case, the greater the proportion, the greater the degree of influence on the culture process development is evaluated to be. This allows a parameter that has a large overlap between the initial first-scale experimental range and the range that cannot be used in the second scale to be recognized as having a large degree of influence on the culture process development.

[0052] In this embodiment, as additional configurations for improving accuracy, "extraction as past information" and "extraction from additional consideration" as described below may be added.

[0053] [3] Extraction of past information As shown in FIG. 2C, the planning unit 42 can extract parameters and parameter ranges that were previously considered important for the first scale Input experimental conditions 2C1 for the parameters X and Y of the parameter candidates based on the past information stored in the storage unit 3. The parameters can be extracted from information that may be specifically affected in the input culture object. That is, the parameters can be extracted as a range 2C2 that is affected by performance in an experiment at the first scale or a range that is considered to be affected by past information. It is also possible to check necessary information from commonly used literature for this past information. It is also possible to input information on important parameters that are arbitrarily held in advance as knowledge into the storage unit 3 as past information. In particular, when the conditions of the parameters that are affected are similar to the experimental conditions in the input first scale culture equipment, it is desirable to extract them from past information such as the information on the important parameters. It is desirable to be able to arbitrarily select the degree of similarity. As mentioned above, extracting parameters and parameter ranges that were previously considered important and considering them as information regarding the order or priority when creating an experimental plan at the first scale can contribute to improving the efficiency of experiments at the first scale.

[0054] [4] Extraction from additional studies 2D, the planning unit 42 can recommend an additional experiment in advance as necessary when the number of parameters and the information thereof in the input first scale Input experimental condition 2D1 are insufficient compared to past studies, based on the past information stored in the storage unit 3. It is preferable that the conditions can be selected arbitrarily. In addition, it is possible to conduct experiments to measure the degree of influence or to identify influencing factors as necessary based on the above information such as past information and scale differences, and these can also be recommended. As for these experiments, it is possible to conduct experiments (experiments in the first scale initial experimental range 2D2) with a wide range of experimental conditions (the second scale analysis distribution range and the first experimental recommended range). This makes it possible to extract important parameters again. In addition, when it is difficult to identify parameters that may have an influence, it is possible to derive differences and extract them as important parameters by, for example, analyzing culture components from experiments that have an influence or may have an influence, and using techniques such as machine learning or statistical techniques. Furthermore, it is also possible to estimate or derive them from information such as the metabolic pathway of the target culture. By adding this information to the memory unit 3 and the planning unit 42, it is possible to extract important parameters.

[0055] In this embodiment, the above [1] to [4] can be applied in appropriate combination. This makes it possible to more appropriately grasp which range should be experimented with the first-scale culture equipment in consideration of the second-scale culture equipment. That is, a more preferable first-scale experimental range can be recommended. Here, FIG. 2E is an explanatory diagram for explaining the recommendation of a more preferable first-scale experimental range. Note that FIG. 2E shows an example in which all of the above [1] to [4] are applied.

[0056] As shown in FIG. 2E, when there is a range 2E2 in which the analysis distribution range (second-scale analysis distribution range) of analyzed parameters X and Y in the second-scale culture equipment is not included in the experimental condition range (initial first-scale experimental range 2E1) of the initial first-scale culture equipment, the planning unit 42 recognizes that the range 2E2 includes important parameters and extracts them. Furthermore, when the planning unit 42 analyzes the second scale for parameters X and Y of a certain analyzed parameter candidate and finds conditions (range 2E4 that is difficult to control at the second scale) in which the first-scale input experimental conditions 2E3 cannot be realized in the second-scale culture equipment under the first-scale input experimental conditions 2E3, the planning unit 42 extracts the range 2E4 as an important parameter. Furthermore, for the candidate parameters X and Y, the planning unit 42 can extract parameters that have been considered important in the past in the memory unit 3 for the first scale Input experimental conditions 2E3 (for example, a range 2E5 that is significantly affected by performance in an experiment at the first scale or a range 2E6 that is considered to be affected based on past information) as important parameters. Furthermore, the planning unit 42 can recommend an additional experiment in advance as necessary when the number of parameters and information thereof in the input first-scale input experimental conditions 2E3 are insufficient compared to past studies. Such additional experiments can include an increase in the number of samples in the first-scale input experimental conditions 2E3, as well as an experiment in the range of experimental conditions (an experiment in the recommended culture condition range 2E7 that is not listed in the ranges 2E1, 2E2, 2E4 to 2E6).

[0057] FIG. 3 is an explanatory diagram for explaining the solution concept in the process development support system S according to this embodiment. As shown in Figure 3, the process development support system S of this embodiment can input first-scale experimental data when culturing a culture target at a first scale and scaled-up second-scale equipment information, and output recommended first-scale experimental conditions required for process development for culturing a culture target in second-scale culture equipment.

[0058] Specifically, chemical engineering calculations and simulations of the culture environment at the second scale are performed based on the above input information. Input information on the first scale experimental data includes, for example, initial conditions such as the host, biological characteristics, viscosity, various concentrations, and equipment information, as well as operating conditions such as temperature, pH, DO concentration, stirring rotation, pressure, aeration, and additives. Input information on the second scale equipment information includes, for example, capacity, aspect ratio, blade tank ratio, auxiliary equipment, drawings, and various control conditions.

[0059] Based on these, the planning unit 42 analyzes the difference between the behavior in the first scale and the behavior in the second scale for multiple parameters that may affect the culture result. In this analysis, for example, the state of the culture equipment in the second scale, such as temperature, pH, DO concentration, distribution of metabolites, flow force, shear force, etc., is output. The state of the culture equipment in the second scale can be, for example, temperature: 0 to 0, pH: 0 to 0, DO concentration: 0 to 0, target substance concentration: 0 to 0, shear force: 0 to 0, etc.

[0060] Then, the planning unit 42 performs differential analysis on important parameters that should be noted when scaling up the target process based on the analysis results, and extracts them, for example, as in the above-mentioned items (1) to (4). The planning unit 42 uses the extracted information of the important parameters to create recommendation information (newly output first culture conditions) regarding the first-scale experiment recommendation conditions, and outputs them to the output device 7 as output information. The first-scale experiment recommendation conditions can be, for example, temperature: 0 to 0, pH: 0 to 0, DO concentration: 0 to 0, various component concentrations: 0 to 0, and agitator blade rotation speed: 0 to 0. In this case, as a method for deriving the first culture conditions from the information of the important parameters, for example, conversion can be performed based on a chemical engineering theoretical formula (theoretical model) showing the relationship between various parameters and the variables of the culture conditions. In addition, as a different method, the first culture conditions may be derived from the parameter information based on information on the correspondence between the culture conditions and parameters included in the condition range information. As an example, as a method for deriving the first culture conditions from the state of the second-scale culture equipment, the shear force is determined from the specifications of the agitator, which are composed of the shape and rotation speed of the agitator blades, from the viewpoint of chemical engineering. If there is a range of culture conditions for the shear force in the second-scale culture equipment, for example, the rotation speed of the agitator in the first-scale culture equipment can be found from the shape of the agitator blades in the agitator in the first-scale culture equipment based on the possible values ​​of the shear force. This rotation speed condition can be output as a recommended condition for the first-scale experiment.

[0061] When outputting recommendation information regarding the first-scale experiment recommended conditions, the planning unit 42 can output priority information for the first culture conditions or information on the importance of the first culture conditions based on information on the magnitude of the influence of various parameters when culturing a culture target in a second-scale culture facility output by the planning unit 42. As an example, an experiment using a culture condition corresponding to a parameter evaluated to have a high influence may be determined to have a high priority, and information on the priority of the culture condition may be output together with the information on the culture condition. Also, as an example, a culture condition corresponding to a parameter evaluated to have a high influence may be determined to have a high influence, and information on the influence of the culture condition may be output together with the information on the culture condition.

[0062] In this way, the process development support system S according to this embodiment can carry out an experiment in the first-scale culture facility taking into consideration the specific culture conditions in the second-scale culture facility. As a result, even without experimental data information in the second-scale culture facility, the process development support system S according to this embodiment can prevent a decrease in productivity in the second scale caused by the culture facility by almost eliminating uncertain conditions that cannot be reproduced and unanticipated constraint conditions.

[0063] (Preferred embodiment) A preferred embodiment of the process development support system S according to the present embodiment described above will be described below.

[0064] (Aspect 1) The first culture conditions preferably include information on set values ​​of a plurality of operating conditions (culture conditions) for controlling the first-scale culture equipment. Moreover, it is preferable that the planning unit 42 outputs a range for changing the set value in the culture experiment based on the experimental data and the condition range information. In other words, it is preferable that the input value and the output value of the process development support system S are set values ​​of the items of the operating conditions (culture conditions). Here, the method for outputting the range for changing the set value of the culture condition in the culture experiment can be performed by the above-mentioned method for extracting important parameters and the method for deriving the first culture condition from the information of the important parameters. In this way, the possible range of the primary parameters (explanatory variables) of the culture experiment in the first-scale culture equipment can be determined, so that the above-mentioned calculation unit 41 and planning unit 42 can more appropriately create an experimental plan for the first-scale culture equipment.

[0065] (Aspect 2) It is preferable that the planning unit 42 outputs information on the magnitude of the influence when culturing the culture target in the second-scale culture equipment based on information on a plurality of parameters included in the experimental data and information on a plurality of parameters included in the condition range information. The information on the magnitude of the influence when culturing the culture target in the second-scale culture equipment may be information on the influence of the various parameters described above. In this way, it is possible to identify secondary parameters (which in this embodiment are the same as the primary parameters) that are important when culturing in the second-scale culture equipment, and it is expected that this can be done more appropriately when actually culturing in the second-scale culture equipment.

[0066] (Aspect 3) The storage unit 3 preferably stores first equipment information related to multiple candidates for the first-scale culture equipment. The first equipment information may store, for example, information related to equipment conditions including at least shape information related to the first-scale culture equipment, similar to the items included in the equipment information. The first equipment information may also store information such as the name, manufacturer, provider, base, location, cost of use, usage history, usage status, and peripheral equipment in addition to the specifications of the first-scale culture equipment. The first equipment information may be information in multiple types of standard formats related to the equipment specifications. In addition, it is preferable that the planning unit 42 outputs information on the culture equipment to be used in the culture experiment from among the first equipment information. The information on the culture equipment to be used in the culture experiment from among the first equipment information may be information on device conditions that meet the experiment recommendation conditions of the first scale.

[0067] FIG. 4 is an explanatory diagram for explaining an example in which the planning unit 42 outputs information about a device that meets the first-scale experiment recommendation conditions. 4, when conditions (recommended first-scale experiment conditions) are input from the input unit 6, the planning unit 42 performs analysis based on the first equipment information. The recommended first-scale experiment conditions may be information output by the planning unit 42. Examples of the recommended first-scale experiment conditions include temperature, pH, DO concentration, metabolite concentration, and stirring flow conditions.

[0068] Based on the analysis result, the planning unit 42 outputs information on the equipment suitable for the first-scale experiment recommended conditions as equipment conditions for the culture experiment in the first-scale culture facility. Examples of the equipment conditions to be output include concentration distribution experiment: equipment A, stirring condition experiment: stirrer B, oxygen condition experiment: aeration device C, toxicity test experiment: equipment D, etc. In this manner, the planning unit 42 can output information regarding a plurality of candidates for equipment that meets the first-scale experiment recommendation conditions. When the memory unit 3 and the planning unit 42 perform these processes, it is possible to appropriately recommend the culture equipment to be used for the culture experiment on the first scale.

[0069] (Aspect 4) The storage unit 3 preferably stores second equipment information related to multiple candidates for second-scale culture equipment. The second equipment information may store, for example, information related to equipment conditions including at least shape information related to the second-scale culture equipment, similar to the items included in the equipment information. The second equipment information may also store information such as the name, manufacturer, provider, base, location, cost of use, usage history, usage status, and peripheral equipment in addition to the specifications of the second-scale culture equipment. The second equipment information may be information in multiple types of standard formats related to equipment specifications. In addition, the planning unit 42 preferably outputs information on candidates for culture equipment to be used as the second-scale culture equipment from information on the range and behavior of the same parameters as the multiple parameters, information on important parameters to be noted when scaling up the process to be cultured (i.e., important parameters in the process development of scaling up from the first-scale culture equipment to the second-scale culture equipment), and the second equipment information. The information on candidates for culture equipment to be used as the second-scale culture equipment may be device conditions that meet the experiment recommendation conditions for the second scale.

[0070] FIG. 5 is an explanatory diagram for explaining an example in which the planning unit 42 outputs information about a device that meets the second-scale experiment recommendation conditions. 5, the planning unit 42 performs analysis based on the second equipment information when conditions (recommended second-scale experiment conditions) are input from the input unit 6. Examples of the recommended second-scale experiment conditions include temperature, pH, DO concentration, metabolite concentration, and stirring flow conditions. The second-scale experiment recommendation conditions required for input may be output by the planning unit 42 together with the first-scale experiment recommendation conditions. In this case, the second-scale experiment recommendation conditions may be information on the conditions of the second-scale culture equipment required to minimize items with large distributions and parameters with high influence based on the important parameters and condition range information. In this case, as an example, the shape of the culture tank, the stirring blades used in the culture tank, the stirring conditions, the air diffuser conditions for the bubble diameter, etc. are output.

[0071] Based on the analysis result and the second equipment information, the planning unit 42 outputs information on equipment suitable for the second-scale experiment recommendation conditions as equipment conditions related to the second-scale culture equipment. Examples of the output equipment conditions include culture tank capacity: 0 to 0, aspect ratio: 0 to 0, agitator specifications: 0 to 0, impeller diameter / tank diameter ratio: 0 to 0, various equipment ancillary equipment conditions, and various control device conditions. In addition, the planning unit 42 may output information on candidates for second-scale culture equipment based on the specifications, name, manufacturer, provider, base, location, cost of use, usage history, usage status, or peripheral equipment information of the culture equipment included in the second equipment information, together with the equipment conditions suitable for the second-scale experiment recommendation conditions. In this manner, the planning unit 42 can output information regarding a plurality of candidates for equipment that meets the second-scale experiment recommendation conditions. When the memory unit 3 and the planning unit 42 perform these processes, it is possible to appropriately recommend the culture equipment to be used for the culture experiment on the second scale.

[0072] (Aspect 5) The first culture condition is preferably at least one of viscosity, concentration of various components, temperature, pH, DO concentration, agitation speed, aeration amount, and pressure. When the first culture conditions are selected from these, a culture experiment can be suitably carried out using a first-scale culture facility.

[0073] (Aspect 6) The above-mentioned equipment conditions are preferably at least one of the aspect ratio of the culture tank, an aeration device, an agitator, a pH adjusting device, and a controller for controlling the dissolved oxygen concentration, and their specifications. When the facility conditions are selected from these, the cultivation can be suitably performed in the second-scale cultivation facility. In addition, this can be provided as useful information for matching, which will be described later. Examples of pH adjustment equipment include devices that add acidic or alkaline chemicals.

[0074] (Aspect 7) It is preferable that the calculation unit 41 simulates the behavior of various parameters when culturing is performed in the second-scale culture equipment, based on the second culture conditions and the second-scale equipment information. Moreover, the various parameters are preferably at least one of a shear force and a DO concentration. If the calculation unit 41 performs the above processing and the various parameters are selected from the above, this can be suitably carried out when culturing in the second-scale culturing equipment.

[0075] (Aspect 8) In the production of useful substances by fermentation using microorganisms, only those who own the culture tank can carry out the cultivation. In addition, the information about the culture tank is often held by the holder. In addition, holders of culture tanks may provide culture tanks through contract work, but the contractor or user of the culture tank does not know the details of the culture tank, making it difficult to determine whether the culture tank is suitable for the desired cultivation conditions. Furthermore, there is a lack of information on the period when it can be used and appropriate culture tanks, so they are forced to search for one at random. On the other hand, the operating rate of culture tanks varies among holders, and there are periods when they are not in use, resulting in maintenance costs. Therefore, if there is a user who wishes to use second-scale culture equipment and a provider (the holder described above) who provides second-scale culture equipment, and they can be matched, it will be efficient to carry out culture in the second-scale culture equipment.

[0076] Therefore, the process development support system S according to this embodiment preferably includes a database that stores information on candidates for second-scale culture equipment and information on the specifications and use of each of the candidates. The information on candidates for second-scale culture equipment may be information such as the name, provider, base, and location of each candidate culture tank or culture device corresponding to the second-scale culture equipment. The information on the specifications of the candidates for second-scale culture equipment may be information on the product of the culture equipment, information on the chassis for culture, tank capacity, and other equipment specifications. The information on the use of the candidates for second-scale culture equipment may be information on the cost, usage history, usage status, reservation status, or peripheral equipment. In addition, the information on the equipment specifications may further include the aspect ratio of the culture tank, the tank diameter-to-blade diameter ratio, the shape of the stirring blade, and other incidental equipment information. By using this information, it is possible to more accurately predict candidates for culture equipment suitable for the conditions desired by the user. Such database information may be information acquired from an external server via the communication interface 2. In addition, the above-mentioned database may be stored in the storage unit 3 as a matching DB.

[0077] In addition, the process development support system S according to this embodiment preferably includes an input unit 6 into which the conditions of the second-scale culture equipment are input. For example, information on the specifications of the culture tank or culture device corresponding to the second-scale culture equipment that the user wants to use is input. As another example, the user can input at least one of the information on the specifications of the culture tank or culture device corresponding to the second-scale culture equipment that the user wants to use, information on the overview of the product, etc., and the functions of the culture tank or culture device. The functions of the culture tank or culture device may be information on a specific function in the control during culture in the culture tank or culture device, or information on related auxiliary equipment. In addition to the above, conditions related to information on the use of the culture equipment may be input.

[0078] Furthermore, the process development support system S according to this embodiment preferably includes an extraction unit 43 that extracts one or more candidates of second-scale culture equipment related to the conditions input to the input unit based on the information input to the input unit 6 and the information stored in the database. As an example, one or more similar culture tanks or culture devices may be extracted from the information stored in the database based on the information on the chassis, product, and tank capacity input to the input unit 6. This allows accurate extraction of candidates of culture equipment suitable for the conditions desired by the user. In addition, in order to accurately execute the processing by the extraction unit 43, items in the information on the specifications and use of the candidates of second-scale culture equipment stored in the database may be configured to correspond to items in the conditions of the second-scale culture equipment input to the input unit 6, respectively. Here, each item does not necessarily have to correspond one-to-one, and an item on one side may correspond to two or more items on the other side. In addition, a table defining this correspondence may be further stored in the database, and the processing by the extraction unit 43 may be executed based on the information in the table.

[0079] In addition, the process development support system S according to this embodiment preferably includes a proposal output unit 44 that proposes candidates for culture equipment extracted by the extraction unit 43 and information on the use of each of the candidates. There may be a plurality of candidates for culture equipment to be proposed. In addition, information on the available schedule of the culture tank or culture device, which is a candidate for culture equipment, may be proposed as the information on the use. Here, the information on the available schedule may be specified from information on the use history, the use status, the reservation status, etc. in the database. Information on the similarity between the conditions of the second-scale culture equipment input to the input unit 6 and the candidate may be output together with the candidate for culture equipment. The information on the similarity may be indicated by a predetermined index. For example, such an index may be calculated based on the number of items that satisfy the conditions by comparing the items in the conditions of the second-scale culture equipment input to the input unit 6 with the items in the information on the specifications and use of the candidate for the second-scale culture equipment stored in the database that correspond to the items in the conditions. In addition, information on the past use status regarding the conditions of the second-scale culture equipment input to the input unit 6 may be output together with the candidate for culture equipment. With such a configuration, it is possible to support the user in selecting the second-scale culture equipment. The extraction unit 43 and the proposal output unit 44 can be realized by the above-mentioned control unit 4 executing a program (culture facility matching program) that performs these functions.

[0080] In this aspect, one or more available second-scale culture facilities can be extracted and proposed based on information such as the use of the culture tank contained in the database and the content input by the user. That is, in this aspect, a matching system can be provided that matches a user who wants to use a culture tank with a provider who provides a culture tank or culture device to the user. As a result, in this aspect, the efficiency of culturing in the second-scale culture facility can be improved. That is, this aspect can solve the problem of providing a matching system that matches a user who wants to use a culture tank with a provider who provides a culture tank or culture device to the user, and the problem of improving the efficiency of culturing in the second-scale culture facility. In addition, in this embodiment, the specifications of the culture tank and the time when it can be used are known, and the optimal culture tank is proposed, so that the user can use the optimal culture tank. Furthermore, the holder of the culture tank can reduce the vacancy, which leads to the development of the bioproduction field.

[0081] An example of using the present invention in a solution for matching culture tanks will be described. As an example, the database stores information on candidates of second-scale culture equipment owned by one or more vendors (holders / providers) capable of providing second-scale culture equipment, acquired via the communication interface 2, and information on the specifications and use of each of the candidates. Information on the second-scale culture equipment that a cell owner (user) who wishes to use a second-scale culture tank wants to use is input to the input unit 6. Then, after executing the process of the extraction unit 43 described above, the proposal output unit 44 may be configured to output the information on the candidates of culture equipment extracted by the extraction unit 43, information on the holders of each of the candidates, and information on the use of each of the candidates on a screen for the cell owner's administrator.

[0082] An example of such a process development support system S includes a database (memory unit 3) that stores information on candidates for second-scale culture equipment owned by one or more vendors capable of providing second-scale culture equipment, obtained via a communication interface 2, and information regarding the specifications and usage of each of the candidates; an input unit 6 into which conditions for second-scale culture equipment related to a cell owner who wishes to use the second-scale culture equipment are input; an extraction unit 43 that extracts one or more candidates for culture equipment related to the conditions input into the input unit 6 from the candidates for second-scale culture equipment based on the information input into the input unit 6 and the information stored in the database; and a proposal output unit 44 that outputs information on the candidates for culture equipment extracted by the extraction unit 43, information on the owners of each of the candidates, and information regarding the usage of each of the candidates on a screen for the cell owner's administrator.

[0083] FIG. 6 is a flowchart illustrating an example of the culture facility matching program. As shown in Fig. 6, the storage unit 3 stores the device condition information. Examples of the device condition information include the specifications of the culture device, such as culture tank capacity: 0 to 0, aspect ratio: 0 to 0, agitator specifications: 0 to 0, impeller diameter / tank diameter ratio: 0 to 0, various device ancillary equipment conditions, and various control device conditions. The device condition information may also include the usage history and usage status of the culture device in addition to the above.

[0084] In addition, the user inputs a proposed equipment condition from the input unit 6. The proposed equipment condition may include, like the equipment condition information, specifications of the culture equipment such as culture tank capacity: ___, aspect ratio: ___, agitator specifications: ___, impeller diameter / tank diameter ratio: ___, various equipment ancillary equipment conditions, and various control device conditions. The proposed equipment condition may also include an overview and functions of the culture equipment in addition to the above.

[0085] The culture equipment matching program analyzes the equipment condition proposal and the equipment condition information, and determines the similarity between them. Then, the culture equipment matching program (extraction unit 43) extracts similar culture equipment, and lists the culture equipment in order of the degree of similarity. Next, the culture equipment matching program (proposal output unit 44) proposes the extracted and listed equipment conditions (culture tank or culture equipment) and the time when they can be used. The listed equipment conditions can be presented, for example, as Recommendation 1: Equipment A, Recommendation 2: Equipment B, Recommendation 3: Equipment C, etc. In addition, information such as the equipment number (HT00000001, etc.), the similarity (80%, etc.), and the name of the area where the culture tank is located (XX City, etc.) can be presented to the user as Proposal 1, Proposal 2, Proposal 3, etc., as a "List of optimal culture tank proposals for customers." In addition, for example, when Proposal 1 is selected, information on past usage such as "Comment: Often used for fermentation production using E. coli" and information such as "Culture tank type: Fermenter" can be obtained, as shown in FIG. 6. Such information can be obtained from the device condition information stored in the storage unit 3.

[0086] (Aspect 9) In the eighth embodiment, it is preferable that the information input to the input unit 6 includes information on the bacterial strain, cell line, or organism to be cultured, and the planned culture volume, so that matching can be performed with higher accuracy.

[0087] (Aspect 10) In this embodiment, first, a culture experiment is conducted under the culture conditions (first culture conditions) of the culture experiment in the first-scale culture equipment previously output (i.e., this culture experiment is the second or subsequent culture experiment), and new experimental data is obtained that includes information regarding the amount of change in multiple parameters that indicate the state within the first-scale culture equipment. Then, it is preferable that the calculation unit 41 performs the above-mentioned simulation based on the new experimental data and the second-scale equipment information, and outputs condition range information, which is information indicating the relationship between the second culture conditions and multiple parameters, based on the results of the simulation. Moreover, it is preferable that the planning unit 42 performs analysis based on new experimental data and condition range information, and outputs new culture conditions (first culture conditions) for a culture experiment in the first-scale culture equipment.

[0088] In this embodiment, a culture experiment is conducted under the previously output first culture conditions, and a simulation is performed using the experimental data to output condition range information, so that the newly output first culture conditions have improved accuracy. In this embodiment, these processes can be repeated any number of times. Also, in this embodiment, these processes can be repeated until the newly output first culture conditions are sufficiently accurate, for example, until the newly output first culture conditions are substantially the same multiple times. In this way, a sufficient simulation is performed at the first scale, and the accuracy of the first culture conditions is further improved.

[0089] Improving the accuracy of the first culture conditions can improve the probability of success when cultured in a second-scale culture facility, for example, the probability of maintaining a certain level of productivity. This leads to avoiding failure after moving to the second scale (i.e., inability to maintain a certain level of productivity) and having to start over from the first scale. As a result, this can reduce the time and costs required for consideration.

[0090] (Aspect 11) In the tenth aspect, it is preferable that the calculation unit 41 performs a clustering analysis on new experimental data before performing the above-mentioned simulation. It is also preferable that the planning unit 42 outputs at least one of the optimal culture conditions in the second culture conditions and important parameters that should be noted when scaling up the process to be cultured, based on the result of the clustering analysis. It is also preferable that the planning unit 42 performs the above-mentioned simulation using at least one of the optimal culture conditions and the important parameters. In this embodiment, the calculation unit 41 performs a clustering analysis before performing the above-mentioned simulation, so that the planning unit 42 can more accurately extract and output the optimal culture conditions in the second culture conditions and important parameters that should be noted when scaling up the process to be cultured. Therefore, the simulation results obtained using these are more accurate.

[0091] Next, a process development support method according to the present embodiment will be described. FIG. 7 is a flowchart for explaining the contents of the process development support method according to this embodiment. As shown in FIG. 7, the process development support method according to this embodiment includes an acquisition step S1, a calculation step S2, and a planning step S3.

[0092] (Acquisition step S1) In the acquisition step S1, the experimental data and the second-scale equipment information are acquired. The experimental data and the second-scale equipment information have already been explained, so the explanation will be omitted. These can be acquired from the storage unit 3, but they may also be acquired from information transmitted via the communication interface 2 or the input unit 6.

[0093] (Calculation step S2) In the calculation step S2, a simulation is performed based on the experimental data and the second-scale equipment information regarding the amount of change in the same parameters as the above-mentioned multiple parameters when the culture target is cultured under the second culture conditions in the second-scale culture equipment. Then, in the calculation step S2, condition range information, which is information indicating the relationship between the second culture condition and the multiple parameters, is output based on the result of the simulation. The calculation step S2 can be performed by the calculation unit 41.

[0094] (Planning step S3) In the planning step S3, the culture conditions for the culture experiment in the first-scale culture facility are output based on the experimental data and the condition range information. The planning step S3 can be performed by the planning unit .

[0095] (A concrete example of a process development support method) FIG. 8 is a flowchart illustrating a specific example of the process development support method according to the present embodiment. 8, at least one piece of information among the specifications, overview, and functions of a culture tank or culture device corresponding to the second-scale culture equipment that the user wishes to use is input to the input unit 6 (step S11), and the information is stored in the storage unit 3 of the process development support system S. The user also inputs experimental data including information regarding the amount of change in a plurality of parameters that indicate the state inside the first-scale culture equipment when a culture experiment is performed on a culture target under first culture conditions in the first-scale culture equipment to the input unit 6 (step S11), and the information is stored in the storage unit 3 of the process development support system S. Next, the calculation unit 41 acquires the first-scale experimental data and the second-scale equipment information from the storage unit 3 (step S12).

[0096] Next, the calculation unit 41 performs a simulation regarding the amount of change in a plurality of parameters when culturing the culture target in the second-scale culture facility, based on the first-scale experimental data and the second-scale facility information (step S13).

[0097] Next, the calculation unit 41 outputs condition range information, which is information indicating the relationship between the culture conditions (second culture conditions) when culturing the culture target in the second-scale culture equipment and multiple parameters, based on the results of the simulation (step S14). Next, the planning unit 42 extracts candidates for important parameters based on the first-scale experimental data and the condition range information, etc. (step S15).

[0098] Next, the planning unit 42 outputs culture conditions (new first culture conditions) for a new culture experiment at the first scale based on the first experimental data and the condition range information (step S16). Here, the culture conditions for the new culture experiment may be configured such that the planning unit 42 calculates important parameters in the process development of the scale-up from the first-scale culture equipment to the second-scale culture equipment based on the condition range information and the experimental data, and outputs the culture conditions for the new culture experiment based on the information on the important parameters. In this way, since the culture conditions for the new culture experiment are output based on the information on the important parameters, a culture experiment in the first-scale culture equipment performed based on this will obtain more suitable results taking into account the specific culture conditions at the second scale. Then, the planning unit 42 displays the output information on the display unit (output device 7) (step S17).

[0099] (Description of effects and alternative configurations) The planning unit 42, which outputs the culture conditions for the culture experiment to be considered on the first scale, can not only set the range of conditions, but also propose and recommend the conditions of the culture equipment to obtain those conditions. For example, if there is a concentration distribution of the substrate, it is possible to propose an apparatus that can reproduce the concentration distribution. Furthermore, this also includes proposals for the shape of the stirring blades.

[0100] Furthermore, the process development support system S and the process development support method can propose and recommend conditions for the second-scale culture equipment required to minimize items with a large distribution or parameters with a high influence when the important parameters and condition range information are taken into consideration. For example, the process development support system S and the process development support method can propose and recommend the shape of the culture tank, the stirring blades and stirring conditions used in the culture tank, the aeration device conditions for the bubble diameter, etc. Furthermore, the process development support system S and the process development support method can propose information on recommended culture equipment from equipment information stored in the memory unit 3. When recommending culture equipment, it is preferable to display the installation location, operating status, usage history, etc. in addition to equipment information and specifications.

[0101] By using such a method, it is possible to understand the specific culture conditions at the second scale and support the creation of an experimental plan at the first scale while taking these conditions into consideration. As a result, even if sufficient experimental data information at the second scale is not available, it is possible to reduce uncertain conditions that cannot be reproduced and unanticipated constraints, and to prevent a decrease in productivity at the second scale due to equipment. Ultimately, it is preferable to use the data from the first-scale experiments to conduct a simulation of the conditions at the second scale to confirm whether they are within expectations, i.e., to conduct cultivation experiments in the second-scale cultivation equipment to confirm productivity, etc. In addition, although an example has been shown in which the first-scale culture equipment is used to acquire data to be examined under the proposed culture conditions, it is not necessarily required to conduct the experiment at the first scale. In other words, the proposed culture conditions may be examined using culture equipment at a scale other than the first scale. In this case, when outputting the experiment recommendation conditions of the planning unit 42, information on the available scale may also be output. EXAMPLES

[0102] (Example of Microorganism A) Here, an example will be described in which the process development support system S and the process development support method described in this embodiment are applied to a process in which sugars are used as raw materials and microorganism A is batch-cultured to produce organic compounds.

[0103] In this example, the following experimental data were prepared. First, the culture conditions and experimental data in a 10 L culture tank were used as the first scale. The experimental data included information on microorganism A, as well as temperature, pH, DO concentration, and medium concentration as addition conditions, liquid volume, viscosity, and the like. In addition, the conditions of aeration volume, stirring speed, and pressure were prepared as control indexes for adjusting the environment. Next, we prepared information on a 1000 L culture facility as the second scale for culturing. As equipment conditions, we prepared the aspect ratio of the culture tank, aeration device, agitator, pH adjustment device, and a control device for controlling DO concentration, as well as their specifications.

[0104] Based on these, the amount of change in the parameters of the culture conditions in a 1000L culture tank was analyzed using fluid analysis software. Changes in temperature, pH, DO concentration, medium concentration, additive concentration, etc. were analyzed to clarify the distribution of various concentrations. In this example, we will focus on the DO concentration. Taking into account the degree of oxygen dissolution from the agitator rotation conditions, aeration conditions, viscosity conditions, temperature, etc., the distribution of DO concentration in a steady state was found.

[0105] It was confirmed that there was variation in the DO concentration due to the agitator rotation conditions and aeration conditions based on the initial conditions. Here, it was confirmed that the DO concentration in the culture tank ranged from 0.5 to 8 mg / L. In addition, we found that the shear stress increases when the agitator rotation speed increases, while the DCO2 concentration increases when the DO concentration is low, demonstrating the relationship between the culture conditions and multiple parameters.

[0106] From the first-scale experimental data, it was confirmed that the DO concentration in the 10L culture tank culture condition test was 5mg / L or more as a representative value of one sensor point, but since there was no condition for the range of DO concentration, it was designated as an important parameter. There was almost no data in the first-scale experimental data for DCO2 concentration and shear stress, but it was found that there was a certain range for them, so they were designated as important parameters.

[0107] In the planning section 42, the culture conditions including the range of DO concentration of 0.5 to 8 mg / L were specified as the experimental conditions and output. In addition, the culture condition range satisfying the conditions of the DCO2 concentration and the shear stress extracted in the same manner was output. In addition, a culture facility capable of changing the DO concentration by using nitrogen gas and oxygen gas was proposed and output to the display section.

[0108] Based on this, the experimenter carried out an organic compound productivity test in a 500 mL culture tank with a DO concentration of 0.5 to 8 mg / L. As a result, it was confirmed that productivity significantly decreased when the DO was less than 1 mg / L, more specifically, at 0.5 mg / L.

[0109] A test was conducted to confirm whether there was an effect on DCO2 concentration and shear stress under conditions where the DO concentration was 1 mg / L or more under the conditions of the second-scale cultivation facility. As a result, it was confirmed that there was no significant effect on organic compound production.

[0110] Based on these conditions, we performed another simulation and confirmed that a 1000 L fermenter tank was sufficient. Taking the above into consideration, we were able to find the optimal culture conditions for the 1000 L fermenter tank.

[0111] Although the process development support system S and the process development support method according to the present invention have been described in detail above through the embodiments and examples, the present invention is not limited to the above-mentioned embodiments and examples, and various modified examples are included. For example, the above-mentioned embodiments have been described in detail to easily explain the present invention, and the present invention is not necessarily limited to those having all of the configurations described. In addition, it is possible to replace a part of the configuration of one embodiment with the configuration of another embodiment, and it is also possible to add the configuration of another embodiment to the configuration of one embodiment. In addition, it is possible to add, delete, or replace a part of the configuration of each embodiment with another configuration. [Explanation of symbols]

[0112] S Process Development Support System 1 Management Server 2. Communication Interface 3 Storage section 4. Control section 41 Arithmetic section 42 Planning Department 43 Extraction part 44 Proposal output section 5. Memory 6 Input section 7 Output Devices 2A1 Second scale analysis distribution range 2A2 Initial first scale experiment range 2B1 First scale input experimental conditions 2B2 Range 2B3 Second scale analysis distribution range 2C1 First scale input experimental conditions 2C2 Range 2D1 First scale Input experimental conditions 2D2 First scale initial experimental range 2E1 Initial first scale experiment range 2E2 Range 2E3 First scale input experimental conditions 2E4 range 2E5 range 2E6 range 2E7 Culture Condition Range

Claims

1. a storage unit that stores first-scale experimental data including information about amounts of change in a plurality of parameters that indicate a state within a first-scale culture facility when a culture subject is cultured under first culture conditions in the first-scale culture facility, and second-scale equipment information that is information about equipment conditions including at least shape information about a second-scale culture facility that is larger than the first-scale culture facility; a calculation unit that performs a simulation based on the first-scale experimental data and the second-scale equipment information, without using experimental data obtained by culturing the culture target in the second-scale culture equipment, based on fluid analysis, regarding the amount of change in parameters that are the same as the plurality of parameters when the culture target is cultured under second culture conditions in the second-scale culture equipment, and outputs condition range information that is information indicating the relationship between the second culture conditions and the plurality of parameters, based on the results of the simulation; a planning unit that outputs culture conditions for a culture experiment in the first-scale culture facility based on the experimental data and the condition range information; A process development support system comprising:

2. The planning unit identifies important parameters in the process development for scaling up from a first-scale culture facility to a second-scale culture facility based on the condition range information and the experimental data, and outputs culture conditions for the culture experiment at the first scale based on information on the important parameters.

2. The process development support system according to claim 1.

3. The planning unit extracts, from among the plurality of parameters, parameters whose analytical distribution range at the second scale has a range that is not included in the experimental condition range of the culture equipment at the first scale as the important parameters.

3. The process development support system according to claim 2.

4. The planning unit extracts, from among the plurality of parameters, parameters whose analysis distribution range at the second scale has a proportion of a range that is not included in the experimental condition range of the culture equipment at the first scale that is greater than a predetermined threshold, as the important parameters.

3. The process development support system according to claim 2.

5. the first culture conditions include information on setting values ​​of a plurality of operating condition items for controlling the first-scale culture equipment, The planning unit outputs a range for changing the set value in the culture experiment based on the experimental data and the condition range information.

2. The process development support system according to claim 1.

6. The planning unit outputs information regarding the magnitude of influence of various parameters when culturing the culture target in the second-scale culture equipment, based on information regarding the plurality of parameters included in the experimental data and information regarding the plurality of parameters included in the condition range information.

2. The process development support system according to claim 1.

7. the storage unit stores first equipment information related to a plurality of candidates for the first-scale culture equipment, The planning unit outputs information about the culture equipment to be used in the culture experiment, among the first equipment information.

2. The process development support system according to claim 1.

8. the storage unit stores second equipment information related to a plurality of candidates for the second-scale culture equipment, The planning unit outputs information about candidates for culture equipment to be used as the second-scale culture equipment from information about ranges and behaviors of parameters identical to the plurality of parameters, information about the important parameters, and the second equipment information.

3. The process development support system according to claim 2.

9. 2. The process development support system according to claim 1, wherein the first culture condition is at least one of viscosity, concentration of various components, temperature, pH, dissolved oxygen concentration, agitation rotation speed, aeration amount, and pressure.

10. 2. The process development support system according to claim 1, wherein the equipment conditions are at least one of an aspect ratio of a culture tank, an aeration device, an agitator, a pH adjustment device, and a control device for controlling dissolved oxygen concentration, and their specifications.

11. the calculation unit simulates behavior of various parameters when culturing is performed in the second-scale culture equipment based on the second culture conditions and the second-scale equipment information, 2. The process development support system according to claim 1, wherein the various parameters are at least one of shear force and dissolved oxygen concentration.

12. A database storing information on candidates for the second-scale culture equipment held by a provider of the second-scale culture equipment and information on the specifications and use of each of the candidates; an input unit into which conditions of the second-scale culture equipment of a user who wishes to use the second-scale culture equipment are input; an extraction unit that extracts one or more candidates for culture equipment related to the conditions inputted into the input unit from among the candidates for the second scale culture equipment based on the information inputted into the input unit and the information stored in the database; a proposal output unit that proposes to the user the candidates for the culture equipment extracted by the extraction unit and information on the use of each of the candidates; 2. The process development support system according to claim 1, further comprising:

13. 13. The process development support system according to claim 12, wherein the information input to the input unit includes information about the bacterial strain, cell line, or biological species to be cultured, and the planned culture volume.

14. conducting a culture experiment under culture conditions for the culture experiment in the first-scale culture facility, and obtaining new experimental data including information on amounts of change in a plurality of parameters that indicate a state in the first-scale culture facility; the calculation unit performs the simulation based on the new experimental data and the second-scale equipment information, and outputs condition range information that is information indicating a relationship between the second culture conditions and the plurality of parameters based on a result of the simulation; The planning unit performs an analysis based on the new experimental data and the condition range information, and outputs new culture conditions for a culture experiment in the first-scale culture facility.

2. The process development support system according to claim 1.

15. the calculation unit performs a clustering analysis on the new experimental data before performing the simulation; 15. The process development support system according to claim 14, wherein the planning unit outputs at least one of optimal culture conditions under the second culture conditions and important parameters that should be noted when scaling up the process to be cultured, based on a result of the clustering analysis, and performs the simulation using the optimal culture conditions and at least one of the important parameters.

16. an acquisition step of acquiring first-scale experimental data including information on amounts of change in a plurality of parameters indicating a state in a first-scale culture facility when a culture subject is cultured under first culture conditions in the first-scale culture facility, and second-scale equipment information, which is information on equipment conditions including at least shape information on a second-scale culture facility that is larger than the first-scale culture facility; a calculation step of performing a simulation based on the first-scale experimental data and the second-scale equipment information, without using experimental data obtained by culturing the culture target in the second-scale culture equipment, based on fluid analysis, regarding the amount of change in the same parameters as the plurality of parameters when the culture target is cultured under second culture conditions in the second-scale culture equipment, and outputting condition range information, which is information indicating the relationship between the second culture conditions and the plurality of parameters, based on the result of the simulation; a planning step of outputting culture conditions for a culture experiment in the first-scale culture facility based on the experimental data and the condition range information; A process development support method comprising:

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