Digital control unit for a bioprocess device

Abstract

The invention relates to a digital control unit for a bioprocess device (2) for controlling a bioprocess, wherein the digital control unit (1) comprises a local data storage (4) and a local processor unit (5), wherein the digital control unit (1) comprises a bioprocess interface (6) for sending and receiving bioprocess control data, wherein the digital control unit (1) is configured to execute a bioprocess control routine (19) via the local processor unit (5) to control the bioprocess, wherein in the bioprocess control routine (19) the digital control unit (1) generates bioprocess data (16) depending on actuator data (8) and / or sensor data (12) and / or user control command data (18). It is proposed that the digital control unit (1) is configured to execute a signing routine (24) via the local processor unit (5) and in the signing routine (24) the digital control unit (1) digitally signs documentation data (23) derived from the bioprocess data 16 by generating a digital signature (26).

Description

Technical Field

[0001] The present invention relates to a digital control unit for a biological process apparatus for controlling a biological process according to a general part of claim 1, a biological process apparatus having such a digital control unit according to claim 17, a method for operating such a digital control unit according to claim 18, use of such a digital control unit according to claim 19, a data processing system according to claim 20, a computer program product according to claim 21, and a computer-readable storage medium according to claim 22. Background Technology

[0002] The term "bioprocess" currently refers to biotechnology and biopharmaceutical processes that involve the manufacture of desired therapeutic biological products (such as biologics, vaccines, components for cell or gene therapy) or non-therapeutic biological products (such as pigments, biofuels, or nutritional supplements). Such biological products can be manufactured from living cells, or the cells themselves can be biological products, or the biological product can be the result of cell-free manufacturing based on cellular components of natural or non-natural origin.

[0003] "Bioprocess apparatus" includes at least one device or a combination of two or more devices involved in a bioprocess, such as a bioreactor, digital control unit (DCU), filtration equipment, chromatographic equipment, centrifuge, freeze dryer and analytical equipment, which may be single-use or reusable equipment.

[0004] To at least partially automate biological processes, the digital control unit in question comes into play. An example of such a digital control unit, which serves as the starting point of this invention, is shown in DE10237082A1. Known digital control units include all the electronic components for controlling biological processes, receiving sensor data, and communicating with the user via a user interface. This allows for the execution of biological process control routines, wherein biological process data is generated to document the real-life execution of the desired biological process.

[0005] The aforementioned bioprocess data is particularly important, for example, if a new drug product undergoes compliance procedures before entering the market. Such compliance procedures typically require proof that the corresponding processes in the bioprocess laboratory conform to predefined rules. This is especially important during clinical trials, due to the quality control standards and administrative measures required by the relevant national drug regulatory agency, such as the FDA, for the approval process of new drugs. However, this involves not only the experimental phase, where documentation of process steps and sensor data is primarily relevant, but also the manufacturing phase, where documentation of process quality plays a crucial role according to GMP standards. GMP, or Good Manufacturing Practice, is the standard required to comply with guidelines recommended by agencies such as the FDA, which control the authorization and licensing of the manufacture and sale of pharmaceuticals. These guidelines define minimum manufacturing requirements that must be met to ensure that the corresponding product is of high quality for its intended use. Compliance with GMP standards is overseen globally by regulatory agencies.

[0006] In any of the above situations, the integrity of biological process data is essential. This means that it must be ensured that the biological process data has not been manipulated, whether arbitrarily or unintentionally.

[0007] To ensure the integrity of biological process data, it has been proposed to submit the data in an online calendar and externally sign the data using commonly known signing methods (US 8,719,576B2). This known concept leaves room for manipulation of biological process data within a biological process laboratory. Summary of the Invention

[0008] The object of the present invention is to provide an apparatus for improving the integrity of data related to biological process data, which has been generated in the biological process, with low effort.

[0009] By utilizing the features of the feature portion of claim 1, the aforementioned problem is solved for a digital control unit having the features of the general portion of claim 1.

[0010] First, it has been found that the integrity of biological process data can be positively affected by components present in virtually any biological process apparatus used to control the biological process. According to the invention, this component is the digital control unit of the biological process apparatus, which is a central electronic component for controlling the biological process. The expression "control" currently includes any action that helps to influence the corresponding target (here, the biological process) in a reproducible manner, which typically includes sending data to the target and retrieving and storing data from the target.

[0011] The digital control unit includes a local data storage device and a local processor unit, and it is currently considered to be a core component for digital data processing.

[0012] The digital control unit also includes a bioprocess interface for sending and receiving bioprocess control data. This bioprocess interface includes an actuator interface for sending actuator data to at least one actuator to influence the bioprocess and a sensor interface for receiving sensor data related to the bioprocess from at least one sensor. For example, a stirrer or valve can be such an actuator, and the associated corresponding actuator data can be a stirring frequency in revolutions per minute (rpm) or a fluid flow rate in milliliters per minute (mL / min). Exemplary sensors can be biomass sensors, pH sensors, or oxygen sensors reflecting the corresponding data.

[0013] The digital control unit also generates biological process data, which describes the biological processes, as will be explained. This biological process data forms the basis for the documentation required for the aforementioned compliance processes.

[0014] In addition, the digital control unit includes a user interface for displaying at least a portion of the bioprocess data to the user and for receiving user control command data. The user interface provides the user with the possibility of influencing the bioprocess during both the experimental development and manufacturing phases. Common exemplary parameters set by the user include stirring speed, temperature, pH, and oxygen saturation.

[0015] Finally, the digital control unit is configured to execute bioprocess control routines via a local processor unit to control the bioprocess. Here, automation occurs, if necessary. In the bioprocess control routine, the digital control unit receives sensor data from sensors. Additionally, in the bioprocess control routine, the digital control unit generates actuator data based on user control command data and / or sensor data, and influences the bioprocess by controlling the actuators by sending the actuator data to them. This control can derive the actuator data based on simple logical operations between user control command data and / or sensor data. It can also be based on a control loop that derives the actuator data to achieve a target value. Finally, it can be based on sequence control, which is typically implemented by software as described below. Therefore, the digital control unit can, on the one hand, provide coordination for the entire bioprocess, and on the other hand, it can simply be an execution tool executing requests from at least one other control unit.

[0016] In the bioprocess control routine, the digital control unit also generates bioprocess data from actuator data and / or sensor data and / or user control command data.

[0017] The underlying concept of this invention is to execute a complete signature routine within a digital control unit, including generating digital signatures for biological process data, in order to improve data integrity associated with such biological process data. This means that the digital control unit is configured as a trusted device for generating the aforementioned digital signatures.

[0018] In detail, the private key data is stored in a local data storage device, which forms the basis for executing the data security routine. The digital control unit is configured to execute this data security routine via a local processor unit, which is also configured to execute the bioprocess control routine described above.

[0019] The digital control unit is also configured to execute a documentation routine within a data security routine via the aforementioned processor unit. In the documentation routine, the digital control unit generates documentation data from biological process data, which is then signed, as will be explained below.

[0020] Therefore, the digital control unit is configured to execute a signing routine via the aforementioned local processor unit within a data security routine. In this signing routine, the digital control unit extracts a cryptographic private key from the private key data and digitally signs the document compilation data using the cryptographic private key by generating a digital signature. In short, the digital signing of the document compilation data is performed based on asymmetric cryptography, which is itself known in the prior art, in a signing routine executed entirely within the local processor unit.

[0021] If the private key data includes a cryptographic key or is even the same as the cryptographic private key, then extracting the cryptographic private key from the private key data, as mentioned above, is particularly simple. However, extraction can be more complex. For example, the cryptographic private key can be derived from the private key data based on unpredictable random numbers.

[0022] It is worth noting that, according to the present invention, not only the signing routine, but also the document compilation routine in which the document compilation data to be signed is executed entirely in the local processor unit.

[0023] Because the security routines can be designed to generate digital signatures with very little data processing, the proposed solution can be implemented using a wide variety of existing digital control units without adding any additional hardware. This not only offers a cost advantage but also facilitates the introduction of the proposed solution into existing laboratories.

[0024] Since the digital control unit under discussion is an electronic control component that is closest to the sensors and actuators of the biological process device, it has virtually no opportunity to manipulate the relevant biological process data. Furthermore, the proposed solution does not require complex concepts such as distributed ledger technology (DLT), which necessitates consensus algorithms such as proof-of-work or proof-of-stake.

[0025] According to claims 2 and 3, in the documentation routine, biological process data is divided into data blocks, which are then processed in a hashing step. According to a preferred embodiment, the data blocks are hashed in a tree structure, such as a Merkle tree. The signatures of these documentation data may include the complete hash tree structure or may only include the hash root, in either case requiring minimal data processing, as described above.

[0026] Claims 4 to 9 relate to preferred variations of the data flow relating to biological process data. To prevent manipulation of the biological process data, a documentation routine is executed during the control of the biological process in the biological process control routine, and preferably a signature routine is also executed. This is particularly advantageous with respect to the signature routine, because after the signature routine is executed, unnoticed modifications to the biological process data are impossible.

[0027] Claims 6 to 8 relate to more than one signature routine executed within a biological process. Preferably, subsequent biological process datasets assigned to subsequent signature routines are linked to each other in one or another manner to ensure no data is missed between two subsequent biological process datasets. In any case, as preferred in claim 9, the digital control unit adds a timestamp to the documentation data within the signature routine. Here, the time information in the digital control unit provides the necessary reference.

[0028] To further reduce the chance of manipulating biological process data, according to claim 10, sensor data and / or user control command data can be protected from external manipulation after being received by the digital control unit. For this purpose, it is preferably assumed that this data can remain unmodified via the user interface and also via any other interface.

[0029] Various preferred embodiments exist for generating biological process data. In addition to simply arranging the corresponding sensor data, actuator data, and user control command data sequentially, link information regarding the logical relationships between at least a portion of these data can be generated, and biological process data can be generated based on this link information. This link information can be, for example, a logical relationship between control actuators and expected changes in sensor data (claims 11 and 12).

[0030] Claims 13 to 15 relate to a preferred structural arrangement of the digital control unit. Here, it is evident that the digital control unit in question provides a process-oriented control architecture, such as a control loop (claim 13), and even the hardware of the digital control unit is directly linked to the biological process (claim 14). The intermediate link between the digital control unit and the sensors and / or actuators is defined by a preferred direct data connection between the biological process interface and the sensors and / or actuators (claim 15). The expression "direct" means that no data processing occurs between the sensors and / or actuators and the biological process interface.

[0031] The digital signature generated based on document compilation data can be stored in the local data storage device of the digital control unit. It can also be stored in any other data storage device connected to the digital control unit via a data transmission interface. Both possibilities are defined by claim 16 to clarify that, after the signature routine is executed, unnoticed manipulation of the biological process data as described above is impossible, rendering the storage location of the digital signature ineffective.

[0032] According to another teaching of claim 17, the entire biological process apparatus having the proposed digital control unit is thus claimed.

[0033] The proposed bioprocess apparatus preferably includes a bioreactor and all components and / or equipment for performing the corresponding upstream and downstream treatment stages.

[0034] The upstream processing stage of a bioprocess typically comprises all actions and workflows from the development, optimization, screening, and selection of strains or cell lines to their culture and the manufacture of the desired bioproduct from cells or cell components. This culture can be conducted at various scales (microliters to thousands of liters) using different reactor settings and geometries (rocking motion, stirred tanks, bubble cap towers, fixed beds, etc.) by applying different operating modes (batch, batch feed, continuous, especially perfusion, or combinations thereof). The culture is typically monitored, analyzed, and controlled based on various sensor technologies (soft, electrochemical, biochemical, optical, etc.; offline, online, atline). Typically, after the manufacture of the desired bioproduct, it is purified. Here, the culture medium is separated from the desired bioproduct (e.g., monoclonal antibodies, polyketides, enzymes, vaccines).

[0035] Downstream processing stages of biological processes typically encompass a variety of techniques and methods for the recovery, purification, analysis, and characterization of the desired biological product. These involve methods such as cell disruption, sedimentation, centrifugation, precipitation, crystallization, extraction, filtration, pH and conductivity adjustment of the liquid, enzymatic or chemical modification, dilution, buffer exchange, evaporation, adsorption, and chromatography. Analytical and characterization steps may be included to ensure the purified biological product meets critical quality attributes (e.g., antibody glycosylation patterns, endotoxin concentrations). Final formulation steps involving buffer exchange, drying, freeze-drying, or crystallization may be performed to bring the purified biological product to a state suitable for storage and distribution before filling and packaging.

[0036] Another preferred variation includes means for performing the upstream process, which is continuously connected to the downstream means.

[0037] All explanations given regarding the proposed digital control unit, the method of operating such a digital control unit, the purpose of such a digital control unit, the data processing system, the computer program product, and the computer-readable storage medium are fully applicable to the biological process device.

[0038] Another teaching of claim 18, which is equally important, relates to a method for operating the proposed digital control unit.

[0039] The proposed method represents the working principle of the proposed digital control unit, allowing for further reference to all explanations given regarding the proposed digital control unit.

[0040] As is equally important as another teaching of claim 19, it relates to the use of the proposed digital control unit for digitally signing document compilation data using a cryptographic private key. Again, all interpretations given regarding the proposed digital control unit are fully applicable.

[0041] Another teaching of claim 20 relates to a data processing system for implementing the proposed method, and in particular for implementing the corresponding routines. Preferably, the data processing system includes at least a local data storage device and a local processor unit for the digital control unit. All explanations given regarding the proposed digital control unit again fully apply to the proposed data processing system.

[0042] Another teaching of claim 21, of equal importance, also claims protection for a computer program product used in the proposed data processing system. The computer program product is configured to implement the proposed method, specifically, to implement the above-described routines. Again, all interpretations given regarding the proposed method fully apply to the proposed computer program product.

[0043] Another teaching of claim 22, which is equally important, claims protection for a computer-readable storage medium on which a computer program is stored. Again, all interpretations given for the proposed method are fully applicable to the proposed readable storage medium. Attached Figure Description

[0044] Embodiments of the present invention will now be explained with reference to the accompanying drawings. The drawings show:

[0045] Figure 1 It is the proposed digital control unit of the proposed biological process device.

[0046] Figure 2 according to Figure 1 The operating principle of the digital control unit, including biological process control routines and data security routines, and

[0047] Figure 3 It is a hash tree structure a) such as in according to Figure 2 The data security routines generated in b) and the corresponding hash tree structure based on manipulated biological process data. Detailed Implementation

[0048] The proposed bioprocess device 2 has a digital control unit 1 for controlling bioprocesses, such as the culture of microorganisms or mammalian cells using a bioreactor 3 and components (not shown) for corresponding upstream and downstream treatments.

[0049] like Figure 1 As shown, the digital control unit 1 includes a local data storage device 4 and a local processor unit 5 for data processing. Units 4 and 5, namely the local data storage device 4 and the local processor unit 5, are implemented as electronic components. It can be noted that the local processor unit 5 preferably includes only one data processor that performs all the functions of the digital control unit 1; however, it can be assumed that the local processor unit 5 includes more than one data processor that interacts with each other to perform all the functions of the digital control unit 1.

[0050] Similarly, Figure 1As shown, the digital control unit 1 includes a bioprocess interface 6 for sending and receiving bioprocess control data. Specifically, the bioprocess interface 6 includes an actuator interface 7 for sending actuator data 8 to at least one actuator 9, 10 to influence the bioprocess. Actuators 9, 10 should be understood as any component that can be controlled to be actuated to influence the bioprocess. In this document and preferably, actuator 9 is a stirrer including an impeller 9a within the bioreactor 3, while actuator 10 is preferably a valve for introducing fluid, preferably nutrient solution, into the bioreactor 3. Other possible actuators are pumps, liquid handling units, heating and / or cooling systems, etc. It can be noted that the bioprocess device 2 may include any number of actuators 9, 10, all of which can be controlled by actuator data 8. Furthermore, the bioprocess device is not limited to upstream equipment.

[0051] The bioprocess interface 6 also includes a sensor interface 11 for receiving sensor data 12 related to the bioprocess from at least one sensor 13, 14, 15. Such sensors 13, 14, 15 can be any sensor related to describing the bioprocess, such as a biomass sensor, pH sensor, or oxygen sensor. The functionality of these sensors can be well provided by soft sensors, also known as “virtual sensors.” Soft sensors derive sensor values ​​from other sensing sources based on a data model. Depending on the application, there are various possibilities for implementing the necessary data processing hardware assigned to the respective soft sensors.

[0052] Sensors 13, 14, and 15, as described above, may have their own sensor interface 11, which allows them to connect to the bioprocess interface 6, preferably their sensor interface 11, for transmitting sensor data 12. Depending on their operating principle, sensors 13, 14, and 15 may be connected to the sensor interface 11 of the bioprocess interface 6, for example, via electrical, optical, pneumatic, or hydraulic connections. Figure 1 In the preferred embodiment shown, and by way of example only, electrical connections are illustrated. Again, the bioprocess device 2 may include any number of sensors 13, 14, 15, all of which provide sensor data 12 to the digital control unit 1.

[0053] The digital control unit 1 generates biological process data 16, which describes the biological process and will be described below. The biological process data 16 is added to [the system / system] immediately after its generation. Figure 2 The continuous data stream S shown.

[0054] The digital control unit 1 also includes a user interface 17 for displaying at least a portion of the biological process data 16 to the user and for receiving user control command data 18. This user control command data 18 may be commands to start and stop the biological process and / or to set certain control parameters (such as the stirring speed of the impeller 9a assigned to the actuator 9).

[0055] Furthermore, the digital control unit 1 is configured to execute the biological process control routine 19 via the local processor unit 5 to control the biological process. This also... Figure 2 As shown in the diagram. In the bioprocess control routine 19, the digital control unit 1 receives sensor data 12 from corresponding sensors 13, 14, and 15. In the bioprocess control routine 19, the digital control unit 1 also generates actuator data 8 based on user control command data 18 and / or sensor data 12, and controls actuators 9 and 10 by sending actuator data 8 to actuators 9 and 10, thereby influencing the bioprocess. In the bioprocess control routine 19, the digital control unit 1 generates bioprocess data 16 based on actuator data 8 and / or sensor data 12 and / or user control command data 18.

[0056] The biological process control routine 19 is preferably based on control software running on the local processor unit 5, which can be configured as a sequence program that may include rules for controlling actuators 9, 10, control loops, etc.

[0057] As described above, according to the present invention, data integrity regarding biological process data 16 is ensured by applying asymmetric cryptography within the digital control unit 1, wherein the digital control unit 1 is a trusted device. To this end, firstly, private key data 20 is stored in the local data storage device 4. Secondly, the digital control unit 1 is configured to execute a data security routine 21 via a local processor unit 5. The data security routine 21 relies on security software, which also runs on the local processor unit 5.

[0058] The security routine 21 includes a documentation routine 22. Specifically, the digital control unit 1 is configured to execute the documentation routine 22 via the local processor unit 5 within the data security routine 21. In this documentation routine 22, the digital control unit 1 generates documentation data 23 from the biological process data 16, which is digitally signed.

[0059] The key point of the invention is that the data security routine 21 includes a signature routine 24. Therefore, the digital control unit 1 is configured to execute the signature routine 24 via the local processor unit 5 within the data security routine 21, and in the signature routine 24, the digital control unit 1 extracts a cryptographic private key 25 from the private key data 20 and digitally signs the document compilation data 23 with the cryptographic private key 25 by generating a digital signature 26.

[0060] like Figure 2 As shown, document compilation routine 22 includes dividing biological process data into 16 data blocks d. i Steps and hash data blocks d i To generate data block di hash h i The steps, whereby, according to data block d i hash h i Generate document compilation data 23. Preferably, the document compilation routine 22 includes hashing data blocks d in the form of a tree structure using a standard hash function. i hash h i The steps. Figure 3 a) shows the resulting hash tree H. Here, and preferably, the tree structure is a Merkle tree structure.

[0061] A particularly preferred option is data block d. i The hash is structured into a root hash h0, from which document compilation data 23 is generated. In a particularly simple variant, the document compilation data 23 is identical to the root hash h0.

[0062] A key advantage of the above hashing is the following fact: data block d i Any and all modifications will result in corresponding modifications to the hash root h0, making the hashed data block d... i Any modifications can be easily detected. Another advantage is the fact that simply introducing the hash root h0 into the document compilation data 23 results in simple data processing with low data processing requirements.

[0063] Various algorithms can be applied to the hashes described above. Preferably, hash algorithms "SHA-1", "SHA-2", and "BLAKE2" can be used. For the signatures described above, preferably, elliptic curve digital signature algorithms, particularly the signature algorithm "ECDSA", can be used.

[0064] In order to minimize the chance of manipulating the biological process data 16, during the control of the biological process in the biological process control routine 19, the digital control unit 1 executes the documentation routine 22, and here and preferably also the signature routine 24.

[0065] Especially during long-term biological processes that may last for days or even weeks, it is preferable to execute the signature routine 24 more than once during a single biological process. Herein and preferably, during at least a portion of a single biological process, the digital control unit 1 continuously receives sensor data 12 from sensors 13, 14, 15 in the biological process control routine 19, and continuously sends actuator data 8 to actuators 9, 10, thereby influencing the biological process. The term "continuously" generally means herein that the receiving of sensor data 12 and the sending of actuator data 8 are ongoing and systematic, preferably periodically repeated.

[0066] The biological process data is divided into 16 data blocks d. i Steps and / or hash data blocks d i The steps are preferably initiated at the start of the biological process. Here, the signature routine 24 is executed for the first time and at least once more during a single biological process, wherein subsequent signature routines 24 based on subsequent biological process data steps are executed after previous signature routines 24 based on previous biological process datasets. Here, and preferably, the corresponding previous biological process datasets and the corresponding subsequent biological process datasets overlap each other, thereby ensuring that all data of the biological process data 16 is included in the signature routine 24.

[0067] To ensure that the document compilation data 23 correctly represents the sequence of biological process data, it can also be assumed that the digital control unit 1 adds the identifier of the corresponding previous biological process dataset to the corresponding subsequent biological process dataset.

[0068] For the same reason, it can also be assumed that in signature routine 24, digital control unit 1 adds a timestamp to document compilation data 23. This timestamp is correspondingly related to the time of execution of signature routine 24. Alternatively or supplementally, biological process data 16 may also include a timestamp defining each biological process data item it creates.

[0069] To further prevent manipulation of the biological process data 16, it is also preferable to protect the sensor data 12 and / or user control command data 18 from external manipulation after they are received by the digital control unit 1. This can be accomplished through control measures or mechanical measures. Control measures may be, for example, specific designs of control software and / or security software that make it impossible to access the relevant data via the user interface 17. In this sense, mechanical measures involve designing the digital control unit 1 in a mechanically robust manner.

[0070] In the bioprocess control routine 19, as described above, the digital control unit 1 generates bioprocess data 16 based on sensor data 12 and / or actuator data 8 and / or user control command data 18. According to the easiest method, this data is arranged sequentially based on specific rules that define which data will be assigned to documentation data 23. Preferably, each data item in the bioprocess data 16 includes at least the aforementioned individual timestamp, data item name, and data item value.

[0071] Typically, it is preferred that the generation of biological process data 16 is continuous, preferably periodic, relative to time periods or data volume. Additionally, during document compilation routine 22, the biological process data 16 is divided into data blocks d. i The steps are preferably performed sequentially. Furthermore, it is preferable to continuously execute the data block d during document preparation routine 22.i The hashing of biological process data 16. This continuous generation and segmentation into data blocks d. i Hash is advantageous because the timeframe in which data manipulation is still possible is reduced to a minimum.

[0072] As a result of the above, it can be expected that for a single timestamp, there exists a total number of biological process data items that must be arranged in the biological process data 16. To ensure the deterministic generation of the biological process data 16, preferably, the data items of the biological process data 16 with the same single timestamp are arranged in the biological process data 16 according to a predefined total order function, such as a predefined sorting function.

[0073] However, according to another approach, it is assumed that in the documentation routine 22, the digital control unit 1 generates link information about the logical relationships between at least a portion of the sensor data 12 and / or actuator data 8 and / or user control command data 18, and also generates biological process data 16 based on the link information.

[0074] As its core function, the digital control unit 1 controls biological processes by communicating with actuators 9 and 10 and sensors 13, 14, and 15. To this end, the digital control unit 1 is configured to execute feedback routines to implement the control loop described above, thereby influencing the biological processes. This control loop can be used to maintain certain sensor data 12 stable by correspondingly controlling actuators 9 and 10.

[0075] Here, and preferably, the digital control unit 1 has a housing 27, which should be robust against manipulation as described above. Alternatively or supplementary, the digital control unit 1 is a mobile unit that can be moved through the laboratory along with the local processor unit 5 and the local data storage device 4. Alternatively or supplementary, it is assumed that the local processor unit 5 and the local data storage device 4 are here, and preferably, connected to the sensors 13, 14, 15 and / or actuators 9, 10 via cables and / or short-range wireless communication. Again, alternatively or supplementary, the user interface 17 may also include a user display and user input devices, particularly a touchscreen, each of which is located in or on the housing 27 of the digital control unit 1.

[0076] Preferably, the bioprocess interface 6 includes a direct, electrical data connection to sensors 13, 14, 15 and / or actuators 9, 10. This further reduces the opportunity to manipulate data within the connection. For a definition of "direct," please refer to the above.

[0077] Preferably, the digital signature 26 generated by signing the document compilation data 23 is stored in the local data storage device 4. Alternatively or supplementarily, the digital control unit 1 may include a data transmission interface 28, wherein the digital control unit 1 transmits the digital signature 26 and / or the document compilation data 23 and / or the biological process data 16 or portions thereof to an external data storage device 29, which may typically be a process control system, or itself may be another digital control unit. Here, and preferably, the external data storage device 29 is a so-called "multi-fermentation tank" control system (MFCS), which includes a local processor unit and the local data storage device itself. The MFCS also provides a centralized process management system that dispatches requests to the digital control unit 1; however, this is not applicable to this particular invention.

[0078] The proposed solution is particularly advantageous when biological process data generated in a biotechnology environment during a biological process needs to be transferred from the sender to the receiver. As an example, at least biological process data 16 and a digital signature 26 are sent to the receiver. The sender may be an operator of the biotechnology environment in which the corresponding biological process has been performed. The receiver may be a government organization applying compliance procedures to the biological process in question.

[0079] Based on the digital signature 26 of the document compilation data 23, the recipient of the biological process data 16 can verify the integrity of this biological process data 16. For this to be possible, the public key corresponding to the private key 25 must also be made available to the recipient. The public key can be provided directly to the recipient by the sender of the biological process data 16 or provided using a Trusted Key Infrastructure (TKI).

[0080] Using the aforementioned public key, the recipient can decrypt the digital signature 26 to receive the document compilation data 23, which can be... Figure 3 The hash root h0 or the complete hash tree H shown in a) is now applied to the received biological process data 16 to generate a hash tree, which is referred to below as the "verification hash tree V" and its... Figure 3 As shown in b).

[0081] However, in Figure 3 In the example shown, the biological process data d4 has been manipulated, resulting in hashes h4′, h34′, h1234′, and h0′ that differ from the original hashes h4, h34, h1234, and h0. If the document compilation data 23 is based solely on the hash root h0, the receiver knows at least some data blocks d. i It is corrupted. If document compilation data 23 is based solely on the complete hash tree H, the receiver can even deduce that data block d4 is corrupted by comparing hash tree H and verifying hash tree V.

[0082] The above example demonstrates that by making the digital control unit 1 a trusted device for signing the document compilation data 23, it is possible to verify data integrity with high reliability, and due to the use of the hash described above, it is possible to verify data integrity with low data processing and thus with low hardware workload.

[0083] According to another independent teaching, protection is claimed for a biological process device 2 having the proposed digital control unit 1. All the explanations given above are fully applicable to this teaching.

[0084] Based on another teaching, a method for operating the proposed digital control unit 1 is proposed, which represents the working principle of the proposed digital control unit 1. Again, please refer to all the explanations given previously.

[0085] Another independent teaching involves using the proposed digital control unit 1 to digitally sign the aforementioned document compilation data 23 with the cryptographic private key 25. Again, all the explanations given above are fully applicable.

[0086] Finally, the independent teachings relate to a data processing system for implementing the above methods, preferably including a local data storage device 4 and a local processor unit 5, to a computer program product for a data processing system, and to a computer-readable storage medium on which the computer program product is stored.

Claims

1. A digital control unit of a bioprocess device (2) for controlling a bioprocess, wherein the digital control unit (1) comprising a local data storage (4) and a local processor unit (5), wherein the digital control unit (1) comprises a bioprocess interface (6) for sending and receiving bioprocess control data, wherein the bioprocess interface (6) comprises an actuator interface (7) for sending actuator data (8) to at least one actuator (9, 10) to influence the bioprocess, wherein the bioprocess interface (6) comprises a sensor interface (11) for receiving sensor data (12) related to the bioprocess from at least one sensor (13, 14, 15), wherein the digital control unit (1) generates bioprocess data (16), wherein the digital control unit (1) comprises a user interface (17) for displaying at least part of the bioprocess data to a user and for receiving user control command data (18), wherein the digital control unit (1) is configured to execute a bioprocess control routine (19) via the local processor unit (5) to control the bioprocess, wherein in the bioprocess control routine (19) the digital control unit (1) receives the sensor data (12) from the sensors (13, 14, 15), wherein in the bioprocess control routine (19) the digital control unit (1) generates the actuator data (8) based on the user control command data (18) and / or the sensor data (12) and controls the actuators (9, 10) by sending the actuator data (8) to the actuators (9, 10) to influence the bioprocess, wherein in the bioprocess control routine (19) the digital control unit (1) generates the bioprocess data (16) from the actuator data (8) and / or the sensor data (12) and / or the user control command data (18), characterized in that: a private key data (20) is stored in the local data storage (4), the digital control unit (1) is configured to execute a data security routine (21) via the local processor unit (5), the digital control unit (1) is configured to execute a documentation routine (22) in the data security routine (21) via the local processor unit (5), in which documentation routine (22) the digital control unit (1) generates documentation data (23) from the bioprocess data (16), the digital control unit (1) is configured to execute a signing routine (24) in the data security routine (21) via the local processor unit (5) and in which signing routine (24) the digital control unit (1) extracts a cryptographic private key (25) from the private key data (20) and digitally signs the documentation data (23) with the cryptographic private key (25) by generating a digital signature (26).

2. The digital control unit of claim 1, wherein, The documentation routine (22) comprises the steps of grouping the bioprocess data (16) into data blocks (d i ) and hashing the data blocks (d i ) to generate hashes (h i ) of the data blocks (d i ), and the documentation data (23) is generated from the hashes (h i ) of the data blocks (d i ).

3. The digital control unit of claim 2, wherein, The documentation routine (22) comprises a step of hashing the hashes (h i ) of the data blocks (d i ) in the form of a tree structure, in particular in the form of a Merkle tree structure, into a hash root (h0), and the documentation data (23) is generated from the hash root (h0).

4. The digital control unit according to any of the preceding claims, characterized in that, The digital control unit (1) executes the documentation routine (22) and preferably the signature routine (24) during control of a bioprocess in the bioprocess control routine (19).

5. The digital control unit according to any of the preceding claims, characterized in that, grouping the bioprocess data (16) into data blocks (d i ) and / or hashing the data blocks (d i ) is initiated at the beginning of the bioprocess.

6. The digital control unit according to any of the preceding claims, characterized in that, During at least part of a single bioprocess, the digital control unit (1) continuously receives the sensor data (12) from the sensors (13, 14, 15) and continuously sends actuator data (8) to the actuators (9, 10) in the bioprocess control routine (19), thereby influencing the bioprocess, and executes the signature routine (24) for the first time and at least once more during a single bioprocess, wherein a subsequent signature routine based on a subsequent bioprocess data set is executed after a previous signature routine based on a previous bioprocess data set.

7. The digital control unit of claim 6, wherein, The respective previous bioprocess data set and the respective subsequent bioprocess data set overlap each other.

8. The digital control unit according to claim 6 or 7, characterized in that The digital control unit (1) adds an identifier of the respective previous bioprocess data set to the respective subsequent bioprocess data set.

9. The digital control unit according to any of the preceding claims, characterized in that, In the signature routine (24), the digital control unit (1) adds a time stamp to the documentation data (23).

10. The digital control unit according to any of the preceding claims, characterized in that, After receipt by the digital control unit (1), the sensor data (12) and / or the user control command data (18) are protected against external manipulation.

11. The digital control unit according to any of the preceding claims, characterized in that, In the bioprocess control routine (19), the digital control unit (1) generates the bioprocess data (16) based on the sensor data (12) and / or the actuator data (8) and / or the user control command data (18).

12. The digital control unit of claim 11, wherein, In the bioprocess control routine (19), the digital control unit (1) generates link information about a logical relationship between at least parts of the sensor data (12) and / or the actuator data (8) and / or the user control command data (18), and generates the bioprocess data (16) also based on the link information.

13. The digital control unit according to any of the preceding claims, characterized in that, The digital control unit (1) is configured to execute a feedback routine to implement a control loop to thereby influence the bioprocess.

14. The digital control unit according to any of the preceding claims, characterized in that, The digital control unit (1) has a housing (27), in or on which the local processor unit (5) and the local data storage (4) are located completely, and / or the digital control unit (1) is a mobile unit that is movable together with the local processor unit (5) and the local data storage (4) through a laboratory, and / or the bioprocess interface (6) is connected to the sensors (13, 14, 15) and / or the actuators (9, 10) via, in particular, a cable and / or short-range wireless communication, and / or the user interface (17) comprises a user display and a user input device, in particular a touch screen, which are located in or on the housing (27).

15. The digital control unit according to any of the preceding claims, characterized in that, The bioprocess interface (6) comprises a direct, electrical, data-like connection to the sensors (13, 14, 15) and / or the actuators (9, 10).

16. The digital control unit of any of the preceding claims, characterized by The digital signature (26) generated by signing the documentation data (23) is stored in the local data storage (4), and / or the digital control unit (1) comprises a data transmission interface (28), and the digital control unit (1) transmits the digital signature (26) and / or the documentation data (23) and / or the bioprocess data (16) or parts of the respective data via the data transmission interface (28) to an external data storage (29), in particular a process control system.

17. Bioprocess apparatus with a digital control unit (1) according to any one of the preceding claims.

18. A method of operating a digital control unit (1) according to any one of claims 1-16, wherein, The digital control unit (1) generates bioprocess data (16), wherein in the bioprocess control routine (19) the digital control unit (1) receives the sensor data (12) from the sensors (13, 14, 15), wherein in the bioprocess control routine (19) the digital control unit (1) generates the actuator data (8) based on the user control command data (18) and / or the sensor data (12) and controls the actuators (9, 10) by sending the actuator data (8) to the actuators (9, 10) thereby influencing the bioprocess, wherein in the bioprocess control routine (19) the digital control unit (1) generates the bioprocess data (16) from the actuator data (8) and / or the sensor data (12) and / or the user control command data (18), wherein the digital control unit (1) executes a data security routine (21) via the local processor unit (5), wherein the digital control unit (1) executes a documentation routine (22) via the local processor unit (5) in the data security routine (21), wherein in the documentation routine (22) the digital control unit (1) generates documentation data (23) from the bioprocess data (16), wherein the digital control unit (1) executes a signing routine (24) via the local processor unit (5) in the data security routine (21), and wherein in the signing routine (24) the digital control unit (1) extracts a cryptographic private key (25) from the private key data (20) and digitally signs the documentation data (23) with the cryptographic private key (25) by generating a digital signature (26).

19. Use of a digital control unit according to any one of claims 1 to 16 for digitally signing documentation data (23) with a cryptographic private key (25), wherein The digital control unit (1) generates bioprocess data (16), wherein in the bioprocess control routine (19) the digital control unit (1) receives the sensor data (12) from the sensors (13, 14, 15), wherein, in the bioprocess control routine (19), the digital control unit (1) generates the actuator data (8) based on the user control command data (18) and / or the sensor data (12) and controls the actuators (9, 10) by sending the actuator data (8) to the actuators (9, 10) thereby influencing the bioprocess, wherein, in the bioprocess control routine (19), the digital control unit (1) generates the bioprocess data (16) from the actuator data (8) and / or the sensor data (12) and / or the user control command data (18), wherein the digital control unit (1) executes a data security routine (21) via the local processor unit (5), wherein the digital control unit (1) executes a documentation routine (22) via the local processor unit (5) in the data security routine (21), wherein, in the documentation routine (22), the digital control unit (1) generates documentation data (23) from the bioprocess data (16), wherein the digital control unit (1) executes a signing routine (24) via the local processor unit (5) in the data security routine (21), and wherein, in the signing routine (24), the digital control unit (1) extracts a cryptographic private key (25) from the private key data (20) and digitally signs the documentation data (23) with the cryptographic private key (25) by generating a digital signature (26).

20. A data processing system for implementing the method according to claim 18.

21. A computer program product for a data processing system according to claim 20, configured to implement the method according to claim 18.

22. A computer readable storage medium having stored thereon, preferably in a non- volatile manner, the computer program product according to claim 21.

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