Freeze-drying system and method for freeze-drying a bulk product containing a liquid

Abstract

The compact freeze dryer (200) removes liquid from bulk powder products. The freeze dryer utilizes a single cryogenic vessel (210) to freeze the liquid contained in the bulk product and to condense the vapors generated by sublimating the frozen liquid. A vacuum pump (212) is connected to the cryogenic vessel (210) for evacuating the cryogenic vessel (210) and the drying vessel (260). The vapors generated by sublimating the frozen liquid in the drying vessel (260) are suctioned into the cryogenic vessel (210) and condensed.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 033,049, filed on June 1, 2020, entitled "FREEZE DRYING WITH COMBINED FREEZING CHAMBER AND CONDENSER", Attorney Docket No. EDW.13A.WO, which is currently pending, and is hereby incorporated by reference in its entirety, and this application claims priority to such patent application. Technical Field

[0003] The present invention generally relates to freeze - drying processes and equipment for removing moisture from products by sublimation under vacuum and low temperature. Background Art

[0004] Freeze - drying is a process for removing solvents or suspension media from products. Although this disclosure uses water as an exemplary solvent, other media (such as ethanol) can also be removed in the freeze - drying process, and other media can be removed using the methods and equipment of this disclosure.

[0005] In a freeze - drying process for removing water, the water in the product is frozen to form ice. Under vacuum, the ice sublimes, and the resulting water vapor flows to a condenser. The water vapor condenses to ice on the condenser and is then removed. Freeze - drying is particularly useful in the pharmaceutical industry because the integrity of the product is maintained during the freeze - drying process, and the stability of the product can be ensured for a relatively long time. The products to be freeze - dried are usually but not necessarily biological substances.

[0006] Pharmaceutical freeze - drying is typically a sterile process, and such a sterile process requires sterile conditions within the freeze - drying system. It is crucial to ensure that all components in the freeze - drying system that come into contact with the product are sterile.

[0007] Bulk freeze - drying under sterile conditions can be carried out in a freeze - dryer that has shelves for supporting trays for the products. In Figure 1 An example of a prior - art freeze - drying system 100 as shown, a batch of products 112 is placed in a freeze - dryer tray 121 within a freeze - drying chamber 110. The freeze - dryer shelves 123 are used to support the trays 121 and transfer heat to and from the trays and products as required by the process. A heat - transfer fluid flowing through pipes within the shelves 123 is used to remove or add heat.

[0008] Under vacuum, the frozen product 112 is slightly heated to sublime the ice within the product. The water vapor generated by the sublimation of the ice flows through the channel 115 into the condensation chamber 120, which houses a condensation coil or other surface 122 maintained below the condensation temperature of the water vapor. A coolant passes through the coil 122 to remove heat, causing the water vapor to condense into ice on the coil.

[0009] The freeze-drying chamber 110 and the condensation chamber 120 are both maintained under vacuum during the drying process by a vacuum pump 150 connected to the exhaust port of the condensation chamber 120. The non-condensable gases contained in the chambers 110, 120 are removed by the vacuum pump 150 and discharged through the higher-pressure outlet 152.

[0010] A technique for preparing a product suspension or solution for freeze-drying is spray-freezing, in which the product is atomized in a spray-freezing vessel and exposed to a freezing medium such as cold nitrogen gas. The particle size of the atomized product can be controlled to form a frozen powder with a large surface area to mass ratio, thereby enhancing the efficiency of the subsequent drying process.

[0011] In certain applications, a batch process as described above can be used, in which the freezing step is completed for a batch of products before drying the frozen products in the drying chamber. This arrangement in pilot processes and product development equipment allows experimental flexibility and allows the use of simpler and lower-cost equipment.

[0012] Improved equipment and techniques are needed for low-volume applications such as pilot processes and product development. The equipment should have a minimum footprint for a laboratory environment. The equipment should be capable of producing sterile products for product trials. The equipment should be simple, low-cost, and energy-efficient. Summary of the Invention

[0013] The present disclosure addresses the above needs by providing a freeze-drying system for freeze-drying bulk products by removing liquid. The system includes a cryogenic container having a cooling element, a product introduction inlet in communication with the interior of the cryogenic container and connected to a bulk product source, and a drying chamber having a warming element. A selectively openable and closable product transfer conduit connects the cryogenic container to the drying chamber, and at least one selectively openable and closable bypass conduit connects the cryogenic container to the drying chamber via at least one vapor inlet of the cryogenic container. A selectively operable vacuum pump is in communication with the interior of the cryogenic container via a vacuum outlet of the cryogenic container, the vacuum outlet of the cryogenic container being separate from at least one vapor inlet of the cryogenic container.

[0014] Another embodiment includes a lyophilization system for lyophilizing bulk products by removing liquid. The lyophilization system includes a cryogenic container having a cooling element, a product introduction inlet in communication with the interior of the cryogenic container and connected to a bulk product source, and a drying chamber having a warming element. A selectively openable and closable product transfer conduit connects the cryogenic container to the drying chamber via at least one vapor inlet of the cryogenic container. A selectively operable vacuum pump is in communication with the interior of the cryogenic container via a vacuum outlet of the cryogenic container, and the vacuum outlet of the cryogenic container is separated from at least one vapor inlet of the cryogenic container.

[0015] Another embodiment of the present invention is a method for lyophilizing bulk products containing liquid. The method includes: providing a cryogenic container having a cooling element; providing a drying chamber having a warming element, the cryogenic container and the drying chamber being in fluid communication via a transfer conduit blocked by a transfer valve; isolating the cryogenic container from the drying chamber by closing the transfer valve; introducing the bulk product containing the liquid into the cryogenic container, the cryogenic container containing a gas having a first pressure and a temperature below the freezing point of the liquid, whereby the liquid is frozen in the cryogenic container to form a bulk product containing frozen liquid; removing the isolation of the cryogenic container from the drying chamber by opening the transfer valve; transferring the bulk product containing frozen liquid from the cryogenic container to the drying chamber via the transfer conduit; subjecting the cryogenic container and the drying chamber to a vacuum pressure below the first pressure while the cryogenic container and the drying chamber are in fluid communication, whereby the frozen liquid in the drying chamber sublimes to form vapor; pumping the vapor from the drying chamber to the cryogenic container; and condensing the vapor in the cryogenic container. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is a schematic view of a prior art lyophilization system.

[0017] Figure 2A is a partially cut-away schematic perspective view of a lyophilization system according to an embodiment of the present disclosure.

[0018] Figure 2B is Figure 2A schematic perspective of the lyophilization system of Figure 2B-2B .

[0019] Figure 3 is a flowchart showing a method according to one aspect of the present disclosure. DETAILED DESCRIPTION

[0020] The present disclosure describes systems and methods for lyophilizing bulk materials in an efficient manner using a compact, low-cost system. The systems and methods of the present disclosure relate to a bulk powder lyophilizer that is optimized to freeze and dry a product to produce a powder form.

[0021] The processes and equipment can be used to dry pharmaceutical products that require aseptic or sterilization treatment, such as injectables. However, the methods and equipment can also be used to process materials that do not require aseptic treatment but do require removal of moisture while preserving the structure. For example, the disclosed techniques can be used to produce ceramic / metal products that are used as superconductors or for forming nanoparticle or microcircuit heat sinks.

[0022] The presently described system advantageously utilizes a single cryogenic vessel that serves both as (1) a freezing chamber for freezing a medium containing a bulk product during the freezing stage of the process and as (2) a condenser for condensing the sublimated medium during the drying stage. In an embodiment, the cryogenic vessel is a spray-freezing tower having a cooled wall. During the freezing stage of certain embodiments, a solution or slurry containing the bulk product and the medium is sprayed from one or more nozzles at the top of the cryogenic vessel, and the medium freezes as it falls through the tower, thereby producing a powdered frozen product. The product transfer conduit between the spray-freezing tower and the drying chamber can be opened intermittently to allow the powdered frozen product to fall from the cryogenic vessel into the drying chamber.

[0023] During the drying stage of certain embodiments, a vacuum pump in communication with the cryogenic vessel is activated, thereby evacuating the cryogenic vessel. One or more bypass conduits between the cryogenic vessel and the drying chamber can bypass the product transfer conduit and provide fluid communication between the cryogenic vessel and the drying chamber during the drying stage.

[0024] Accordingly, the drying chamber is also evacuated by the vacuum pump via the cryogenic vessel and the bypass conduit, and the medium containing the bulk product sublimates in the drying chamber. The sublimated medium enters the cryogenic vessel as a vapor through the bypass conduit, and the cryogenic vessel is maintained in a cold condition during the drying stage by continuing to cool the wall after the freezing stage. The vapor condenses in the cryogenic vessel. The condensate produced is removed periodically.

[0025] By using the same vessel to freeze the medium during the freezing stage and to condense the evaporated medium during the drying stage, the presently disclosed system eliminates the need for a separate condensation chamber, thereby reducing the size and volume of the system. In addition, the system is more energy-efficient because only a single chamber is cooled rather than both a freezing chamber and a condenser. The initial cost of the system is lower because there are fewer components.

[0026] Figure 2A and Figure 2BAn exemplary system 200 in accordance with one disclosed embodiment is shown. The cryogenic vessel 210 serves both as a freezer chamber for freezing products and as a condenser for removing condensable gases from the effluent generated during drying of the products. The system 200 can be used to perform a batch freeze-drying process that includes a freezing stage and a drying stage. In one example, the maximum batch size can be about 5 L of product / media suspension or solution.

[0027] In the illustrated embodiment, the interior of the vessel 210 is cooled by circulating a cryogenic fluid such as liquid nitrogen through the inlet 220, through the double walls of the vessel 210, and through the outlet 230. In other embodiments, cooling elements other than the walls can be used to cool the contents of the vessel 210. The vessel can be cylindrical with vertically curved sidewalls. The vessel can include a conical bottom for guiding the frozen product to the isolation valve 268. During the freezing stage, the interior of the vessel 210 can be filled with sterile gaseous nitrogen, and the sterile gaseous nitrogen can be filtered using a sterile filter 232. The sterile nitrogen can also be used to regulate other pressures in the system.

[0028] The nozzle 240 is connected to a liquid product reservoir 266 that holds a bulk product suspended or dissolved in a liquid medium, e.g., a suspension or solution of biosolids in water or another liquid. The liquid product reservoir includes a cooling system (e.g., a Peltier plate) to hold the product in a refrigerated state if necessary to preserve the product. The amount of suspension or solution in the liquid product reservoir 266 can be monitored by a weighing scale 267 that measures the weight of the reservoir system including the product.

[0029] Pressurized nitrogen is used to flow the suspension or solution from the liquid product reservoir 266 to the nozzle 240. The nitrogen can pass through the sterile filter 232. The nozzle 240 is arranged to atomize the product within the cryogenic vessel 210. Atomization of the product results in fine particles being dispersed within the cryogenic vessel 210. Both the size of the particles and the distribution of particle sizes depend on the spraying technique. For example, the geometry of the nozzle, the product flow rate, and the placement of the nozzle within the chamber can affect those process outputs. The particle size and size distribution are important for product applications. For example, for powder handling, a particle size greater than 100 microns is preferred, while for pulmonary applications, the particle size should be about 6 microns.

[0030] In an embodiment, the frozen product can fall through a nitrogen atmosphere cooled by the wall of the cryogenic vessel 210. The dimensions of the vessel are such that the product is allowed sufficient time to contact the nitrogen atmosphere to allow the product to freeze before reaching the bottom of the chamber. The spray-frozen liquid product is collected as a frozen powder at the bottom of the cryogenic vessel 210. The spray-freezing process produces small particles of the rapidly frozen product because the smaller particles have a larger surface area to mass ratio and thus the least resistance to heat input. This property also accelerates the drying process.

[0031] The isolation valve 268 separates the cryogenic vessel 210 from the drying chamber 260 and can be actuated during one or both of the freezing and drying phases. The isolation valve can remain closed during spray-freezing within the cryogenic vessel to maintain sufficiently cold conditions within the vessel without also cooling the drying chamber. In certain embodiments, after a sufficient amount of the liquid product has been spray-frozen and has been collected in the lower portion of the cryogenic vessel 210, the isolation valve 268 is opened to allow the frozen product to fall from the cryogenic vessel 210 into the drying chamber 260 via the product transfer conduit 269. The isolation valve 268 can be opened once at the end of the freezing phase of the process or can be opened periodically during the freezing phase to prevent excessive accumulation of the frozen product at the bottom of the cryogenic vessel 210. For example, the isolation valve 268 can be opened after freezing every 0.5 L of product / media suspension or solution, the frozen product transferred, and then the isolation valve closed to continue freezing more product until the entire batch (e.g., 5 L) has been accumulated in the drying chamber 260. This process avoids warming of the frozen product due to excessive accumulation of the frozen product on the isolation valve 268. The isolation valve communicates directly with the drying chamber and is not temperature-controlled.

[0032] In another example, the isolation valve is opened every 15 minutes to discharge the frozen product into the drying chamber. In other examples, the isolation valve is opened every hour or every 30 minutes.

[0033] The temperature-controlled shelf 250 in the drying chamber 260 holds the frozen product entering the chamber. A heat transfer fluid circulated with the shelf 250 is used to maintain the processing temperature of the frozen product. For example, while additional product is being frozen in the cryogenic vessel 210, the product within the drying chamber 260 can be maintained in its frozen state and the product within the drying chamber 260 can be slightly heated during the drying phase to cause sublimation of the medium.

[0034] The vibration unit 251 is connected to the shelf 250 to vibrate the shelf and impart a vibratory motion to the frozen product. The shelf 250 can be vibrated after completion of the freezing phase or after each transfer of the frozen product. The vibrating shelf spreads and levels the frozen product collected on the shelf, thereby creating or maintaining a product bed of uniform thickness, which improves drying efficiency.

[0035] After completion of the freezing phase, a drying phase is carried out, in which the now frozen medium is removed from the product by means of sublimation treatment. During the drying phase of the disclosed freeze-drying process, the cryogenic container 210 is kept cold, for example, by continuing to circulate the cryogenic fluid in the double walls of the container. A vacuum pump 212 connected to the cryogenic container 210 is activated to evacuate the system. The cryogenic container 210 is directly evacuated by the vacuum pump 212. The vacuum pump 212 can be a separate, independently operating vacuum pump as Figure 2A shown, or alternatively can be part of a vacuum pump group 270 that also includes a liquid ring pump.

[0036] During the drying phase, the valve 268 can be used to close the product transfer line 269 and the valves in one or more bypass lines 214 are opened to connect the cryogenic container 210 to the drying chamber 260 via the vapor inlet 215 of the cryogenic container. The bypass lines 214 bypass the product transfer line 269 and the valve 268 to allow the drying chamber 260 to be evacuated via the cryogenic container 210 without causing blockage of the vacuum pump 212, which might otherwise occur due to the small size of the product transfer line 269. Additionally, if the product transfer line remains open during the drying phase, ice or condensate might accumulate and block the area where the product transfer line enters the cryogenic container. In an embodiment, the geometry of this area is designed to direct the frozen product into the drying chamber during the freezing phase and is not designed to avoid ice accumulation during the drying phase. In other embodiments, during the drying phase, both the bypass line and the product transfer line can be open and used as vapor inlets. In still other embodiments, no bypass line is provided and the product transfer line is used both to transfer the product from the cryogenic container to the drying chamber and as a vapor inlet for allowing vapor to flow from the drying chamber to the cryogenic container.

[0037] During the drying phase of the process, the frozen medium in the drying chamber 260 is subjected to a vacuum and is slightly heated by the shelf 250, causing the medium to sublime and produce vapor. The vapor is withdrawn from the drying chamber and enters one or more vapor inlets of the cryogenic container 210 via the bypass line 214 and / or the product transfer line 269. The vapor condenses into ice on the inner wall of the cryogenic container or on other cooling elements in the container. The condensed vapor is removed from the cryogenic container periodically or before starting a subsequent freeze-drying batch, where the container will be used to freeze the product / media suspension.

[0038] The vacuum pump 212 is connected to the cryogenic vessel 210 via a vacuum outlet 213 of the cryogenic vessel. The vacuum outlet 213 is separate from the vapor inlet 215 of the cryogenic vessel 210 such that a condensable vapor stream flowing out of the drying chamber flows through the cryogenic vessel 210 and condenses on the walls or other cooling elements within the cryogenic vessel. As used herein, "separate" means that the vacuum outlet and the vapor inlet are different openings into the interior of the cryogenic vessel. The two openings are advantageously spaced apart and not adjacent to each other. In one example, the vacuum outlet 213 of the cryogenic vessel 210 may be near the top of the vessel while the vapor inlet 215 may be near the bottom of the vessel 210, thereby providing substantially the entire length of the cryogenic vessel for condensing vapor from the drying chamber.

[0039] After the drying phase is completed, both the drying chamber 260 and the cryogenic vessel 210 are returned to atmospheric pressure. The shelves 250 may be tilted and / or vibrated to transfer the dried product from the shelves to the dried product harvest container 262. After completion of a batch, the sight glass 264 may be used for on-line NIR moisture determination. The cryogenic vessel may be isolated from the drying chamber again to begin freezing a new batch of product.

[0040] Figure 3 The flowchart 300 shown illustrates a method for lyophilizing a bulk product containing liquid according to an embodiment of the present invention. The system is initially conditioned as shown in block 310. The cryogenic vessel 210 is cooled by circulating liquid nitrogen through a double wall or by using other cooling elements. The cryogenic vessel is purged with an atmosphere such as sterile nitrogen. Then at block 320, pressurized nitrogen is used to load the liquid product from the liquid product reservoir 266 into a nozzle supply system adjacent to the nozzle 240.

[0041] Then the freezing phase of the lyophilization process is started as shown in block 330. The liquid product is dispensed through the nozzle and frozen in the cryogenic vessel 210. The isolation valve 268 is periodically opened to allow a dose of the frozen product to fall onto the cooled shelves 250 of the drying chamber 260. In the above example, the valve is opened after freezing every 0.5 L of product / media suspension.

[0042] After the isolation valve has been opened one or more times to transfer the product into the drying chamber, the freezing phase of the lyophilization process ends at block 340. In an exemplary embodiment, the maximum batch size is 5 L of product / media suspension, resulting in a bed depth of 8 - 11 mm on the shelves 250. Each time the isolation valve 268 is opened to discharge the frozen product onto the shelves 250, a vibration actuator is used to level the product on the shelves as shown in block 350.

[0043] As shown in block 360, once the shelf 250 is loaded, the isolation valve 268 is closed and the valve in the bypass line is opened. The vacuum pump 212 is started to evacuate the drying chamber 260 using the bypass line 214 that connects the drying chamber to the cryogenic vessel 210. Then, as shown in block 370, a defined temperature and pressure sequence is run to dry the batch of product. This sequence can be stored as part of a program in the programmable logic controllers of the various components of the control system. After the drying operation is complete, the drying chamber and the cryogenic vessel are returned to atmospheric pressure, the shelf 250 is tilted to harvest the dried product, and the NIR residual moisture can be measured online using the sight glass 264.

[0044] The systems and methods described herein may be performed, in part, by an industrial controller and / or computer used in conjunction with the processing equipment described below. The equipment is controlled by a programmable logic controller (PLC) having operating logic for valves, motors, etc. An interface to the PLC is provided via a PC. The PC loads user-defined recipes or programs onto the PLC for operation. The PLC uploads historical data of the run to the PC for storage. The PC may also be used for manual control of the apparatus, operating specific steps (such as freezing, defrosting, in-line steam sterilization, etc.).

[0045] The PLC and the PC include a central processing unit (CPU) and a memory, as well as an input / output interface connected to the CPU via a bus. The PLC is connected to the processing equipment via the input / output interface to receive data from sensors that monitor various conditions of the equipment, such as temperature, position, speed, flow rate, etc. The PLC is also connected to operating devices that are part of the equipment.

[0046] The memory may include a random access memory (RAM) and a read-only memory (ROM). The memory may also include removable media such as a hard disk drive, a tape drive, etc. or a combination thereof. The RAM may be used as a data memory for storing data used during the execution of programs in the CPU and as a work area. The ROM may be used as a program memory for storing programs including steps to be executed in the CPU. The programs may be located on the ROM and may be stored on removable media or any other non-volatile computer-usable media in the PLC or the PC as computer-readable instructions stored thereon for execution by the CPU or other processors to perform the methods disclosed herein.

[0047] The foregoing detailed description should be understood in every respect to be illustrative and exemplary, not restrictive, and the scope of the invention disclosed herein should not be determined by the detailed description, but rather by the claims construed in accordance with the full scope permitted by patent law. It should be understood that the embodiments shown and described herein are merely examples of the principles of the invention and that those skilled in the art may make various modifications without departing from the scope and spirit of the invention.

Claims

1. A freeze-drying system for freeze-drying bulk products by removing liquids, comprising: a cryogenic container (210) having a cooling element; a product introduction inlet that is in communication with the interior of the cryogenic container (210) and is connected to a bulk product source; a drying chamber (260) having a warming element; a selectively openable and closable product transfer duct (269) that connects the cryogenic container (210) to the drying chamber (260); at least one selectively openable and closable bypass duct (214) that connects the cryogenic container (210) to the drying chamber (260) via at least one vapor inlet (215) of the cryogenic container (210); and a selectively operable vacuum pump (212) that is in communication with the interior of the cryogenic container (210) via a vacuum outlet (213) of the cryogenic container (210), the vacuum outlet (213) of the cryogenic container (210) being separate from the at least one vapor inlet (215) of the cryogenic container (210), wherein the freezing medium in the drying chamber (260) is subjected to a vacuum and is slightly heated, causing the medium to sublime and produce vapor, wherein the bypass duct (214) is configured to bypass the product transfer duct (269) to allow the vapor from the drying chamber (260) to be discharged via the cryogenic container (210) without causing blockage of the vacuum pump (212) due to the small size of the product transfer duct (269).

2. The freeze-drying system according to claim 1, wherein, the product introduction inlet further includes at least one nozzle (240) that is connected for spraying the bulk product into the cryogenic container (210).

3. The freeze-drying system according to claim 2, wherein, the cryogenic container (210) further includes a cylindrical container having a curved vertical wall, the at least one nozzle (240) is connected at the top of the cylindrical container, and the cooling element includes the curved vertical wall.

4. The freeze-drying system according to claim 1, further comprising a controller that includes a memory storing a program that, when executed by the controller, causes the freeze-drying system to perform: a freezing stage, wherein, the bulk product is introduced through the product introduction inlet to produce a frozen powder in the cryogenic container (210) at a first pressure, and wherein the frozen powder is transferred to the drying chamber (260) via the product transfer duct (269); and a drying stage, wherein the vacuum pump (212) evacuates the cryogenic container (210) and the drying chamber (260) to a vacuum pressure lower than the first pressure, and wherein the sublimated frozen liquid is suctioned from the drying chamber (260) into the cryogenic container (210) via the at least one bypass duct (214) to condense on the cooling element.

5. The freeze drying system according to claim 1, in, The low-temperature container (210) is located above a vacuum drying chamber (260), and the product transfer pipe (269) connects the bottom of the low-temperature container (210) with the drying chamber (260).

6. The freeze drying system according to claim 1, in, The drying chamber (260) also includes a shelf (250) positioned to receive product from the product transfer conduit (269).

7. The freeze drying system according to claim 6, in, The temperature increasing element comprises a heat transfer fluid circulation system in the shelf (250).

8. The freeze-drying system according to claim 6, further comprising a vibration unit (251) connected to vibrate the shelf (250).

9. The freeze-drying system according to claim 6, further comprising a tilting unit connected for tilting the shelf (250).

10. A method for freeze drying a bulk product comprising a liquid, include: Providing a cryogenic container (210) having a cooling element; Providing a drying chamber (260) having a temperature increasing element; The cryogenic container (210) and the drying chamber (260) are in fluid communication via a product transfer conduit (269) interrupted by a transfer valve; Providing at least one bypass pipe (214) that can be selectively opened and closed, wherein the bypass pipe connects the low-temperature container (210) to the drying chamber (260) via at least one vapor inlet (215) of the low-temperature container (210); Providing a selectively operable vacuum pump (212), the vacuum pump being in communication with the interior of the cryogenic container (210) via a vacuum outlet (213) of the cryogenic container (210), the vacuum outlet (213) of the cryogenic container (210) being separate from the at least one vapor inlet (215) of the cryogenic container (210); isolating the low-temperature container (210) from the drying chamber (260) by closing the transfer valve; introducing the bulk product comprising the liquid into the cryogenic container (210), the cryogenic container containing a gas having a first pressure and a temperature below the freezing point of the liquid, whereby the liquid is frozen in the cryogenic container (210) to form a bulk product comprising frozen liquid; removing the isolation between the cryogenic container (210) and the drying chamber (260) by opening the transfer valve; transferring the bulk product containing the frozen liquid from the cryogenic container (210) to the drying chamber (260) via the product transfer conduit (269); subjecting the cryogenic container (210) and the drying chamber (260) to a vacuum pressure lower than the first pressure while the cryogenic container (210) and the drying chamber (260) are in fluid communication, whereby the frozen liquid in the drying chamber (260) sublimates to form vapor; pumping the vapor from the drying chamber (260) to the cryogenic container (210); and Condense the vapor in the cryogenic container (210), wherein the bypass conduit (214) is configured to bypass the product transfer conduit (269) to allow the evacuation of vapor from the drying chamber (260) via the cryogenic container (210) without causing blockage of the vacuum pump (212) due to the small size of the product transfer conduit (269).

11. The method according to claim 10, wherein, introducing the bulk product containing the liquid into the cryogenic container (210) includes: spraying the bulk product.

12. The method according to claim 10, wherein, opening the transfer valve to remove the isolation between the cryogenic container (210) and the drying chamber (260) further includes: opening the isolation valve (268) in the selectively closable product transfer conduit (269).

13. The method according to claim 12, further including: after transferring the bulk product, closing the isolation valve (268) and opening the selectively closable bypass conduit (214) that bypasses the selectively closable product transfer conduit (269).

14. The method according to claim 13, wherein, transferring the bulk product containing the cryogenic liquid from the cryogenic container (210) to the drying chamber (260) further includes periodically: opening the isolation valve (268) in the selectively closable product transfer conduit (269); transferring a portion of a batch of bulk product containing the cryogenic liquid onto the temperature-controlled shelf (250) in the drying chamber (260); closing the isolation valve (268); and repeating the introduction of the bulk product containing the liquid into the cryogenic container (210).

15. The method according to claim 10, wherein, transferring the bulk product containing the cryogenic liquid from the cryogenic container (210) to the drying chamber (260) further includes transferring it onto the shelf (250) in the drying chamber (260); the method further includes: vibrating the shelf (250) to form a substantially uniform depth of the bulk product containing the cryogenic liquid on the shelf (250).

16. The method according to claim 10, further including: circulating a cryogenic fluid in the cooling element of the cryogenic container (210) during the introduction of the bulk product containing the liquid into the cryogenic container (210) containing a gas at a first pressure and during subjecting the cryogenic container (210) and the drying chamber (260) to a vacuum pressure lower than the first pressure.

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