Cooling system for freeze dryers

Abstract

In the freeze-drying system and freeze-drying method, the cooling system is supplemented during peak loads with a cold heat energy storage (CTES) system utilizing a phase change material (PCM), which allows the use of alternative cooling systems, such as turbo-compressor cooling systems, while still meeting peak cooling capacity requirements.

Description

Technical Field

[0001] The present invention generally relates to freeze-drying processes and apparatuses for removing moisture from products by sublimation. More specifically, the present invention relates to systems and methods for cooling a freeze-drying chamber and a freeze-dryer condenser using a cold thermal energy storage (CTES) system.

Background Art

[0002] Freeze-drying is a process of removing solvents or suspensions (generally water) from products. Freeze-drying is a low-pressure and low-temperature condensation pump process widely used in the manufacture of pharmaceuticals. In the freeze-drying process of removing moisture, the moisture in the product is frozen to form ice, and the ice is sublimated under vacuum, and the resulting water vapor is flowed to a condenser. The water vapor is condensed as ice in the condenser and then removed from the condenser. 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 is guaranteed for a relatively long period. Freeze-dried products are usually, but not necessarily, biological substances.

[0003] A typical freeze-drying process used in the pharmaceutical industry can process either bulk products or products filled in vials. In the example of the bulk freeze-drying system 100 shown in FIG. 1, a batch of bulk product 112 is placed on a freeze-drying tray 121 in a freeze-drying chamber 110. A freeze-drying shelf 123 is used to support the tray 121. Alternatively, product-filled vials are placed on the shelf. The freeze-drying shelf functions as a heat exchanger for transferring heat between the tray or vial as required in the process. The heat transfer fluid flowing through the conduits in the shelf 123 is used to remove heat or heat up.

[0004] The suspended or dissolved product is frozen by removing heat with a heat transfer fluid. Under vacuum, the frozen product 112 is heated by the heat transfer fluid, and the ice within the product sublimes. The vapor resulting from the sublimation of the ice flows through the passage 115 into a condensation chamber 120, which includes a condensation coil or other surface 122 that is kept below the condensation temperature of the vapor. The heat exchange fluid removes heat as it passes through the coil 122, causing the vapor to condense as ice on the coil.

[0005] Both the freeze-drying chamber 110 and the condensing chamber 120 are maintained under vacuum during the process by a vacuum pump 150 connected to the exhaust of the condensing chamber 120. Non-condensable gases contained within chambers 110 and 120 are removed by the vacuum pump 150 and discharged to the outlet 152 on the higher pressure side.

[0006] Condensed Room 120 and freeze-drying chamber 110 shelf 123 The heat exchange fluid circulating through the system may be cooled by the same cooling system or by different cooling systems. [Overview of the Initiative]

[0007] This disclosure addresses the above-mentioned requirements by providing a freeze-drying system. The system includes a freeze-drying chamber, which includes a chamber heat exchanger for cooling and heating products within the freeze-drying chamber. The system further includes a freeze-drying condenser connected to the freeze-drying chamber to receive exhaust gases from the freeze-drying chamber. The condensing surface of the freeze-drying condenser is provided for condensing the exhaust gases.

[0008] The first heat exchange fluid circuit is selectively connected to the condensation surface to circulate the first heat exchange fluid to the condensation surface. The turbo compressor cooling system is connected to cool the first heat exchange fluid.

[0009] A second heat exchange fluid circuit is connected to circulate the second heat exchange fluid through a room heat exchanger. An inter-circuit heat exchanger is connected to exchange thermal energy between the first heat exchange fluid and the second heat exchange fluid.

[0010] The cold thermal storage system is connected to cool at least a second heat exchange fluid. The cold thermal storage system includes a phase change material for storing low-temperature thermal energy.

[0011] Another embodiment of the present invention is a method for freeze-drying a product. This method includes sterilizing a freeze-drying chamber using a stationary washing arrangement; loading the product into the freeze-drying chamber; refilling the cold storage system by cooling the phase change material of the cold storage system using a turbo compressor cooling system during at least one of the sterilization and loading of the freeze-drying chamber; cooling the inside of the freeze-drying chamber to process temperature using a turbo compressor cooling system supplemented by the cold storage system after refilling the cold storage system; freezing the components of the product in the freeze-drying chamber to form frozen components; sublimating the frozen components in the freeze-drying chamber to form vapor; condensing the vapor in a condenser using a turbo compressor cooling system; and removing the product from the freeze-drying chamber. [Brief explanation of the drawing]

[0012] [Figure 1] Figure 1 is a schematic diagram of a conventional freeze-drying system. [Figure 2] Figure 2 is a schematic diagram of a turbo compressor cooling system according to one embodiment of the present disclosure. [Figure 3] Figure 3 is a graph showing the component temperatures at several steps of the freeze-drying cycle according to embodiments of this disclosure. [Figure 4] Figure 4 is a schematic diagram of the freeze-drying system operating during the transition portion of the freeze-drying cycle according to an embodiment of the present disclosure. [Figure 5] Figure 5 is a schematic diagram of a freeze-drying system operating during the freezing portion of a freeze-drying cycle according to an embodiment of the present disclosure. [Figure 6] Figure 6 is a schematic diagram of a freeze-drying system operating during the freeze-drying portion of a freeze-drying cycle according to an embodiment of the present disclosure. [Figure 7] Figure 7 is a schematic diagram of a freeze-drying system according to another embodiment of the present disclosure. [Figure 8] Figure 8 is a flowchart showing a method according to one aspect of the present disclosure. [Modes for carrying out the invention]

[0013] Currently, commercially available freeze dryer cooling systems often use working fluids that are greenhouse gases. Prior to the 1987 Montreal Protocol on Substances that Deplete the Ozone Layer, freeze dryer cooling system working fluids were often based on chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs), which are potent ozone-depleting substances. This treaty led to the discontinuation of most of these working fluids. CFCs and HCFCs were replaced by hydrofluorocarbons (HFCs), such as R-410a and R-507a, which are now widely used. However, HFCs are also potent greenhouse gases. Currently, various countries around the world restrict or ban the use of HFC-based refrigerants. Several companies, including pharmaceutical companies, are actively considering eliminating the use of artificial refrigerants in processing equipment, including freeze dryers.

[0014] To address the potential environmental risks associated with the use of working gases, the authors utilized a turbocompressor cooling system to perform the primary cooling function of a freeze-drying system. The turbocompressor cooling system utilizes air or nitrogen as the working fluid in a Bell-Coleman cycle (also known as the inverse Brayton cycle), where the expansion and compression phases approximate isentropic processes and the cooling and heating phases approximate isobaric processes. The system includes a configuration where the turbocompressor and turboexpander share a common shaft with an electric motor. Mechanical energy from the turboexpander complements energy from the motor to drive the turbocompressor, increasing efficiency. The cryogenic working fluid from the expander is used to cool the condenser and freeze-drying chamber of the freeze-drying system.

[0015] A schematic diagram of an example of a turbo compressor cooling system 200 is shown in Figure 2. Energy is extracted from a gaseous working fluid (such as air or nitrogen) compressed by the expander 210 to produce a low-pressure cryogenic gas 221. The energy extracted from the expander 210 is transmitted to the compressor unit 214 via the drive shaft 216. The low-pressure cryogenic gas 221 is sent to one or more heat exchangers 295 of the freeze-drying system 290, where it absorbs thermal energy from the condenser and shelves in the freeze-drying chamber.

[0016] The freeze dryer return line 220 from the freeze drying system 290 passes through a heat transfer heat exchanger 225, where additional thermal energy is exchanged between the freeze dryer return line 220 and the compressor output 215, increasing system efficiency. As a result, the low-temperature, low-pressure working fluid generated in the freeze dryer return line 220 is sent to the inlet of the compressor 214.

[0017] Using the mechanical energy from the motor 212 and from the expander 210, the compressor 214 compresses the working fluid and generates a high-pressure and high-temperature working fluid in the compressor output 215. Heat is discharged from the working fluid to the atmosphere by an air cooler 230 or a water cooler or other similar devices. As described above, additional thermal energy is transferred from the compressor output 215 to the freeze dryer return line 220 by the heat transfer type heat exchanger 225. The resulting high-pressure and low-temperature working fluid is sent to the expander 210 to complete the cycle.

[0018] A typical temperature cycle 300 of a commercial freeze drying system is schematically shown in FIG. 3. In the schematic view, the temperature 305 of the freeze drying chamber shelf and the temperature 310 of the condenser coil are shown as functions of the continuous process 315 of the freeze drying cycle including loading 316, freezing 317, freeze drying 318, unloading 319 and turnaround 320.

[0019] During the loading part 316 of the cycle, the shelf temperature and the condenser coil temperature are maintained near ambient temperature when vials or bulk materials are loaded into the chamber, or alternatively, the shelf may be cooled as required by the product procedure. During the turnaround part 320 of the cycle, the system is unloaded, thawed, washed, sterilized, dried and leak tested. The ice on the condenser coil is melted and discharged. A high-temperature cleaning agent can be used to clean or sterilize the freeze drying components including the freeze drying chamber and the condenser. A Clean-in-Place (CIP) arrangement and a Clean-in-Place sterilization arrangement that do not require the disassembly of the freeze dryer may be used. For example, a permanently installed steam nozzle or a sterilizing sprayer for cleaning the interior of the device can be used. The freeze dryer cooling system can be used to warm the condenser during defrosting and to cool the shelf during loading during the turnaround part of the cycle. The shelf loading temperature is between ambient temperature and -50°C according to the process conditions. The freeze dryer cooling system can also be used for cooling the system after drying. During leak testing, the freeze dryer cooling system is operated to evaluate coolant leakage.

[0020] During the freezing part 317 of the cycle, it is necessary to lower the temperature of the product in the freezing chamber from the ambient conditions to -40°C or lower. The rate of temperature change during the freezing part 317 of the cycle directly affects the overall cycle time of the freeze-drying system because other processes of the cycle may not be carried out during this process. Therefore, the cooling capacity of the cooling system of the freeze-dryer directly affects the cycle time. Furthermore, the freezing rate must be carefully controlled to control important product quality characteristics within the frozen product. Therefore, it is very important to have a freeze-drying system with sufficient capacity to maintain the desired cooling rate.

[0021] During the freeze-drying part 318 of the cycle, the freeze-drying chamber is maintained at a low process temperature. The freeze-dryer cooling system must absorb heat from the condensation in the condenser and maintain the freeze-drying chamber at the process temperature. Furthermore, in order to carry out the sublimation process, it is necessary to introduce heat into the system (shelf). The sublimation of ice in the product takes energy from the product, and sublimation causes the product to cool until sublimation stops. In order to maintain the progress of the sublimation process, a considerable amount of heat needs to be added through the shelf.

[0022] During the primary drying phase 318a, the ice of the water of crystallization is slowly sublimated to avoid the formation of liquid water that may deteriorate the product. During the secondary drying phase 318b, since the phase change from ice to water is no longer a concern, the remaining individual water molecules are removed at a higher temperature. For example, typical shelf temperatures in primary drying may be around -10°C to +10°C or 20°C, and secondary drying may be at 20°C to 40°C. In the secondary phase, the shelf hardly or does not need to be cooled at all. In another case, the product requires a very slow process on a shelf at -30°C. In such cases, since pump energy tends to heat the system, extraction during cooling may be required for control.

[0023] Most commercially available pharmaceutical freeze-dryers have maximum floor space requirements for installation in laboratories or manufacturing facilities, and new freeze-dryer cooling systems need to occupy an area comparable to that occupied by conventional HFC-based systems.

[0024] The authors found that reasonably sized turbo compressor cooling systems lack the peak capacity necessary to maintain the cooling / freezing cycles of commercially available freeze dryers within acceptable cycle times. To leverage the environmental benefits of turbo compressor cooling systems in commercial freeze dryer systems, the authors complemented the turbo compressor cooling system with a cold thermal energy storage (CTES) system while meeting the system's peak cooling requirements and maximum floor area specifications.

[0025] CTES systems store and recover cold energy for low-temperature applications. CTES utilizes the latent heat storage properties of materials. This technology can store heat through temperature differences or in different phases, and store energy for later use.

[0026] Two approaches / types of energy storage materials can be used: sensible heat and latent heat. The sensible heat approach uses a large amount of cold fluid and relies on the latent heat storage of that fluid. Thermal energy is gradually transferred to the fluid as its temperature rises.

[0027] Latent heat systems utilize the phase change energy of phase change materials (PCMs) to provide a nearly constant temperature energy sink. Latent heat systems use smaller volumes for greater energy storage.

[0028] Examples of PCMs for low-temperature applications include paraffin (organic) (~-37°C), petroleum-derived materials, plant-derived materials, eutectic salts (~-65°C), and alcohol / glycol (~-100°C). In one embodiment of the system described herein, a eutectic salt-based PCM is used to complement the turbo compressor cooling system of a freeze dryer.

[0029] Figures 4 to 6 schematically show a freeze-drying oven cooling system 400 according to one embodiment of the present disclosure. The flow paths in bold indicate the flow of heat transfer fluid in a specific step of the freeze-drying cycle. In particular, Figure 4 shows the flow path in the turning portion of the cycle, Figure 5 shows the freezing portion of the cycle, and Figure 6 shows the freeze-drying portion of the cycle.

[0030] The freeze-drying components of the system include a freeze-drying chamber 410 having cooling shelves 423 and a condenser 420, both of which are cooled during the freeze-drying cycle. The cooling system 400 includes two separate circuits, each containing a heat transfer fluid; the first circuit 491 includes the condenser 420 and the second circuit 490 includes the freeze-drying chamber 410. Both circuits 490, 491 pass through an inter-circuit heat exchanger 450, such as a brazing plate heat exchanger, for transferring thermal energy between the two circuits. Preferably, the heat exchange between the fluids in the two circuits occurs without the use of an intervening, i.e., intermediate heat transfer fluid. The heat transfer fluid in each of the first and second circuits 491, 490 may be a liquid heat transfer oil.

[0031] The first circuit 491 includes a turbocompressor cooling system 440 connected to cool the heat transfer fluid in the first circuit. The heat transfer fluid in the first circuit is circulated by a circulation pump 430. Adjustable valves 441, 442 control the ratio of heat transfer fluid circulated from the turbocompressor cooling system 440 through the condenser 420 to heat transfer fluid circulated through the inter-circuit heat exchanger 450.

[0032] The turbocompressor cooling system includes a heat exchanger for transferring thermal energy between the working fluid of the turbocompressor and the heat transfer fluid of the first circuit. Preferably, the heat exchange between the working fluid of the turbocompressor and the heat transfer fluid of the first circuit is performed without the use of an intermediary, i.e., an intermediate heat transfer fluid.

[0033] The second circuit 490 of the freeze dryer cooling system 400 cools the shelves 423 or other heat transfer elements of the freeze dryer chamber 410. Heat is removed from the heat transfer fluid of the second circuit 490 by the intercircuit heat exchanger 450 and transferred to the heat transfer fluid of the first circuit 491. The heat transfer fluid of the second circuit 490 is circulated by the shelf / CTES circulation pump 470.

[0034] The CTES system 460 is selectively included in (or excluded from) the second circuit 490 using bypass valves 463 and valves 461, 462. As will be described in more detail below, heat is transferred from the CTES 460 to the heat transfer fluid in the first circuit 491 (refrozenting the CTES), i.e., the stored cold energy is transferred from the CTES to the heat transfer fluid (supplementing the turbo compressor cooling system when cooling the shelves). Preferably, the heat exchange between the CTES 460 and the fluid in the second circuit 490 is carried out without the use of an intervening or intermediate heat transfer fluid, i.e., without the use of any other heat transfer fluid to transfer heat between the CTES 460 and the heat transfer fluid in the first circuit 491.

[0035] In the sublimation portion of the freeze-drying cycle, a heater circuit 425 is provided to selectively heat the heat transfer fluid flowing to the freeze-drying chamber 410. Valve 426, together with bypass valve 411, regulates whether the heat transfer fluid flow passes through the shelf 423 or bypasses the shelf circuit during the refreezing of the CTES.

[0036] The bold circuit lines in the exemplary cooling system 400 shown in Figure 4 illustrate the flow of heat transfer fluid in two circuits 490, 491 during the turnaround portion 320 of the freeze-drying cycle (Figure 3), where the CTES system is refreezed for use in the next freeze-drying cycle. Meanwhile, the freeze-drying chamber 410 and condenser 420 are not used for freeze-drying, and no product is processed within the freeze-drying chamber.

[0037] In the configuration shown in Figure 4, by closing valve 442 and opening valve 441, the heat transfer fluid in the first circuit 491 circulates between the turbo compressor cooling system 440 and the inter-circuit heat exchanger 450 without cooling the condenser 420. Therefore, the entire cooling capacity of the turbo compressor cooling system 440 is directed to cooling the heat transfer fluid in the second circuit 490 via the inter-circuit heat exchanger 450.

[0038] Furthermore, as shown in Figure 4, the heat transfer fluid of the second circuit 490 is circulated directly from the inter-circuit heat exchanger 450 to the CTES system 460. The freeze-drying chamber 410 of the second circuit 490 is bypassed by opening valve 411 and closing valve 426.

[0039] The bolded flow paths shown in Figure 4 allow the CTES system 460 to be refreezed and prepared for the next freeze-drying cycle during a portion of the turnaround section 320 of the freeze-drying cycle when either or both of the freeze-drying chamber 410 and the condenser 420 are bypassed by the cooling system. The cooling system is available to refreeze the CTES system 460 when these freeze-drying components are bypassed during one or more of the operations performed during the turnaround section of the cycle, such as removal, defrosting, washing, sterilization, drying, and leak testing. It can be seen that such an arrangement allows the CTES system 460 to be used to complement the turbocompressor cooling system 440 with little to no increase in overall cycle time resulting from the refreezing of the CTES system.

[0040] The bolded flow paths in the exemplary cooling system 500 shown in Figure 5 illustrate the operation of the system during the frozen portion 318 of the freeze-drying cycle and the flow of heat transfer fluid in the two circuits 490, 491. The heat transfer fluid in the first circuit 491 is distributed to both the condenser 420 and the inter-circuit heat exchanger 450 by opening both valves 441, 442. The flow to the condenser 420 is controlled to bring its components to process temperature.

[0041] As shown in Figure 5, the heat transfer fluid in the second circuit 490 is cooled by the turbocompressor cooling system 440 via the inter-circuit heat exchanger 450. The heat transfer fluid in the second circuit 490 is further cooled by the CTES 460 before circulating through the shelves 423 of the freeze-drying chamber 410. Thus, the combined cooling capacity of the turbocompressor cooling system 440 and the CTES 460 is available to rapidly cool the shelves to handle the temperature and maintain them there during the freeze-drying portion 317 of the freeze-drying cycle. Thus, the increased cooling capacity by the CTES reduces the cycle time spent on the freeze-drying portion of the cycle. The CTES can also be used to supplement the turbocompressor cooling system 440 during the freeze-drying portion 318 of the freeze-drying cycle, if necessary.

[0042] The exemplary cooling system 600 shown in Figure 6 illustrates the operation of the system during the freeze-drying portion 318 (Figure 3) of the freeze-drying cycle and the flow of heat transfer fluid in the two circuits 490, 491. The CTES system 460 can be bypassed during freeze-drying by closing valve 462 and opening bypass valve 463. The CTES does not need to supplement the turbocompressor cooling system 440 to maintain the process temperature in the freeze-drying chamber 410.

[0043] The heater circuit 425, which is not activated during the freezing portion of the cycle, is used to add thermal energy to the shelf to allow sublimation under vacuum during the freeze-drying portion of the cycle.

[0044] Both the condenser 420 and the shelf 423 are cooled by the turbocompressor cooling system 440, but these two freeze-drying system components have different cooling requirements. The condenser 420 generally has lower temperature requirements than the shelf, but does not require high cooling capacity to achieve and maintain these low temperatures. In contrast, the shelf 423 does not need to be cooled to temperatures as low as those required by the condenser, but requires a greater cooling capacity than the condenser 420. In the freeze-drying cooling systems shown in Figures 4, 5, and 6, the condenser 420 is located in a first circuit 491 with the turbocompressor cooling system 440, and the shelf 423 is located in a second circuit 490 with the CTES 460. The turbocompressor cooling system 440 meets the cooling capacity requirements of the condenser 420 without supplementation by the CTES 460. By supplementing the turbocompressor with the CTES in the second circuit 490, the cooling requirements of the shelf are met without unnecessarily cooling the heat transfer fluid used in the first circuit 491 that cools the condenser.

[0045] The exemplary cooling system 700 shown in Figure 7 illustrates another embodiment of the system. In the configuration of Figure 7, the CTES 760 is located in the first heat exchange fluid circuit 791, shown in bold, rather than in the second heat exchange fluid circuit as shown in Figures 4-6. In the cooling system 700 of Figure 7, the CTES 760 is located in series with the turbo compressor cooling system 740.

[0046] By placing the CTES 760 in a separate circuit 791 from the circuit 790 which includes the freeze-drying chamber 710, the shelf circuit 723 of the freeze-drying chamber can be heated simultaneously with the refilling of the CTES. During the freeze-drying process, the heater 725 is typically activated, and the heat transfer fluid in circuit 790 is at a temperature above the refrozen temperature of the CTES. These conditions prevent the refilling of the CTES located in the same circuit 790 as the shelf 723. In the cooling system 700 shown in Figure 7, the CTES is placed in series with the turbo-compressor expander in the primary cooling circuit 791. In this configuration, by placing the CTES in circuit 791, the CTES can be refilled because there is a portion of the cycle where there is excess energy from the turbo-compressor expander that allows refrozenness to begin, particularly during primary and secondary drying, while the freeze-drying process is taking place. In this case, the primary cooling circuit runs at a temperature sufficient to allow the refrozenness process to occur.

[0047] If the setpoint of the condenser 720 is above the setpoint of the primary circuit 791, valve 742 opens in proportion to the amount of cooling required to maintain the condenser at its setpoint. Valve 741 may be closed and valve 743 opened to bypass the inter-circuit heat exchanger 750, the second circuit 790 and the shelf 723, in which case a primary cooling circuit is formed. This primary cooling circuit is independent of the cooling of the shelf or condenser and includes a pump 730, a turbo compressor 740 and a CTES 760 to directly and efficiently refill the CTES.

[0048] A method 800 according to an embodiment of the present disclosure is shown in Figure 8. The freeze-drying chamber is first disinfected, i.e., sterilized (operation 810) after the product processed in the previous cycle has been removed. In pharmaceutical manufacturing, all equipment components that come into contact with the product or process are typically cleaned using a clean-in-place (CIP) arrangement and sterilized using a steam or chemical fluid cleaner permanently installed in the equipment. No product is present in the freeze-drying chamber during the cleaning and sterilization operations.

[0049] Next, the products are loaded into the freeze-drying chamber by placing them on shelves (operation 820). The products may be in bulk form or in vials with partially open stoppers to allow water vapor to escape from the vials during the freeze-drying process. Both the products and the shelves in the freeze-drying chamber are at ambient temperature or pre-cooled during the loading process. In one embodiment, a CTES system is used to speed up the pre-cooling process. In another embodiment, the CTES system is bypassed during the pre-cooling process to conserve its thermal energy and is used to cool the products loaded shelf by shelf.

[0050] The CTES system is refilled during one or more operations of the turning portion 320 of the freeze-drying cycle (Figure 3) (operation 830). The CTES system is refilled by cooling the phase change material of the CTES system using a turbo compressor cooling system. In the embodiment described above with reference to Figure 4, two separate heat transfer fluid circuits 490, 491 are used for refilling the CTES. The heat transfer fluid of the first circuit 491 is cooled by the turbo compressor cooling system. This heat transfer fluid is used to cool the heat transfer fluid of the second circuit 490, which then refreezes the phase change material through the CTES system.

[0051] Since the refilling operation 830 is performed in parallel with the sterilization and loading operations 810 and 820, the use of the CTES system to supplement the turbocompressor cooling system does not excessively lengthen the overall freeze-drying cycle time.

[0052] Once the CTES system is refilled, the freeze-drying chamber is cooled (operation 840), and the product is frozen using the turbocompressor cooling system supplemented by the CTES. The length of time required to perform this operation is reduced by supplementing the turbocompressor cooling system with the CTES. In embodiments including a CTES system based on a phase-change material, the phase-change material is maintained at a substantially constant temperature as heat is transferred from the shelves of the freeze-drying chamber by the heat transfer fluid. During this operation, the condenser may be cooled using the heat transfer fluid cooled by the turbocompressor cooling system as preparation for the freeze-drying operation.

[0053] After the product is frozen, it is freeze-dried in a freeze-drying chamber (operation 850). The freeze-drying operation typically involves keeping the product frozen while exposing it to vacuum pressure. A small amount of heat is added to the product to initiate sublimation of the freezing solvent or suspension medium.

[0054] Finally, the chamber is returned to substantially ambient pressure and temperature, and the freeze-dried product is removed from the chamber (operation 860). Since neither the freeze-drying chamber nor the condenser is cooled during this operation, a refill operation 830 may be initiated during removal in preparation for the next freeze-drying cycle.

[0055] The above-mentioned detailed description is to be understood as descriptive and illustrative in all respects, but not restrictive, and the scope of the invention disclosed herein should not be determined by the description of the invention, but by the claims, which should be interpreted in accordance with all the scope permitted by patent law. The embodiments shown and described herein are merely illustrative of the principles of the invention, and it should be understood that various modifications can be made by those skilled in the art without departing from the scope and spirit of the invention.

Claims

1. A freeze-drying chamber including a chamber heat exchanger for cooling and heating products inside the freeze-drying chamber, A freeze dryer condenser connected to the freeze dryer chamber to receive exhaust gas from the freeze dryer chamber, The condensing surface of the freeze dryer condenser for condensing the exhaust gas, A first heat exchange fluid circuit is selectively connected to the condensing surface in order to circulate the first heat exchange fluid to the condensing surface, A turbo compressor cooling system connected to cool the first heat exchange fluid, A second heat exchange fluid circuit is connected to circulate a second heat exchange fluid through the aforementioned room heat exchanger, An intercircuit heat exchanger connected to exchange thermal energy between the first heat exchange fluid and the second heat exchange fluid, A thermal energy storage system comprising a phase change material for storing thermal energy and connected to at least the second heat exchange fluid for cooling, A bypass passage is provided in the second heat exchange fluid circuit to selectively bypass the aforementioned cold heat storage system, A freeze-drying system equipped with the following features.

2. The freeze-drying system according to claim 1, wherein the cold heat storage system is connected to cool the second heat exchange fluid without using an intermediate heat exchange fluid.

3. The freeze-drying system according to claim 1, further comprising a bypass passage in the second heat exchange fluid circuit for selectively bypassing the aforementioned room heat exchanger.

4. The freeze-drying system according to claim 3, further comprising a valve in the first heat exchange fluid circuit to selectively bypass the freeze-dryer condenser.

5. The freeze-drying system according to claim 4, further comprising one or more circulation pumps in the first heat exchange fluid circuit for circulating the first heat exchange fluid.

6. The freeze-drying system according to claim 5, further comprising one or more circulation pumps in the second heat exchange fluid circuit for circulating the second heat exchange fluid.

7. The freeze-drying system according to claim 6, further comprising a heater circuit connected to the second heat exchange fluid circuit for selectively heating the second heat exchange fluid.

8. The freeze-drying system according to claim 1, wherein the cold heat storage system is connected to cool the first heat exchange fluid without using an intermediate heat exchange fluid.

9. The freeze-drying system according to claim 8, further comprising a bypass passage in the first heat exchange fluid circuit to selectively bypass the inter-circuit heat exchanger.

10. Sterilizing the freeze-drying chamber using a fixed washing arrangement, Loading the product into the aforementioned freeze-drying chamber, During at least one of the periods between sterilization and loading, the first heat transfer fluid is cooled using a turbo compressor cooling system, the second heat transfer fluid is cooled using the first heat transfer fluid via an intercircuit heat exchanger, and the phase change material of the cold heat storage system is cooled using the second heat transfer fluid to refill the cold heat storage system. After refilling the cold thermal storage system, the inside of the freeze-drying chamber is cooled to the process temperature using the turbo compressor cooling system, which is supplemented by the cold thermal storage system connected to at least the second heat transfer fluid, While the interior of the freeze-drying chamber is cooled to the process temperature, the first heat transfer fluid is circulated through the turbo compressor cooling system, through the inter-circuit heat exchanger, and through a bypass line that bypasses the condenser. The process involves freezing the components of the product in the freeze-drying chamber to form frozen components, Sublimation of the frozen components in the freeze-drying chamber to form vapor, The first heat transfer fluid is selectively circulated through a condenser coil having a condensing surface in the condenser, and the steam is condensed on the condensing surface using the turbo compressor cooling system. While the frozen components are sublimated and the steam is condensed, the first heat transfer fluid is passed through the turbo compressor cooling system, through the intercircuit heat exchanger, and through the condenser, While the aforementioned freezing components are sublimated and the steam is condensed, the second heat transfer fluid is passed through the intercircuit heat exchanger, through a bypass line that bypasses the cold heat storage system, and through the freeze-drying chamber for circulation. Removing the product from the freeze-drying chamber, A method for freeze-drying the product, comprising the above-mentioned components.

11. While the interior of the freeze-drying chamber is cooled to the process temperature, the second heat transfer fluid is circulated by passing it through the inter-circuit heat exchanger, through the cold heat storage system, and through the freeze-drying chamber. While the cold heat storage system is being refilled, the second heat transfer fluid is circulated by passing it through the intercircuit heat exchanger, through the cold heat storage system, and through a bypass line that bypasses the freeze-drying chamber. The method according to claim 10, further comprising:

12. Refilling the aforementioned thermal storage system is To cool the phase change material of the cold thermal storage system using a first heat transfer fluid that transfers thermal energy between the cold thermal storage system and the turbo compressor cooling system without using an intermediate heat transfer fluid, The method according to claim 10, further comprising:

13. While the interior of the freeze-drying chamber is cooled to the process temperature, the first heat transfer fluid is circulated by passing it through the turbo compressor cooling system, the cold heat storage system, the inter-circuit heat exchanger, and a bypass line that bypasses the condenser. While the frozen components are sublimated and the steam is condensed, the first heat transfer fluid is circulated by passing it through the turbo compressor cooling system, through a bypass line that bypasses the cold heat storage system, through the inter-circuit heat exchanger, and through the condenser. The method according to claim 12, further comprising:

14. While the interior of the freeze-drying chamber is cooled to the process temperature, the second heat transfer fluid is passed through the inter-circuit heat exchanger and circulated through the freeze-drying chamber. While the aforementioned cold heat storage system is being refilled, the second heat transfer fluid is circulated through the inter-circuit heat exchanger and through a bypass line that bypasses the freeze-drying chamber. The method according to claim 13, further comprising:

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