JP2011509685A - Information acquisition, management system and method in bioreactor system and manufacturing facility - Google Patents

Abstract

The present invention, in certain aspects, identifies, tracks and determines the location of the following, determines material consumption by: removing waste from: positioning components in or on: And a system and method including the following assembly. The following refers to a container, a unit operation unit, or a component of a cell culture, cell storage, bioreactor, chemical manufacturing, or pharmaceutical manufacturing system. Certain containers, unit controls, devices, or other components of the present invention are used to perform all or part of the biological, chemical, or pharmaceutical manufacturing processes contained therein. In some embodiments, the method of the present invention is used to assemble system components, verify that the system components are correctly assembled, protect against the use of counterfeit components, and the like. Other embodiments of the invention include materials that allow automated assembly of bioreactor systems.
[Selection figure] None

Description

  The present invention relates generally to manufacturing systems including reactors or bioreactors, or components thereof, and in certain embodiments, identifying and tracking and assembling or cell culture, cell containment of containers and unit operations. , Systems and methods including components of bioreactors, purification, formation, finishing, packaging, chemical manufacturing, or pharmaceutical manufacturing systems.

  Various containers, devices, components and unit controls are available that manipulate fluids or perform chemical, biochemical or biological processes. For example, biological materials including mammalian, plant or insect cells (eg, animal and plant cells) and microbial cultures are processed using a bioreactor. Conventional bioreactors, typically designed as fixed reusable tanks or containers, or disposable bioreactors that utilize plastic aseptic bags are used for this purpose. Disposable single-use manufacturing systems can be assembled from component parts (eg, tubes, filter media, bags, accessories, connections, sensors, etc.) into disposable assemblies. The performance of component parts and portable assemblies, on the one hand, provides conveniences such as flexibility to quickly change the configuration of the assembly. On the other hand, portable module assemblies offer the possibility of human error in assembly, installation and use. To address these specific advantages and constraints, a comprehensive system that ensures proper use, inventory management, and protection against counterfeiting components and assemblies will be effective.

  The present invention relates generally to manufacturing systems including a retarder or bioreactor, purification, formation, filling / completion and packaging operations, raw material or product handling and storage including sample operations and process plans, or components thereof. In certain embodiments, the present invention relates to systems and methods that include the acquisition and management of information in bioreactor systems and manufacturing facilities. Certain embodiments of the present invention provide an apparatus and method for identifying, tracking and assembling unit operations, containers and other components of a biological, chemical or pharmaceutical manufacturing system. The subject matter of the present invention includes, in some cases, interrelated products, alternative solutions to specific problems, or multiple different uses of one or more systems or materials.

  In certain embodiments, the present invention relates to a method for configuring a customizable manufacturing system. In one embodiment, the method comprises providing a first unit operating unit configured to perform a biological, chemical or pharmaceutical manufacturing process or an operation of such a process, the first unit operating unit Comprises or is arranged inside the first module, and the first unit operation unit has a first identifier encoded or associated with information about the unit operation unit. Furthermore, the method of this embodiment comprises the step of providing a second unit operating unit configured to perform a biological, chemical or pharmaceutical manufacturing process or an operation of such a process, said second unit The operation unit includes or is disposed inside the second module, and the second unit operation unit includes a second identifier that is encoded or associated with information about the second unit operation unit. In the method of this embodiment, at least one of the first and second modules is configured to be movable. The method of this embodiment further comprises interconnecting the first module and the second module, and obtaining information by processing or detecting at least one of the first and second identifiers.

  In another embodiment, the method comprises providing a unit operation configured to perform a biological, chemical or pharmaceutical manufacturing process or the operation of such a process, said unit operation The unit has a first identifier that is encoded or associated with information about the unit operation unit. The embodiment further comprises providing a module configured to be operatively associated with the unit operator, wherein the module is encoded or associated with information about the module. With the identifier, the module is configured to be movable. The method of this embodiment further comprises obtaining information by processing or detecting at least one of the first and second identifiers. Further, the method relates to associating, based at least in part, on the information obtained in the step of determining whether to install the unit operation unit and the module in association with each other or obtaining the information. Determining to configure.

In yet another embodiment, the method includes an interior housing a first unit operating portion configured to perform at least one specific task of a biological, chemical, or pharmaceutical manufacturing process. Providing a first module comprising or having a first identifier encoded or associated with information about the first module, the method further comprising:
Determining an operation to be performed by the first module based on information encoded in or associated with the first identifier. Furthermore, in this embodiment, the method comprises a second module having an interior housing a second unit operating portion configured to perform at least one specific operation of a biological, chemical or pharmaceutical manufacturing process. Providing, wherein the second module comprises a second identifier encoded or associated with information about the second module, and the method is further based on information encoded or associated with the second identifier And determining a work to be performed by the second module. Further, in this embodiment, each of the first and second unit operation units includes at least one connection device associated with the operation unit so as to interconnect the unit operation units. The method of this embodiment further comprises determining a connectivity configuration based on information encoded or associated on at least one of the first and second identifiers, and according to the connectivity configuration, the module Interconnecting the first and second unit operation units and disposing the module.

In another aspect, the invention relates to a customizable manufacturing system. In certain embodiments, the system comprises at least two modules, each of the modules comprising an interior space interconnectable with the interior space of the other module, at least in a biological, chemical or pharmaceutical manufacturing process. Contains one or more components configured to perform one specific task;
At least one of the modules is configured to be movable and includes an identifier encoded on information about the module or an identifier associated with information about the module. Further, the system of this embodiment comprises a control system configured to perform operation and process control of one or more components, the control system further comprising at least one on at least one of the modules. Configured to access and process information associated with or obtained from an identifier and associated with information encoded by at least one identifier on at least one module or at least one identifier on at least one module Configured to perform functions based on the information to be received.

  In certain embodiments, the present invention relates to a customizable manufacturing system. The system comprises at least two portable modules, each of which is one or more unit operations for performing at least one specific task of a biological, chemical or pharmaceutical manufacturing process The system further includes a connection port associated with each of the modules for interconnecting the modules, and information about the components of the customizable manufacturing system. With an identifier to be encoded, after connection, each of the modules can be moved relative to the other module without breaking the connection.

  In another embodiment, the invention comprises a container configured to contain a volume of liquid, the container containing an identifier encoded with information about the container and the liquid A foldable bag configured as described above and a reusable support structure that surrounds and houses the foldable bag.

  In yet another embodiment, the present invention comprises a foldable bag that includes an identifier encoded using information about the foldable bag and a flexible wall. And a rigid portion including a base including a shaft configured to support the magnetic impeller, and the rigid portion is connected to the flexible wall portion.

  Other advantages and novel features of the invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying drawings. In cases where the present specification and a document incorporated by reference include conflicting or inconsistent disclosure, the present specification shall control. If two or more documents incorporated by reference contain conflicting or inconsistent disclosures in relation to each other, the document with the closest issue date shall prevail.

FIG. 1 is a schematic diagram illustrating the interconnection of several modules used in a manufacturing system, according to one embodiment of the invention. FIG. 2 is a schematic diagram illustrating an exemplary module used in a manufacturing system, according to one embodiment of the invention.

Non-limiting embodiments of the present invention will now be described by way of example in conjunction with the accompanying figures. The figures are schematic and are not drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For clarity, not all components are shown in all figures, and not all components of each illustrated embodiment of the invention are shown in all figures. Indeed, illustrations are not necessary for those skilled in the art to understand the invention.

In one aspect, the present invention relates to components, reagents, or products used in container, unit operation unit identification, tracking, assembly, or cell culture, cell containment, bioreactor, chemical manufacturing, or pharmaceutical manufacturing systems. And a method. Certain containers, unit controls, devices, or other components of the system are used to perform all or part of a biological, chemical, or pharmaceutical manufacturing process. In some embodiments, from the use of counterfeit, improper or unauthorized components, etc., to verify that the system components are correctly assembled to guide proper assembly of the system components. To protect, the technique of the present invention can be used.

  For example, in certain embodiments, a unique identifier is used and is associated with one or more components or materials used in the manufacturing system. An “identifier”, as described in greater detail below, is “encoded” information about the component that contains the identifier (ie, transport, storage, generation or transport, such as a radio frequency identification (RFID) tag or barcode) Information is transported or contained, such as by using device information), or any unencoded information about a component. Rather, the identifier is associated only with information contained in, for example, a database on a computer or a database on a computer readable medium. In the latter example, information associated with the database is retrieved and used by detecting an identifier or the like. An identifier that is “encoded” with information about a component need not necessarily be encoded with a complete set of information about the component. For example, in certain embodiments, additional information related to the component (eg, type, usage, ownership, location, location, connectivity, contents, etc.) is stored in isolation and is simply associated with an identifier. The identifier is encoded using information (eg, related to serial number, part number, etc.) that only allows unique identification of the device. “Information about unit operation unit, module, material, component, etc.” refers to unit operation unit, module, material, or component identity, positioning, or location, module, unit operation unit, or This is arbitrary information related to the identity, positioning, or location of the contents of the component, and may further include information related to the unit operation unit, material, nature of the component or content, state, or configuration. The unit operation unit, module, or component, or its contents “information about” identifies the unit operation unit, module, component, or its contents, and the unit operation unit, module, component, or its contents. May be included to distinguish one from the other. For example, what is a unit operator, module, or component or its contents, where it should be, where it should be located, how it should be positioned, unit operator, module, Or the function or purpose of a component or its contents, a unit operator, a module, how a component or its contents should be assembled, or how it should be connected to other components of the system, unit It represents information indicating the lot number, origin, purpose, ownership, etc. of the operation unit, module, component, or its contents.

  In one example, the first module of all systems that include a first identifier may be connected to a second module that includes a second identifier. In this case, each identifier is encoded or associated with information about the component with which it is associated. The two modules can be interconnected and connectivity compatibility can be verified based at least in part on information encoded or associated with the first and second identifiers. As another example, the order of connectivity may be selected based at least in part on information encoded or associated with the first and second identifiers. Other embodiments of the invention include an identifier that facilitates automated assembly of the bioreactor system.

  Although much of the description herein includes typical applications of the present invention related to bioreactors (or biochemical, chemical reaction systems including liquid containment devices), the present invention and its use are limited. Rather, aspects of the invention include systems for containment and processing of fluids (eg, liquids or gases) in containers (eg, mixing systems), systems for biological, chemical, or pharmaceutical manufacturing processes (eg, temporary recovery, filtration). And other systems related to chromatography systems, cell culture systems, microscopy, or other analytical devices), as well as other settings, including other applications. While many examples provided herein also include the use of a foldable bag or a container with a flexible container, embodiments of the present invention are non-foldable or rigid containers, and It should also be understood that other configurations for liquid containment may be associated.

  In one embodiment, the invention relates to configuring a customizable system such as a biopharmaceutical manufacturing system. As seen in the embodiment shown in FIG. 1, a typical customizable biopharmaceutical manufacturing system (10) comprises a first module (20). The module is configured to perform a biological, chemical, or pharmaceutical manufacturing process, or perform an operation of such a process. The first module (20) includes a first unit operation unit (21), which is a container, or another processing apparatus, or a component thereof. Optionally, the unit operation unit (21) is surrounded by a unit operation unit which is a storage device (24).

  The first unit operating section (21) includes an identifier (22) that can be encoded or associated with information about the first component. In general, as used herein, the term “identifier” refers to information about the unit operation to which the identifier is associated or attached (eg, one or more identities of the unit operation or its components, Any item that can provide a location, or information including location / positioning), or any item that can be identified and detected, and information about a unit operator with which an identifier is associated Refers to the identification and detection events associated with. Non-limiting examples of identifiers used in the context of the invention include radio frequency identification (RFID) tags, barcodes, serial numbers, colored tags, fluorescent lights, visual tags (eg, use of quantum dots), chemical compounds, Includes wireless tags and magnetic tags. Non-limiting examples of unit operations of biopharmaceutical manufacturing systems that can include identifiers include flexible containers (eg, disposable bags or bioreactor liners, or mixing containers), reusable supports Structures (eg, for housing and supporting disposable bags or bioreactor liners or mixing vessels), sensors, tubes, valves, reagent containers, agitation systems (eg, impellers), ports, and pillars, Includes centrifuges, control system components, computer hardware or software components, spargers, accessories such as accessories, or other functional components of the manufacturing system.

  In certain embodiments, as will be described in more detail later, they work together in a manner that verifies component positioning and the location of each other component to ensure proper assembly. In one exemplary embodiment, the first identifier is provided on a foldable bag and the second identifier is provided on a reusable support structure for storing and supporting the bag. The first and second identifiers indicate or are associated with information about proper or improper assembly when they are located in a certain close proximity to each other or at a certain relative position to each other. .

  The first module (20) in some cases comprises only one unit operating part (21) with one identifier. Alternatively, in certain embodiments, the first module (20) comprises a plurality of unit controls comprising identifiers that are interconnected or otherwise operatively associated with each other. In certain embodiments, the unit operation (21) may be operatively associated with the receiving device (24). As used herein, it generally indicates the following “operably associated” with one or more other unit controls. That is, such unit operation units are directly connected to each other in direct physical contact. The unit operation parts are not connected or attached to each other, or are not directly connected to or in contact with each other. Alternatively, the unit operation unit is sufficiently associated with the unit operation unit by being interconnected or associated mechanically, magnetically, electrically (including via electromagnetic signals transmitted through space), or fluidically. This makes it possible to perform a desired function. In some embodiments, the containment device (24) also includes an identifier (26). As will be described later, information encoded on identifiers (22) and (26) or associated with identifiers (22) and (26) is associated with the unit operation unit (21) and the accommodating device (24). Used to confirm the suitability of

  The unit operating part (21) and the receiving device (24) can take various configurations depending on the needs and requirements of the special manufacturing process. Located inside the device (24). In one embodiment, the containment device (24) is an environmental containment enclosure. As used herein, an “environment containment enclosure”, at least in part, encloses and creates a space that is substantially closed or can be closed (“closed space”), and is sterile during operation. An enclosure that has a substantially particle-free or low-particle enclosure internal environment (as compared to the environment surrounding the enclosure). The containment device is in fluid flow with a ventilator (not shown) that helps maintain such an environment within the containment device. The ventilator is either external to the enclosure or partially or fully contained within the enclosure. Alternatively, some other environmental treatment system is used to create and maintain a sterile, substantially particle-free or low-particle environment instead of or in addition to the ventilator. For example, ultraviolet or other forms of radiation sterilizers, water vapor sources, chlorine dioxide, ethylene oxide, hydrogen peroxide vapor, or other disinfectants.

  In certain embodiments, the containment device (24) is a container with a reusable support structure, such as a stainless steel tank, and the unit operation (21) is adapted to contain a liquid. A disposable container (for example, a foldable bag). In other embodiments, other containers, or other processing devices, or components thereof, are housed in the module (20). In general, for simplicity and brevity, the term “container” is similar to the term “unit operator”, unless the surrounding context prohibits, the support structure for supporting a liquid, volumetric container, Or cell culture, cell containment, bioreactor, chemical production, pharmaceutical production, or other components that form at least part of other production systems, or other devices, or adapted to contain those components It can be used as an abbreviation to indicate the volumetric container that has been made. For example, the container (21) takes the form of a component configured to perform a particular stage or operation of a biological, chemical or pharmaceutical manufacturing process. Non-limiting examples of unit operation units employed in the biological, chemical and pharmaceutical manufacturing processes of the invention include stirred tank bioreactors, filtration systems, seed culture expansion systems, primary recovery systems, chromatography systems, packing systems , Closed media / buffer formulation / accommodation / supply systems, and water purification systems (eg, distilled water for injection (WFI) systems). An additional containment enclosure (not shown), which is one or more environmental containment enclosures, surrounds and houses both the containment device (24) and the container (21) in certain embodiments.

  In some embodiments, a second module (30) will also be provided. The second module (30) includes a second unit operating unit (31) configured to perform biological, chemical, or pharmaceutical manufacturing processes or operations of such processes. The second unit operation unit (31) includes an identifier (32) that is encoded or associated with information about the second unit operation unit. The second unit operation unit (31) includes an independent device, or is positioned inside the storage device (34) as described above. In some embodiments, the containment device (34) also includes an identifier (36).

  In some cases, the first and second modules are interconnected via a connection device (40), such as fluidly, electrically, physically, etc. The connection device (40) also includes an identifier (42) that includes or may be associated with information about the connection device. The connection between modules (20) and (30) can be made before, during or after processing is performed on the first module (20). In some embodiments, the connection device (40) is a fluid flow such as a conduit, tube, pipe, duct, etc. that allows fluid flow between the modules. Optionally, the modules can be physically connected, but it is not fluidly coupled between the interiors of the modules.

  The transfer of material from module (20) to module (30) helps the material be further processed or manipulated in module (30), which is a function in module (20) (eg, different unit controls). It has functionality different from sex. For example, the module (20) comprises a unit operation in the form of a reactor for producing biological, chemical or pharmaceutical substances, while the module (30) contains the substances formed in the module (20). It will include a unit operator configured to purify.

  Some embodiments of the invention include the use of a control system (50). The control system may be configured or programmed to perform a variety of functions including directing assembly, electronic collection, and data storage, process control, diagnostics, among others described below. The control system optionally comprises control software, one or more computers that optionally execute one or more alarms, as well as other components.

  In some embodiments, the control system is configured to address or detect an identifier in the system, and is configured to obtain information about a unit operation associated with the identifier from the identifier, or to detect or detect the identifier. Upon detection, it is configured to associate information about the unit controls associated with the identifier contained on the exterior of the identifier (eg, in a computer in the control system or in a database stored elsewhere). The The identifier is activated and dealt with, and information is obtained from the identifier via a communication path (indicated by the dotted line emanating from the identifier in FIG. 1) by using a detector, or reader (54). . The activation, reading, detection, etc. of the identifier can be accomplished by various methods known to those skilled in the art, depending on the nature of the particular identifier employed. Non-limiting examples of detectors include RFID readers, barcode scanners, chemical detectors, cameras, radiation detectors, magnetic field or electric field detectors, microphones, among others. The type of detection and the appropriate type of detector depends on the particular identifier used, for example optical imaging, fluorescence excitation and detection, mass spectrometry, nuclear magnetic resonance, prioritization, mating, electrophoresis, spectroscopy, microscopy Inspection etc. can be included. In some embodiments, the detector is mounted at a particular location or pre-installed, while in other embodiments the detector is portable. In some cases, the detector is integrated with the control system (50) via a communication path (illustrated by the dashed line in FIG. 1). Communication between the detector and the control system takes place along a network embedded in hardware or transmitted wirelessly.

  The functions performed by the control system (50) are determined at least in part by information encoded or associated with one or more identifiers of system components. Directing the separation or attachment of components, directing the movement of components, starting, interrupting, continuing, especially in the unconstrained examples of control system functions associated with or using such information Or select specific processes, adjust environmental parameters (eg temperature, barometric pressure), adjust chemical levels, activate one or more alarms, add data to a database or automated report or database or Extracting data from automated reports, including verifying identity, ownership, or component or substance reliability.

  In some cases, information encoded on or associated with an identifier verifies, at least in part, the identity or function of a unit operator, module, connection device, or other system component. Can be used to The identifier is also used to determine the location of, for example, a unit operation unit, module, connection device, or other system component. In some cases, determining the location or identity or function of a component is performed as part of an inventory management process or a regulatory compliance process. Information regarding the identity or function of components may be used in conjunction with location and connectivity information in some embodiments to aid in assembly, disassembly, or operation of the biopharmaceutical manufacturing system. In some cases, the foregoing operations can be automated when performed in parallel with the control system (50).

  In some embodiments, the information obtained from or associated with at least one identifier is an operational relationship between: (for example, connecting an incorrect tube or product A Can be used to verify the suitability of the batch B). That is, between unit operation units, between unit operation units and modules, between two modules, between a connection device and unit operation units or modules, or between any two components of the system. In some cases, the operable relationship to be verified includes connectivity between the two components. If it is determined that the two components are compatible, they can be placed in operative association with each other. If it is determined that the two components are not compatible, an alarm or lockout condition is triggered to prevent their interconnection, or if already connected, a lockout condition that avoids activation is triggered, Alternatively, the component is automatically disconnected.

  As an example, the control system of a bioreactor system may identify an identifier of a particular component (eg, convey information about or relate to information about a model, manufacturer, size, etc.) It can be programmed to recognize that it is compliant and connected. In some embodiments, the compatibility of the connectivity of the two components includes determining the order of connection of the components. Verifying the compatibility of the connectivity of two components can also be achieved by using the material contained in the first component, the material contained in the second component, or the material from which the second component is manufactured, and biology. To determine whether they are chemically or chemically compatible. Such perception of component identity is, for example, a system that requires assembly of many different parts, a system that requires assembly of parts in a particular configuration, a system that is designed to be assembled or disassembled (e.g., Portable system), or helping to assemble the system by people who are not familiar with the system. Identifiers associated with one or more components of the bioreactor system are designed and disassembled (partially or completely), especially for customers at the first location, and then at the second location. This is particularly beneficial for systems transported to other customers, ie when the bioreactor system has to be reassembled (partially or fully) before use.

  In another example, a bioreactor system identifier or system component can be associated with predetermined or programmed information contained in a database regarding: That information relates to the use of the system or component for the reagent, user, etc., for a specific purpose, user or product, or for special reaction conditions. If an incorrect combination is detected or the identifier is not activated, the process is stopped or the system is rendered inoperable until the user is notified or as soon as the user recognizes it.

  Information encoded on or associated with the identifier is also used, for example, to determine whether the component associated with the identifier is genuine or counterfeit. In some embodiments of the present invention, the determination of the presence of counterfeit components causes a system lockout. In one example, the identifier includes a unique identity code. In this example, the process control software or module did not attempt to allow a system restart when a foreign or non-conforming identity code (or non-identity code) was detected (eg, the system fails) ). If the identifier is an RFID tag, for example (but not limited to), radio frequency identification (RFID), or a specific location in the system, eg, on or near the module, container wall Verification can be done via other proximity readers located in In certain embodiments, an RFID identifier connected to a component triggers the appropriate proximity reader to indicate that the appropriate unit, assembly, material, etc. are in the proper location. Similarly, the RFID identifier incorporated into the liner is used to indicate that the liner is properly positioned within the support container prior to activation of an external agitator drive motor (see discussion of FIG. 2 below). Can interact with the reader within the support container. When the manufacturing system is operated using the control system (50), system lockout is automated.

  In certain embodiments, the information obtained from the identifier or the information associated with the identifier is the identity of the customer from whom the component was sold or the customer from whom the biological, chemical, or pharmaceutical process is performed. Can be used to verify. In some cases, the information obtained from or associated with the identifier is used as part of the process of collecting data for system repair. The identifier also contains or is associated with information such as batch history, assembly process and instrumentation diagrams (P and ID), repair history, among others. System repair is in some cases accomplished through remote access or diagnostic software or the like. The control system (50) is used as part of the repair process.

 Information encoded on or associated with the identifier is also used to ensure that the biopharmaceutical manufacturing system is operating properly. In some cases, the information encoded on or associated with the identifier is used to verify that the unit operator, module, connection device, or other system component is functioning properly. Can also be used. Information from or associated with the identifier is also used to determine whether the unit controls, modules, connection devices, or other system components are properly assembled. In yet another embodiment, the detection or acquisition of information from the identifier can be performed to verify that appropriate reagents are being used for biological, chemical, or pharmaceutical manufacturing processes. . In some cases, the control system (50) is used to automatically shut down the system for anomalies in the system based on information encoded on or associated with the identifier. In addition, the control system (50) is used in some cases to help or guide improper assembly of system components or the use of inappropriate reagents.

  In some cases, information encoded on or associated with an identifier may result in a unit operator, module, connection device, or the like that leads to one or more product lots manufactured using system components. Used to track other components. In one embodiment, tracking includes establishing an interconnection cross-link connection between the process data and the raw bar code or RFID tag. In some cases, such tracking systems can be used in a manner that triggers an alarm condition or causes a lockout when an inappropriate or unauthorized use of components or detection of raw material occurs, for example. Constructed to ensure prevention of cross-mixing and confusion of components, or use of raw materials for multiple products. Information from or associated with the identifier may in some embodiments be stored for future reference and record management purposes, eg, in computer memory or on computer readable media. . For example, a particular control system may identify which component or component type was used in a particular chemical or biological reaction, date, time, duration of use, conditions of use, etc. In addition, information from or associated with the identifier is used. Such information is also used, for example, to determine whether a component should be removed or replaced. The identifier also reports or records the location or identity of the component (or set of components) at any point in time. Optionally, a manufacturing system that includes information encoded by or associated with an identifier is a collection of information that includes information that can be used to provide compliance with regulatory standards or proof of quality control verification. However, a report can be created from the collected information.

  The control system of the present invention is responsive to a change in a second environmental factor associated with one or more components of the manufacturing system and a change in the first environmental factor associated with one or more components of the manufacturing system. Configured to produce. Environmental factors are measurable properties in system components, such as temperature, pressure, pH, flow field, dissolved gas concentration, molar concentration, osmolality, glucose concentration, glutamine concentration, pyruvate concentration, phosphorous ash Includes, but is not limited to, stone concentration, color, turbidity, viscosity, amino acid concentration, vitamin concentration, hormone concentration, serum concentration, ion concentration, shear rate, and degree of agitation. In some embodiments, environmental factors may include the location or identity of components (eg, modules, unit controls, connection devices, etc.), presence of counterfeit components, presence of improperly assembled components, etc. Including external factors such as

  In some cases, the manufacturing system of the present invention also includes an actuator operatively associated with the system components. In one set of embodiments, the sensor, or identifier, is operatively associated with an actuator or microprocessor that can produce an appropriate change in an intra-module environmental factor. In one particular example, the actuator is connected to an external pump, which causes the removal of material from the reservoir. In another example, the actuator selectively heats a component or its contents, or selectively selects certain types of cells or certain types of cells that are sensitive to a certain amount of energy produced by the actuator. Create energy to kill. It should be understood that any control system and technique disclosed herein may be provided in combination in any combination with other control systems and techniques.

  The control system described herein can be implemented in many ways. This technique uses dedicated hardware or firmware, or uses a processor programmed to perform the functions listed above or any suitable combination of the above using microcode or software There is. The control system may be one or more operations of a unit operation of biological, biochemical or chemical reaction, or one or more operations of a plurality (separate or interconnected) unit operations. To control.

  Each of the systems described herein and their components may be software (eg, C, C #, C ++, Java, or combinations thereof), hardware (eg, one or more application specific integrated circuits). ), Firmware (eg, electrically programmed memory), or any combination thereof.

  In accordance with the present invention, the various embodiments described herein are implemented on one or more computer systems. These computer systems include, for example, Intel PENTIUM-type and XScale-type processors, Motorola Power PC, Motorola DragonBall, IBM HPC, Sun UltraSPARC, Hewlett-Packard PA-RISC processors, Advanced Micro Devices (AMD) A general purpose computer based on the various processors available in or any other type of processor. It should be appreciated that one or more of any type of computer system can be used to implement various embodiments of the invention. Computer systems include specially programmed, special purpose hardware such as application specific integrated circuits (ASICs). Aspects of the invention are implemented in software, hardware, or firmware, or any combination thereof. Moreover, the methods, acts, systems, system elements and components described above may be implemented as part of the described computer system or as independent components.

  In certain embodiments, the control system operably associated with the modules or containers described herein is portable. The control system performs, for example, fluid manipulations that process or detect identifiers, retrieve information from specific identifiers, or associate information with special identifiers and take actions based on such information (eg, mixing and Reaction), including all or part of the necessary controls and functions required for measuring and controlling control process parameters in the manufacturing system, etc. Such mobile / portable control systems include supports and casters for ease of transport, and are optionally physically connected to, eg, mounted on, the module or container. A control system is operatively associated with the container. Advantageously, a portable control system such as that described above is programmed with programmed instructions and can be transported and attached to the container as required (optionally with the container) as needed, over conventional control systems. It is possible to prepare for process control in a short time (eg, less than 1 week, less than 3 days, less than 1 day, less than 12 hours, less than 6 hours, less than 3 hours, or less than 1 hour). In certain embodiments in which a manufacturing system includes multiple modules and the multiple modules include individual control systems associated with them, the modules may be used to facilitate manufacturing system integration and comprehensive control. As soon as the manufacturing system is assembled, such control systems are installed in operative and cooperative association with each other. In certain such embodiments, the module individual control system is in communication with or controlled by a higher level master controller.

  Both modules are configured to be movable / portable. A caster (not shown in FIG. 1) or any other component to facilitate the movement / portability of the module can be included in any module shown in FIG. In certain embodiments, an identifier may be mounted on the module to identify the location of the module or passage through the facility or storage location. Advantageously, modules that are individually moveable / portable can be used after being used, for example in a different arrangement, using different chemical or chemical steps performed using the module, or biological, chemical Or can be reconfigured to perform pharmaceutical processes within a module. For example, after the material in the module (20) is transferred to the module (30), the modules (20) and (30) are cut and the module (20) is used to perform different steps. In some cases, the second step is not related to the first step performed using the module, eg, the first step includes drug synthesis and the second step includes cell harvesting. The identifier is encoded or associated with information about compatibility of the module (20) with another process step, and the identifier is used to ensure proper reassembly of the module (20) into the second system assembly. Used as part of In other cases, the second step is related to the first step. For example, the first step is to form a drug precursor, and the second step is to react the drug precursor with a compound to form the drug.

  The use of disposable components within the module can facilitate reconfiguration of the module. For example, after the first step is performed in a disposable bag bioreactor (e.g., the unit operation unit (21) in this case) and the material is transferred from the module (20) to the module (30), the disposable bag The body is removed from the module (20) and a new disposable bag can be inserted into it. This arrangement allows the second step to be performed in module (20) while the transferred material is processed in module (30). Similarly, after the second step in module (20) is performed, the material in the module can be transferred to module (30). Alternatively or alternatively, module (20) may be interconnected with third module (60) via connection (70), as described in more detail below. In certain embodiments, one or more steps can be performed simultaneously using the system (10), saving user time and space.

  The systems described herein are self-sufficient and are independently customized to perform specific biological, chemical, or pharmaceutical processes. Thus, for example, the system (10) is customized to perform a specific process at a first location, disassembled, and shipped to a second location to perform the same process at a second location. It becomes possible. Since modules and other components in certain embodiments contain identifiers that facilitate assembly, the time and expertise required to disassemble the module at the first location and assemble the module at the second location Knowledge is reduced. The use of a control system that provides identifiers and automation can also facilitate easier operation of the module, especially when the user is not trained or accustomed to the system. This feature is particularly advantageous when operating the system at a remote location.

  In one embodiment, the at least one identifier encoded with information used in the manufacturing system comprises an RFID tag. RFID tags include integrated circuits (eg, for storing and processing information, modulating and demodulating radio frequency (RF) signals, etc.) and antennas for receiving and transmitting signals. RFID tags can be passive, quasi-passive (eg, motor-assisted), or active. RFID tags are generally known in the art, and any suitable RFID tag can potentially be used in the context of the present invention as described above. The identifier of the present invention is connected to the component in any suitable manner, either directly or indirectly. Methods of attaching identifiers to system components are discussed in detail later. The identifier confirms that all disposable / product contact materials have been removed from the module or device before all disposable / product contact materials specified for the second product have been introduced. Can be used to

  As previously mentioned, the customizable biopharmaceutical manufacturing system shown in FIG. 1 is configured to include more than two modules or unit controls. Referring to FIG. 1, the third module (60) is provided or configured to perform biological, chemical, or pharmaceutical manufacturing processes or operations of such processes. The third module (60) includes a third unit operation unit (61) which is a container containing a liquid, a separation device, another processing device or a component thereof. For example, the third module (60) is required when further processing or manipulation of the material in the second module (30) is required, and at such times the module (60) is interconnected with the module (30). (Not shown). In certain embodiments, the third module (60) is advantageous when more than one process is operating in parallel, as previously described. The third module is designed and configured to perform a different process than the first or second module. For example, the third unit operation part (61) includes a container comprising an ultrafiltration device for separation of a desired product produced in a bioreactor comprising the unit operation part (21) of the module (20), The unit operation unit (31) of the module (30) includes an intermediate supply / storage / mixing device or system.

  As shown, the third unit operation unit (61) includes an identifier (62) that is encoded or associated with information about the third unit operation unit. The third unit operating part is independent and itself has a module or is positioned inside the receiving device (64). The identifier (62) can be used in the execution of any of the functions noted above. In some embodiments, the containment device (64) also includes an identifier (66). The connection device (70) interconnects the modules (20) and (60) and also includes an identifier (72) containing information about the connection device such as the module or connectivity. In other embodiments of the invention, additional modules or unit controls are added in a similar manner to perform additional processing functions.

  As previously mentioned, the unit operations, modules, or other components are at least partially surrounded by an environmental containment enclosure. The enclosure is part of an environmental containment system configured to maintain a sterile, sterile, substantially particle-free or particle-reduced environment within the enclosure. In certain embodiments, access to the material housed within the module or unit operator is made without exposing the material to the external atmosphere surrounding the environmental containment enclosure. Thus, such environmental containment systems can reduce or reduce the amount of contamination of substances contained in containers from personnel, equipment, and outside air, or the degree to which a user is exposed to the substances, for example. . These systems are particularly useful for producing or separating poisons and other infectious materials in containers with improved safety. Furthermore, the use of modules with environmental containment enclosures allows the modules to be used for processes where such an environment is required in an unclean environment where the module is not sterilized. This is because the enclosed space formed by the environmental containment enclosure can be operated in a sterilized, sterile, substantially particle-free or particle-reduced situation. This property can substantially reduce costs because a clean space or other facility is not required. Environmental containment systems and associated methods are described in more detail in co-owned US patent application Ser. No. 11 / 879,033 filed Jul. 13, 2007 entitled “Environmental Containment Systems”. And incorporated herein by reference.

  Connections between modules occur through various means such as rigid or flexible tubes, latches, electrical wiring, and the like. The connecting device includes an identifier that assists in assembling the manufacturing system. In certain embodiments, the connecting tube contains a built-in line that connects to the identifier in both the module or unit controls connected by the tube. In some examples, a flexible connection between the modules is formed so that each module can be moved to a different orientation, even when connected to each other. This property is particularly beneficial in systems where module movement is automated. The interconnection between a module and its associated method is described in more detail in co-owned US Patent Application Publication No. 2005/0226794, which is incorporated herein by reference.

  An unrestricted example of a bioreactor system comprising a module or module unit operation is illustrated in FIG. Module (100) includes a container (118), which can be, for example, a flexible container. The container (118) includes an identifier (119). The identifier (119) is, for example, incorporated into the container wall, otherwise attached, displayed on the container wall (eg as a barcode), suspended in the liquid contained in the container, etc. Associated with the container (118) in various ways. The module (100) further comprises a reusable support structure (114) (eg, a stainless steel tank) that surrounds, supports, and houses the container (118). In some cases, the support structure (114) includes an identifier (115). In some embodiments, the container is configured as a foldable bag (eg, a polymer bag). In other embodiments, the container may be a rigid container such as a rigid plastic carboy. Additionally or alternatively, all or part of the foldable bag or other container may comprise a substantially rigid material, such as a rigid polymer, metal, or glass. In some of these embodiments, the container (118) comprises a foldable bag having a flexible wall portion and a rigid portion with a base. In some embodiments, the rigid portion of the foldable bag with the base is sealed to the flexible wall portion. In some cases, the rigid portion comprising the base includes a shaft or other receiver configured to support a means for agitation (eg, an impeller). The container is disposable and configured to be easily removed from the support structure. In some cases, the container is incompletely connected to the support structure.

    When using a foldable bag, the foldable bag is constructed and arranged to contain the liquid (122), and the foldable bag is a chemical, biochemical or biological reaction. Contain reactants, media, organisms or other components to perform the desired steps such as. Further, the foldable bag may be configured such that the liquid (122) substantially contacts only the foldable bag during use and does not contact the support structure (114). In such an embodiment, the bag is disposable and used for a single reaction or a single series of reactions and is disposed of after the reaction. Since the foldable bag liquid does not contact the support structure, the support structure can be reused without cleaning. That is, after the reaction has occurred in the container (118), the container can be detached from the support structure and replaced with a second (eg, disposable) container. The second reaction can be carried out in the second container without having to clean either the first container or the reusable support structure. The identifier can be used to track inventory paths inside and outside the module to verify that the module has all the appropriate reagents, components, etc. before enclosing and starting the operation. Inventory data can be used to track inventory and to verify the use of each component in a batch operation. The identifier may also be configured and employed to work with or act as a leak detection sensor that indicates the status of leaks from the unit controls or components. For example, the use of identifiers in connection with leak detection is particularly advantageous for the following identifiers: That is, the identifier is an identifier incorporated in or associated with the foldable bag container of the system of the present invention, or a reusable support structure that houses or supports the foldable bag container of the system of the present invention. An identifier that is incorporated or associated.

  The module (100) can optionally include mixing means such as one or more impellers (151) positioned in the container (118), which impeller (151) can be external to the motor ( 152) (eg, about a single axis). In one embodiment, the identifier (153) is included in any part of the impeller (eg, base, vane, etc.). In some embodiments, the impeller and the motor are magnetically coupled. The mixing system or other modular components can be controlled by a control system (134) that also processes or detects identifiers and receives information from identifiers and information. Can be programmed or configured to process, store, and act on information. The control system (150) communicates with mixing means or other components to provide process control in some embodiments. In some cases, control of the mixing means is aided by an identifier associated with the mixing means or container.

  The identifier can be directly or indirectly, using any suitable method, on the unit operator, module, impeller, or any part of the system (or any component of the manufacturing system (10) of FIG. 1). Can be connected. For example, the identifier can be incorporated into the wall of a flexible container, container, or other component. The attachment may be reversible or impossible, but in many instances the identifier is non-reversibly attached to the component (eg, glued, incorporated, adhesive used, lamination, encapsulation, fastening) Or any other suitable way of mounting components).

In some embodiments, an identifier (such as an RFID tag) is placed in the bioprocess fluid (122). The identifier is used, for example, to measure and optionally store the value of the liquid in the unit operation, at least one characteristic. Non-limiting examples of properties that are recorded and optionally tracked using identifiers placed in the liquid include, for example, pH, temperature, pressure, fluid flow patterns, oxygen levels, CO ₂ levels, reagent levels, product levels Metabolic level, conductivity, or other reactor or process parameters. The support structure or container may also include, in some embodiments, one or more ports used for sampling, analysis (eg, determining pH or amount of gas dissolved in a liquid), or other purposes ( 154). In some cases, the identifier is incorporated to work with a sampling or analysis tool. The parameter can also be measured upstream from the reaction site or downstream. In some examples, during or after a bioprocess operation is performed, one or more identifiers are added to the fluid and are remotely sensed and analyzed (eg, continuously or periodically). In yet other embodiments, the identifier itself does not carry information about the unit operator, but rather comprises a detectable material or substance suspended or dissolved in the processing fluid. There, the detection of the material or substance is associated with information about the unit operator / processing fluid by the control system.

In some cases, chemical or biological reaction products or containers or unit controls that contain such products can be labeled with an identifier that contains stored information contained therein, Thereby, the components, conditions, and set of conditions used to form the product can be quickly and easily identified when needed. An identifier associated with a package of products may further allow product authentication.

As also shown in FIG. 2, the optional inflow port (142) and optional exhaust port (146) can be formed in the container (118) and optionally in a reusable support structure, from the container. This makes it easier to efficiently take in and out the liquid or gas. The container has a suitable number of inlet ports and an appropriate number of outlet ports. For example, a plurality of inlet ports are used to supply various gas compositions (eg, via a plurality of spargers (147)) or to separate gases before being taken into the container. The port is located in a suitable location for the container (118). For example, in certain containers including spargers, the container has one or more gas inlet ports located at the bottom. The tube is connected to an inflow port or an outflow port, for example, forming a delivery tube and an intake tube, each of which draws liquid in and out of the container. The port may optionally include an identifier (not shown) used for functions such as port type identification, identification of the appropriate port to associate with the appropriate connector, and so forth. Optionally, the container or support structure comprises a utility tower (150), wherein the utility tower (150) includes one or more devices inside the container or support structure, one or more pumps, control devices, or electronics. Useful for interconnecting equipment (eg, sensor electronics, electronic interfaces, pressurized gas control devices) or other devices. Such devices are controlled using a control system (134). The control system (134) is the same as the device used to control assembly and operation of the manufacturing system (eg, the control system (50) of FIG. 1), or it is another device dedicated to controlling the module (100). is there. In general, the various identifiers and control systems of module (100) are configured and operated to perform any of the following functions. Identification, authentication, inventory / source / destination management, assembly and compatibility verification, correlation with the use of specific components of a product lot (eg, specific disposable bag containers), data collection and regulation The functions described above for the module identifier of the system (10) of FIG. 1, such as compliance management.

  For systems including multiple spargers, the control system (134) is operatively associated with each of the spargers and is configured to operate the spargers independently of each other. Thereby, for example, it is possible to control a plurality of gases introduced into the container. The sparger, in some embodiments, allows the control system to ensure proper gas identity, supply, and connectivity (eg, ensuring compatibility between the sparger identifier and other identifiers on the gas supply cylinder connected to it). Includes identifiers that guarantee and facilitate automated control of the sparger, or allow other functions to be performed in addition to or instead of these.

  Additionally or alternatively, the module (100) may comprise an antifoaming system, such as a mechanical antifoaming device. As shown in the embodiment of FIG. 2, the defoaming device may also include an impeller (161) that can be rotated (eg, magnetically) using, for example, a motor (162) disposed outside the container. It doesn't matter. The impeller may be used to disperse the foam contained in the container upper space (163). In some embodiments, the antifoam system is in electrical connection with a sensor (143) (eg, a foam sensor) via a control system (134). In certain embodiments, the defoaming devices or portions thereof or the bubble sensor include one or more identifiers encoded in or associated with information about the component with which they are associated. This sensor (143) may determine, for example, the liquid level or volume of the foam in the headspace, or the pressure in the container, thereby inducing adjustment or control of the defoaming system. In other embodiments, the antifoam system is operated independently of any sensor. The anti-foaming device is co-owned, "GAS DELIVERATIONS, FOAM CONTROL SYSTEMS, AND BAG MODING METHODS AND ARTICLES FOR COLLAPSIBLE BAG VESSTO AND date of the 7th filing in the United States" 11 / 818,901, which is more fully described and is incorporated herein by reference.

  The support structure (114) also includes one or more site windows (160) for viewing the liquid level in the container (118). In some embodiments, the level sensor is incorporated into the site window. The level sensor allows fluid level communication to the control system (134). One or more connections (164) are located at the top of the container or other suitable location. The connecting portion (164) includes an opening, a tube, or a valve for taking liquid, gas, and the like out of the container, and each of the connecting portions (164) optionally includes a flow sensor or a filter (not shown). As mentioned above, these connections include identifiers that help ensure proper assembly or function of the module. The support structure further comprises a plurality of legs (166) and optionally has casters (168) to facilitate container transport.

  Not all the characteristics shown in FIG. 2 are required in all embodiments of the present invention, and the illustrated components may be positioned or configured differently. Please note. Similarly, the components described here may be added in other embodiments.

Various embodiments described herein include a container, such as a foldable bag. As used herein, “flexible container”, “flexible bag”, and “foldable bag” are used when a container or bag is exposed to internal pressure. That the shape or structural integrity cannot be maintained without the benefit of the individual support structure (due to the weight or hydrostatic pressure of the contained liquid or gas expected during operation) Pointing. The foldable bag is essentially made of a flexible material such as many plastics, or is usually made of what is considered a rigid material (eg glass or a specific metal), but is expected during operation. When exposed to applied internal pressure, due to its thickness or physical properties, the container can maintain its overall shape or structural integrity without the benefit of individual support structures. Can not. In some embodiments, the foldable bag comprises a combination of flexible and rigid materials, e.g., the bag is a connection, a port, an identifier such as one or more RFID tags, a mixing system or A rigid component such as a support part such as an antifoaming system is provided.

    The container (eg, a foldable bag) has an appropriate size for containing the liquid. For example, containers include 0.1-40 liters, 40-100 liters, 100-200 liters, 200-300 liters, 300-500 liters, 500-750 liters, 750-1000 liters, 1000-2000 liters, 2000- There is a capacity of 5000 liters, or 5000-10000 liters. In some examples, the container has a capacity of more than 1 liter, and in other examples a capacity of more than 10 liters, 20 liters, 40 liters, 100 liters, 200 liters, 500 liters, or 1000 liters. The same is possible even with a capacity of 10,000 liters or more.

  In some embodiments, the foldable bag is disposable and formed from a compatible flexible material. The flexible material is one of the USP Class VI certifications such as silicon, polycarbonate, polyethylene, and polypropylene, or is not certified for pharmaceutical use. Non-limiting examples of flexible materials include polyethylene (eg, linear low density polyethylene and ultra low density polyethylene), polypropylene, polyvinyl chloride, polyvinyl dichloride, polyvinylidene chloride, ethylene vinyl acetate, polycarbonate , Polymers such as polymethacrylate, polyvinyl alcohol, nylon, silicone rubber, other synthetic rubbers, or plastics. As described above, a portion of the flexible container comprises a rigid material such as a rigid polymer (eg, high density polyethylene), metal, or glass (eg, in the area that supports the instrument). In other embodiments, the container can be made of a substantially rigid material. Optionally, all or a portion of the container is optically transparent so that the contents inside the container can be viewed. The material or combination used to form the container can be flexible, puncture, tensile, liquid and gas permeable, opaque, and blow molded, injection molded, or rotational molded (eg, seamless folding) Selected based on one or more characteristics, such as adaptability to a particular process (such as to form a possible bag).

  The container (eg, foldable bag) has a suitable thickness to contain the liquid and is designed to be resistant to puncture during operation or handling. For example, the container wall is 250 mils or less (1 mil is 25.4 micrometers), 200 mils or less, 100 mils or less, 70 mils or less (1 mil is 25.4 micrometers), 50 mils or less, 25 mils or less. , 15 mils or less, or 10 mils or less overall thickness. In some embodiments, the container may have more than one material layer, and the more than one material layer may be either laminated together or attached to each other to give the container certain properties. . For example, a certain layer is formed of a material that hardly penetrates oxygen. Another layer is formed of a material that provides strength to the container. Additional layers may be included to provide chemical resistance to the fluid contained within the container. It should be understood that the container is formed from several layers of matching combinations. A container (eg, a foldable bag) may have, for example, one layer, two or more layers, three or more layers, or five or more layers of material. Each layer may have a thickness of 200 mils or less, 100 mils or less, 50 mils or less, 25 mils or less, 15 mils or less, or 10 mils or less, 5 mils or less, or 3 mils or less, or combinations thereof.

  As described above, in certain embodiments, the module (24) takes the form of a support structure that can enclose and house the unit operating portion (20), as shown in FIG. The support structure has an appropriate shape and can surround or contain the container. In some cases, the support structure is reusable. The support structure is formed of a substantially rigid material. Non-constrained embodiments of materials that can be used to form a reusable support structure include stainless steel, aluminum, glass, resin-impregnated fiberglass or carbon fiber, polymers (eg, high density polyethylene, Polyacrylates, polycarbonates, polystyrenes, nylons or other polyamides, polyesters, phenolic polymers), and combinations thereof. The material is compensated for its use in the environment where it is used. For example, a material that does not shed is used in an environment that requires the generation of minimum fine particles.

  In some embodiments, the reusable support structure is designed to have a height and diameter similar to a standard industrial scale stainless steel bioreactor (or other standard reactor or vessel). Its structure can be reduced to a desktop reactor system with a small capacity. Thus, the reusable support structure has the appropriate capacity to perform the desired chemical, biochemical, or biological reaction. In many instances, the reusable support structure has approximately the same capacity as the container. For example, a single reusable support structure is used to support and contain a single container having approximately the same capacity. However, in other cases, the reusable support structure is used to accommodate more than one container. Reusable support structures are for example 01-100 liters, 100-200 liters, 200-300 liters, 300-500 liters, 500-750 liters, 750-1000 liters, 1000-2000 liters, 2000-5000 liters, Or having a capacity of 5000-10000 liters. In some examples, the reusable support structure has a capacity greater than 1 liter, and in other examples, 10 liters, 20 liters, 40 liters, 100 liters, 200 liters, 500 liters, or 1000 liters. Has a capacity exceeding. A volume greater than 10,000 liters is also possible.

  However, in other embodiments, the unit operations of the present invention do not include individual containers (eg, foldable bags) and modules, but instead include self-supporting disposable or reusable containers. . The container may be, for example, a plastic container, optionally with a stirring system or a removable stirring system integrally attached to the container. The agitation system is disposable with the container. In certain embodiments, such a system comprises an impeller welded or secured to a polymer container. Thus, the container configurations and characteristics described herein for containers and support structures (eg, seamless containers, sparge systems, defoamers, etc.) are also applicable to self-supporting disposable containers. Please note that.

  The following co-owned patent applications and publications describe in more detail the various components described above that may be useful for carrying out certain embodiments of the present invention. Each of the following is hereby incorporated by reference in its entirety: US Provisional Patent Application No. 60 / 903,977, filed February 28, 2007, entitled “Weight Measurements of Liquids in Flexible Containers” by P.A. Mitchell, et al. US Provisional Patent Application No. 60 / 830,997 filed July 14, 2006, entitled “Stirred Tank Bioreactor Having Environmental Containment” by G. Hodge, et al. US patent application Ser. No. 11 / 147,124 filed Jun. 6, 2005, entitled “Disposable Bioreactor Systems and Methods” by G. Hodge, et al. Published as Japanese Patent Application No. 2005/0272146. International Patent Application No. PCT / US2005 / 020083, filed 6 June 2005, entitled “Disposable Bioreactor Systems and Methods” by G. Hodge, et al, which is WO 2005/118771 on 15 December 2005. It is published as an issue. US patent application Ser. No. 11 / 050,133 filed Feb. 3, 2005, entitled “System and Method for Manufacturing” by G. Hodge, et al. Published as Japanese Patent Application No. 2005/0226794. International patent application PCT / US2005 / 002985 filed on February 3, 2005, titled “System and Method for Manufacturing” by G. Hodge, et al, which was published on August 18, 2005 in WO 2005/076093. It is published as an issue. US patent application Ser. No. 11 / 147,124 filed Jun. 6, 2005, entitled “Disposable Bioreactor Systems and Methods” by G. Hodge, et al. Published as Japanese Patent Application No. 2005/0272146. US Patent Application No. 60 / 962,671, filed July 30, 2007, entitled “Continuous Perfusion Bioreactor System” and “Bag Wrinkle Remover, Leak Detection Systems, and Electromagnetic Agitation for Liquid Containment Systems” US patent application filed on the same date as the title.

  While some embodiments of the invention are described and depicted herein, one of ordinary skill in the art will perform the function or result or one or more of the features described herein. Other means or structures for obtaining the effect can be easily conceived. Such variations or modifications are also considered to be within the scope of the present invention. Further, it will be appreciated by those skilled in the art that all parameters, dimensions, materials and configurations described herein are exemplified, and that actual parameters, dimensions, materials or configurations are specific to the application or teaching of the invention. Is based on the application used. Those skilled in the art will understand or understand without using routine experimentation and many equivalents of the specific embodiments described herein. Accordingly, the foregoing embodiments are presented as examples only. Also, within the scope of the appended claims and their equivalents, the present invention may be practiced otherwise than as specifically described in the description and claims. The present invention is directed to each individual feature, system, substance, material, kit, or method described herein. Further, combinations of two or more such features, systems, materials, materials, kits or methods are within the scope of the present invention. Only if the features, systems, materials, materials, kits or methods are not contradictory to each other.

All definitions defined and used herein will, of course, use the definition of a dictionary, the definitions in the literature incorporated herein by reference, or the ordinary meaning of a term.

  The indefinite articles "a" and "an" used in the specification and claims of this invention naturally mean "at least one" unless explicitly stated to the contrary.

  Also, unless explicitly stated to the contrary, more than one step or action of the method claimed herein, or the order of steps or actions of the method need not necessarily be limited.

  As used herein in the specification and in the claims, the expression “or” shall mean “either or both” of the elements to be coordinated, that is, the elements are in some cases connected and others In the case of, it exists disjunctively. There may optionally be other elements besides the elements specifically identified by the expression “or”, regardless of whether or not they are specifically associated with the identified elements. Thus, as an unconstrained example, reference to “A or B” refers to only A (optionally including elements other than B) in one embodiment, and only B (optional) in other embodiments. In other embodiments, both A and B (optionally including other elements) and the like can be expressed. For example, when separating items in a list, "or" should be interpreted as inclusive, i.e. including at least one of a number of elements or elements of a list, and more than one, It also includes items that are optionally not listed further. Only expressions that are explicitly presented in the opposite sense, such as “only one of” or “exactly one of”, can be used for exactly a certain number of elements or list elements. It represents including one. Generally, an expression of exclusivity such as “either”, “one of”, “only one of” or “exactly one of” is prefixed. Sometimes the expression “or” as used herein should only be interpreted as referring to an exclusive option (ie “one or the other, not both”).

    In the claims as in the above specification, all transitional phrases are used in a non-limiting manner. Transition phrases include, for example, “comprising”, “including”, “carrying”, “having”, “containing”, “involving”, “holding” "" Composed of ". Non-limiting means that it includes, but is not limited to. Only the transitional phrases “consisting of” and “consisting essentially of” are respectively limited or semi-limiting transitional phrases.

Claims (113)

A method for configuring a customizable manufacturing system comprising:
Providing a first unit operating unit configured to perform a biological, chemical or pharmaceutical manufacturing process or an operation of such a process, wherein the first unit operating unit is located inside the first module. The first unit operation unit has a first identifier encoded or associated with information about the unit operation unit,
The method further comprises:
Providing a second unit operating unit configured to perform a biological, chemical or pharmaceutical manufacturing process or an operation of such a process, wherein the second unit operating unit is arranged inside the second module. Or the second unit operation unit includes a second identifier encoded or associated with information about the second unit operation unit, and at least one of the first and second modules is Configured to be movable,
The method further comprises:
Interconnecting the first module and the second module;
A method for constructing a customizable manufacturing system comprising obtaining information by processing or detecting at least one of the first and second identifiers.   The step of obtaining the information verifies the compatibility of the connectivity of the first and second unit operating units based at least in part on the information encoded or associated with the first and second identifiers. The method of claim 1, further comprising a step.   The method according to claim 2, wherein the step of verifying compatibility of the connectivity of the first and second unit operation units comprises verifying an assembly order of the unit operation units.   The method of claim 1, wherein obtaining the information further comprises verifying the identity or function of the unit operation unit.   The step of acquiring the information further comprises verifying the identity of a customer who sold the unit operation unit or a customer who performs the biological, chemical, or pharmaceutical manufacturing process. The method according to claim 1.   The method of claim 1, wherein obtaining the information further comprises collecting information from at least one of the first and second identifiers for repair of the system.   The step of obtaining the information further includes determining the location of the unit operation unit based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. The method of claim 1, comprising the step of determining.   The method of claim 7, wherein obtaining the information is performed as part of an inventory management process.   The step of obtaining the information may further include the unit operating unit appropriately based on information encoded on the first and second identifiers or information associated with the first and second identifiers. The method of claim 1, comprising verifying functionality.   The step of obtaining the information further includes the unit operation unit based on at least partly information encoded on the first and second identifiers or information associated with the first and second identifiers. The method according to claim 1, comprising the step of determining whether the operating part is a counterfeit.   The method of claim 10, wherein determining the presence of a counterfeit component causes a lockout of the system.   The step of obtaining the information further comprises using the unit operation unit based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. The method according to claim 1, comprising the step of tracking the unit operations leading to a product lot to be manufactured.   The step of obtaining the information further comprises at least one unit operation unit based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. The method of claim 1, comprising determining whether the can be properly assembled.   The step of obtaining the information further includes removing a first batch of a reagent or product of material produced using the system from the system prior to producing a second batch of material produced by the system. The method of claim 1, comprising verifying.   The step of obtaining the information further comprises determining whether the appropriate reagent is based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. The method according to claim 1, comprising verifying that it is used in a biological, chemical or pharmaceutical manufacturing process.   The method according to claim 1, wherein the first unit operation unit includes a container.   The method of claim 16, wherein the container comprises a foldable bag and a support.   The foldable bag includes an identifier encoded or associated with information about the foldable bag, a tube connected to the foldable bag, and a filter associated with the foldable bag. The method according to claim 17, comprising a connecting device connected to the foldable bag or the contents of the foldable bag.   The method according to claim 18, wherein the foldable bag comprises an impeller.   The method of claim 19, wherein the impeller comprises an identifier encoded or associated with information about the impeller.   The method of claim 1, wherein the at least one identifier comprises a radio frequency identification (RFID) tag.   The method of claim 1, wherein the at least one identifier comprises a barcode.   The method according to claim 1, wherein the at least one identifier comprises a detectable substance or material contained in the processing fluid in the at least one unit operation unit. A method for configuring a customizable manufacturing system comprising:
Providing a unit operating unit configured to perform a biological, chemical or pharmaceutical manufacturing process or an operation of such a process, the unit operating unit encoding information about the unit operating unit Or having an associated first identifier,
The method further comprises:
Providing a module configured to be operatively associated with the unit operator, the module comprising a second identifier encoded or associated with information about the module; Is configured and possible
The method further comprises:
Obtaining information by processing or detecting at least one of the first and second identifiers;
Determining whether to install the unit operation unit and the module in association with each other in an operable manner, or associating and configuring the information based on information obtained in the step of obtaining the information. A method of configuring a customizable manufacturing system, comprising the step of determining.   The method of claim 24, further comprising installing the unit operation unit and the module so as to be operatively associated with each other.   26. The method of claim 25, wherein installing the unit operation unit and the module so as to be operatively associated with each other comprises connecting the unit operation unit to the module.   26. The method of claim 25, wherein installing the unit operation unit and the module so as to be operatively associated with each other comprises installing the unit operation unit inside the module.   28. The method according to claim 27, wherein the unit operation unit includes a foldable bag, and the module includes a support container.   Information encoded in at least one of the first and second identifiers or information associated with at least one of the first and second identifiers is used, so that the unit operation unit and the module have compatibility. 25. A method according to claim 24, characterized in that it comprises or is properly combined or assembled.   The unit operation unit functions appropriately by using information encoded in at least one of the first and second identifiers or information associated with at least one of the first and second identifiers. 25. The method of claim 24.   The method according to claim 24, wherein the module includes a container, and the unit operation unit includes a foldable bag.   The method according to claim 24, wherein the module includes a bioreactor, and the unit operation unit includes a reagent or culture solution supply container.   The method of claim 24, wherein at least one identifier comprises an RFID tag.   The method of claim 24, wherein the at least one identifier comprises a barcode.   The method according to claim 24, wherein the at least one identifier comprises a detectable substance or material contained in a processing fluid in the unit operation unit.   25. A method according to claim 24, characterized in that two or more modules are connected to each other.   The method of claim 24, wherein the module comprises an environmental containment enclosure.   38. The method according to claim 37, wherein the unit operation unit includes a bioreactor, and at least a part of the bioreactor is housed in the environment housing enclosure.   38. The method of claim 37, wherein the unit operation unit comprises a separation system.   40. The method of claim 39, wherein the separation system comprises column chromatography.   40. The method of claim 39, wherein the separation system comprises a centrifuge.   The method according to claim 37, wherein the unit operation unit includes a culture medium storage container. A method for configuring a customizable manufacturing system comprising:
Providing a first module comprising or having an interior housing a first unit operating portion configured to perform at least one specific operation of a biological, chemical, or pharmaceutical manufacturing process;
The first module comprises a first identifier encoded or associated with information about the first module;
The method further comprises:
Determining work to be performed by the first module based on information encoded in or associated with the first identifier;
Providing a second module having an interior housing a second unit operating portion configured to perform at least one specific operation of a biological, chemical or pharmaceutical manufacturing process;
The second module comprises a second identifier encoded or associated with information about the second module;
The method further comprises:
Determining work to be performed by the second module based on information encoded or associated with the second identifier;
Each of the first and second unit operation units includes at least one connection device associated with the operation unit so as to interconnect the unit operation units,
The method further comprises:
Determining a connectivity configuration based on information encoded on at least one of the first and second identifiers;
A method of configuring a customizable manufacturing system, comprising: interconnecting the first and second unit operating units in the module and arranging the module according to the connectivity configuration.   The step of determining comprises determining a first connection order configured to generate a manufacturing system, the manufacturing system encoded or associated with at least one of the first and second identifiers. Based on at least part of the information, produces a first product of a biological, chemical or pharmaceutical manufacturing process, or a specific first sequence of work of a biological, chemical or pharmaceutical manufacturing process. 44. The method of claim 43, wherein the method is configured to perform.   45. The method according to claim 44, wherein the arranging step comprises the step of interconnecting the first and second unit operation units in the module and arranging the module in the first connection order. Method.   The determining may be based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers, so that the first and second unit operation units 44. The method of claim 43, comprising verifying the connectivity suitability.   45. The method of claim 44, wherein verifying compatibility of the connectivity of the first and second unit operation units comprises verifying the order of the unit operation units.   The step of determining further comprises verifying the identity or function of the unit operating unit based at least in part on information encoded on or associated with the first and second identifiers. 44. The method of claim 43.   The determining step further comprises a customer for which the unit operation is sold or a customer's biopharmaceutical manufacturing process that is performed based at least in part on information encoded or associated with the first and second identifiers. 44. The method of claim 43, comprising verifying identity.   44. The method of claim 43, wherein the determining step further comprises determining a location of the module.   44. The method of claim 43, wherein the determining step further comprises collecting information from at least one of the first and second identifiers for repair of the system.   The determining step further comprises determining a location of the module based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. 44. The method of claim 43, wherein:   53. The method of claim 52, wherein the determining is performed as part of an inventory management process.   The determining step further includes the unit operation unit functioning appropriately based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. 44. The method of claim 43, comprising verifying.   The determining step further comprises whether the unit operation unit is a counterfeit based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. 44. The method of claim 43, comprising determining whether.   56. The method of claim 55, wherein determining the presence of a counterfeit component causes a system lockout.   The determining step further includes a case where an identifier is expected to be present, an inappropriate identifier, or an incorrect orientation or position of one or more modules or components of the system. 44. The method of claim 43, comprising determining that the identifier does not exist.   If the presence of an identifier is expected, the presence of an inappropriate identifier, or an incorrect orientation or position of one or more modules or components of the system, the absence of an identifier 56. The method of claim 55, wherein the determining step causes a system lockout.   The determining step is further manufactured using the unit operation unit based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. 44. The method according to claim 43, comprising the step of tracking said unit operation unit leading to a product lot.   The determining step may further include determining whether at least one of the unit operation units is appropriate based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. 44. The method of claim 43, comprising determining whether to assemble.   The determining step further comprises biopharmaceutical manufacturing processes for suitable reagents based at least in part on information encoded on the first and second identifiers or information associated with the first and second identifiers. 45. The method of claim 43, comprising verifying that it is used in   44. The method of claim 43, wherein at least one of the modules comprises a foldable bag housed within a support.   64. The method of claim 62, wherein the foldable bag comprises an impeller.   64. The method of claim 63, wherein the impeller comprises an identifier encoded on information about the impeller or an identifier associated with information about the impeller.   The foldable bag includes an identifier encoded on information about the foldable bag or an identifier associated with information about the foldable bag, and a tube connected to the foldable bag. 63. A method according to claim 62, comprising: a filter associated with the foldable bag; a connection device connected to the foldable bag; or the contents of the foldable bag. .   44. The method of claim 43, wherein the at least one identifier comprises an RFID tag.   44. The method of claim 43, wherein the at least one identifier comprises a barcode.   44. The method of claim 43, wherein the at least one identifier comprises a detectable substance or material contained in the processing fluid in the at least one unit operation. A customizable manufacturing system,
Comprising at least two modules, each of which comprises an internal space interconnectable with the internal space of the other module, and performs at least one specific operation of a biological, chemical or pharmaceutical manufacturing process Contains one or more components configured such that
At least one of the modules is configured to be movable and includes an identifier encoded on information about the module or an identifier associated with information about the module;
The system further includes:
A control system configured to perform operation and process control of one or more components, the control system further associated with or obtained from at least one identifier on at least one of the modules Based on information associated with at least one identifier on at least one module or information encoded with at least one identifier on at least one module A customizable manufacturing system characterized by being configured to perform.   70. The customizable manufacturing system of claim 69, wherein at least one of the modules comprises an environment control system for controlling the environment within the module.   The control system comprises a computer configured and programmed to generate a quality control verification report based at least in part on information encoded by at least one identifier or information associated with at least one identifier. 70. The customizable manufacturing system of claim 69.   The control system function performed based on information encoded by at least one identifier or information associated with at least one identifier comprises verifying proper connection of the at least two modules 70. A customizable manufacturing system according to claim 69.   The control system function performed based on information encoded by at least one identifier or information associated with at least one identifier comprises verifying the identity or function of at least two modules 70. A customizable manufacturing system according to claim 69.   The control system function performed based on information encoded by at least one identifier or information associated with at least one identifier determines the location or relative position of at least one module of the at least two modules; 70. A customizable manufacturing system according to claim 69, comprising:   The control system function performed based on information encoded by at least one identifier or information associated with at least one identifier comprises verifying that the container functions properly; 70. A customizable manufacturing system according to claim 69.   The control system function performed based on information encoded by at least one identifier or information associated with at least one identifier comprises determining whether at least one module is a counterfeit or counterfeit component 70. The customizable manufacturing system of claim 69.   77. The customizable manufacturing system of claim 76, wherein the presence of a counterfeit module or counterfeit component determines to cause a system lockout.   The control system function performed based on information encoded by at least one identifier or information associated with at least one identifier comprises tracking a module that leads to a product lot manufactured using the module. 70. The customizable manufacturing system of claim 69.   The control system function performed based on information encoded by at least one identifier or information associated by at least one identifier comprises determining whether at least one of the unit operations is properly assembled. 70. A customizable manufacturing system according to claim 69.   The control system function executed on the basis of information encoded by at least one identifier or information associated with at least one identifier is such that suitable reagents are used in biological, chemical or pharmaceutical manufacturing processes. 70. The customizable manufacturing system of claim 69, comprising verifying.   70. The customizable manufacturing system of claim 69, wherein at least one of the modules comprises a container.   82. The customizable manufacturing system of claim 81, wherein the container comprises a foldable bag and a support structure.   83. The customizable manufacturing system of claim 82, wherein the foldable bag comprises an impeller.   84. The customizable manufacturing system of claim 83, wherein the impeller comprises an identifier encoded or associated with information.   82. The customizable manufacturing system of claim 81, wherein the foldable bag comprises an identifier encoded or associated with information.   70. The customizable manufacturing system of claim 69, wherein the at least one identifier comprises an RFID tag.   70. The customizable manufacturing system of claim 69, wherein the at least one identifier comprises a barcode.   70. The customizable manufacturing system according to claim 69, wherein the at least one identifier comprises a detectable substance or a material contained in a processing fluid in at least one unit operation. A container configured to contain a volume of liquid,
An identifier encoded using information about the container;
A foldable bag configured to contain the liquid;
A container configured to contain a volume of liquid, characterized in that it comprises a reusable support structure surrounding and containing said foldable bag.   90. Container according to claim 89, characterized in that the container is part of a reactor in a biological, biochemical or chemical reaction system.   90. A container according to claim 89, wherein the identifier is incorporated in a wall of the container.   90. A container according to claim 89, wherein the information about the container comprises information regarding at least one characteristic of the liquid contained within the foldable bag. The at least one property of the liquid is at least one of pH, temperature, pressure, fluid flow pattern, oxygen level, CO ₂ level, reagent level, product level, metabolic level or conductivity. The container according to claim 92.   90. A container according to claim 89, wherein the information encoded on the identifier comprises information regarding compatibility of the container with other components of the manufacturing system.   90. A container according to claim 89, wherein the information encoded on the identifier comprises information regarding the identity or function of the container.   90. A container according to claim 89, wherein the information encoded on the identifier comprises information regarding the location or position of the container.   90. A container according to claim 89, wherein the information encoded on the identifier comprises information regarding verification that the container is functioning properly.   90. The container of claim 89, wherein the information encoded on the identifier comprises information regarding reliability verification.   90. The container of claim 89, wherein the information encoded on the identifier comprises information associating the container with a product lot manufactured using the container.   90. A container according to claim 89, wherein the foldable bag comprises an impeller.   90. A container according to claim 89, wherein the identifier comprises a detectable material or substance, which is suspended or dissolved in a processing fluid contained in the container.   102. The container of claim 101, wherein the information about the container comprises information about the processing fluid contained in the container. An identifier encoded with information about the foldable bag,
A flexible wall,
A foldable bag comprising a rigid portion having a base including a shaft configured to support a magnetic impeller, wherein the rigid portion is connected to the flexible wall portion .   104. The foldable bag according to claim 103, wherein the foldable bag is part of a reactor in a biological, biochemical or chemical reaction system.   104. The foldable bag according to claim 103, wherein the identifier is incorporated into the wall portion of the foldable bag.   104. The foldable bag according to claim 103, wherein the information about the foldable bag comprises information about at least one characteristic of a liquid contained in the foldable bag. The at least one property of the liquid is at least one of pH, temperature, pressure, fluid flow pattern, oxygen level, CO ₂ level, reagent level, product level, metabolic level or conductivity. The foldable bag according to claim 106.   The information encoded on the identifier comprises information regarding the compatibility of the foldable bag with respect to other components of a manufacturing system in which the foldable bag is used. 103. The foldable bag according to 103.   104. The foldable bag of claim 103, wherein the information encoded on the identifier comprises information regarding the identity of the owner of the foldable bag.   104. The foldable bag of claim 103, wherein the information encoded on the identifier comprises information regarding verification that the foldable bag functions properly.   104. The foldable bag according to claim 103, wherein the information encoded on the identifier comprises information relating to reliability verification.   104. The foldable according to claim 103, wherein the information encoded on the identifier comprises information associating the foldable bag with a product lot manufactured using the foldable bag. Bag body. A customizable manufacturing system,
Comprising at least two portable modules, each of which comprises one or more unit operator components for performing at least one specific task of a biological, chemical or pharmaceutical manufacturing process Has an interior containing,
The system further includes:
A connection port associated with each of the modules for interconnecting the modules;
Comprising an identifier encoded with information about a component of the customizable manufacturing system;
A customizable manufacturing system, characterized in that after connection, each of the modules can be moved relative to the other module without releasing the connection.

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