Asymmetric skid

Abstract

A modular single use skidded system includes a cloud driven communication protocol. The modular single use skidded system further includes a device having an automated visual identification protocol controlled by the cloud driven communication protocol. The automated visual identification protocol includes at least one camera and at least one proximity switch. The automated visual identification protocol, the cloud driven communication protocol providing recipes in manufacturing processes including Asymmetric Dialysis, Traditional TFT (Tangential Flow Filtration) for Perfusion or Ultrafiltration and Diafiltration (UF / DF), Co-Current TFF, Single Pass TFF, Viral Filtration with Inline Gold Particle Test Configuration.

Description

ASYMMETRIC SKIDFIELD OF THE INVENTION

[0001] The present invention pertains to a Modular System Design Capable of Adaption and Automation Configuration Recognition for Multiple Unique Filtration Unit Operations for Biopharmaceutical Manufacturing.BACKGROUND

[0002] Filtration, specifically size exclusion based filtration mechanisms, play a vital role in multiple sections of a typical biopharmaceutical manufacturing workflow. Whether the goal of the end point process is to filter out process impurities, perform buffer exchanges, or filter out specific biopharmaceutical products, a typical biopharmaceutical manufacturer invests large portions of workflow capital on multiple single use pieces of equipment to allow for the performance of filtration-based unit operations.

[0003] In a typical manufacturing workflow this may result in the capital acquisition and management of 3-6 unique equipment assets, unique automation per asset, and unique single use flow kits per asset which increase the total operational capital floor of the manufacturing process while introducing increased supply risk via multiple unique single use flow kits which must be managed individually within the normal supply chain.

[0004] In an idealized manufacturing facility and pharmaceutical manufacturing workflow this capital allocation could be drastically minimized through the procurement of a skidded system solution which could be multi -configured and utilize the same flow kit sections throughout the device, but in different configurations, to deliver the necessary myriad of filtration unit operations normally used within the commercial manufacturing process.

[0005] A multi -function, multi-configurable, system design is proposed using modular single use flow kits and a visual recognition automated protocol to allow for multiple typical biopharmaceutical filtration unit operations to be executed from the same modularized mechanical device. This includes execution of Traditional TFF, Asymmetric Dialysis, Co-Current TFF, Single Pass TFF, and Viral Filtration unit operations as well as multiple sub-configuration process derivatives. These unit operations are all fully automated within the device and delivered via a local or cloud driven automation and controls strategy.SUMMARY

[0006] A modular single use skidded system includes a cloud driven communication protocol. The modular single use skidded system further includes a device having an automated visual identification protocol controlled by the cloud driven communication protocol. The automated visual identification protocol includes at least one camera and at least one proximity switch. The automated visual identification protocol, the cloud driven communication protocol providing recipes in manufacturing processes including Asymmetric Dialysis, Traditional TFF (Tangential Flow Filtration) for Perfusion or Ultrafiltration and Diafiltration (UF / DF), Co-Current TFF, Single Pass TFF, Viral Filtration with Inline Gold Particle Test Configuration.BRIEF DESCRIPTION OF DRAWINGS

[0007] In the following, the present invention is described in more detail with references to the drawings in which:

[0008] Figure 1 illustrates a schematic view of a Modular Feed Single Use Flow Kit Assembly;

[0009] Figure 2 illustrates a schematic view of a Modular Retentate Single Use Flow Kit Assembly;

[0010] Figure 3 illustrates a schematic view of a Modular Permeate Assembly 1 Single Use Flow Kit Assembly;

[0011] Figure 4 illustrates a schematic view of a Modular Permeate Assembly 2 Single Use Flow Kit;

[0012] Figure 5 illustrates a schematic view of a Asymmetric Dialysis Single Use Flow Kit Configuration;

[0013] Figure 6 illustrates a schematic view of a Traditional TFF (Perfusion, UF / DF) Single Use Flow Kit Configuration;

[0014] Figure 7 illustrates a schematic view of a Co-Current TFF Single Use Flow Kit;

[0015] Figure 8 illustrates a schematic view of a Single Pass TFF Single Use Flow Kit Configuration; and

[0016] Figure 9 illustrates a schematic view of a Viral Filtration with Gold Particle Test Single Use Flow Kit.DETAILED DESCRIPTION OF THE EMBODIMENTS

[0017] The following invention outlines a modular single use skidded system designed to allow an end user to change the location of the modular single use flow kit assemblies in Figures 1-4 on the device, thus allowing for the skidded system to facilitate up to 5 major filtration based unit operations.

[0018] The single use design is designed to allow the user to replicate the modularity and multi operational functionality of the device across tubing I.D. scales from 1 / 8” - 1” tubing.

[0019] In the exemplary embodiment, Figure 1- Figure 4 displays the modular flow kits which are designed to be replaced and moved around a centralized flat sheet or hollow fiber or similar based filter to enable the device to facilitate the 5 major unit operation classes. Operations and modular components are also designed to connect to a variety of commercially available hollow fiber and flat sheet filters used for viral filtration, ultrafiltration, diafiltration, and size exclusion filtration applications currently prevalent in the manufacturing of biological agents including mAb’s, and mAb like conjugates, and advanced therapeutics including gene therapies and mRNA manufacturing processes.

[0020] In the exemplary embodiment, movement of the flow kits in Figure 1- Figure 4 of the device allow for multiple unit operation configurations as unique instances of the device displayed in Figures 5 - 9 to enable manufacturing processes for Asymmetric Dialysis, Traditional TFF (Tangential Flow Filtration) for Perfusion or Ultrafiltration and Diafiltration (UF / DF), Co-Current TFF, Single Pass TFF, Viral Filtration with Inline Gold Particle Test Configuration.

[0021] In the exemplary embodiment, in multiple configurations and instances of the device (Figures 5-9), the device is designed to leverage an automated visual identification protocol to allow the device to auto-determine the configuration of the equipment prior to end user manual conformation. This visual identification protocol is driven via cameras, proximity switches, IR switches, or other mechanical positioners or a combination of these to allow the automation to predetermine the systems final processing configuration defined by the user.

[0022] In the exemplary embodiment, in multiple configurations and instances of the device (Figures 5-9) the device is designed to be fully autonomous and driven by process equipment and control modules, phases, recipes, operations, and unit operations in accordance with general system control standards.

[0023] In the exemplary embodiment, in multiple configurations and instances of the device (Figures 5-9) the automated control of the device may be driven either through a locally based PLC or via a cloud driven communication protocol.

[0024] In the exemplary embodiment, in multiple configurations and instances of the device (Figures 5-9), the automated control of the device may incorporate and control outside subsystems such as mixing vessels, weigh scales, reactors, pumps, mechanical drives, sensing transmitters which are not local to the device but necessary to complete the specified unit operation configuration (Figure 5-9). This control may either be facilitated via hardware signal communication or cloud driven signal communication protocols.

[0025] In the exemplary embodiment, in multiple configurations and instances of the device (Figures 5-9) the automated controls of the device allow the users to specify unit operations and unit operation derivates that are unique process derivates and modes of action from the central base configuration.

[0026] In the exemplary embodiment, these include the following sub modes of action listed inTable 1 per primary configuration:

[0027] In the exemplary embodiment, in multiple instances of the device the primary modes of action and sub modes of action are designed to be delivered over multiple process scales with scaled single use flow kits for the device covering the following tubing ranges listed in Table 2: Table 2: Single Use Tubing Inner Diameter (I.D) scales for major device configurations Figure 5-

[0028] In the exemplary embodiment, in multiple instances of the device (Figure 5-9) fluid is designed to be delivered to the device via single use positive displacement pumps, centrifugal pumps, gear pumps, or positively pressured fluid vessels.

[0029] In the exemplary embodiment, in multiple instances of the device, the device is designed to use single use sensors to facilitate in process monitoring and controls protocols including sensors for UV- Vis, Raman, Conductivity, Pressure, pH, Temperature.

[0030] In the exemplary embodiment, in multiple instances of the device, the device is designed to use sensors with built in offset corrections such as temperature corrections or similar.

[0031] In the exemplary embodiment, in multiple instances of the device, the device is designed to interface with a pre-filtration unit, such as a depth filter or an in-line mesh or sock screen device for removing coagulants or flocculants from a feed stream, and to simultaneously precondition that feed stream for a subsequent chromatography operation using UF / DF functionality, TFF / Perfusion functionality, Co-Flow TFF functionality, Asymmetric Dialysis functionality or a combination of these in series or in parallel.

[0032] In the exemplary embodiment, in multiple instances of the device, the device is designed with multiple outlets or inlets via block valves, valve banks, or other such transfer panel like configurations, driven by end user modular configuration adaption of the device to facilitate the multiple major unit operation configurations and sub operation configurations outlined in Table 1 and Figures 5-9.

[0033] In the exemplary embodiment, in multiple instances and configurations of the device, Figures 5-9, the device is designed to deliver automated recipes from an on premise or offpremise cloud server and is designed via this cloud server to enable integration of advanced algorithmic control strategies including machine learning / Al or similar advanced controls protocols.

[0034] In the exemplary embodiment, in multiple instances and configurations of the device, multiples of the same devices can be connected in series or in parallel with the same or different configurations to achieve semicontinuous / continuous manufacturing of multiple filtration based unit operations in series or in parallel to optimize manufacturing processing and time in motion and to aid in the minimization of room temperature residence time of advanced therapeutic or biological agents during commercial scale manufacturing.

[0035] In the exemplary embodiment, in instances of the device, the device can be preconfigured to allow for multiple unique unit operations to progress via a single configuration. An example of such multi-functionality is a configuration of the device to allow for both Asymmetric Dialysis and Co-flow TFF. In this example, the device is capable of using Co-flow TFF functionality to minimize gel layer formation on a filter while connected to a bioreactor or product pool vessel for the removal of coagulants or flocculants or other such process impurities from the feed stream while concentrating the feed stream to a specific target concentration for downstream filtration or chromatographic operations. Once concentration has been completed using the Co-flow TFF functionality and configuration on the device, the device is capable of switching the location of the inlets and outlets of the device without modifying the single use tubing configuration to then allow for feed stream buffer exchange and conditioning of the product pool via Asymmetric Dialysis prior to downstream processing.

[0036] The above description is only for the specific embodiment of the present invention and is not intended to limit the scope of the present invention. The equivalent changes or modifications made by the structures, features and principles of the present invention should be included in within the scope of the patent application of the present invention.

Claims

WHAT IS CLAIMED:

1. A modular single use skidded system, comprising: a cloud driven communication protocol; a device having: an automated visual identification protocol controlled by the cloud driven communication protocol having: at least one camera; and at least one proximity switch, the automated visual identification protocol, the cloud driven communication protocol providing recipes in manufacturing processes including Asymmetric Dialysis, Traditional TFF (Tangential Flow Filtration) for Perfusion or Ultrafiltration and Diafiltration (UF / DF), Co-Current TFF, Single Pass TFF, Viral Filtration with Inline Gold Particle Test Configuration.

2. The modular single use skidded system of claim 1, wherein tire device moves across tubing with an inner diameter from 1 / 8" - 1” tubing.

3. The modular single use skidded system of claim 2, wherein the automated visual identification protocol, auto-determines by process equipment and control modules, phases, recipes, operations, and unit operations in accordance with general system control standards of the cloud driven communication protocol.

4. The modular single use skidded system of claim 3, wherein the cloud driven communication protocol controls mixing vessels.

5. Tire modular single use skidded system of claim 4, wherein the cloud driven communication protocol, controls weigh scales.

6. The modular single use skidded system of claim 5. wherein the cloud driven communication protocol controls reactors.

7. The modular single use skidded system of claim 6, wherein the cloud driven communication protocol controls pumps.

8. Tire modular single use skidded system of claim 7, wherein tire cloud driven communication protocol controls mechanical drives.

9. The modular single use skidded system of claim 8, wherein the cloud driven communication protocol controls sensing transmitters.

10. The modular single use skidded system of claim 1, wherein the modular single use skidded system includes primary configurations and secondary configurations.

11. The modular single use skidded system of claim 10, wherein the secondary configurations are submodes for the primary configurations.

12. The modular single use skidded system of claim 11, wherein a fluid is designed to be delivered to the device through single use positive displacement pumps, centrifugal pumps, gear pumps, or positively pressured fluid vessels.

13. The modular single use skidded system of claim 12, wherein the device is designed to use single use sensors to facilitate in process monitoring and controls protocols including sensors for UV-Vis, Raman, Conductivity, Pressure, pH, Temperature.

14. The modular single use skidded system of claim 13. wherein the device is designed to use sensors with built in offset corrections such as temperature corrections.

15. The modular single use skidded system of claim 14, wherein the device is designed to interface with a pre -filtration unit, such as a depth filter or an in-line mesh or sock screen for removing coagulants or flocculants from a feed stream, and to simultaneously pre-condition the feed stream for a subsequent chromatography operation using UF / DF functionality. TFF / Perfusion functionality. Co-Flow TFF functionality, a Asymmetric Dialysis functionality or a combination of these in series or in parallel.

16. The modular single use skidded system of claim 15, wherein the device is designed with multiple outlets or inlets which includes block valves or valve banks, driven by end user modular configuration adaption of the device to facilitate the primary configurations and secondary configurations.

17. The modular single use skidded system of claim 1, wherein the recipes are automated from an on premise or off premise cloud server and is designed through this cloud server to enable integration of advanced algorithmic control strategies including machine learning protocols.

18. The modular single use skidded system of claim 16, wherein a plurality of devices can be connected in series or in parallel with the same or different configurations to achieve semicontinuous / continuous manufacturing of multiple filtration based unit operations in series or in parallel to optimize.

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