WO2020025174A1 - Procédé et dispositif pour fournir un milieu utilisé dans la fabrication d'un produit biopharmaceutique - Google Patents

Procédé et dispositif pour fournir un milieu utilisé dans la fabrication d'un produit biopharmaceutique Download PDF

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Publication number
WO2020025174A1
WO2020025174A1 PCT/EP2019/056599 EP2019056599W WO2020025174A1 WO 2020025174 A1 WO2020025174 A1 WO 2020025174A1 EP 2019056599 W EP2019056599 W EP 2019056599W WO 2020025174 A1 WO2020025174 A1 WO 2020025174A1
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WO
WIPO (PCT)
Prior art keywords
medium
manufacturing process
measuring
container
measurement
Prior art date
Application number
PCT/EP2019/056599
Other languages
German (de)
English (en)
Inventor
Christian Grimm
Original Assignee
Sartorius Stedim Biotech Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sartorius Stedim Biotech Gmbh filed Critical Sartorius Stedim Biotech Gmbh
Publication of WO2020025174A1 publication Critical patent/WO2020025174A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48—Automatic or computerized control
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84—Systems specially adapted for particular applications
    • G01N2021/8411—Application to online plant, process monitoring
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84—Systems specially adapted for particular applications
    • G01N2021/8411—Application to online plant, process monitoring
    • G01N2021/8416—Application to online plant, process monitoring and process controlling, not otherwise provided for
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/12—Circuits of general importance; Signal processing
    • G01N2201/129—Using chemometrical methods

Definitions

  • the invention relates to a method and a device arrangement for providing a medium used in the production of a biopharmaceutical product, in particular a nutrient medium or a buffer or a feed solution.
  • a nutrient medium is used to support growth and / or the multiplication and contains all nutrients that are necessary for the metabolism of the cells.
  • a feed solution can be “fed” with important nutrients, vitamins, amino acids or trace elements.
  • a buffer i.e. a mixture of substances for pH stabilization, is required as a basis for nutrient media and for various tasks in downstream processing, i.e. for process steps for the separation and purification of cell cultivation products in order to ensure or increase the purity of the end products.
  • a particularly important piece of information for the correct production of such media is the use of raw materials or intermediate products with the correct, desired properties and quality attributes.
  • the composition of the medium used for a cell culture is of crucial importance for the process and product quality of the cultivation.
  • the production of cell culture media, especially on a production scale (large volume) is nowadays mostly done by dissolving or mixing a concentrate (solid mixture, mostly in Powder form, or stock solution) in high-purity water (English: Water for Injection, abbr .: WFI).
  • Additional additives, in particular unstable constituents, such as glutamine, may be added directly before the start of the culture.
  • the high-purity water in a container e.g. B. in a reusable stainless steel tank or in a disposable plastic bag, before the concentrate is added via an access and mixed.
  • Typical components of the concentrate for a nutrient medium are vitamins, amino acids, trace elements, salts, lipids, nutrients or other components such as insulin.
  • the number of different constituents often varies in the range from several dozen to 100.
  • Chemically defined constituents that is to say no complex constituents such as yeast extract, whey powder etc., are usually used for animal cell cultures.
  • the pH and / or the electrical conductivity of the mixture in the container is usually determined with a known recipe and the desired target value by adding water, concentrate and / or liquid acid or alkali set. Corresponding sensors are provided on the container for this.
  • the medium in particular for large reactors, can also be produced in a continuous or quasi-continuous process. With such a manufacturing process, the medium should be made available continuously and “on demand”.
  • a so-called "in-line” mixture is provided for the production using a mixing tool integrated in a pipe system.
  • the sensors in particular for determining pH, conductivity or flow, are then also integrated “in-line” downstream in the line system.
  • an “on-line” measurement ie in a bypass path, is also possible.
  • the correct weight of the medium and the correct volume of the concentrate as well as the correct setting of the pH value and / or the conductivity value will also achieve the correct quality of the medium.
  • individual components vary within the concentrate. It is known from experience, for example, that powder-based concentrates can generally have widely fluctuating proportions of the ingredients. Fluctuations in the composition can also be due to media components with a short shelf life. In these cases it is not ensured that the desired quality of the medium is achieved by setting the desired pH or conductivity value, since different mixture compositions can result in the same pH value and conductivity value. It is therefore possible that the actual quality of the medium deviates significantly from the target quality and leads to a qualitatively and / or quantitatively unsatisfactory product or process.
  • the object of the invention is to create a possibility of making the process of providing a medium used in the context of a cultivation, in particular a nutrient medium or a buffer or a feed solution, less risky and ensuring qualitative security.
  • the method according to the invention for providing a medium used in the production of a biopharmaceutical product comprises the following steps:
  • the invention is based on the knowledge that the risk of providing a medium that does not meet the specified quality requirements can be minimized if the checking of the medium is fundamentally expanded during the manufacturing process, so that a clear statement about the quality is possible.
  • This is achieved according to the invention by checking the medium based on the measurement of a multivariate parameter.
  • a multivariate parameter is to be understood here abstractly to mean a parameter which, in contrast to a univariate parameter, is dependent on a plurality of variables. According to the invention, this plurality of variables is measured simultaneously, i. H. in the same measurement process.
  • An example of a multivariate parameter in the sense of the invention is a spectrum measured by a spectrometer, i. H. spectroscopic data, which together form a complex data type.
  • An absorption or emission spectrum of the medium examined depends on its composition, that is on the individual components of the medium and thus on several variables.
  • the identity check is carried out during the production of the medium - in the sense of the invention this is also to be understood to mean preparation of the medium or the like. This makes it possible to correct the manufacturing process if necessary intervene. This eliminates the hassle of taking samples later and examining them.
  • the method according to the invention ensures that no large amounts of the medium have to be disposed of if it is only subsequently determined that the medium produced does not meet the quality requirements.
  • the multivariate parameter is measured in situ in a container filled with the medium with the aid of a measuring device coupled to the container.
  • This first process variant is suitable for the case that the manufacturing process is a batch process, i.e. when a limited amount of substance is produced (batch production).
  • the multivariate parameter is then measured exactly where the medium is mixed together during production (in situ).
  • the multivariate parameter is measured in-line in a line system with the aid of a measuring device integrated in the line system.
  • This second method variant is suitable in the event that the manufacturing process is a continuous or quasi-continuous process.
  • the multivariate parameter is then measured in the main flow path of the manufacturing process (in-line).
  • a measurement in a bypass path is also possible (on-line).
  • a spectroscopic measuring method is particularly suitable for determining a multivariate parameter, in particular a molecular spectroscopic measuring method that provides a spectrum from which so much information about the medium can be learned that sufficient selectivity is given and a clear one Quality assessment is possible.
  • a spectroscopic measurement method is preferred which is based on at least one of the following spectroscopy techniques:
  • NIR Near Infrared Spectroscopy
  • a continuous, i.e. H. Repeated measurement of the multivariate parameter during the manufacturing process is advantageous in order to observe the quality of the medium not only selectively, but over a longer period of time. This can either ensure that the quality of the medium does not change unnoticed during production, or it can be determined during the production process whether and if so when a desired quality of the medium has been achieved.
  • the measurement data of the multivariate parameter are preferably recorded and processed in real time. This avoids delays in the ongoing manufacturing process, since it is possible to intervene immediately in the manufacturing process if necessary. In addition, the waste in medium production can be reduced to a minimum, which is particularly important given the economic value of the medium.
  • the identity of the medium can be checked in different ways depending on the type of multivariate parameter and the measurement technology selected. In general, it makes sense to compare the measured multivariate parameter with comparison data relating to the multivariate parameter, which are stored in a database.
  • the comparison data can in particular be reference data, e.g. B theoretical ideal values or limits of permissible value ranges or similar
  • the measurement data of a recorded spectrum compared on the basis of a predetermined metric in the scoring room with scores from at least one target spectrum from the database.
  • the method according to the invention provides that the production process is influenced depending on the result of the verification of the identity of the medium. This can be done by controlling at least one connected process component, in particular by outputting corresponding control signals to the process component. So automatically, d. H. can intervene in the manufacturing process in a controlling or regulating manner without the interaction of the operating personnel.
  • the method according to the invention can be supplemented by additionally measuring at least one univariate parameter during the manufacturing process and including the measured value in the verification of the identity. This measure allows the security of the manufacturing process to be increased even further, since the identity check is expanded by an additional criterion.
  • the additional univariate parameter is preferably one of the following variables, which can be measured reliably in a proven manner:
  • At least one further multivariate parameter can be measured during the manufacturing process and the measured value can be included in the verification of the identity in order to minimize the risk.
  • the invention also provides a device arrangement for providing a medium used in the production of a biopharmaceutical product, in particular a nutrient medium or a buffer or a feed solution.
  • the device arrangement according to the invention comprises a container or a line system in which the medium is produced in a manufacturing process, and a first measuring device for measuring at least one multivariate parameter which is characteristic of the medium during the manufacturing process.
  • the device arrangement further comprises an evaluation and control device connected to the first measuring device, which is set up to check the identity of the medium using the measurement of the multivariate parameter during the manufacturing process and to output information as a function of the result of the check during the manufacturing process and / or to influence the manufacturing process.
  • the device arrangement according to the invention either a first embodiment in which the first measuring device is coupled to the container or a second embodiment in which the first measuring device is integrated in the line system.
  • the container or the line system are preferably formed from disposable components or essentially from disposable components.
  • the first measuring device can also comprise disposable components.
  • these are the components which are attached directly to the container or are arranged in the container.
  • these are the ones Components that come into direct contact with the medium flowing through in the pipe system.
  • the first measuring device preferably comprises a spectroscopic measuring system, in particular a molecular spectroscopic measuring system.
  • a spectroscopic measuring system can be coupled to the container or the line system via an optical access.
  • the optical access can be designed as an optical window on the container or in the form of a transparent flow cell in the line system of the device arrangement.
  • the first measuring device is set up for the continuous measurement of the multivariate parameter.
  • An evaluation and control device that is set up in such a way that it can record and process the measurement data of the first measurement device in real time is particularly advantageous. This enables quick and targeted intervention in the manufacturing process before a large amount of scrap is produced.
  • the evaluation and control device preferably has access to a database in which comparison data relating to the multivariate parameters are stored, so that the identity check can be carried out using uniform, comprehensible criteria.
  • the evaluation and control device is connected to at least one process component used in the manufacturing process.
  • the evaluation and control device is set up to control the process component depending on the result of the verification of the identity of the medium, in particular by outputting corresponding control signals to the process component.
  • the evaluation and control device of the device arrangement according to the invention can be part of a Process control entity, in particular a SCADA system, or include such a process control entity.
  • Achieve embodiment of the device arrangement according to the invention in which at least a second measuring device for measuring a univariate parameter characteristic of the medium is coupled to the container or the line system.
  • the second measuring device is in particular set up to measure one of the following variables: pH value;
  • At least one further first measuring device for measuring a further multivariate parameter characteristic of the medium can also be coupled to the container or the line system.
  • FIG. 1 is a schematic representation of a first embodiment of a device according to the invention for providing a medium used in a cultivation
  • - Figure 2 is a schematic representation of a second embodiment of the device according to the invention.
  • - Figures 3a, 3b, 3c an exemplary flow diagram of a method for providing a medium used in the context of a cultivation.
  • FIG. 1 shows a first embodiment of a device arrangement 10 which is suitable for a batch process.
  • the device arrangement 10 comprises a container 12 which is provided for the production of a nutrient medium for the cultivation of microorganisms or parts of such organisms, in particular animal cells.
  • the container 12 can, however, also be provided for the production or processing of another medium used in the cultivation, in particular a buffer or a feed solution.
  • the container 12 is preferably a disposable component, in particular a sterilized plastic bag. Further process components, preferably also disposable components, may be present in the container 12, such as a stirrer for mixing the medium.
  • At least one first measuring device 14 for measuring a multivariate parameter characteristic of the medium is coupled to the container 12.
  • the first measuring device 14 can consist of several components, which do not necessarily have to be combined in a single device.
  • An example of a coupling of such a measuring device 14 to the container is an optical access 14a on the container 12 for a spectroscopic measuring system 14b arranged outside the container 12, which will be discussed in more detail below.
  • At least one second measuring device 16 for measuring a univariate parameter characteristic of the medium can also be coupled to the container 12.
  • sensors for measuring the pH value, the electrical conductivity, the turbidity, the color or the capacity of the medium can be introduced into the wall of the container 12.
  • Other arrangements of such measuring devices 16 on the container 12 are also possible. All components of the second measuring devices 16 which are attached directly to the container 12 or arranged in the container 12 are preferably disposable components.
  • All measuring devices 14, 16 are connected to an evaluation and control device 18, a connection being understood to mean any possibility of transmitting the measurement data of the measuring devices to the evaluation and control device.
  • the evaluation and control device 18 is capable of acquiring and processing at least the measurement data of the first measurement device 14 for measuring the multivariate parameter in real time. Ideally, this applies to the measurement data of all measuring devices 14, 16.
  • the evaluation and control device 18 has access to at least one database in which comparison data relating to the multivariate parameter or parameters are stored.
  • evaluation and control device 18 is able to influence an ongoing process, in particular by at least one of the following measures:
  • warnings optical and / or acoustic
  • the evaluation and control device 18 is part of a process control entity, for. B. a SCADA system (English abbreviation for Supervisory Control and Data Acquisition), or it includes such a process control entity.
  • SCADA Supervisory Control and Data Acquisition
  • FIG. 2 shows a second embodiment of the device arrangement 10, which is suitable for a continuous or quasi-continuous process control.
  • the at least one first measuring device 14 for measuring the multivariate parameter which is characteristic of the medium is not coupled to a container, but rather is integrated in a line system 20, i. H. at least a part of the first measuring device 14 that is relevant for the measurement is located in the flow path of the medium.
  • the device arrangement 10 can comprise a disposable hose system with aseptic connections, a static mixer 22 and an optical flow measuring cell 14c for coupling a spectroscopic measuring system 14b.
  • At least one second measuring device 16 for measuring a univariate parameter which is characteristic of the medium can also be integrated in the line system 20.
  • sensors for measurement the pH value and / or the electrical conductivity of the medium can be introduced as flow measuring cells.
  • At least those components that come into direct contact with the medium flowing through are preferably sterilized disposable components.
  • FIGS. 3a, 3b and 3c Possible sequences of the provisioning process are shown in an overall diagram on the basis of a detailed example, the following explanation not covering all the details shown in FIGS. 3a to 3c.
  • the medium in a manufacturing process set up for this purpose, in addition to a measurement of a characteristic univariate physical or physicochemical quantity for the medium, such as pH value, conductivity, temperature, turbidity, color, capacity etc., in the container 12 or in the line system 20, using the second measuring device 16, a measurement of a multivariate parameter characteristic of the medium is also carried out using the first measuring device 14 in order to check the identity of the medium.
  • a measurement of a multivariate parameter characteristic of the medium is also carried out using the first measuring device 14 in order to check the identity of the medium.
  • the identity of the medium can be checked solely by evaluating the measurement of the multivariate parameter.
  • the result of the measurement of one or more univariate parameters or further multivariate parameters can also be included in the check. For the sake of simplicity, only the measurement and evaluation of a multivariate parameter is considered below.
  • the multivariate parameter is measured in situ, i.e. in the container 10 in which the essential steps of the manufacturing process (filling in the starting materials, mixing or dissolving etc.) take place, or in-line, that is to say in the line system 20 through which the medium flows in the manufacturing process.
  • a measurement in a bypass path is also possible (on-line).
  • a spectroscopic measuring method is preferably used for the measurement of the multivariate parameter, in particular a molecular spectroscopic method.
  • a spectrum obtained with such a measurement method represents a "fingerprint" of the medium with sufficient selectivity for the individual important molecular species of the medium with sufficient sensitivity (detection limit) of the components.
  • one of the following spectroscopy techniques can be used: Raman spectroscopy , Medium infrared spectroscopy (MIR), near infrared spectroscopy (NIR), UV / VIS absorption spectroscopy and fluorescence spectroscopy, scattering spectroscopy.
  • MIR Medium infrared spectroscopy
  • NIR near infrared spectroscopy
  • UV / VIS absorption spectroscopy and fluorescence spectroscopy
  • scattering spectroscopy can be used.
  • the spectrum of the medium is continuously during the manufacturing process - at least during the execution of the essential manufacturing steps - by the first measuring device 14, i. H. repeated at regular or irregular intervals, recorded and transmitted to the evaluation and control device 18. There, after any necessary data pretreatment steps (e.g. scatter correction, smoothing, etc.), a comparison of the spectrum measured in each case with a predetermined ideal spectrum, previously stored in the database, for this individual finished medium is carried out.
  • any necessary data pretreatment steps e.g. scatter correction, smoothing, etc.
  • the multivariate analysis includes a calculation of e.g. B. PCA and / or PLS scores of the spectrum and a comparison of the spectrum using a metric in the scoring room with scores of at least one target spectrum from the database (e.g. Euclidean distance, Mahalanobis distance, Hotelling's T-square distribution etc. ).
  • PCA stands for “Principal Component Analysis”
  • PLS for “Partial Least Squares” - regression.
  • the process control is returned with the information that the mixture has been reached or that the correct spectral identity (fingerprint) has been reached.
  • a suitable comparison metric e.g. correlation matrix
  • the evaluation and control device 18 can also actively intervene in the manufacturing process take place, for example by having the manufacturing process continue with the current settings or by ending the current process step as successfully completed and possibly initiating a subsequent process step.
  • the evaluation and control device 18 reacts by issuing an optical and / or acoustic warning and / or by specifically controlling connected process components.
  • the evaluation and control device 18 can stop a batch process entirely or switch a valve so that the unsatisfactory medium is directed into a sealing container.
  • the evaluation and control device 18 orders a manual sampling and examination.
  • the evaluation and control device 18 is set up in such a way that it recognizes and analyzes the error that has led to the negative identity check and then controls corresponding control loops.
  • the selective or quantitative supply of high-purity water, concentrate (powder or stock solution) or another missing or underrepresented component, such as glucose, glutamine, other amino acids etc. is adjusted accordingly to compensate for the error ,
  • a positive identity check ensures that the medium produced has the desired composition and the associated properties.
  • the staff is at least informed that the medium is not (yet) of the desired quality, and the manufacturing process can be intervened accordingly (manually or automatically).
  • the measurement and evaluation of the multivariate parameter based on a specific spectroscopic technique can be combined in a suitable manner with the measurement and evaluation of a univariate parameter (pH value, electrical conductivity, etc.) and / or another multivariate parameter (other spectroscopic technique) ,
  • a univariate parameter pH value, electrical conductivity, etc.
  • another multivariate parameter other spectroscopic technique

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  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Computer Hardware Design (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne un procédé pour fournir un milieu utilisé dans la fabrication d'un produit biopharmaceutique, en particulier un milieu nutritif ou une solution tampon ou d'alimentation, comprenant les étapes suivantes : préparation du milieu à partir de plusieurs composants, en particulier par mélange des composants, dans un processus de fabrication ; mesure d'au moins un paramètre à plusieurs variables caractéristique du milieu pendant le processus de fabrication ; vérification de l'identité du milieu à l'aide de la mesure du paramètre à plusieurs variables pendant le processus de fabrication ; et émission d'informations et/ou influence du processus de fabrication en fonction du résultat de la vérification de l'identité du milieu pendant le processus de fabrication. Un dispositif (10) pour la mise à disposition d'un milieu utilisé au cours d'une culture, en particulier d'un milieu nutritif ou d'une solution tampon ou d'alimentation, comprend un récipient (12) ou un système de tuyaux (20), dans lequel le milieu est produit dans un processus de fabrication, et un premier dispositif de mesure (14) pour mesurer au moins un paramètre à plusieurs variables caractéristique du milieu pendant le processus de fabrication. L'ensemble de dispositifs (10) comprend en outre un dispositif d'évaluation et de commande (18) qui est connecté au premier dispositif de mesure (14) et est configuré pour vérifier l'identité du milieu en utilisant la mesure du paramètre à plusieurs variables pendant le processus de fabrication et, en fonction du résultat de la vérification pendant le processus de fabrication, pour délivrer des informations et/ou influencer le processus de fabrication.
PCT/EP2019/056599 2018-08-02 2019-03-15 Procédé et dispositif pour fournir un milieu utilisé dans la fabrication d'un produit biopharmaceutique WO2020025174A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE202018104472.9 2018-08-02
DE202018104472.9U DE202018104472U1 (de) 2018-08-02 2018-08-02 Vorrichtungsanordnung zur Bereitstellung eines im Rahmen einer Produktion eines biopharmazeutischen Produkts eingesetzten Mediums

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WO2020025174A1 true WO2020025174A1 (fr) 2020-02-06

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Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102019001995B3 (de) * 2019-03-21 2020-07-16 Sartorius Stedim Biotech Gmbh Behälter zur Aufbewahrung, Mischung und/oder Kultivierung eines Mediums
EP4058550A1 (fr) * 2019-11-14 2022-09-21 Corning Incorporated Récipients de culture cellulaire et systèmes de surveillance pour la surveillance non invasive d'une culture cellulaire

Citations (4)

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US20090312851A1 (en) * 2005-07-25 2009-12-17 Biogen Idec Ma Inc. System and Method for Bioprocess Control
US20160298072A1 (en) * 2013-11-20 2016-10-13 Cmc Biologics A/S A bioreactor system and method for producing a biopol ymer
EP3173782A1 (fr) * 2015-11-26 2017-05-31 Karlsruher Institut für Technologie Procede de commande de chromatographie en continu et agencement de chromatographie multicolonne
EP3291038A1 (fr) * 2016-08-31 2018-03-07 Sartorius Stedim Biotech GmbH Contrôle et/ou surveillance d'un procédé de production d'un produit chimique, pharmaceutique ou biotechnologique

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Publication number Priority date Publication date Assignee Title
US20090312851A1 (en) * 2005-07-25 2009-12-17 Biogen Idec Ma Inc. System and Method for Bioprocess Control
US20160298072A1 (en) * 2013-11-20 2016-10-13 Cmc Biologics A/S A bioreactor system and method for producing a biopol ymer
EP3173782A1 (fr) * 2015-11-26 2017-05-31 Karlsruher Institut für Technologie Procede de commande de chromatographie en continu et agencement de chromatographie multicolonne
EP3291038A1 (fr) * 2016-08-31 2018-03-07 Sartorius Stedim Biotech GmbH Contrôle et/ou surveillance d'un procédé de production d'un produit chimique, pharmaceutique ou biotechnologique

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Title
"Process Analytical Equipment for Monitoring, Control and Cost Optimization of Inline Dilution Processes turning science into solutions", 1 January 2012 (2012-01-01), XP055118436, Retrieved from the Internet <URL:http://www.sartorius.de/fileadmin/fm-dam/sartorius_media/Bioprocess-Solutions/Process_Analytical_Technology/Application_Notes/Appl_PAT_Equipment_for_Inline_Dilution_Processes_W--1125-e.pdf> [retrieved on 20140516] *

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