EP-4737551-A2 - A METHOD AND SYSTEM FOR CONFIGURING AND/OR SETUP OF A DOWNSTREAM PROCESS FOR PROCESSING A BIOMASS

EP4737551A2EP 4737551 A2EP4737551 A2EP 4737551A2EP-4737551-A2

Abstract

The present invention relates to a computer-implemented method, a computer program product and a system for configuring and/or setup and/or controlling of a downstream process for processing a biomass. The method comprises receiving at least one measurement value of at least one feature an upstream process by which the biomass to be processed in the downstream process has been obtained and/or of at least one feature of a downstream process stage or operation; determining at least one downstream process parameter based on the received at least one measurement value; and configuring and/or setup and/or controlling at least one downstream process stage or process operation based on the determined at least one downstream process parameter. The at least one feature includes titer, and wherein the determining of the at least one downstream process parameter comprises determining, based on the received measurement value of the titer, at least one process parameter of a chromatography stage or operation, said at least one process parameter including one or more of a dimensioning, loading volume, cycle time, flow rate and number of chromatography columns. The invention further relates to a respective method and a system for processing biomass.

Inventors

LEUPOLD, Marco
LEUTHOLD, MARTIN
BARROSO ESPACHS, Alexandre
HUSEMANN, BERNWARD
RODENBERG, MICHAEL
MATUSZCZYK, Jens
KAMPMANN, MARKUS
WORTMEYER, Johannes
FRIESE, THOMAS
SCHOLZ, JOCHEN

Assignees

Sartorius Stedim Biotech GmbH

Dates

Publication Date: 20260506
Application Date: 20211006

Claims (15)

A computer-implemented method for configuring and/or setup and/or controlling of a downstream process for processing a biomass, comprising: receiving at least one measurement value of at least one feature (22) of an upstream process by which the biomass to be processed in the downstream process has been obtained and/or of at least one feature of a downstream process stage or operation (12, 18, 34A-34D, 38A-38D, 40, 42A-42C, 44; 120, 181-186); determining at least one downstream process parameter (20) based on the received at least one measurement value; and configuring and/or setup and/or controlling at least one downstream process stage or process operation (12, 18, 34A-34D, 38A-38D, 40, 42A-42C, 44; 120, 181-186) based on the determined at least one downstream process parameter (20), wherein the at least one feature includes titer, and wherein the determining of the at least one downstream process parameter (20) comprises determining, based on the received measurement value of the titer, at least one process parameter of a chromatography stage or operation, said at least one process parameter including one or more of a dimensioning, loading volume, cycle time, flow rate and number of chromatography columns.
The method according to claim 1, wherein the downstream process is a batch process, the chromatography stage or operation comprises at least one chromatography column, and wherein determining of the at least one downstream process parameter (20) comprises: determining an overall amount of the product to be processed in the chromatography stage or operation based on the measurement value of the titer, and based on the determined overall amount of product to be processed, i) determining and setting one or more of one of the dimensioning, loading volume, cycle time and/or flow rate of the at least one chromatography column required for processing the product within a predetermined time; or ii) for a given dimension of the at least one chromatography column, determining and setting the processing time of the at least one chromatography column and/or the puffer amount for the at least one chromatography column.
The method according to claim 1, wherein the downstream process is a continuous process, the chromatography stage or operation comprises at least one chromatography column, wherein the at least one feature further includes flow rate or volume flow rate and wherein determining of the at least one downstream process parameter (20) comprises: based on the titer and a volume flow or volume flow rate, i) determining, one or more of a number of chromatography columns necessary to ensure continuous flow and processing of the biomass; and/or ii) determining a number of cycles and/or the timing of a chromatography column(s) exchange; and/or iii) determining and/or adjusting at least one recipe of the downstream process, wherein optionally said determining and/or adjusting at least one recipe comprises setting or adjusting a loading volume and/or a volume flow rate.
The method according to any one of the preceding claims, wherein the at least one feature (22) further includes a viable cell density, biomass, capacitance, cell viability and/or turbidity, and wherein the determining of the at least one downstream process parameter (20) comprises: selecting a purification stage or operation (34A-34D, 38A-38D, 40, 42A-42C); determining, based on the received at least one measurement value of the viable cell density, biomass, capacitance and/or cell viability, at least one process parameter of the selected purification stage or operation (34A-34D, 38A-38D, 40, 42A-42C) and/or determining a biomass dilution parameter.
The method according to claim 4, wherein: wherein selecting a purification stage or operation includes selecting between a filter stage or operation and a centrifugal stage or operation, wherein: if a filter stage or operation is selected, the at least one process parameter further includes at least one of the following parameters: a type of the filter stage or operation, number of filters, filter area, pressure, flow rate amount of diatomaceous earth and process time; if the centrifugal stage or operation is selected, the at least one process parameter further includes the process time, process volume and centrifugal force.
The method according to any one of the preceding claims, wherein the at least one feature (22) further includes a host cell protein and/or DNA concentration and wherein the determining of the at least one process parameter (20) further comprises determining of the at least one process parameter of an anion or a cation exchange chromatography stage or operation based on the received measurement value of the host cell protein and/or DNA concentration, said at least one process parameter including one or more of a volume of the chromatography column and/or membrane adsorber, buffer volume, number of cycles, and process time; and/or the at least one feature (22) further includes the pH value and/or the amount of at least one pH correctant, and wherein the determining of the at least one downstream process parameter (20) further comprises determining, based on the received measurement value of the pH value and/or the amount of at least one pH correctant, the amount and/or type of at least one pH correctant for use in the downstream process; and/or wherein the at least one feature (22) further includes the type and/or amount of at least one contaminant, and wherein the determining of the at least one downstream process parameter (20) further comprises determining, based on the received measurement value of the type and/or amount of at least one contaminant, a biomass dilution parameter, cycle time and/or processing column size, and wherein optionally the at least one feature further includes the amount of antifoam and/or amount of block polymers.
The method according to any one of the preceding claims, wherein the at least one feature (22) further includes the amount of lipids and/or long epidermal growth factor, and/or peptides and/or other media, and wherein the determining of the at least one downstream process parameter (20) further comprises determining, based on the received measurement value of the amount of lipids and/or long epidermal growth factor and/or peptides and/or other media, at least one purification operation parameter; and/or wherein the at least one feature (22) further includes at least one critical quality attribute, and wherein the determining of the at least one downstream process parameter (20) further comprises determining, based on the received measurement value of the at least one critical quality attribute, whether to start a downstream process; and/or wherein the at least one feature (22) includes further the process temperature, and wherein the determining of the at least one downstream process parameter (20) further comprises determining, based on the received process temperature, a cooling or heating of process fluid for the downstream process; and/or wherein the at least one feature (22) includes further turbidity, and wherein the determining at least one downstream process parameter (20) further comprises determining, based on the received measurement value of the turbidity, at least one purification operation parameter; and/or wherein the at least one feature (22) further includes media buffer system and/or capacity, and wherein the determining of the at least one downstream process parameter (20) further comprises determining, based on the received measurement value of the media buffer system and/or capacity, a pH adjustment parameter; and/or wherein the at least one feature (22) further includes process volume, and wherein the determining of the at least one downstream process parameter (20) further comprises determining, based on the received measurement value of the process volume, dimensioning of the downstream process.
The method according to any one of the preceding claims, wherein said receiving comprises receiving a plurality of measurement values of respective plurality of process features (22) of an upstream process by which the biomass to be processed in the downstream process has been obtained and/or of a downstream process stage or operation.
The method according to any one of the preceding claims, wherein the downstream process comprises a plurality of downstream process stages or operations that are connectable in parallel and/or sequentially (34A-34D, 38A-38D, 40, 42A-42C), the at least one process parameter (20) further includes the number and/or type of downstream process stages or operations to be connected or disconnected, and the configuring and/or setup and/or controlling comprises connecting or disconnecting the determined number and/or type of downstream process stages.
The method according to claim 9, wherein the downstream process stage or operation to be connected or disconnected is a purification stage or operation (34A-34D, 38A-38C, 40, 42A-42C), and wherein optionally said purification stage or operation is one of a filtration stage, pre-filtration stage, chromatography stage or centrifugation stage._
The method according to claim 9 or 10, wherein the at least one process parameter (20) further includes at least one parameter characterizing the dimensioning of the determined number and/or type of downstream process stages or operations (34A-34D, 38A-38D, 40, 42A-42C); and/or wherein the at least one feature (22) includes at least one of the following features: pressure, volume flow, volume flow rate, turbidity, viscosity, product amount and/or concentration, amount and/or concentration of contaminants, cell viability, temperature.
A computer program product comprising instructions which, when the program is executed by a computer, cause the computer to carry out the method of any one of the preceding claims.
A system (10) for configuring and/or setup and/or controlling a downstream process for processing a biomass to obtain a product, said system comprising at least one processor (104) and at least one actuator (36A- 36D) controlled by the processor configured to carry out the method of any one of claims 1 to 11.
A method for processing a biomass comprising: configuring and/or setup and/or controlling of a downstream process for processing the biomass according to the method of any one of claims 1 to 11; processing the biomass by using the so configured and/or setup and/or controlled downstream process.
A system (100) configured to process a biomass, said system comprising: a system (10) for configuring and/or setup and/or controlling a downstream process according to claim 16, said system comprising at least one processor (104) configured to perform a method for configuring and/or setup of a downstream process for processing the biomass according to any one of claims 1 to 11; at least one process stage (12, 18, 34A-34D, 38A-38D, 40, 42A-42C, 44; 120, 181-186) configured to process the biomass by using the so configured and/or setup and/or controlled downstream process.

Description

The technical field of the present application is methods and systems for configuring, setup and/or control of a downstream process for biomass processing. In particular an aspect of the application relates to an interconnection between upstream and downstream processes for biomass processing and/or between the process stages of a downstream process comprising a plurality of process stages. A process for processing a biomass to obtain a product (bioprocess) is a process using cells and/or their components to obtain desired products. A bioprocess typically comprises a plurality of different stages or operations, for example cell growth stage, cell harvesting stage, media preparation stage, separation stage, chromatography stage, filter (filtering or filtration) stage, stirring stage, etc. Generally, a bioprocess may be divided in an upstream process and a downstream process. The upstream process (upstream part of the bioprocess) relates to the first part of a bioprocess, in which the cell culture, microbes, etc. is/are grown. An upstream process typically involves a plurality of steps or stages. For example, an upstream process may comprise culture inoculation, culture growth, fermentation, etc. A downstream process (downstream part of the bioprocess) typically involves processing the biomass produced by the upstream process to obtain a final product meeting certain quality and purity requirements. A downstream process typically involves a plurality of stages, such as for example a plurality of purification stages at which waste, impurities and/or other undesired substances are removed. For example, a downstream process may comprise a primary recovery at which cells and/or debris are removed, separation stage (e.g. by centrifugation), filter stage, chromatography stage, buffer exchange stage, material hold stage, viral inactivation stage, other purification stages, etc. Each of the stages of the upstream and downstream process may comprise a plurality of sub-stages. Each individual stage or operation has one or more process parameters or settings that need to be configured, setup and/or controlled to obtain the required final product. There are various challenges involved in the configuring or setup up and controlling the different stages of a complex bioprocess. An object of the present invention is to provide an improved methods and systems for configuring, setup and/or control of a bioprocess. The object is solved by a method for configuring and/or setup and/or controlling of a downstream process for A computer-implemented method for configuring and/or setup and/or controlling of a downstream process for processing a biomass, a respective computer program product, a system for configuring and/or setup and/or controlling a downstream process, a method for processing a biomass and a system for processing a biomass as defined in the claims. In particular, according to a first aspect of the present disclosure, there is provided a computer-implemented method for configuring and/or setup of a downstream process for processing a biomass, comprising: receiving at least one measurement value of at least one feature of an upstream process by which the biomass to be processed in the downstream process has been obtained;determining at least one downstream process parameter based on the received at least one measurement value. The downstream process and more specifically at least one process stage or process operation of the downstream process is configured and/or setup based on the determined at least one downstream process parameter. Thus, the downstream process is carried out in accordance with the at least determined downstream process parameter. According to a second aspect of the present disclosure, there is provided a computer-implemented method for controlling of a downstream process for processing a biomass, comprising: receiving at least one measurement value of at least one feature of an upstream process by which the biomass to be processed in the downstream process has been obtained;determining at least one downstream process parameter based on the received at least one measurement value;controlling at least one process stage or process operation of the downstream process based on the determined at least one downstream process parameter. In particular, the control may be predictive control, based on measured values of the at least one feature of the upstream process. Examples of the biomass to be processed include bacteria, yeasts, molds, animal cells, plant cells, etc. Further ingredients may include chemical compounds, proteins (such as enzymes), various additives, etc. The downstream processing of the biomass results in a biopharmaceutical product. Some non-limiting examples of such products include recombinant and non-recombinant proteins, vaccines, gene vectors, DNA, RNA, antibiotics, secondary metabolites, growth factors, cells for cell therapy or regenerative medicine, half-synthesized products (e.g