Process control system for an automated cell engineering system

Abstract

Systems and methods are provided for process control of an automated cell engineering system. The automated cell engineering system provides automated cell processing functions. The automated process control system provides control, interconnectivity, monitoring, data archiving, software updates, and other supervisory functions for the automated cell engineering system. Additionally, a central control process system provides control, monitoring, data archiving, software updates, and other supervisory functions for the automated process control system.

Description

Technical Field

[0001] Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 874,119, filed Jul. 15, 2019, which is hereby incorporated by reference in its entirety for all purposes.

[0002] This disclosure relates to the control of automated cell engineering systems. In particular, the disclosure relates to methods and systems for providing process control and interconnectivity to automated cell engineering systems.

Background Art

[0003] As the expectation for the accelerated clinical adoption of advanced cell therapies grows, more attention is being directed to the manufacturing strategies that will underpin the ability of patients worldwide to benefit from these therapies. Although cell therapies are clinically quite promising, high manufacturing costs relative to reimbursement are a formidable barrier to commercialization. Thus, due to the need for cost-effectiveness, process efficiency, and product consistency, efforts toward automation in many areas of cell therapy, and particularly in T cell immunotherapy, are underway (see, e.g., Wang 2016).

[0004] Recent successful clinical results of immunotherapy trials using chimeric antigen receptor (CAR) T cells have brought new hope to patients suffering from cancers that were previously untreatable (see, e.g., Lu 2017, Berdeja 2017, Kebriaei 2016). As these new therapies transition from the clinical trial stage to commercial scale-up, challenges related to cell manufacturing arise (see, e.g., Morrissey 2017).

[0005] The production of these cells can require a great deal of manual involvement for patient-specific products. The automation of CAR T cell culture is particularly difficult due to multiple delicate unit operations including cell activation, transduction, and expansion. Activation is particularly important because the efficiency of this process can affect transduction and expansion.

[0006] Integrating cell activation, transduction, and proliferation into a commercial manufacturing platform is important for making these important immunotherapies accessible to a wide patient population. To make these life-saving treatments applicable to a global patient population, manufacturing technologies must be transformed to support personalized medicine. The benefits of automation have already been described. These benefits include savings in labor hours associated with the use of automation, improved product consistency, reduced room partitioning, reduced cleanroom footprint, reduced training complexity, and improved scale-up and tracking logistics. Additionally, software can be used to streamline the documentation process by providing a history of all processing equipment, reagents, patient identification, operator identification, in-process sensor data, etc., using automatically generated electronic batch records.

[0007] Title 21 of the Code of Federal Regulations (CFR Title 21 Part 11) defines the U.S. FDA's regulations regarding electronic records. Specifically, Part 11 defines the criteria under which electronic records are considered reliable, trustworthy, and equivalent to paper records. Part 11 defines rules for various record management processes, including but not limited to validation, protection, access control, personnel management, duplication, and auditing. One challenge for automation systems is maintaining compliance with Part 11.

[0008] The benefits of automation may not be fully realized without proper automation control. This application provides a technical solution to the technical problems related to the automation control of an automated cell engineering system. SUMMARY OF THE INVENTION

[0009] In some embodiments, provided herein is a method for controlling an automated cell engineering system configured to produce a cell culture. The method includes establishing, by a central computer system, a network connection with the automated cell engineering system, receiving, via the network connection, process information including one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, component or patient identification information, and optical density information from the automated cell engineering system, and providing, via the network connection, a control signal to cause the automated cell engineering system to adjust one or more process parameters of the automated cell engineering based on the received process information.

[0010] In another embodiment, provided is a method for controlling a plurality of automated process control systems via a central control system. The method includes establishing a network connection with a plurality of computer systems corresponding to a plurality of automated process control systems each configured to control a plurality of automated cell engineering systems configured for the production of cell cultures, accessing, by the central control system, a control information history of a first computer system from the plurality of computer systems, and providing to the first computer system at least one of a cell culture growth protocol update and a cell engineering software update.

[0011] In another embodiment, provided is a method for the automated production of a cell culture by an automated cell engineering system. The method includes initiating a cell culture growth protocol within the automated cell engineering system, monitoring process information of the cell culture growth protocol, adjusting one or more parameters of the cell culture growth protocol based on the monitoring, stopping the cell culture growth protocol, recording a stage within the cell culture growth protocol at which the stopping occurred, and resuming the cell culture growth protocol at the stage within the cell culture growth protocol.

[0012] In another embodiment, a method is provided for utilizing excess capacity within a network of automated cell engineering systems configured for the automated production of cell cultures. The method includes receiving measurements of the excess capacity of the automated cell engineering system from a plurality of automated process control systems within the network, determining a capacity requirement according to patient requirements for the cell culture, matching the capacity requirement with an automated cell engineering system selected according to the measurements of the excess capacity, and transferring a biological sample to the selected cell engineering system for the production of a cell culture.

[0013] In another embodiment, a method for the automated production of cell cultures implemented by an automated cell engineering system is implemented. The method includes initiating a cell culture growth protocol within the automated cell engineering system, receiving updated cell culture delivery requirements from an authorized user, and adjusting one or more parameters of the cell culture growth protocol based on the updated cell culture delivery requirements.

[0014] In another embodiment, a method for the automated production of cell cultures by an automated cell engineering system is provided. The method includes initiating a cell culture growth protocol within the automated cell engineering system, monitoring one or more parameters of the cell culture growth protocol, predicting a cell culture delivery date according to the monitoring, and warning an authorized user prior to the cell culture delivery date.

Brief Description of the Drawings

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Mode for Carrying Out the Invention

[0016] The present disclosure provides systems and computer-implemented methods for controlling and interacting with automated cell engineering systems. Automated cell engineering systems provide a powerful tool for producing a variety of engineered cells and tissues. The systems and methods described herein provide a technical solution to the technical problems associated with the adjustment and control of one or more automated cell engineering systems. The systems and methods provided herein facilitate the control of and access to one or more automated cell engineering systems, thereby amplifying the capabilities of the automated cell engineering systems, whether they are arranged with each other or with a control system.

[0017] One automated cell engineering system that conforms to an embodiment of the present invention is the Cocoon™ platform, which is described in further detail below. The Cocoon™ platform is described in further detail in U.S. Patent Application No. 16 / 119,618, filed on September 1, 2017, the content of which is incorporated herein by reference in its entirety.

[0018] Automated cell processing As described herein, the installation and comprehensive verification of automated production provide solutions to the logistical and operational challenges associated with the production of engineered cells and tissues. An important approach for introducing automation into the production process is to identify the key modular steps that apply physical or chemical changes to the production materials, referred to as "unit operations." In the case of cell manufacturing, this includes steps such as cell separation, genetic manipulation, proliferation, washing, concentration, and cell collection. Manufacturers often cite local process bottlenecks as a direct opportunity to introduce automation. This is reflected in the technical operating ranges of most commercially available bioreactors, which tend to focus on individual process steps. The process challenges in cell manufacturing (from maintaining aseptic conditions to sample tracking) are addressed here by comprehensive automation that improves the inevitable process variability while generating consistent cell output. The methods described herein also provide simplification, and the associated electronic records are useful for compliance with GMP standards (see, for example, Trainor 2014).

[0019] Automation of Unit Operations and Key Process Sensitivities Recent rapid advances in the therapeutic development of various cell cultures, including modified autologous T cells for cancer immunotherapy, have led to plans for the associated translation and scale-up / out predictions.

[0020] Specific cell culture growth protocols can vary depending on the cell manufacturing, but a generalized cell culture production process is shown in Figure 1 (including the production of autologous T cells). Figure 1 illustrates the unit operations of cell manufacturing, for example, from the initial processing of a patient's blood sample to the formulation of the output cells for autologous T cell therapy.

[0021] As described herein, to achieve automation of cell manufacturing, the methods described herein provide an understanding of the state of cells at each transition point and how they are affected by specific unit operations. Micro-lot production for patient-specific therapies must respect important process sensitivities that affect the feasibility of automation. The automation described herein makes good use of various process steps.

[0022] Table 1 below highlights the challenges of some of the process steps identified for the automated production of cell cultures, including the automation of T cells. Note that for all unit operations, the open movement of cells between devices is an important sensitivity due to the risk of contamination. [Table 1]

[0023] By adjusting the automation of manual processes near the sensitivities listed in Table 1, translation, maintenance, or improvement regarding the implementation of cell therapy can be successful.

[0024] A single all-in-one system can significantly expand space efficiency and minimize the floor area required in an expensive GMP cleanroom. For example, as shown in Figure 2, a fully integrated automated system is designed to maximize the required floor area and reduce the expensive GMP cleanroom space. Figure 2 shows, for example, an end-to-end unit for 96 patient individuals implemented in a standard experimental space.

[0025] A single system also makes data tracking easier, but in the case of individual systems, corresponding software for linking all electronic data files may not be provided. Software platforms such as VINETI (Vineti Ltd) and TRAKCEL (TrakCel Ltd) enable the electronic monitoring and organization of supply chain logistics. However, a single all-in-one culture system can go further by incorporating into batch records the history of both processes being handled, process information, biomonitoring of culture conditions (also called production information), and user control history related to each unit operation. Therefore, the advantages of end-to-end integration provide a significant competitive advantage.

[0026] Commercial platform for unit operation integration The success of many autologous cell therapy clinical trials, particularly in immunotherapy for hematological cancers, emphasizes the importance of being able to convert new clinical protocols to robust production platforms to meet the projected clinical demand (see, for example, Levine 2017, Locke 2017). In the case of autologous therapies, the processing of cell therapy for each individual patient makes good use of comprehensive manufacturing activities and operation management. The methods herein link unit operations in a turnkey automated system to achieve process optimization, security, and economy.

[0027] There are two challenges in the design of autologous processes. First, unlike allogeneic manufacturing where different processing steps can be performed on physically separate optimized devices, a scaled-out autologous platform preferably performs the necessary steps in a single closed self-contained automated environment. Second, unlike allogeneic processes where all implementations theoretically start with high-quality vials from a cell bank with known quality and predictable process behavior, the starting materials for autologous processes are highly variable and generally from individuals with compromised health.

[0028] Accordingly, provided herein is a method that can sense culture conditions and thus respond as a sophisticated bioreactor by controlling factors such as physical agitation, pH, feeding, and gas handling. Further, compared to allogeneic therapies, there are significantly different challenges associated with the technology transfer of autologous therapies. Autologous products can have greater limitations with respect to stability between the manufacturing process and patient treatment. Sites can be globally located without a single center. In a locked-down (e.g., fully closed) all-in-one system, the technology transfer process between sites is significantly improved.

[0029] Source variability cannot be eliminated, but automation helps eliminate variability in the final autologous product through standardization and reproducibility. This approach has been adopted by major cell line suppliers to obtain cell performance reference points via biosensors that monitor the state of the active cell culture. In end-to-end integration, the output from specific stages of the process must be within acceptable parameters for the process to proceed.

[0030] As described herein, in embodiments, the methods provided utilize the Cocoon™ platform (Octane Biotech (Kingston, ON)) that integrates multiple unit operations onto a single turnkey platform (see, e.g., U.S. Patent Application Publication No. 2019 / 0169572, which is hereby incorporated by reference in its entirety). However, it is understood that other fully or partially automated cell culture devices, including commercially available ones such as PRODIGY available from Miltenyi Biotech, Inc., XURI and SEFIA available from General Electric Healthcare, and systems available from Atvio Biotech Ltd., can be used in accordance with embodiments of the present invention. A plurality of cell culture growth protocols are provided for very specific cell processing purposes. To provide efficient and effective automation, the methods described utilize the concept of application-specific / sponsor-specific disposable cassettes that combine multiple unit operations, all focused on the central requirements of the final cell therapy product.

[0031] The methods described herein are used to grow CAR-T cells in a fully integrated closed automated system (including activation, viral transduction and growth, concentration and washing) (Figure 3).

[0032] Automated cell engineering system. In some embodiments, the methods described herein are implemented in a fully closed automated cell engineering system 600 (see FIGS. 4A and 4B), which suitably has instructions for performing activation, transduction, proliferation, enrichment, and collection steps of cell culture. The cell engineering system (also referred to throughout as the automated cell engineering system) provides for the automated production of cell cultures. As used herein, "cell culture" refers to any suitable cell type, including individual cells, as well as cells that can be formed into multiple cells or tissue structures. Exemplary cell cultures include blood cells, skin cells, muscle cells, bone fat, cells from various tissues and organs, and the like. In embodiments, genetically modified immune cells, including CAR T cells, can be produced as described herein. An exemplary automated cell engineering system is also referred to throughout as Cocoon™, or the Cocoon™ system.

[0033] For example, a user can provide a cell engineering system pre-filled with cell cultures and reagents (e.g., activation reagents, vectors, cell culture media, nutrients, selection reagents, etc.) and cell production parameters (e.g., starting cell number, type of media, type of activation reagent, type of vector, number of cells or dose produced, etc.), and the cell engineering system can implement a method for producing a processed cell culture, including a genetically modified immune cell culture including CAR T cells, without further input from the user. At the end of the automated production process, the cell engineering system may alert the user (e.g., by playing a warning message or sending a warning on a mobile app) to collect the produced cells. In some embodiments, the fully closed cell engineering system includes a sterile cell culture chamber. In some embodiments, the fully closed cell engineering system minimizes contamination of the cell culture by reducing exposure of the cell culture to a non-sterile environment. In further embodiments, the fully closed cell engineering system minimizes contamination of the cell culture by reducing the work of the user on the cells.

[0034] As described herein, the cell engineering system preferably includes a cassette 602 (see FIG. 4B). As used herein, "cassette" refers to a largely self - contained, removable, and replaceable element of a cell engineering system that includes one or more chambers for performing various elements of the methods described herein, and preferably also includes one or more of cell culture medium, activation reagents, vectors, etc. The cassette can include a flexible bag, a rigid container, or other structural elements. In some embodiments, the cassette can be configured for single - use.

[0035] FIG. 4B shows an embodiment of the cassette 602 according to an embodiment of the present invention. In the embodiment, the cassette 602 preferably includes a low - temperature chamber 604 for storing cell culture medium, and a high - temperature chamber 606 for performing activation, transduction, and / or proliferation of immune cell cultures. Preferably, the high - temperature chamber 606 is separated from the low - temperature chamber 604 by a thermal barrier 1102 (see FIG. 5B). As used herein, "low - temperature chamber" refers to a chamber for maintaining a cell culture medium, etc. at a refrigerated temperature, preferably below room temperature, and more preferably maintained at about 4°C to about 8°C. The low - temperature chamber can include a bag for the medium or other holder containing about 1L, about 2L, about 3L, about 4L, or about 5L of fluid. Additional medium bags or other fluid sources can be connected to the cassette externally and can also be connected to the cassette via access ports.

[0036] As used herein, "high - temperature chamber" refers to a chamber preferably maintained at a temperature higher than room temperature, and more preferably at a temperature that enables cell proliferation and growth, i.e., about 35 - 40°C, and more preferably about 37°C.

[0037] In the embodiment, the high - temperature chamber 606 preferably includes a cell culture chamber 610 (also referred to throughout as a growth chamber or cell growth chamber) as shown in FIGS. 4D and 4E.

[0038] The cassette may further include, in some embodiments, one or more fluidics pathways connected to the cell culture chamber, where the fluidics pathway provides for recirculation, waste removal, and homogeneous gas exchange and distribution of nutrients to the cell culture chamber without disturbing the cells within the cell culture chamber. Cassette 602 also further includes, as described herein, one or more pumps 605 including a peristaltic pump for driving fluid through the cassette, and one or more valves 607 for controlling the flow through the various fluid pathways.

[0039] In an exemplary embodiment, as shown in FIG. 4D, the cell culture chamber 610 is a flat, non-flexible chamber (i.e., made of a substantially non-flexible material such as plastic) that does not easily bend or flex. By using a non-flexible chamber, it is possible to maintain the cells in a substantially quiescent state. As shown in FIG. 4E, the cell culture chamber 610 is oriented such that an immune cell culture can spread across the entire bottom 612 of the cell culture chamber. As shown in FIG. 4E, the cell culture chamber 610 is preferably maintained in a position parallel to the floor or table, maintaining the cell culture in a quiescent state and allowing the cell culture to spread over a large area of the bottom 612 of the cell culture chamber. In an embodiment, the overall thickness of the cell culture chamber 610 (i.e., the chamber height 642) is low, on the order of about 0.5 cm to about 5 cm. Preferably, the cell culture chamber has a volume of about 0.50 ml to about 300 ml, more preferably about 50 ml to about 200 ml, or the cell culture chamber has a volume of about 180 ml. By using a low chamber height 642 (less than 5 cm, preferably less than 4 cm, less than 3 cm, or less than 2 cm), effective medium and gas exchange very close to the cells is possible. The ports are configured to allow mixing by recirculation of the fluid without disturbing the cells. Taller static containers can create concentration gradients and cause limitations in oxygen and fresh nutrients in the region near the cells. Controlled hydrodynamics allows medium exchange to be performed without disturbing the cells. The medium can be removed from an additional chamber (where no cells are present) without the risk of cell loss.

[0040] As described herein, in an exemplary embodiment, the cassette is pre-filled with one or more of a cell culture, a culture medium, an activation reagent, and / or a vector, any combination thereof. In further embodiments, these various elements can be added later via suitable injection ports and the like.

[0041] As described herein, in embodiments, the cassette preferably further includes one or more of a pH sensor, a glucose sensor, an oxygen sensor, a carbon dioxide sensor, a lactate sensor / monitor, and / or an optical density sensor. The cassette may also include one or more sampling ports and / or injection ports. Examples of such sampling ports and injection ports (1104) are shown in FIG. 5A and may include access ports for connecting the cartridge to an external device such as an electroporation unit or a further medium source. FIG. 5A also shows the location of a cell input 1105, a reagent warming bag 1106 that can be used to warm the cell culture medium, etc., and a culture zone 1107 that holds various components for use in the culture medium, including, for example, cell culture medium, vectors, nutrients, and waste.

[0042] FIG. 5B shows an automated cell engineering system with the cassette 602 removed. In FIG. 5B, components of the cell engineering system are shown including a gas control seal 1120, a warming zone 1121, an actuator 1122, a pivot 1123 for rocking or tilting the cell engineering system as needed, and a cryogenic zone 1124 for holding a cryogenic chamber 604. Also shown is an exemplary user interface 1130 that may include the ability to receive input by a barcode reader and / or a QR code (registered trademark) reader, and a touchpad or other similar device. The user interface 1130 may further include a component identification sensor such as a barcode reader, a QR code reader, a radio frequency ID interrogator, or other component identification sensors. In some aspects, the cassette 602 may include a first identification component such as a barcode, and the user interface 1130 may include a reader configured to identify the first identification component. FIG. 5E shows a further detailed view of the cassette 602 including a second chamber 1150 that can be used if additional cell culture volume is needed and a collection chamber 1152 that can be used to collect the final cell culture produced herein.

[0043] In an exemplary embodiment, as shown in FIG. 4F, the cell culture chamber 610 further includes at least one of a distal port 620 configured to allow removal of bubbles from the cell culture chamber and / or configured as a recirculation port, an intermediate port 622 configured to function as a recirculation inlet port, and a proximal port 624 configured to function as a drain port for cell removal.

[0044] In yet another embodiment, provided herein is a cassette 602 for use in an automated cell engineering system 600 that includes a cell culture chamber 610 for performing activation, transduction, and / or proliferation of an immune cell culture, having a chamber volume configured to contain the immune cell culture and a satellite volume 630 (i.e., the satellite volume is cell-free) for increasing the cell culture chamber by providing additional volume for the medium and other working fluids without containing the immune cell culture. Preferably, the satellite volume is in fluid connection with the cell culture chamber such that the medium can be exchanged with the cell culture chamber without disturbing the immune cell culture. In an exemplary embodiment, the satellite volume is a bag, and in other embodiments, the satellite volume is a non-deformable chamber. In an embodiment, the satellite volume is from about 0.50 ml to about 300 ml, and more preferably from about 150 ml to about 200 ml. FIGS. 4D-4E show the location of the satellite volume 630 in the cassette 602.

[0045] Figure 4G shows a schematic diagram depicting the connection between the cell culture chamber 610 and the satellite volume 630. Also shown in Figure 4G are various sensors (e.g., pH sensor 650, dissolved oxygen sensor 651), as well as sampling / sample ports 652 and various valves (control valve 653, bypass check valve 654), and the positioning of one or more fluid paths 640 connecting the components, preferably including a silicone-based tubing component. As described herein, the use of a silicone-based tubing component enables oxygen supply through the tubing component, facilitating optimal oxygen supply for gas transport and cell culture. Also shown in Figure 4G is the use of one or more hydrophobic filters 655 or hydrophilic filters 656 in the flow path of the cassette, in conjunction with pump tube 657 and bag / valve module 658.

[0046] In an embodiment, the satellite volume 630 is further configured to enable removal of the medium without loss of cells from the immunocyte culture. That is, the medium exchange between the satellite volume and the cell culture chamber is performed in such a way that the cells are not disturbed and are not removed from the cell culture chamber.

[0047] In a further embodiment, as shown in Figure 4G, the cassette 602 preferably further includes a crossflow reservoir 632 for holding additional medium or the like as needed. Preferably, the crossflow reservoir has a volume of from about 0.50 ml to about 300 ml, more preferably from about 100 ml to about 150 ml.

[0048] In some embodiments, the cell engineering system includes a plurality of chambers. In further embodiments, each of the activation step, transduction step, proliferation step, enrichment step, and collection step of the methods related to cells described herein is performed in a different chamber of the plurality of chambers of the cell engineering system. In some embodiments, the cells are not substantially disrupted while moving from one chamber to another. In other embodiments, the steps of the method are performed in the same chamber of the cell engineering system, and the cell engineering system automatically adjusts the chamber environment as needed for each step of the method. Thus, it is further possible to keep the cells from being disrupted during the various steps.

[0049] The yield from genetically modified immune cell production, including CAR T cell production, can be affected by activation and transduction efficiency and cell growth conditions. Activation efficiency can be improved by making the contact between the cells and the activation reagent more stable. Movement of cells across the culture vessel can lead to an uneven distribution of cells and, thus, a local effect may be obtained when the activation reagent is added to the cell culture chamber. In contrast to flexible culture bags, cells grown in a non-deformable chamber remain undisturbed during the activation process, which can contribute to higher activation efficiency.

[0050] Also provided herein is a method for the automated production of genetically modified immune cell cultures, which method is implemented by a cell engineering system, and which method comprises activating an immune cell culture with an activation reagent to produce an activated immune cell culture in a first chamber of the cell engineering system, and transducing the activated immune cell culture. In an exemplary method, transduction comprises transferring the activated immune cell culture from the first chamber to an electroporation unit, electroporating the activated immune cell culture with a vector to produce a transduced immune cell culture, and transferring the transduced immune cell culture to a second chamber of the cell engineering system (see U.S. Patent Application No. 16 / 119,618, filed September 1, 2017, the contents of which are incorporated herein by reference in their entirety).

[0051] The method further comprises expanding the transduced immune cell culture, concentrating the expanded immune cell culture of (d), and collecting the concentrated immune cell culture of (d) to produce a genetically modified cell culture.

[0052] For example, as shown in FIG. 6, an activated immune cell culture is transferred from a cassette 602 of a cell engineering system 600 to an electroporation unit 1706, e.g., via connecting tubing 1704. The electroporation unit 1706 preferably includes an electroporation cartridge 1708, which holds the cell culture during the electroporation process. After the electroporation process, the transduced immune cell culture is returned to the cell engineering system 600 via connecting tubing 1704. FIG. 6 also shows the use of two optional reservoirs 1710 and 1712, used to hold the cell culture before and after electroporation, to assist in the transfer between the cell engineering system and the electroporation unit as a result of different pump speeds, required pressures, and flow rates. However, such reservoirs can be removed and the cell culture can be transferred directly from the cell engineering system 1702 to the electroporation unit 1706.

[0053] In an exemplary embodiment, the cell engineering system described herein includes a plurality of chambers, and each of the steps of the various methods described herein is performed in a different chamber of the plurality of chambers of the cell engineering system, and each of the activation reagent, the vector, and the cell culture medium is included in a different chamber of the plurality of chambers prior to the start of the method, and at least one of the plurality of chambers is maintained at a temperature (e.g., about 37 °C) for growing cells, and at least one of the plurality of chambers is maintained at a refrigeration temperature (e.g., about 4 to 8 °C).

[0054] In an embodiment, monitoring includes monitoring with a temperature sensor, a pH sensor, a glucose sensor, an oxygen sensor, a carbon dioxide sensor, and / or an optical density sensor. Thus, in some embodiments, the cell engineering system includes one or more of a temperature sensor, a pH sensor, a glucose sensor, an oxygen sensor, a carbon dioxide sensor, and / or an optical density sensor. In further embodiments, the cell engineering system is configured to adjust the temperature, pH, glucose, oxygen level, carbon dioxide level, and / or optical density of the cell culture based on a predefined culture size. For example, if the cell engineering system detects that the current oxygen level of the cell culture is too low to achieve the growth required for the desired cell culture size, the cell engineering system may, for example, introduce an oxygen-containing cell culture medium, replace the cell culture medium with an oxygen-containing cell culture medium, or flow the cell culture medium through an oxygen supply component (i.e., silicone tubing) to automatically increase the oxygen level of the cell culture. In another example, if the cell engineering system detects that the current temperature of the cell culture is too high and the cell growth is too rapid (e.g., if the cells may become overcrowded, which may lead to undesirable characteristics), the cell engineering system automatically decreases the temperature of the cell culture to maintain a constant growth rate (or an exponential growth rate if desired) of the cells. In yet another embodiment, the cell engineering system automatically adjusts the schedule of cell supply (i.e., provides fresh medium and / or nutrients to the cell culture) based on the cell growth rate and / or cell number, or other monitored factors such as pH, oxygen, glucose. The cell engineering system may be configured to store the medium (and other reagents such as wash solutions) in a low-temperature chamber (e.g., 4°C or -20°C), warm the medium in a room-temperature chamber or a high-temperature chamber (e.g., 25°C or 37°C respectively), and then introduce the warmed medium into the cell culture.

[0055] Automatic Process Control System The automated process control system can interact with one or more automated cell engineering systems 600, receive inputs from one or more automated cell engineering systems 600, provide inputs to one or more automated cell engineering systems 600, and, among other things, provide all aspects of the control of one or more automated cell engineering systems 600.

[0056] FIG. 7 shows an automated process control system that controls the installation of an automated cell engineering system. In FIG. 7, an embodiment of a network environment is illustrated. The network environment can include one or more automated cell engineering systems (ACES) 600, one or more data retention systems 190, one or more clients 104, and one or more automated process control systems (APCS) 102 that communicate via one or more networks 199. The automated cell engineering system 600 can be disposed within an automated cell engineering system installation 111, also referred to herein as an automated cell engineering system bank.

[0057] The automated cell engineering system 600 shown in FIG. 7 can, in one embodiment, be a Cocoon (trademark) system as described herein. In further embodiments, the automated cell engineering system 600 can be any automated cell engineering system that can interact with a computing environment as described herein. As described above, an automated cell engineering system consistent with embodiments of the present invention can collect, record, and store various types of data and information. Such data and information can be stored locally within the computer memory of the automated cell engineering system 600.

[0058] The data and information stored in the automated cell engineering system 600 may include the following information. As used herein, "automated cell engineering system data" refers to any and all data that can be recorded and stored on or within the memory of the automated cell engineering system 600. The automated cell engineering system data can be stored in any suitable data format and can be sortable by production batch, production date, or any other suitable parameter. "Process information" refers to information about variables and parameters of a cell culture process, including, for example, temperature information, pH information, glucose concentration information, oxygen concentration information, component or patient identification information, and optical density information, as used herein. Production information may refer to information regarding the growth of a cell culture, including, for example, cell count, cell characteristics, conversion rate %, etc., as used herein. Control information history refers to information and data regarding the actions of a user incorporated into the system, as used herein. The control information history may include data regarding the actions and the user who took such actions. The control information history may include data and information regarding control actions taken by the user, such as process parameter adjustments, and physical actions taken by the user when directly interacting with the automated cell engineering system 600. "Notification information" refers to information regarding notifications, alerts, warnings, and other messages directed to various users of the system, as used herein. Each of the foregoing data and / or information may be stored as a complete batch record (i.e., all data regarding a particular cell growth batch), a collective database, a data extract (i.e., a selected portion of the data). Each of the foregoing data and / or information may be accessed in substantially real time by the automated process control system 102 discussed herein.

[0059] The automated process control system 102 can be configured as a server (e.g., having one or more server blades, processors, etc.), a personal computer (e.g., desktop computer, laptop computer, etc.), a smartphone, a tablet computing device, and / or other devices that can be programmed to interface with the automated cell engineering system 600. In one embodiment, any or all of the functions of the automated process control system 102 can be implemented as part of a cloud computing platform. The automated process control system 102 is further discussed below with respect to FIG. 8.

[0060] One or more clients 104 may be configured as a personal computer (e.g., desktop computer, laptop computer, etc.), a smartphone, a tablet computing device, and / or other devices that can be programmed with a user interface for access to the automated cell engineering system 600 and / or the automated process control system 102. In an embodiment, one or more clients 104 may include a plurality of devices such as a facility management system including a network of servers, workstations, additional clients, etc. In an embodiment, the automated process control system 102 and the client 104 may exist within a single system such as a laptop, desktop, tablet, or other computing device having a user interface. A suitably configured client 104 may provide a user with access to all of the functions of the automated process control system 102 described herein.

[0061] The network environment shown in FIG. 7 is an exemplary embodiment of an automatic process control system 102 configured to control an automatic cell engineering system installation 111. Although shown as being connected via a network 199, any suitable series of individual or network connections can be employed to enable the automatic process control system 102 to control the automatic cell engineering system installation 111 and access the necessary resources such as various data retention systems 190.

[0062] The network 199 can be connected via a wired or wireless link. Wired links can include digital subscriber line (DSL), coaxial cable, Ethernet®, or fiber optic cable. Wireless links can include Bluetooth®, Bluetooth Low Energy (BLE), ANT / ANT+, ZigBee®, Z-Wave, Thread, Wi-Fi®, Worldwide Interoperability for Microwave Access (WiMAX®), Mobile WiMAX®, WiMAX®-Advanced, NFC, SigFox, LoRa, Random Phase Multiple Access (RPMA), Weightless-N / P / W, infrared channel, or satellite band. Wireless links can also include any cellular network standard for communicating between mobile devices, including standards certified as 2G, 3G, 4G, or 5G. The wireless standards can use various channel access methods, such as FDMA, TDMA, CDMA, or SDMA. In certain embodiments, different types of data can be transmitted via different links and standards. In other embodiments, the same type of data can be transmitted via different links and standards. Network communication can be connected via any suitable protocol, including, for example, http, tcp / ip, udp, Ethernet, ATM, etc.

[0063] Network 199 can be a network of any kind and / or form. The geographical scope of the network can vary widely, and Network 199 can be a Body Area Network (BAN), a Personal Area Network (PAN), a Local Area Network (LAN), for example, an intranet, a Metropolitan Area Network (MAN), a Wide Area Network (WAN), or the Internet. The topology of Network 199 can be in any form and can include, for example, any of the following: between two points, bus, star, ring, mesh, or tree. Network 199 can be one having any such network topology known to those skilled in the art that can support the operations described herein. Network 199 can utilize layers or stacks of different technologies and protocols, including, for example, Ethernet protocol, Internet Protocol Suite (TCP / IP), ATM (Asynchronous Transfer Mode) technology, SONET (Synchronous Optical Networking) protocol, or SDH (Synchronous Digital Hierarchy) protocol. The TCP / IP Internet Protocol Suite can include an application layer, a transport layer, an Internet layer (e.g., IP v 4 and IP v 4 included), or a link layer. Network 199 can be a type of broadcast network, a telecommunications network, a data communication network, or a computer network.

[0064] The data retention system 190 may include any type of computer storage medium and / or computer-readable storage device. Such a computer storage medium or device may be configured to store data and provide access to the data. Examples of computer storage media or devices include, but are not limited to, electronic storage devices, magnetic storage devices, optical storage devices, electromagnetic storage devices, semiconductor storage devices, or any suitable combination thereof, such as computer disks, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), static random access memory (SRAM), portable compact disk read-only memory (CD-ROM), digital versatile disk (DVD), memory sticks, and the like.

[0065] FIG. 8 shows an automatic process control system consistent with an embodiment of the present specification. The automatic process control system 102 includes one or more processors 110 (also referred to interchangeably herein as a plurality of processors 110, processors (plural) 110, or processor 110 for convenience), one or more storage devices 120, and / or other components. In other embodiments, the functionality of the processor can be implemented by hardware (e.g., by use of an application specific integrated circuit (“ASIC”), programmable gate array (“PGA”), field programmable gate array (“FPGA”), etc.), or by any combination of hardware and software. The storage device 120 includes any type of non-transitory computer-readable storage medium and / or non-transitory computer-readable storage device. Such a computer-readable storage medium or device can store computer-readable program instructions for causing the processor to implement one or more of the methods described herein. Examples of computer-readable storage media or devices include, but are not limited to, electronic storage devices, magnetic storage devices, optical storage devices, electromagnetic storage devices, semiconductor storage devices, or any suitable combination thereof, such as computer disks, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), static random access memory (SRAM), portable compact disc read-only memory (CD-ROM), digital versatile disc (DVD), memory stick, etc., but are not limited to only these examples.

[0066] Processor 110 is programmed by one or more computer program instructions stored in a storage device 120 that represents a software protocol. For example, processor 110 is programmed by an automatic process control system (apcs) network manager 252, a process control manager 254, an automatic process control system (apcs) interface manager 255, and an automatic process control system (apcs) data storage manager 256. The functions of the various managers discussed herein are representative and are understood not to be limiting. Further, storage device 120 may act as a data retention system 190 for providing data storage. As used herein, for convenience, the various "managers" are described as performing operations when, in fact, the manager programs processor 110 (and thus automatic process control system 102) to perform the operations.

[0067] The various components of the automatic process control system 102 cooperate to operate to control one or more automated cell engineering systems 600 or automated cell engineering system installations 111 and to provide an interface for a user or other system to interface with one or more automated cell engineering systems 600 or automated cell engineering system installations 111.

[0068] The APCS Network Manager 252 is a software protocol that operates in the Automatic Process Control System 102. The APCS Network Manager 252 is configured to establish network communications between the Automatic Process Control System 102, the Automatic Cell Engineering System 600, the Automatic Cell Engineering System Installation 111, the Data Retention System 190, and the Client 104. The established communication path may utilize any suitable network transfer protocol and may provide one-way or two-way data transfer. The APCS Network Manager 252 may establish the number of network communications necessary to communicate with one or more Automatic Cell Engineering Systems 600 and other components of the Automatic Cell Engineering System Installation 111, the Data Retention System 190, the Client 104, and the like.

[0069] The APCS Network Manager 252 enables the transmission and reception of instructions, process parameters, Automatic Cell Engineering System data, cell growth protocols, software upgrades, user authentication information, and production instructions in one or more Automatic Cell Engineering Systems 600. As used herein, production instructions refer to instructions for the production of one or more cell cultures. Production instructions may include information about the cell culture growth protocol to be used, initial information about the cells prior to the start of the cell culture growth protocol, and other information necessary for the production of the cell culture. The APCS Network Manager 252 may facilitate the reception of process information from the Automatic Cell Engineering System 600, including, but not limited to, one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, carbon dioxide concentration information, optical density information, magnetic state information, and any other process information collected by one or more of the Automatic Cell Engineering Systems 600 discussed herein. The APCS Network Manager 252 may also facilitate the reception of production information from the Automatic Cell Engineering System 600, including, but not limited to, one or more of the number of cells recorded over time, cell characteristics, conversion rate %, and the like.

[0070] The APCS network manager 252 further facilitates the transmission and reception of data including automated cell engineering system status information, complete batch records, data extracts, real-time data, and archived data at one or more clients 104, data analysis generated and / or provided by the automated process control system 102, and compliance and / or reporting information. The APCS network manager 252 also further facilitates the transmission and reception of archived data to and from one or more data retention systems 190.

[0071] The process control manager 254 is a software protocol that operates in the automated process control system 102. The process control manager 254 is configured to provide one or more control signals to one or more automated cell engineering systems 600. The control signals provided by the process control manager 254 are configured to cause adjustment of one or more process parameters of the automated cell engineering system 600. As used herein, "process parameter" refers to any parameter or variable of a production process that can be adjusted by a user via the automated process control system 102. Process parameters include, but are not limited to, gas concentration, media conditions, temperature, pH, waste and nutrient concentrations, and media flow rate. The determination of the control signals can be based on process information received by the APCS network manager 252. The determination of the control signals can further be based on production information received by the APCS network manager 252.

[0072] Using the control signals provided by the process control manager 254, any process enabled by the automated cell engineering system 600 described herein can be initiated and / or controlled. Such processes include, but are not limited to, all steps, processes, and operations related to sorting, cell seeding, activation, transduction, electroporation, feeding, selection, collection, washing, concentration, formulation, and the like.

[0073] In an embodiment, the process control manager 254 can update, change, and / or adjust the process parameters of one or more automated cell engineering systems 600 to which the automated process control system 102 is connected via one or more control signals, as further discussed below. Any updates performed by the process control manager 254 can be automatically performed in response to the information collected and in accordance with the cell culture growth protocol, without user monitoring.

[0074] In an embodiment, the update may require user approval. In such an embodiment, the process control manager 254 can send a request to one or more authorized users to approve the change in the process parameter. Such a request can be sent directly to a screen or the receiving tray of the client 104 connected to the automated process control system 102, and / or can be sent via alternative communication means such as email, text message, or voice message. In some embodiments, the process control manager 254 can interpret the lack of response to the permission request as a rejection of the request after a specific period. In some embodiments, the process control manager 254 can interpret the lack of response to the permission request as an approval of the request after a specific period.

[0075] The process parameters of the automated cell engineering system 600 that can be adjusted by the process control manager 254 include one or more gas concentrations, medium conditions, temperature, pH, waste and nutrient concentrations, and medium flow rate, electroporation conditions, transduction conditions, and the like. The adjustment of these various process parameters can be carried out based on the process information received from the automated cell engineering system 600. As described above, the automated cell engineering system 600 is an autonomous system and may not require external control to maintain the process parameters at a programmed level. However, the process control manager 254 can be configured to adjust the programmed levels of various process parameters based on the process information. The process control manager 254 can operate any or all of the process control operations described herein on an ongoing, real-time, or iterative basis.

[0076] For example, process information such as temperature information, pH information, glucose concentration, component or patient identification information, oxygen concentration information, and / or optical density information may indicate that one or more of these values are different from the expected or programmed values despite autonomous control. Accordingly, the process control manager 254 can adjust the appropriate process parameters in response.

[0077] In another example, the process control manager 254 can be used to change the process parameters according to a cell culture growth protocol (i.e., desired increase in cell volume, transduction time, change in growth rate, etc.). The cell culture growth protocol may require updating the process parameters during the cell engineering process. The process control manager 254 can perform such adjustments.

[0078] In another example, the process control manager 254 can be used to change process parameters in accordance with an update to the cell culture growth protocol. The cell culture growth protocol can be updated during the cell engineering process or otherwise changed. Thus, such an update may require that the update of the process parameters be performed by the process control manager 254.

[0079] In yet another example, the process control manager 254 can update process parameters in the first automated cell engineering system 600 in accordance with production information received from the second automated cell engineering system 600. For example, the first cell engineering process in the first automated cell engineering system 600 may be likely to exceed the production level prediction, and the second cell engineering process in the second automated cell engineering system 600 can adjust its process parameters to reduce or change production.

[0080] In yet another example, cell production in the automated cell engineering system 600 can be different from the level predicted based on the initial process parameters. The production information can indicate that the cell production is more or less than expected. Thus, the process parameters can be adjusted by the process control manager 254 in response to the production information.

[0081] In an embodiment, the process control manager 254 provides a process monitoring function. The process control manager 254 can be configured to access any information measured, generated, and / or stored by the automated cell engineering system 600. The process control manager 254 can further be configured to provide any of such information to the user via the apcs user interface manager 255.

[0082] In a further embodiment, the process control manager 254 may be equipped for the diagnosis of the automated cell engineering system 600. Thus, the process control manager 254 may review system performance including process information, process parameters, user control history, and production information, and compare this information to calibrated levels and / or other benchmarks to determine if the automated cell engineering system 600 is operating within specifications.

[0083] The apcs user interface manager 255 is a software protocol that operates in the automated process control system 102. The apcs user interface manager 255 is configured to provide a user interface that enables user interaction with the automated process control system 102. The apcs user interface manager 255 is configured to receive input from any user input source including, but not limited to, a touch screen, keyboard, mouse, controller, joystick, voice control. The apcs user interface manager 255 is configured to provide a user interface such as a text-based user interface, a graphical user interface, or any other suitable user interface. The apcs user interface manager 255 is configured to provide such user interface services via one or more clients 104 using the apcs network manager 252. The apcs user interface manager 255 may be configured to provide different user interface services depending on the type of client device. For example, a laptop or desktop computer may be equipped with a user interface including a full set of interface options, while a smartphone or tablet may be equipped with a user interface limited to status updates.

[0084] The apcs user interface manager 255 is configured to provide a user authentication service. The user may authenticate, for example, via a password, biometric scanning (such as retinal scanning, fingerprint, voiceprint, face recognition, etc.), key card, token access, and any other suitable means of user authentication. The user authentication service may be provided to control access to one or more automated cell engineering systems 600.

[0085] In embodiments, one or more users may be provided with full access to all functions, process information, and / or production information of the automated cell engineering system 600 or the automated cell engineering system installation 111. One or more users may be provided with limited access to all functions, process information, and / or production information of the automated cell engineering systems within the automated cell engineering system 600 or the automated cell engineering system installation 111. One or more users may be provided with full access to a limited portion of the automated cell engineering system 600 within the automated cell engineering system installation 111. In some embodiments, one or more users may be provided with "read-only" access that allows viewing of process information, production information, etc., but does not allow any adjustment to process parameters. Further, one or more users may be provided with full or limited access to archived data. Access control may be determined according to user identity, user function, user job identity, and any other suitable criteria.

[0086] In an embodiment, the APCS user interface manager 255 may provide one or more users with access to any or all processes and / or production information about one or more automated cell engineering systems 600 via the user interface. The APCS user interface manager 255 may allow a user to perform various tasks on one or more automated cell engineering systems 600 within the automated cell engineering system installation 111. For example, the APCS user interface manager 255 may allow a user to directly adjust or control one or more process parameters. In another example, the APCS user interface manager 255 may allow a user to update a cell culture growth protocol. In another example, the APCS user interface manager 255 may allow a user to adjust a process goal, and the autonomous automated cell engineering system 600 or the process control manager 254 may automatically adjust the process parameters to achieve a specific goal.

[0087] In an embodiment, the APCS user interface manager 255 is configured to provide user training, tutoring, and evaluation for the automated cell engineering system 600. The APCS user interface manager 255 may enter a training mode in cooperation with the automated cell engineering system 600. In the training mode, the APCS user interface manager 255 may provide a user with operation instructions for performing various cell engineering tasks. The APCS user interface manager 255 may operate in cooperation with the automated cell engineering system 600, for example, by causing the automated cell engineering system 600 to perform an operation when the user works in the training mode. In a further embodiment, the APCS user interface manager 255 may also cause the automated cell engineering system 600 to present text prompts, visual highlights, and other instructions to the user to assist with training.

[0088] The APCS Data Storage Manager 256 is a software protocol that operates in the Automatic Process Control System 102. The APCS Data Storage Manager 256 is configured to access one or more Automatic Cell Engineering Systems 600 to receive and / or retrieve Automatic Cell Engineering System data. The Automatic Cell Engineering System data can include, for example, production information that can be obtained substantially in real-time, archived data, and / or data extracts, as well as process information and process parameter information and any other information or data generated by the Automatic Cell Engineering System 600. The APCS Data Storage Manager 256 is further configured to access one or more Data Retention Systems 190 to store and / or receive Automatic Cell Engineering System data stored in the Data Retention Systems 190.

[0089] The APCS Data Storage Manager 256 can provide data to a user via the Automatic Process Control System Interface Manager 255. In an embodiment, the APCS Data Storage Manager 256 is further configured to provide access tools to a user for managing, accessing, and analyzing Automatic Cell Engineering System data. For example, the APCS Data Storage Manager 256 can be configured for creating reports, collating Automatic Cell Engineering System data, cross-referencing Automatic Cell Engineering System data, and loading Automatic Cell Engineering System data into a database, among other things.

[0090] In an embodiment, the APCS data storage manager 256 can provide data retention capabilities. The APCS data storage manager 256 is configured to receive new batch record data from each automated cell engineering system 600 connected to the automatic process control system 102 at configurable intervals - for example, every 10 seconds, every 30 seconds, every minute, every 5 minutes, every 10 minutes, every hour, etc. The configurable intervals can be adjusted according to the cell culture growth protocol. For example, the intervals for important processes that require intensive monitoring may be short, while the intervals for less important processes may be long. In an embodiment, the APCS data storage manager 256 can further be configured to receive new recorded data from one or more automated cell engineering systems 600 according to the occurrence of events in the associated automated cell engineering system 600. In a further embodiment, the APCS data storage manager 256 is further configured to receive new recorded data according to the occurrence of events at certain configurable intervals. When new batch record data is received from each automated cell engineering system 600, the APCS data storage manager 256 stores the new data in a local database associated with the automated cell engineering system 600 on the storage device 120. In an embodiment, data from one or more automated cell engineering systems 600 can be stored in the same database. Each automated cell engineering system 600 can be associated with a specific database on the storage device 120. When a new set of batch record data is generated on an automated cell engineering system 600, for example, for the start of a new cell culture growth protocol, a new database on the automatic process control system 102 can be generated accordingly. In an embodiment, previously created databases can be used to store information from the start of a new cell culture growth protocol. If necessary, for example, since the cell culture is transferred from one automated cell engineering system 600 to another automated cell engineering system 600, the appropriate batch record data is transferred as well, enabling the new automated cell engineering system 600 to access all the necessary information regarding a specific cell culture.

[0091] In an embodiment, the APCS data storage manager 256 may provide enhanced data retention capabilities. At regular intervals as needed, the batch record database stored locally on the storage device 120 of the automatic process control system 102 may be transferred to one or more data retention systems for archival purposes. Newly archived data may be verified by the APCS data storage manager 256. If verification of the data archived in one or more data retention systems 190 fails, the archival process may be repeated based on the batch record database stored on the storage device 120 and / or based on receiving the data again from the automated cell engineering system 600. After verification of the data archive, deletion of the data on the automated cell engineering system 600 and / or the local data copy on the storage device 120 may be scheduled or performed for future use.

[0092] In an embodiment, the APCS data storage manager 256 may be configured to store and manage data records in accordance with federal regulations such as Title 21, Part 11 of the Code of Federal Regulations. For example, the APCS data storage manager 256 may perform user access control, data verification checks, archival backups, data replication, data auditing, and other processes in accordance with federal regulations.

[0093] As described above, the various components of the automated process control system 102 cooperate to control one or more automated cell engineering systems 600 or automated cell engineering system installations 111 and to provide an interface for a user or other system to interface with one or more automated cell engineering systems 600 or automated cell engineering system installations 111. In an embodiment, one or more automated cell engineering systems 600 or automated cell engineering system installations 111 may be controlled by a combination of local direct control of individual automated cell engineering systems 600 and control via the automated process control system 102. All of the process control functions of the automated cell engineering system 600 may be implemented in any combination, either through direct interaction with the automated cell engineering system 600 or via the automated process control system 102, as described above with respect to FIGS. 1-6. Conversely, in further embodiments, all of the functions of the automated process control system 102 may be implemented in any combination, either through direct interaction with the automated cell engineering system 600 or via the automated process control system 102, as discussed with respect to FIG. 8. In further embodiments, the processor of the automated cell engineering system 600 may be configured to execute any of the software protocols described herein with respect to the automated process control system 102 (e.g., apcs network manager 252, process control manager 254, apcs user interface manager 255, and data storage manager 256), and thus to operate as both the automated cell engineering system 600 and the automated process control system 102.

[0094] For example, in an embodiment, process control steps such as those described with respect to FIGS. 1-6 can be performed directly through an operator's interaction with the automated cell engineering system 600. The operator can, for example, directly access the automated cell engineering system 600 to monitor the ongoing process and initiate a new process at an appropriate time. User identification and authorization functions can be implemented in the automated cell engineering system 600 to ensure appropriate access. In such an embodiment, the automated process control system 102 collects and archives data (e.g., process information, production information, and control information) from the ongoing processes in the automated cell engineering system 600, performs system monitoring to ensure proper functioning of the automated cell engineering system 600, adjusts general parameters and settings within the automated cell engineering system 600, and performs any other functions to ensure proper functioning and monitoring of the automated cell engineering system 600. In such an embodiment, the automated process control system 102 performs the supervision of one or more automated cell engineering systems 600 while allowing local process control to be performed directly in the automated cell engineering system 600. For the monitoring function, the automated process control system 102 can be configured to provide warnings, notifications, or other prompts when the local control of the automated cell engineering system 600 deviates from the expected or planned process parameters.

[0095] In a further embodiment, the automated process control system 102 may be employed only for data collection and archival purposes without providing monitoring or control functions. In a further embodiment, the automated process control system 102 may provide coordination among a plurality of automated cell engineering systems 600 of an installation. For example, the automated process control system 102 may provide process information to the automated cell engineering system 600 for use by an operator to access and execute locally via a direct interface with the automated cell engineering system 600. Customer requests for production instructions may be allocated, for example, by the automated process control system 102 across several automated cell engineering systems 600 and then executed by local operators at the individual automated cell engineering systems 600.

[0096] The foregoing description of workflows implemented via the automated cell engineering system 600 or the automated process control system 102 is merely an example. Any combination of the automated cell engineering system 600 functions and the automated process control system 102 functions described herein may be used in the operation of the automated cell engineering system 600.

[0097] FIG. 9 is a flowchart showing a process 900 for controlling an automated cell engineering system 600. The process 900 is implemented in a computer system having one or more physical processors programmed with computer program instructions that, when executed by the one or more physical processors, cause the computer system to perform the method. The one or more physical processors are hereinafter simply referred to as processors. In an embodiment, the various operations of process 900 are performed via an automated process control system 102, via a direct interface with the automated cell engineering system 600, and / or via any combination described herein. The automated process control system 102 is an example of a combination of hardware and software configured to perform process 900, but the execution of process 900 is not limited to the combination of hardware and software of the automated process control system 102. Further details regarding each of the operations of the method can be understood in accordance with the description of the automated process control system 102 as described above.

[0098] In operation 902, process 900 includes establishing a network connection with the automated cell engineering system. The network connection between the automated process control system described herein and the automated cell engineering system described herein can be established via any suitable network transmission protocol or protocol suite including, for example, http, TCP / IP, LAN, WAN, WiFi, etc.

[0099] In operation 904, process 900 includes receiving process information from the automated cell engineering system 600. The automated process control system can receive process information from the automated cell engineering system including, for example, one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, component or patient identification information, and optical density information.

[0100] In operation 906, process 900 includes determining a control signal and adjusting one or more process parameters of the automated cell engineering system. The control signal can be determined by an automated process control system and can respond to received process information. The determination of the control signal can further respond to production information received from the automated cell engineering system, an update or change to the cell culture growth protocol, and / or an update or change initiated by the user. The control signal can further respond to each of these factors.

[0101] In operation 908, process 900 includes providing a control signal to the automated cell engineering system. The control signal determined by the automated process control system can be provided to the automated cell engineering system via a network connection. In response to receiving the control signal, the automated cell engineering system can adjust one or more process parameters to achieve a change in production and / or process conditions.

[0102] As described above, the various functional aspects of process 900 can be implemented either by the automated process control system 102 or via a direct interface with the automated cell engineering system 600. For example, networking and process information operations 902 and 904 can provide process information to the automated cell engineering system 600 via the network, while a local operator can cause the generation and provision of a control signal for adjusting process parameters within the automated cell engineering system 600 via a direct interface with the control of the automated cell engineering system 600.

[0103] FIG. 10 shows a central control process system for controlling a plurality of automated process control system installations. The central control process system 1002 is provided to interface with one or more automated process control systems 102, each of which is connected to an automated cell engineering system installation 111 and a data retention system 190 via a network 199. The central control process system 1002 is configured to interface with each automated process control system 102 via a network 299 and is further capable of accessing a central data retention system 1090. A user can access the central control process system 1002 via direct interaction with the central control process system 1002 and / or via one or more clients 1004.

[0104] The one or more clients 1004 can be configured as a personal computer (e.g., desktop computer, laptop computer, etc.), a smartphone, a tablet computing device, and / or other device that can be programmed with a user interface for accessing the central control process system 1002. In an embodiment, the central control process system 1002 and the client 1004 can be present within a single system such as a laptop, desktop, tablet, or other computing device with a user interface. A suitably configured client 1004 can provide a user with access to all of the functions of the central control process system 1002 described herein.

[0105] The network 299 can have any or all of the characteristics described above with respect to the network 199. In an embodiment, the network 199 and the network 299 can be the same network. Each automated process control system 102 and its associated systems and components correspond to the automated process control system 102 described above with respect to FIGS. 7 and 8.

[0106] The central control process system 1002 is configured to monitor, update, and interact with one or more local automated process control systems 102. The central control process system 1002 can, for example, facilitate software updates, update and manage cell culture growth protocols, manage user access, perform secondary monitoring of the automated cell engineering system 600, perform quality control activities, etc., as described herein. The central control process system 1002 can coordinate the activities and operations of multiple automated cell engineering system installations 111 via their associated automated process control systems 102.

[0107] The central control process system 1002 is connected to a central data retention system 1090. The central data retention system 1090 is a computer information storage device and shares any or all of the above-described characteristics associated with the data retention system 190. Although illustrated as being connected to the central control process system 1002 via the network 299, the central data retention system 1090 can also be co-located with the central control process system 1002 (e.g., the central control process system 1002 and the central data retention system 1090 can share a housing and / or share a computer-readable memory device), and can also be directly connected to the central control process system 1002.

[0108] In a further embodiment, the central control process system 1002 can provide all of the functions of the automated process control system 102 as described above and can be employed to interact with and access any automated cell engineering system 600 within the system in the same manner as the locally associated automated process control system 102. For example, an authorized user can operate the central control process system 1002 to access any particular connected automated cell engineering system installation 111 that has all of the functions and access of the associated local automated process control system 102.

[0109] In a further embodiment, the central control process system 1002 can facilitate access to any automated cell engineering system 600 within the connected system by any given local automated process control system 102. For example, an authorized user in a first automated process control system 102 associated with a first automated cell engineering system installation 111 can access a second automated cell engineering system installation 111 associated with a second automated process control system 102 via the central control process system 1002. Thus, the networked system of the central control process system 1002 and the automated process control system 102 can provide a user with appropriate authorized access and control to any automated cell engineering system 600 within the system. The central control process system 1002 can further facilitate access to the central data retention system 1090 via any automated process control system 102.

[0110] In a further embodiment, any and all functions of the central control process system 1002 can be performed by the automated process control system 102. In yet another embodiment, the central control process system 1002 and the automated process control system 102 can be performed by the same processor(s).

[0111] FIG. 10 shows a system including a single central control process system 1002 and two automated process control systems 102, but the invention is not so limited. The networked system of automated cell engineering system installations 111 can include any number of central control process systems 1002 and automated process control systems 102.

[0112] FIG. 11 shows a central control process system that conforms to an embodiment of the present invention. The central control process system 1002 includes one or more processors 1010 (also referred to interchangeably herein as a plurality of processors 1010, processors (plural) 1010, or processor 1010 for convenience), one or more storage devices 1020, and / or other components. In other embodiments, the functions of the processor can be implemented by hardware (e.g., by the use of application specific integrated circuits (“ASICs”), programmable gate arrays (“PGAs”), field programmable gate arrays (“FPGAs”), etc.), or by any combination of hardware and software. The storage device 1020 includes any kind of non-transitory computer-storage medium and / or non-transitory computer-readable storage device. Such a computer-storage medium or device can store computer-readable program instructions for causing the processor to implement one or more of the methods described herein. Examples of computer-storage medium or device include, but are not limited to, electronic storage devices, magnetic storage devices, optical storage devices, electromagnetic storage devices, semiconductor storage devices, or any suitable combination thereof, such as computer disks, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), static random access memory (SRAM), portable compact disk read-only memory (CD-ROM), digital versatile disk (DVD), memory stick, etc., but are not limited to only these examples.

[0113] Processor 1010 is programmed by one or more computer program instructions stored in a storage device 1020 that represents a software protocol. For example, processor 1010 is programmed by an automatic process control system manager 2050, a central control process system (ccps) network manager 2052, a cell culture growth protocol manager 2054, an update manager 2056, a compliance manager 2058, a volume manager 2060, a central control process system (ccps) user interface manager 2062, and a central control process system (ccps) data storage manager 2064. The functions of the various managers discussed herein are representative and are understood not to be limiting. Further, storage device 1020 may act as a central data retention system 1090 for providing data storage. As used herein, for convenience, the various "managers" are described as performing operations when, in fact, the manager programs processor 1010 (and thus central control process system 1002) to perform the operations.

[0114] The various components of central control process system 1002 operate together to provide control of one or more automatic process control systems 102, automatic cell engineering systems 600, and / or automatic cell engineering system installations 111, and also to provide an interface for a user or other system to interface with these.

[0115] The Automatic Process Control System Manager 2050 is a software protocol that operates on the Central Control Process System 1002. The Automatic Process Control System Manager 2050 is configured to provide the Central Control Process System 1002 with all the functions of the Automatic Process Control System 102 regarding any Automatic Cell Engineering System 600 or Automatic Cell Engineering System Installation 111 to which the Central Control Process System 1002 is connected via a network or other connection. Thus, the Automatic Process Control System Manager 2050 can implement and provide all the functions described herein regarding the APCS Network Manager 252, Process Control Manager 254, APCS User Interface Manager 255, and APCS Data Storage Manager 256.

[0116] For example, the Automatic Process Control System Manager 2050 is configured to provide the Central Control Process System 1002 with production control and management functions. A user of the Automatic Process Control System 102 can create production instructions and manage cell production across one Automatic Cell Engineering System 600 or Automatic Cell Engineering System Installation 111, while a user of the Central Control Process System 1002 can create production instructions and manage cell production across multiple Automatic Cell Engineering Systems 600 and Automatic Cell Engineering System Installations 111 simultaneously.

[0117] The automatic process control system manager 2050 is configured to access one or more control information histories of the connected automatic process control system 102. The control information history includes information and / or data about the performance of the automated cell engineering system 600. Such information includes records of control signals, process parameters, process information, and production information recorded over time. Thus, the control information history includes detailed history information about commands and control signals sent to one or more automated cell engineering systems 600 and history information about the performance of the automated cell engineering systems in response to such commands and control signals. The control information history further includes information and data about the autonomous functions of one or more automated cell engineering systems 600 and / or the automated cell engineering system installations 111 within the system. The control information history can be used by the central control process system 1002 for monitoring, troubleshooting, updating, upgrading, and other methods of control of the performance of one or more automatic process control systems 102 and related automated cell engineering systems 600.

[0118] The ccps network manager 2052 is a software protocol that operates on the central control process system 1002. The ccps network manager 2052 is configured to establish network communications between the central control process system 1002, the automatic process control system 102, the central data retention system 1090, and the client 1004. The ccps network manager 2052 is thus configured to establish network connections with multiple automatic process control systems 102, each of which controls one or more automatic cell engineering systems 600 or automatic cell engineering system installations 111. The established communication paths may utilize any suitable network transfer protocol and may provide one-way or two-way data transfer. The ccps network manager 2052 may establish the number of network communications necessary to communicate with one or more automatic process control systems 102. In further embodiments, the ccps network manager 2052 may be configured to establish network communications with one or more automatic cell engineering systems 600, automatic cell engineering system installations 111, and / or data retention systems 190.

[0119] The ccps network manager 2052 enables the transmission and reception of data, protocols, software upgrades, user authentication information, production instructions, process information, production information, and any other data or information obtained, accessed, or stored by the automatic process control system 102, including instructions, complete batch records, data extracts, near or substantially real-time data, and archived data, using one or more automatic process control systems 102. The ccps network manager 2052 further facilitates communication with one or more clients 1004, enables user access to the central control process system 1002 and communication with the automatic process control system 102, and allows various other software protocols operating on the central control process system 1002 to perform their required functions.

[0120] The cell culture growth protocol manager 2054 is a software protocol that operates on the central control process system 1002. The cell culture growth protocol manager 2054 is configured to create, store, maintain, and update cell culture growth protocols. The cell culture growth protocol manager 2054 stores a plurality of cell culture growth protocols in the central data storage system 1090. The cell culture growth protocol manager 2054 further enables a user to create and update cell culture growth protocols through an interaction via the ccps user interface manager 2062, which is discussed further below. The newly created and updated cell culture growth protocols can be pushed from the cell culture growth protocol manager 2054 to one or more automatic process control systems 102 as new protocols or update protocols to be used by the automatic process control system 102 when controlling the automatic cell engineering system 600 or the automatic cell engineering system installation 111.

[0121] In an embodiment, the cell culture growth protocol manager 2054 may maintain one or more databases of cell culture growth protocols in the central data storage system 1090. The cell culture growth protocol database may include information about which automatic cell engineering systems 600 and / or automatic process control systems 102 have accessed a particular protocol, which versions or protocols can be accessed, and production information related to various protocols and automatic process control systems 102. Such information can be used, for example, for quality control purposes to ensure that similar protocols are implemented on different automatic cell engineering system installations 111 and that similar results are obtained. Such information can further be used to compare production results between multiple versions of the same protocol across multiple automatic cell engineering system installations 111.

[0122] In an embodiment, the cell culture growth protocol manager 2054 may provide protocol development capabilities. The cell culture growth protocol manager 2054 may receive automated cell engineering system data including protocol information, process information, production information, and any other relevant data collected by one or more automated cell engineering system installations 111 associated with the central control process system 1002. The cell culture growth protocol manager 2054 may compare information obtained from multiple automated cell engineering system installations 111 to determine factors that promote the success of the cell culture growth protocol. Such factors may include, for example, various process parameters and / or differences in the cell culture growth protocol. In an embodiment, the cell culture growth protocol manager 2054 may analyze the automated cell engineering system data for the purpose of identifying successful treatment protocols, troubleshooting unsuccessful treatment protocols, and developing successful treatment protocols. The developed and identified successful treatment protocols may be communicated by the cell culture growth protocol manager 2054 to one or more automated process control systems 102 associated therewith. Information regarding troubleshooting may be communicated to the automated process control system 102 associated with the unsuccessful treatment protocol to allow an authorized user to adjust the protocol.

[0123] The update manager 2056 is a software protocol that operates on the central control process system 1002. The update manager 2056 is configured to maintain a record of the cell engineering system software versions used on one or more automated process control systems 102 and one or more automated cell engineering systems 600 to which the central control process system 1002 is connected. The update manager 2056 is further configured to provide cell engineering software updates to one or more automated process control systems 102 and one or more automated cell engineering systems 600 to which the central control process system 1002 is connected.

[0124] In an embodiment, the update manager 2056 is configured to automatically promote software updates to the automatic process control system 102 and the automatic cell engineering system 600 that require updates. In an embodiment, the update manager 2056 is configured to request user permission to provide an update. In a further embodiment, the update manager 2056 is configured to notify an authorized user local to the automatic process control system 102 or the automatic cell engineering system 600 of the availability of a software update.

[0125] In an embodiment, the update manager 2056 is configured to receive a notification from the automatic process control system 102 that no cell engineering software update will be provided until after a certain period of time, until after a certain number of productions have been carried out, or until requested by a specific authorized user. Since the automatic cell engineering system 600 and the automatic process control system 102 can be used to carry out validated cell growth projects and experiments, it may be required to maintain the use of a particular validated software version throughout a particular project.

[0126] The compliance manager 2058 is a software protocol operating in the central control process system 1002. The compliance manager 2058 is configured to analyze the information history collected by the central control process system 1002 to determine whether one or more automatic process control systems 102 and automatic cell engineering systems 600 are being used in compliance. Checks or determinations can be made to ensure that appropriate regulations are being followed and / or to ensure that appropriate guidelines are being followed. Appropriate regulations can include government regulations such as FDA regulations. Appropriate guidelines can include corporate guidelines, ethical guidelines, best practices, and / or other guidelines established by the operator / owner of the central control process system 1002.

[0127] For example, the compliance manager 2058 can be used to analyze the control information history to determine and / or ensure that the automated cell engineering system installation 111 associated with the automated process control system 102 is being used in an ethical manner. The control information history can be compared to the user logs maintained by the apcs user interface manager 255 to determine whether any user is using or not using the automated cell engineering system installation 111 in accordance with the ethical guidelines. In response to a determination that one or more users are not using the automated cell engineering system installation 111 in accordance with the ethical guidelines (or other guidelines, regulations, or best practices), the compliance manager 2058 can operate to change the local user access to the automated process control system 102 via the ccps user interface manager 2062. For example, the compliance manager 2058 can restrict the local user access of one or more local users based on the control information history.

[0128] The Capacity Manager 2060 is a software protocol that operates in the Central Control Process System 1002. The Capacity Manager 2060 is configured to manage capacity across one or more Automated Cell Engineering System Installations 111 to which the Central Control Process System 1002 is connected via network communication. The Capacity Manager 2060 is configured to maintain, for example, records of Automated Cell Engineering Systems 600 that are used or not used across systems connected to the Central Control Process System 1002 and stored in the Central Data Retention System 1090. The Capacity Manager 2060 is further configured to maintain records of the expected future use of Automated Cell Engineering Systems 600 across systems connected to the Central Control Process System 1002. For example, the Capacity Manager 2060 may predict a future date when an Automated Cell Engineering System 600 will no longer be used, according to the protocol and production information of the Automated Cell Engineering System 600. In another example, the Capacity Manager 2060 may access production instruction information of the Automatic Process Control System 102 to determine how many Automated Cell Engineering Systems 600 associated with the Automatic Process Control System 102 may be used in the future.

[0129] The Capacity Manager 2060 may provide the user, via the CCPS User Interface Manager 2062, with insights and / or information regarding the capacity of Automated Cell Engineering Systems 600 at various Automated Cell Engineering System Installation 111 locations. For example, a user or operator who does not have personal access to an Automated Cell Engineering System facility that may include one or more Automated Cell Engineering System Installations 111 may wish to order some cell production instructions based on recently collected cell samples. The user or operator may access the Capacity Manager 2060 to determine which Automated Cell Engineering System Installation 111 locations have the capacity (i.e., available Automated Cell Engineering Systems 600) and the ability (i.e., the ability to implement a particular cell culture growth protocol) to fulfill the production instructions.

[0130] The CCPS User Interface Manager 2062 is a software protocol that operates on the Central Control Process System 1002. The CCPS User Interface Manager 2062 is configured to provide a user interface that enables user interaction with the Central Control Process System 1002. The CCPS User Interface Manager 2062 is configured to receive input from any user input source including, but not limited to, a touch screen, keyboard, mouse, controller, joystick, voice control. The CCPS User Interface Manager 2062 is configured to provide a user interface such as a text-based user interface, a graphical user interface, or any other suitable user interface. The CCPS User Interface Manager 2062 is configured to use the CCPS Network Manager 2052 to provide such user interface services via one or more clients 104. The CCPS User Interface Manager 2062 may be configured to provide different user interface services depending on the type of client device. For example, a laptop or desktop computer may have a user interface that includes a full set of interface options, while a smartphone or tablet may have a user interface limited to status updates.

[0131] The CCPS user interface manager 2062 is further configured to provide user authentication services and access management services. The CCPS user interface manager 2062 manages user authentication and access management in either any automated cell engineering system 600 or an automated cell engineering system installation 111 associated with a network connected to the central control process system 1002 according to any of the functions described above with respect to the automated process control system 102 and / or the APCS user interface manager 255. Thus, the CCPS user interface manager 2062 is configured to control access to any automated cell engineering system 600 within a network connected to the central control process system 1002 and to update, change, or otherwise regulate user access authentication information. As used herein, "connected network" refers to a group of the central control process system 1002, the automated process control system 102, the automated cell engineering system 600, and the automated cell engineering system installation 111 connected via a network connection. The CCPS user interface manager 2062 is further configured to control access to the central control process system 1002 itself, provide user authentication services, and manage user access records according to any of the functions described herein with respect to the APCS user interface manager 255.

[0132] The CCPS data storage manager 2064 is a software protocol that operates on the central control process system 1002. The CCPS data storage manager 2064 is configured to access one or more automated cell engineering systems 600, automated cell engineering system installations 111, and / or automated process control systems 102 to receive and / or retrieve automated cell engineering system data. The automated cell engineering system data can include, for example, production data that can be obtained almost in real time, archived data, and / or data extracts, as well as process information, process parameter information, and any other information collected from one or more automated cell engineering systems 600. The CCPS data storage manager 2064 is further configured to access one or more data retention systems 190 and a central data retention system 1090 to store and / or receive automated cell engineering system data.

[0133] The CCPS data storage manager 2064 can provide data to a user via the CCPS user interface manager 2062. In an embodiment, the CCPS data storage manager 2064 is further configured to provide the user with access tools for managing, accessing, and analyzing automated cell engineering system data. For example, the CCPS data storage manager 2064 can be configured for creating reports, reconciling automated cell engineering system data, cross-referencing automated cell engineering system data, and loading automated cell engineering system data into a database.

[0134] In an embodiment, the ccps data storage manager 2064 may be configured to store and manage data records in accordance with federal regulations such as Title 21, Part 11 of the Code of Federal Regulations. For example, the ccps data storage manager 2064 may perform user access control, data verification checks, archive backups, data replication, data auditing, and other processes in accordance with federal regulations. Further, the ccps data storage manager 2064 may be configured to audit, review, and otherwise check one or more automated process control systems 102 and make determinations in accordance with applicable federal regulations.

[0135] FIG. 12 is a flowchart showing a process 1200 for controlling a plurality of automated process control systems via a central control process system. The process 1200 is implemented in a computer system having one or more physical processors programmed with computer program instructions that, when executed by the one or more physical processors, cause the computer system to implement the method. The one or more physical processors are hereinafter simply referred to as processors. In an embodiment, the process 1200 is implemented via the central control process system 1002 as described herein. The central control process system 1002 is an example of a combination of hardware and software configured to implement the process 1200, but the execution of the process 1200 is not limited to the combination of hardware and software of the central control process system 1002. Further details regarding each of the operations of the method may be understood in accordance with the description of the central control process system 1002 as described above.

[0136] In operation 1202, the process 1200 includes establishing a network connection with an automated cell engineering system. The network connection between the central control process system described herein and the plurality of automated process control systems described herein may be established via any suitable network transmission protocol or protocol suite, including, for example, http, TCP / IP, LAN, WAN, WiFi, and the like.

[0137] In operation 1204, process 1200 includes accessing the control information history of at least one of a plurality of connected automated process control systems. As described above, the control information history includes control information and associated user logs. Operation 1204 may further include accessing any and all automated cell engineering system data stored in data retention system 190 associated with the automated process control system.

[0138] In operation 1206, process 1200 includes providing at least one of a cell culture growth protocol update and a cell engineering software update to at least one automated process control system. In embodiments, the cell culture growth protocol update and / or the cell engineering software update may be provided to any number of automated process control systems 102 to which a central control process system 1002, including all automated process control systems 102, is connected.

[0139] FIG. 13 is a flowchart illustrating a process 1300 for controlling the production of a cell culture. Aspects of process 1300 may be implemented in a computer system having one or more physical processors programmed with computer program instructions to cause the computer system to perform the method when executed by the one or more physical processors. Further aspects of process 1300 may be implemented by an automated cell engineering system. The one or more physical processors are hereinafter simply referred to as processors. In embodiments, process 1300 is implemented via automated process control system 102 or central control process system 1002 described herein in conjunction with automated cell engineering system 600. In embodiments, process 1300 is implemented during a cell culture growth process that requires stopping and restarting the cell culture growth protocol. Further details regarding each of the operations of the method may be understood in accordance with the description of automated process control system 102 and central control process system 1002 as described above.

[0140] In operation 1302, process 1300 includes implementing a cell culture growth protocol within an automated cell engineering system. The cell culture growth protocol can be initiated directly in the automated cell engineering system or via a control system such as an automated process control system. The initiation of the cell culture growth protocol can be performed according to the methods and techniques discussed herein.

[0141] In operation 1304, process 1300 includes monitoring process information of the cell culture growth protocol. As described herein, the process information can include one or more cell growth parameters including at least one of temperature information, pH information, glucose concentration information, oxygen concentration information, component or patient identification information, optical density information, and any other process information collected. In embodiments, production information can also be monitored. The monitoring of this information can provide a summary of information regarding the progress of the cell culture growth protocol. The process information and / or production information can be monitored via a control system such as an automated process control system.

[0142] In operation 1306, process 1300 includes adjusting one or more process parameters of the cell culture growth protocol based on the monitoring. The process parameters can be adjusted to cause a change in the value measured by the process information. The process parameter adjustment can be performed by the automated process control system discussed herein.

[0143] In operation 1308, process 1300 includes stopping a cell culture growth protocol and recording the stage within the cell culture growth protocol at which the stop occurs. The stopping of the cell culture growth protocol can be performed by an automated process control system that initiates a cell growth stop procedure within the automated cell engineering system. Such a growth stop may preferably include stopping the introduction of fresh cell growth medium, stopping the introduction of cell nutrients, or adjusting gas concentration and / or temperature to stop cell growth. Operation 1308 further includes recording the stage within the cell culture growth protocol at which growth has been stopped. By recording the stage within the cell culture growth protocol, the system may facilitate resumption of the cell culture growth protocol. In some embodiments, the system may allow the cell culture growth protocol to continue up to a point within the protocol that facilitates stopping the cell culture growth protocol.

[0144] The stopping of the cell culture growth protocol can be performed for various goals. For example, delaying complete cell growth to better match a patient treatment plan may be desirable, particularly if the treatment plan may have changed. In another example, monitoring process information and production information may reveal defects or abnormalities in the performance of the automated cell engineering system. Thus, stopping the cell culture growth protocol may enable transferring the cell culture from one automated cell engineering system to another prior to resumption. In another example, stopping cell growth can enable troubleshooting potential problems within the automated cell engineering system.

[0145] In operation 1310, process 1300 includes resuming cell culture growth at a recorded stage within the cell culture growth protocol. Operation 1310 enables the automated cell engineering system, whether the original automated cell engineering system or a new automated cell engineering system, to resume the cell culture growth protocol at the same point at which growth was stopped. Resuming the cell culture growth protocol can include providing a new cell growth medium, changing the gas concentration or temperature to resume cell culture growth.

[0146] FIG. 14 shows a capacity utilization service according to an embodiment of the present invention. An automated cell engineering system 600 controlled by an automated process control system 102 and / or a central control process system 1002 separates the geographical location of the automated cell engineering system 600 from the location of the control substances and patients, as described herein. A network of automated cell engineering system centers or installations 111 having different levels of capacity can span a city or state or country. A hospital or treatment center desiring to utilize cell engineering system technology can access the occupancy system to determine which facilities have surplus capacity and thereby arrange for the use of the surplus physical capacity. A treatment center utilizing the surplus physical capacity can maintain process control or monitoring without physical co-location through the use of the central control process system 1002.

[0147] The capacity utilization service operates on the central control process system 1002, particularly via the capacity manager 2060. As shown in FIG. 14, the central control process system 1002 can be connected to a plurality of automatic process control systems 102A, 102B, 102C, 102D. Each automatic process control system 102 can be connected to a plurality of automatic cell engineering systems 600 (for example, automatic cell engineering system installation 111). The automatic process control system 102 stores utilization information indicating the current utilization status of each automatic cell engineering system 600 to which it is connected. The utilization information includes information about which automatic cell engineering system 600 is occupied, information about the cell culture growth protocol currently being executed in the occupied automatic cell engineering system 600, and information about programmed production instructions that may potentially occupy the automatic cell engineering system 600 in the future but have not yet started processing. The capacity manager 2060, as described above, receives the utilization information from each automatic process control system 102 and determines the available capacity of the entire system. FIG. 14 shows various levels of utilization in the automatic cell engineering system 600, ranging from full utilization (automatic cell engineering system 600A) to partial utilization (automatic cell engineering systems 600B, 600C, and 600D).

[0148] A user can access the capacity manager 2060, for example, via a client 1004 configured for interface with a central control process system 1002, or via a client 104 configured for interface with an automatic process control system 102. The user can provide information of the capacity manager 2060 about a desired production instruction, and the capacity manager 2060 can determine which of the one or more automatic cell engineering system installations located therein has surplus capacity. Next, the user can arrange to deliver one or more biological samples to the automatic cell engineering system installation selected for the production of cell cultures. Next, the user can use either the central control process system 1002 or the automatic process control system 102 accessed for monitoring cell culture growth. Via the central control process system 1002 or the automatic process control system 102, the user can access a local data retention system 190 associated with the automatic cell engineering system installation where the cell culture is being produced.

[0149] FIG. 15 is a flowchart showing a process 1500 that utilizes excess capacity within a network of an automated cell engineering system configured for the automated production of cell cultures. Aspects of process 1500 may be implemented in a computer system having one or more physical processors programmed with computer program instructions that, when executed by the one or more physical processors, cause the computer system to implement the method. Further aspects of process 1500 may be implemented by an automated cell engineering system such as automated cell engineering system 600 described herein. The one or more physical processors are hereinafter simply referred to as processors. In an embodiment, process 1500 is implemented via automated process control system 102 or central control process system 1002 described herein in conjunction with one or more automated cell engineering systems 600. Further details regarding each of the operations of the method may be understood in accordance with the description of automated process control system 102 and central control process system 1002 as described above. Each of the process steps described below may be implemented locally via automated process control system 102 and / or centrally by central control process system 1002. Any combination of steps may be implemented by automated process control system 102, an automated cell engineering system, and / or central control process system 1002.

[0150] In operation 1502, process 1500 includes receiving measurements of the excess capacity of the automated cell engineering system from a plurality of automated process control stations within a network. Capacity refers to the available space within an automated cell engineering system or an automated cell engineering system installation within a facility that can be used to produce cell cultures. In an embodiment, measurements of capacity are also received. Capacity refers to the ability to implement a given cell culture growth protocol in a particular facility associated with the automated cell engineering system. The capacity in a facility can be limited by the available supply and the available cell culture growth protocol. The measurement of excess capacity can be derived, as described above, from a combination of the current operating rate and the expected operating rate. The expected operating rate can be determined according to the currently executed cell culture growth protocol and future production instructions. The measurement of excess capacity can be calculated by a local automated process control system and communicated to a central control process system. In a further embodiment, the measurement of excess capacity can be calculated by the central control process system based on automated cell engineering system data received from an automated process control system. The measurement of excess capacity can be provided to any appropriate user, including a physician, clinician, patient, hospital administrator, etc. The measurement of excess capacity can be provided to such users in a variety of ways, such as via a mobile device (e.g., smartphone or tablet), or to a centralized system or clinical management site (e.g., hospital site or clinical hub), or to a database accessible by one or more of the users described herein later.

[0151] In operation 1504, process 1500 includes determining a capacity requirement according to the patient requirements for a cell culture. The capacity requirement can be determined, for example, according to production instructions. In an embodiment, a capacity requirement is also determined. Based on the patient's cell culture requirements, the system (e.g., an automated process control system or a central control process system) determines one or both of the need for capacity and the need for capacity to produce the required cell culture.

[0152] In operation 1506, process 1500 includes matching the selected automated cell engineering system with the capacity requirements according to the measured value of the surplus capacity. In an embodiment, the capacity requirements are also matched and determined. Matching the requirements includes determining which automated cell engineering system facilities have available capacity and capabilities that match what is needed to produce the patient cell culture. Matching the requirements may further include selecting one or more automated cell engineering systems in one or more facilities to perform the required cell culture production. These matching requirements may also be provided to a user (e.g., a hospital, a doctor, a clinic, etc.) in various ways, such as via a mobile device (e.g., a smartphone or a tablet), or to a centralized system or a clinical management site (e.g., a hospital site or a clinical hub), or to a database accessible by one or more of the users described herein later.

[0153] In operation 1508, process 1500 includes transferring a biological sample to the cell engineering system selected for the production of the cell culture. The transfer of the biological sample may include transfer to the selected facility that meets the determined capacity and capacity requirements. One or more biological samples may be transferred to the cell engineering system, and the cell culture growth protocol may be initiated to produce the required patient cell culture. In an embodiment, the user who requested the transfer of the biological sample is provided with authorized access to the automated process control system associated with the automated cell engineering system to which the biological sample was transferred. The user may be permitted access only to the records and functions associated with the transferred sample. Thus, the user may monitor and, if necessary, change the process parameters of the automated cell engineering system in which the required cell culture is produced internally.

[0154] As described above, an automated cell engineering system consistent with the embodiments described herein enables in-situ changes to a cell culture growth protocol through a combination of an automated process control system 102, a central control process system 1002, a client 104, and a client 1004. Authorized users may update, adjust, or otherwise change the cell culture growth protocol or the automated cell engineering system process parameters during cell production. Further, the systems provided herein may provide feedback regarding cell production, i.e., information about production information. Thus, the systems described herein increase the level of interaction between the user (e.g., a physician or other treatment professional) and the cell growth process. Thus, changes in patient requirements can be used to change and regulate cell growth, while cell growth information can be used to change and regulate the patient treatment plan, and these changes or adjustments are potentially reviewed by a quality assurance operator. FIGS. 16 and 17 illustrate examples of such interaction processes.

[0155] FIG. 16 is a flowchart showing a process 1600 for the automated production of a cell growth culture implemented in an automated cell engineering system. In process 1600, cell growth parameters are changed in consideration of the patient's needs and / or the physician's recommendations. Such changes may be implemented in consideration of changes in the patient's condition and / or prognosis. For example, if a patient unexpectedly becomes ill, it may be necessary to provide treatment earlier than locally expected. Thus, it may be necessary to change the cell culture growth protocol to promote faster cell growth.

[0156] Aspects of process 1600 can be implemented in a computer system having one or more physical processors programmed with computer program instructions that, when executed by the one or more physical processors, cause the computer system to implement the method. Further aspects of process 1600 can be implemented by an automated cell engineering system, such as automated cell engineering system 600 described herein. The one or more physical processors are hereinafter simply referred to as processors. In an embodiment, process 1600 is implemented via automated process control system 102 or central control process system 1002 described herein in conjunction with one or more automated cell engineering systems 600. Further details regarding each of the operations of the method can be understood in accordance with the descriptions of automated process control system 102 and central control process system 1002, as described above. Each of the process steps described below can be implemented locally via automated process control system 102, via an automated cell engineering system, and / or centrally by central control process system 1002. Any combination of steps can be implemented by automated process control system 102 and / or central control process system 1002.

[0157] In operation 1602, process 1600 includes initiating a cell culture growth protocol within an automated cell engineering system. The cell culture growth protocol can be initiated directly in the automated cell engineering system or via a control system, such as an automated process control system, and / or a central control process system. Initiation of the cell culture growth protocol can be performed in accordance with the methods and techniques discussed herein.

[0158] In operation 1604, process 1600 includes receiving updated cell culture delivery requirements from an authorized user. The updated cell culture delivery requirements can include updates to the delivery date, updates to the number of cells required, and / or updates to specific cell characteristics, such as the transformation characteristics of the cells (e.g., what genes the cells can carry), antibody expression characteristics, and the like.

[0159] In operation 1606, process 1600 includes adjusting one or more parameters of the cell culture growth protocol based on the updated cell culture delivery requirements. The parameters of the cell culture growth protocol, i.e., the process parameters, can be adjusted based on the updated cell culture delivery requirements to better meet the requirements. For example, if more cells or an earlier completion date is required, the process parameters can be adjusted to accelerate cell growth, such as an increase in supply conditions or cell culture characteristics, temperature, gas exchange, etc.

[0160] FIG. 17 is a flowchart showing a process 1700 for the automated production of a cell growth culture implemented in an automated cell engineering system. In process 1700, patient interactions, treatments, etc. can be driven by updates and reports from the automated cell engineering system on a schedule or otherwise. As the cell growth continues regardless of whether it is on schedule, reports regarding the timing of cell preparation from the cell engineering system can be used by a doctor or treatment specialist to adjust the patient's treatment to prepare the patient for treatment when the cell growth is complete.

[0161] Aspects of process 1700 may be implemented in a computer system having one or more physical processors programmed with computer program instructions that, when executed by the one or more physical processors, cause the computer system to implement the method. Further aspects of process 1700 may be implemented by an automated cell engineering system such as automated cell engineering system 600 described herein. The one or more physical processors are hereinafter simply referred to as processors. In embodiments, process 1700 is implemented via automated process control system 102, automated cell engineering system, or central control process system 1002 described herein in conjunction with one or more automated cell engineering systems 600. Further details regarding each of the operations of the method may be understood in accordance with the description of automated process control system 102 and central control process system 1002 as described above. Each of the process steps described below may be implemented locally via automated process control system 102, automated cell engineering system, and / or centrally by central control process system 1002. Any combination of steps may be implemented by automated process control system 102 and / or central control process system 1002.

[0162] In operation 1722, process 1700 includes initiating a cell culture growth protocol within an automated cell engineering system. The cell culture growth protocol may be initiated directly in the automated cell engineering system or via a control system such as an automated process control system and / or central control process system. Initiation of the cell culture growth protocol may be performed in accordance with the methods and techniques discussed herein.

[0163] In operation 1724, process 1700 includes monitoring process information and / or production information of cell culture growth. As described herein, the process information may include at least one of temperature information, pH information, glucose concentration information, oxygen concentration information, optical density information, component or patient identification information, and any other collected process information. In an embodiment, production information may also be monitored. Monitoring of this information may provide comprehensive information regarding the progress of the cell culture growth protocol. The process information and / or production information may be monitored via a control system, such as an automated process control system.

[0164] In operation 1726, process 1700 includes planning a cell culture delivery date according to the monitoring. The cell culture delivery date refers to the date and time when production has progressed to a point suitable for desired use, such as for administration to a patient. An automated process control system or a central control process system may plan for cell culture delivery based on one or more of the process information, production information, and cell culture growth protocol when production of the required number of cells is completed. An initial prediction of the cell culture delivery date may be based on the cell culture growth protocol. This prediction may be updated based on the process information, for example, when process variables differ from the cell culture growth protocol specifications in a way that accelerates or decelerates cell culture growth. This prediction may also be updated based on the production information, for example, when cell culture growth is faster or slower than originally planned.

[0165] In operation 1728, process 1700 includes notifying authorized users prior to the cell culture delivery date. The notification can be provided via email, text message, and / or messaging within a computing environment provided by an automated process control system and / or a central control process system. The notification can be provided more than one day prior to the expected cell culture delivery date. A physician can use this information to schedule and organize the patient's treatment schedule. Authorized users can include, for example, physicians, patients, clinicians, administrative staff, and any other staff involved in cell culture production and patient treatment. The notification can also be provided to a central hospital or clinical hub that can monitor the process.

[0166] In some aspects, and as described, the automated cell engineering system 600 can include a user interface 1130 that can include a component identification sensor such as a barcode reader, a QR code reader, a radio frequency ID interrogator, or other component identification sensors. In some aspects, the cassette 602 can include a first identification component such as a barcode, and the user interface 1130 can include a reader configured to identify the first identification component. In some aspects, the automated cell engineering system 600 user interface can initiate a handshake interrogation between the cassette 602 and the user interface 1130, whereby the automated cell engineering system 600 can verify that the cassette used is an authorized component, is the appropriate cassette for the protocol selected to be executed on the automated cell engineering system 600, or is otherwise properly paired with the automated cell engineering system 600. The handshake interaction between the automated cell engineering system 600 and the cassette 602 can be monitored, reconsidered, recorded, and checked in other ways by the automated process control system 102 and / or the central control process system 1002.

[0167] In some embodiments, this procedure can enable appropriate device authentication as may be required by applicable laws such as Title 21, Code of Federal Regulations, Part 11. Further, for example, in a facility equipped with multiple automated cell engineering systems 600 operating simultaneously, the automated cell engineering systems 600 can be configured to store component and protocol identifications locally on the automated cell engineering systems 600 or remotely in a database accessible via the aforementioned information path.

[0168] It will be readily apparent to those of ordinary skill in the relevant art that other suitable modifications and adaptations to the methods and uses described herein can be made without departing from the scope of any of the embodiments.

[0169] Although certain embodiments have been illustrated and described herein, it is to be understood that the claims are not limited to the specific forms or arrangements of components described and shown. Although exemplary embodiments are disclosed herein and specific terms are used, they are used for descriptive purposes only and not for purposes of limitation, and are used only in a general and descriptive sense. Modifications and variations of the embodiments are possible in light of the above teachings. Accordingly, it is to be understood that the embodiments can be practiced in ways other than as specifically described.

[0170] More specific embodiments include the following.

[0171] Embodiment 1 is a method of controlling an automated cell engineering system configured to produce a cell culture, the method comprising establishing, by an automated process control system, a network connection with the automated cell engineering system, and receiving, via the network connection, from the automated cell engineering system, process information including one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, component or patient identification information, and optical density information, and providing a control signal to cause the automated cell engineering system to adjust one or more process parameters of the automated cell engineering based on the received process information.

[0172] Embodiment 2 is the method according to Embodiment 1, further comprising providing a plurality of further control signals to a plurality of further cell engineering systems via a plurality of further network connections.

[0173] Embodiment 3 is the method according to Embodiment 1 or 2, wherein the cell culture is a genetically modified cell culture.

[0174] Embodiment 4 is the method according to Embodiments 1 to 3, wherein the cell culture is a genetically modified immune cell culture.

[0175] Embodiment 5 is the method according to Embodiments 1 to 4, wherein the provision of the control signal is performed without user intervention.

[0176] Embodiment 6 is the method according to Embodiments 1 to 5, wherein the provision of the control signal is performed based on user authorization.

[0177] Embodiment 7 is the method according to Embodiments 1 to 6, further comprising receiving production information including cell production information recorded over time, and further comprising sorting the production information in a local database.

[0178] Embodiment 8 is the method according to Embodiments 1 to 7, further comprising monitoring a handshake interrogation procedure performed by the automated cell engineering system in response to the introduction of the cassette via the automated process control system.

[0179] Embodiment 9 is the method according to Embodiments 1 to 8, wherein the control signal is generated in the automated cell engineering system via an operator interaction in the automated cell engineering system.

[0180] Embodiment 10 is a method for controlling a plurality of automatic process control systems via a central control system, the method comprising establishing a network connection with a plurality of computer systems corresponding to the plurality of automatic process control systems configured to control a plurality of automatic cell engineering systems each configured for the production of cell culture, accessing, by the central control system, a control information history of a first computer system from the plurality of computer systems, and providing to the first computer system at least one of a cell culture growth protocol update and a cell engineering software update.

[0181] Embodiment 11 is the method according to embodiment 10, further comprising providing the cell engineering software update to the plurality of computer systems.

[0182] Embodiment 12 is the method according to embodiment 10 or 11, further comprising analyzing the control information history and modifying access of a local user to the first computer system based on the analysis of the control information history.

[0183] Embodiment 13 is the method according to embodiments 10 to 12, further comprising analyzing the control information history to determine local user compliance with best practices or ethical guidelines.

[0184] Embodiment 14 is a method for the automatic production of a cell culture by an automatic cell engineering system, the method comprising starting a cell culture growth protocol within the automatic cell engineering system, monitoring process information of the cell culture growth protocol, adjusting one or more parameters of the cell culture growth protocol based on the monitoring, stopping the cell culture growth protocol, recording a stage within the cell culture growth protocol at which the stopping occurred, and resuming the cell culture growth protocol at the stage within the cell culture growth protocol.

[0185] Embodiment 15 is the method according to Embodiment 13, further comprising moving a cell culture from a first cell engineering system to a second cell engineering system after the stop and before the restart.

[0186] Embodiment 16 is a method of utilizing excess capacity within a network of automated cell engineering systems configured for the automated production of cell cultures, the method comprising receiving a measurement of the excess capacity of the automated cell engineering system from a plurality of automated process control systems within the network, determining a capacity requirement according to patient requirements for the cell culture, matching the capacity requirement with an automated cell engineering system selected according to the measurement of the excess capacity, and transferring a biological sample to the selected cell engineering system for the production of the cell culture.

[0187] Embodiment 17 is a method for the automated production of cell cultures implemented by an automated cell engineering system, the method comprising initiating a cell culture growth protocol within the automated cell engineering system, receiving updated cell culture delivery requirements from an authorized user, and adjusting one or more parameters of the cell culture growth protocol based on the updated cell culture delivery requirements.

[0188] Embodiment 18 is a method for the automated production of cell cultures implemented by an automated cell engineering system, the method comprising initiating a cell culture growth protocol within the automated cell engineering system, monitoring one or more parameters of the cell culture growth protocol, predicting a cell culture delivery date according to the monitoring, and warning an authorized user prior to the cell culture delivery date.

[0189] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

Claims

**Claim 1** A method of controlling an installation of an automated cell engineering system configured to produce cell cultures by an automated process control system including at least one processor, the method comprising: establishing, by the automated process control system, a plurality of network connections with respective ones of a plurality of automated cell engineering systems of the installation of the automated cell engineering system and initiating a cell engineering process in accordance with a cell culture growth protocol of the plurality of automated cell engineering systems; receiving, in the automated process control system via the plurality of network connections, process information including one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, component identification information, and optical density information from the plurality of automated cell engineering systems; providing a plurality of control signals to the plurality of automated cell engineering systems to adjust one or more process parameters of the plurality of automated cell engineering systems in accordance with the cell culture growth protocol based on the process information; establishing a network connection with a central control system; providing the central control system with access to a control information history of the automated process control system; receiving, during execution of the cell engineering process, a cell culture growth protocol update from the central control system; and providing updated ones of the plurality of control signals to the plurality of automated cell engineering systems to adjust one or more process parameters of the plurality of automated cell engineering systems in accordance with the cell culture growth protocol update during execution of the cell engineering process. A method as described above. **Claim 2** The method according to claim 1, wherein the cell culture is a genetically modified cell culture. **Claim 3** The method according to claim 1, wherein the cell culture is a genetically modified immune cell culture. **Claim 4** The method according to claim 1, wherein the providing of the plurality of control signals is performed without user intervention. **Claim 5** The method according to claim 1, wherein the providing of the plurality of control signals is performed based on user authorization. **Claim 6** The method according to claim 1, further comprising receiving production information including cell production information recorded over time from the plurality of automated cell engineering systems, and further comprising sorting the production information in a database. The method according to claim 1. **Claim 7** Monitoring, via the automatic process control system, a handshake interrogation procedure performed by the automatic cell engineering system in response to the introduction of a cassette. The method according to claim 1, further comprising this.

8. Receiving a cell engineering software update from the central control system. The method according to claim 1, including this.

9. Providing a cell engineering software update to a plurality of computer systems. The method according to claim 1, further comprising this.

10. Analyzing the control information history, and Modifying access by a local user to the automatic process control system based on the analysis of the control information history. The method according to claim 1, further comprising this.

11. Analyzing the control information history to determine local user compliance with best practices or ethical guidelines. The method according to claim 1, further comprising this.

12. A method of controlling the installation of an automatic cell engineering system configured to produce a cell culture by an automatic process control system including at least one processor, Establishing, by the automatic process control system, a plurality of network connections with each of the plurality of automatic cell engineering systems. Receiving, in the automatic process control system via the plurality of network connections, process information including one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, component identification information, and optical density information from the plurality of automatic cell engineering systems. Providing a plurality of control signals to the plurality of automatic cell engineering systems to adjust one or more process parameters of the plurality of automatic cell engineering systems based on the process information. Providing a control signal to stop a cell culture growth protocol in one of the plurality of automatic cell engineering systems. Recording the stage within the cell culture growth protocol where the stop occurred, and Providing a control signal to resume the cell culture growth protocol at the stage within the cell culture growth protocol. A method including this.

13. Moving a cell culture from the automatic cell engineering system to a second automatic cell engineering system after the stop and before the resumption. The method according to claim 12, further comprising this. A method for controlling an installation of an automated cell engineering system configured to produce cell cultures by an automated process control system including at least one processor, comprising: establishing, by the automated process control system, a plurality of network connections with respective ones of the plurality of automated cell engineering systems; receiving, in the automated process control system via the plurality of network connections, process information including one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, component identification information, and optical density information from the plurality of automated cell engineering systems; providing a plurality of control signals to the plurality of automated cell engineering systems to adjust one or more process parameters of the plurality of automated cell engineering systems based on the process information; providing a measurement of the excess capacity of the plurality of automated cell engineering systems to a central control system; and receiving a biological sample transferred for the production of cell cultures based on a matching of the volume requirements according to the patient requirements for cell culture and the measurement of the excess capacity; A method comprising the above steps. A method for controlling an installation of an automated cell engineering system configured to produce cell cultures by an automated process control system including at least one processor, comprising: establishing, by the automated process control system, a plurality of network connections with respective ones of the plurality of automated cell engineering systems; receiving, in the automated process control system via the plurality of network connections, process information including one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, component identification information, and optical density information from the plurality of automated cell engineering systems; providing a plurality of control signals to the plurality of automated cell engineering systems to adjust one or more process parameters of the plurality of automated cell engineering systems based on the process information; receiving, from an authorized user, updated cell culture delivery requirements associated with one of the plurality of automated cell engineering systems; and adjusting one or more parameters of the cell culture growth protocol of the one automated cell engineering system based on the updated cell culture delivery requirements; A method comprising the above steps. A method for controlling an installation of an automated cell engineering system configured to produce cell cultures by an automated process control system including at least one processor, comprising: establishing, by the automated process control system, a plurality of network connections with respective ones of a plurality of the automated cell engineering systems; receiving, in the automated process control system via the plurality of network connections, process information including one or more of temperature information, pH information, glucose concentration information, oxygen concentration information, component identification information, and optical density information from the plurality of automated cell engineering systems; providing a plurality of control signals to the plurality of automated cell engineering systems to adjust one or more process parameters of the plurality of automated cell engineering systems based on the process information; monitoring one or more parameters of a cell culture growth protocol associated with one of the plurality of automated cell engineering systems; predicting a cell culture delivery date according to the monitoring; and warning an authorized user prior to the cell culture delivery date. A method comprising the above steps.

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