EP-4739965-A1 - REAL-TIME MEASUREMENT OF DESUBLIMATION IN A FREEZE-DRYING SYSTEM

Abstract

Disclosed herein are embodiments for real-time measurement of drying in a freeze-drying system. In at least one embodiment, the freeze-drying system includes a freeze-drying chamber; a condenser coupled to the freeze-drying chamber; one or more load sensors; and a processing device operatively coupled to the one or more load sensors and configured to measure mass change of components of the freeze-drying system during a freeze-drying process.

Inventors

• COITEUX, PAUL W.

Assignees

• SP Industries, Inc.

Dates

Publication Date

20260513

Application Date

20240813

Claims (20)

1. 1. A freeze-drying system comprising: a freeze-dry ing chamber; a condenser coupled to the freeze-drying chamber; one or more load sensors; and a processing device operatively coupled to the one or more load sensors and configured to measure mass change of components of the freeze-drying system during a freeze-drying process.
2. 2. The freeze-drying system of claim 1, wherein the one or more load sensors are disposed on support structures of the freeze-drying chamber.
3. 3. The freeze-drying system of claim 1. wherein the one or more load sensors are disposed on support structures of the condenser.
4. 4. The freeze-drying system of claim 1, wherein the freeze-drying chamber further comprises a stoppering mechanism configured to apply pressure to a shelf stack disposed within the freeze-drying chamber, and wherein the one or more load sensors are disposed on the stoppering mechanism.
5. 5. A freeze-drying system comprising: a freeze-drying chamber; a condenser coupled to the freeze-drying chamber via one or more conduits; a hydraulic ram configured to apply pressure to a shelf stack disposed within the freeze- drying chamber at a pressure plate; a hydraulic fluid pressure sensor configured to measure pressure on the hydraulic ram; and a processing device operatively coupled to the hydraulic fluid pressure sensor to measure mass change on the shelf stack during a freeze-dry ing process.
6. 6. The freeze-drying system of claim 1. wherein the measured mass change corresponds to ice accumulation on the condenser during the freeze-dry ing process.
7. 7. The freeze-drying system of claim 6. wherein the processing device is further configured to compute a drying parameter of a product in the freeze-drying chamber corresponding to a given point or period in time based on mass transfer from the product to the condenser as accumulated ice during the freeze-drying process.
8. 8. The freeze-drying system of claim 7, wherein the drying parameter is selected from a batch average temperature, cake resistance, and heat transfer coefficient.
9. 9. A method of computing batch average temperature of a product during a freeze-drying process at a given point or period in time, the method comprising: monitoring, by a processing device, mass transfer from the product to a condenser as accumulated ice during the freeze-drying process; and computing, by the processing device, a drying parameter of the product based on the monitored mass transfer.
10. 10. The method of claim 9, wherein the drying parameter is selected from a batch average temperature, cake resistance, and heat transfer coefficient.
11. 11. The method of claim 9, wherein monitoring the mass transfer comprises monitoring mass change via one or more load sensors disposed on support structures of a freeze-drying chamber containing the product.
12. 12. The method of claim 9. wherein monitoring the mass transfer comprises monitoring mass change via one or more load sensors disposed on support structures of the condenser.
13. 13. The method of claim 9. wherein monitoring the mass transfer comprises monitoring mass change via one or more load sensors disposed on a hydraulic ram configured to apply pressure to a shelf stack disposed within a freeze-drying chamber containing the product.
14. 14. The method of claim 9, wherein monitoring the mass transfer comprises monitoring mass change via a hydraulic fluid pressure sensor configured to measure pressure of a hydraulic ram configured to apply pressure to a shelf stack disposed within a freeze-drying chamber containing the product.
15. 15. The method of claim 9. further comprising: causing, by the processing device, a display device to display the drying parameter during the freeze-drying process.
16. 16. A non-transitory machine-readable medium having instructions encoded thereon that, when executed by a processing device of a freeze-drying system, cause the processing device to implement the freeze-drying process of claim 9.
17. 17. A method comprising: implementing, by a processing device, a freeze-do ing process for a freeze-drying system according to a process recipe, the process recipe specifying a drying parameter for a product; monitoring, by the processing device, mass transfer from the product to a condenser as accumulated; computing, by the processing device, the drying parameter at a given point or period in time based on the monitored mass transfer; and periodically adjusting, by the processing device, the process recipe to cause the computed drying parameter reach and stabilize at or near a target batch average temperature.
18. 18. The method of claim 17, wherein the drying parameter is selected from a batch average temperature, cake resistance, and heat transfer coefficient.
19. 19. The method of claim 17, wherein monitoring the mass transfer comprises monitoring mass change via one or more load sensors disposed on support structures of a freeze-drying chamber containing the product.
20. 20. The method of claim 17, wherein monitoring the mass transfer comprises monitoring mass change via one or more load sensors disposed on support structures of the condenser.

Description

REAL-TIME MEASUREMENT OF DESUBLIMATION IN A FREEZE-DRYING SYSTEM CROSS-REFERENCE TO RELATED APPLICATION(S) [0001] This application claims the benefit of priority of U.S. Non-Provisional Patent Application No. 18/800,875, filed August 12, 2024, which claims the benefit of priority of U.S. Provisional Patent Application No. 63/532,610, filed August 14, 2023, the disclosures of which are hereby incorporated by reference herein in their entireties. TECHNICAL FIELD [0002] The present disclosure relates to field of freeze-drying systems, and more particularly, to computing parameters during freeze-drying processes. BACKGROUND [0003] Freeze-drying (e.g., lyophilization, cryodesiccation) is a process to remove water and/or other solvents from products. Freeze-drying has many applications such as preserving a perishable material, making a material more convenient for transport, making of ceramics, producing a product that has a short reconstitution time with acceptable potency levels, and so forth. Freeze-drying can be used for many different materials, including, but not limited to, food, pharmaceuticals, and biological specimens. [0004] In a typical freeze-drying process, the sample, or vials or containers containing the sample, are loaded on temperature-controlled shelves within a chamber and cooled to low temperatures until completely solidified. The freeze-drying chamber pressure is then reduced and the shelf temperature is adjusted to enable removal of the frozen solvent (i.e., drying) via sublimation in a step referred to as “primary drying.” When sublimation is complete, the shelf temperature is raised during a “secondary drying” step to remove additional un-frozen solvent bound to the solid product by, for example, adsorption. When sufficient solvent is removed, the drying process is concluded. If the sample was contained in vials or containers, the vials or containers are then sealed, typically under a sub-ambient pressure of inert gas. [0005] It is important that pharmaceutical products are correctly lyophilized during every’ batch produced. Current processes are often validated though engineering batches, and then shelf temperature, condenser temperature, and pressure data are recorded. However, without product temperature data, excursions from the defined process may be missed and product quality could be affected by small variations. SUMMARY OF THE DISCLOSURE [0006] The following presents a simplified summary of various aspects of the present disclosure in order to provide a basic understanding of such aspects. This summary' is not an extensive overview of the disclosure. It is intended to neither identify key or critical elements of the disclosure, nor delineate any scope of the particular embodiments of the disclosure or any scope of the claims. Its sole purpose is to present some concepts of the disclosure in a simplified form as a prelude to the more detailed description that is presented later. [0007] In one aspect of the present disclosure, a freeze-drying system comprises: a freeze- drying chamber; a condenser coupled to the freeze-drying chamber; one or more load sensors; and a processing device operatively coupled to the one or more load sensors and configured to measure mass change of components of the freeze-drying system during a freeze-drying process. [0008] In at least one embodiment, the one or more load sensors are disposed on support structures of the freeze-drying chamber. In at least one embodiment, the one or more load sensors are disposed on support structures of the condenser. [0009] In at least one embodiment, the freeze-drying chamber further comprises a stoppering mechanism configured to apply pressure to a shelf stack disposed within the freeze-dry ing chamber. In at least one embodiment, the one or more load sensors are disposed on the stoppering mechanism. [0010] In a further aspect of the present disclosure, a freeze-drying system comprises: a freeze-drying chamber; a condenser coupled to the freeze-dry ing chamber via one or more conduits; a hydraulic ram configured to apply pressure to a shelf stack disposed within the freeze-drying chamber at a pressure plate; a hydraulic fluid pressure sensor configured to measure pressure on the hydraulic ram; and a processing device operatively coupled to the hydraulic fluid pressure sensor to measure mass change on the shelf stack during a freeze-drying process. [0011] In at least one embodiment, the measured mass change corresponds to ice accumulation on the condenser during the freeze-drying process. In at least one embodiment, the processing device is further configured to compute a dry- i ng parameter of a product in the freeze- drying chamber corresponding to a given point or period in time based on mass transfer from the product to the condenser as accumulated ice during the freeze-drying process. [0012] In at least one embodiment, the drying parameter is selected from a batch average temperature, cake resistance, and heat t