Equipment and methods for microwave vacuum drying of sterile products

Abstract

A microwave vacuum dryer includes: a loading chamber and a first vacuum pump connected to the loading chamber; a first gate, the first gate isolating the loading chamber from the external environment; a drying chamber adjacent to the loading chamber, a second vacuum pump connected to the drying chamber, and a condenser connected to the drying chamber; a second gate, the second gate isolating the loading chamber from the drying chamber; an unloading chamber adjacent to the drying chamber and a third vacuum pump connected to the unloading chamber; a third gate, the third gate isolating the drying chamber from the unloading chamber; a fourth gate, the fourth gate isolating the unloading chamber from the external environment; and a microwave chamber having a plurality of magnetrons, the microwave chamber being located on a different plane from the loading chamber and the unloading chamber and adjacent to the drying chamber.

Description

Technical Field

[0001] This invention relates to an apparatus and method for microwave vacuum drying of organic materials, including bioactive materials such as vaccines, antibiotics, proteins, and microbial cultures. Background Technology

[0002] Microwave vacuum drying is a drying method that can be applied to dehydrate pharmaceutical biomaterials such as vaccines and antibodies. Microwave vacuum drying (also known as microwave vacuum dehydration) is a rapid drying method that can produce products with improved quality compared to air drying and freeze drying. Because drying is carried out under reduced pressure, the boiling point of water and the oxygen content of the atmosphere are lowered, allowing components sensitive to oxidation and thermal degradation to be retained to a higher degree than air drying. The drying process is also faster than air drying and freeze drying.

[0003] However, large-scale microwave vacuum drying of pharmaceutical biomaterials while simultaneously complying with current Good Manufacturing Practice (cGMP) is challenging. Currently manufactured microwave vacuum dryers are designed to address food safety concerns, not for drying pharmaceutical products in more strictly controlled GMP environments. Microwave vacuum drying under cGMP conditions must minimize particulate matter generated during the drying process, allow for controlled and reproducible drying, and permit the cleaning and sterilization of the drying chamber according to cGMP regulations. Summary of the Invention

[0004] In one aspect of the invention, a microwave vacuum dryer includes: a loading chamber and a first vacuum pump communicating with the loading chamber; a first gate separating the loading chamber from an external environment; a drying chamber adjacent to the loading chamber, a second vacuum pump communicating with the drying chamber, and a condenser communicating with the drying chamber; a second gate separating the loading chamber from the drying chamber; an unloading chamber adjacent to the drying chamber and a third vacuum pump communicating with the unloading chamber; a third gate separating the drying chamber from the unloading chamber; a fourth gate separating the unloading chamber from the external environment; and a microwave chamber having a plurality of magnetrons, the microwave chamber being located on a different plane from the loading chamber and the unloading chamber and adjacent to the drying chamber.

[0005] In another embodiment of the invention, the microwave vacuum dryer described above is provided, wherein the microwave chamber is located below the drying chamber.

[0006] In another embodiment of the invention, there is a microwave vacuum dryer according to the foregoing, wherein the drying chamber has a base plate defining two internal parallel edges and at least two walls, the two edges including removable tray rails.

[0007] In another embodiment of the invention, the microwave vacuum dryer described above is provided, wherein the loading chamber, the drying chamber, and the unloading chamber are each aligned along a central axis.

[0008] In another embodiment of the invention, the microwave vacuum dryer described above is provided, wherein the first gate and the fourth gate are manually operable.

[0009] In another embodiment of the invention, according to the aforementioned microwave vacuum dryer, the second gate and the third gate are automatically operable and allow the second gate and the third gate to move simultaneously.

[0010] In another embodiment of the invention, according to the aforementioned microwave vacuum dryer, the plurality of magnetrons are arranged in an array along the length of the drying chamber located between the second gate and the third gate.

[0011] In another embodiment of the invention, the microwave vacuum dryer described above is provided, wherein the array of magnetrons is arranged in rows.

[0012] In another embodiment of the invention, there is a microwave vacuum dryer as described above, wherein the rows comprise six rows of magnetrons.

[0013] In another embodiment of the invention, according to the aforementioned microwave vacuum dryer, each of the six rows of magnetrons comprises three individual magnetrons.

[0014] In another embodiment of the invention is the microwave vacuum dryer described above, wherein each of the plurality of magnetrons has a predetermined power setting based on its position along the length of the drying chamber.

[0015] In another embodiment of the invention, according to the aforementioned microwave vacuum dryer, the drying chamber includes multiple ports for monitoring the drying of a container of cryogenic solution. In some embodiments, the multiple ports include thermal imaging probes or fiber optic probes.

[0016] In another embodiment of the invention, according to the aforementioned microwave vacuum dryer, at least one of the unloading chamber, the drying chamber, and the loading chamber includes an outer gasket and an inner gasket adjacent to the outer gasket, the outer gasket serving as a microwave seal when one of the chamber gates is closed, and the inner gasket providing a sterile boundary when one of the chamber gates is closed.

[0017] In another embodiment of the invention, according to the aforementioned microwave vacuum dryer, each of the unloading chamber, the drying chamber, and the loading chamber includes an outer gasket and an inner gasket adjacent to the outer gasket, the outer gasket serving as a microwave seal when one of the chamber gates is closed, and the inner gasket providing a sterile boundary when one of the chamber gates is closed.

[0018] In another embodiment of the invention, the microwave vacuum dryer described above further includes a tray unloader housed in the unloading chamber and a tray loader housed in the loading chamber.

[0019] In another embodiment of the invention, according to the aforementioned microwave vacuum dryer, the unloading chamber includes a shut-off valve for partially backfilling the unloading chamber with inert gas, and a plug mechanism for closing a partially plugged container.

[0020] In another aspect of the invention, a method for drying a product (including, but not limited to, pharmaceutical products reflecting GMP requirements) includes: providing a microwave vacuum dryer having a loading chamber and a first vacuum pump communicating with the loading chamber, a first gate separating the loading chamber from an external environment, a drying chamber adjacent to the loading chamber, a second vacuum pump communicating with the drying chamber, and a condenser communicating with the drying chamber via vapor, a second gate separating the loading chamber from the drying chamber, an unloading chamber adjacent to the drying chamber and a third vacuum pump communicating with the unloading chamber, a third gate separating the drying chamber from the unloading chamber, a fourth gate separating the unloading chamber from the external environment, a microwave chamber having a plurality of magnetrons located on a different plane from the loading chamber and the unloading chamber and adjacent to the drying chamber; evacuating air from the drying chamber using the second vacuum pump; and activating at least one of the plurality of magnetrons to generate a microwave field within the drying chamber.

[0021] In another embodiment of the invention, the method for drying the product described above further includes the step of: recirculating water adjacent to the drying chamber to remove excess microwaves from the drying chamber.

[0022] In another embodiment of the invention, the method for drying the product described above further includes the following steps: opening the first gate, loading a first tray carrying one or more containers containing a freezing solution into the loading chamber, closing the first gate, and evacuating air from the loading chamber to balance the environment of the loading chamber with the environment of the drying chamber.

[0023] In another embodiment of the invention, the method for drying the product described above further includes the steps of: opening the second gate, using a pallet loader housed in the loading chamber to advance the first pallet of the container into the drying chamber, and closing the second gate.

[0024] In another embodiment of the invention, the method for drying the product described above further includes the steps of: loading an additional tray into the loading chamber, closing the first gate, and evacuating air from the loading chamber to balance the environment of the loading chamber with that of the drying chamber.

[0025] In another embodiment of the invention, the method for drying products described above is provided, wherein the additional tray carries one or more containers containing a freezing solution, or wherein the additional tray is empty.

[0026] In another embodiment of the invention, the method for drying a product as described above further includes the step of: using a pallet loader housed in the loading chamber to push the additional pallet into the drying chamber, thereby using the additional pallet to further push the first pallet into the drying chamber.

[0027] In another embodiment of the invention, the method for drying products described above further includes the steps of repeatedly loading an additional tray into the loading chamber and pushing a tray in front of the additional tray through the drying chamber until the drying chamber is filled with the tray.

[0028] In another embodiment of the invention, the method for drying a product described above is provided, wherein the plurality of magnetrons are arranged in an array along the length of the drying chamber located between the second gate and the third gate, and wherein the magnetrons in different portions of the array are activated at different power levels before the first tray of the container is pushed into the drying chamber.

[0029] In another embodiment of the invention, the method for drying a product as described above is provided, wherein the plurality of magnetrons are arranged in an array along the length of the drying chamber located between the second gate and the third gate, and wherein the plurality of magnetrons are activated to one or more predetermined power levels, and wherein the plurality of magnetrons are activated after the drying chamber is filled with a tray.

[0030] In another embodiment of the invention, the method for drying the product described above further includes the steps of: opening the third gate and using a tray unloader housed in the unloading chamber to advance the first tray into the unloading chamber.

[0031] In another embodiment of the invention, the method for drying the product described above further includes the step of sequentially advancing all the trays from the drying chamber to the unloading chamber.

[0032] In another embodiment of the invention, the method for drying the product described above further includes the step of removing the first tray from the unloading chamber.

[0033] In another embodiment of the invention, there is a method for drying products as described above, wherein the drying chamber has a base plate defining two internal parallel edges and at least two walls, the two edges including removable tray rails.

[0034] In another embodiment of the invention, the method for drying the product described above further includes operating the microwave vacuum dryer in a semi-continuous mode by sequentially performing the following steps: (i) evacuating air from the drying chamber using the second vacuum pump, (ii) recirculating water in a water chamber above the drying chamber, (iii) generating a microwave field in the drying chamber, (iv) loading a first tray containing a container of freezing solution into the loading chamber and closing the first gate, (v) evacuating air from the loading chamber to equilibrate the environment of the loading chamber with the environment of the drying chamber, and (vi) drying the freezing solution in the container of the first tray in the drying chamber.

[0035] In another embodiment of the invention, the method for drying the product described above further includes operating the microwave vacuum dryer in batch mode by sequentially performing the following steps: (i) evacuating air from the drying chamber using the second vacuum pump, (ii) loading a plurality of trays containing containers of freezing solution into the drying chamber through the loading chamber, (iii) recirculating water in a water chamber above the drying chamber, (iv) generating a microwave field in the drying chamber, and (v) drying the freezing solution in the containers in the drying chamber.

[0036] In another embodiment of the invention, according to the aforementioned method for drying a product, the unloading chamber includes a shut-off valve for partially backfilling the unloading chamber with inert gas, and a plug mechanism for closing a partially clogged container. Attached Figure Description

[0037] This document discloses various embodiments of the currently disclosed apparatus and methods with reference to the accompanying drawings, wherein:

[0038] Figures 1 to 5 These are schematic perspective views, rear view, front view, top view, and exploded perspective views of a microwave vacuum dryer;

[0039] Figures 6 to 7This indicates that the lid is in the open position. Figures 1 to 5 Schematic rear and side views of a microwave vacuum dryer;

[0040] Figure 8 It is a photograph showing the gasket of the chamber;

[0041] Figure 9 The photo shows a removable microwave barrier that can be removed and cleaned.

[0042] Figures 10 to 11 It is a photograph showing the passageway inside the drying chamber; and

[0043] Figure 12 This is a schematic three-dimensional diagram of a room equipped with a microwave vacuum dryer.

[0044] Various embodiments will now be described with reference to the accompanying drawings. It should be understood that these drawings depict only some embodiments of the invention and therefore should not be considered as limiting its scope. Detailed Implementation

[0045] Despite various improvements to microwave vacuum drying, conventional apparatus and methods still have some drawbacks.

[0046] Therefore, there is a need for further improvements to apparatus and methods for microwave vacuum drying, particularly to allow for more efficient production and permit, for example, continuous or semi-continuous production of live virus vaccines. This invention addresses one or more of these needs, among other advantages.

[0047] Figures 1 to 5 An example of a microwave vacuum dryer 100 according to an embodiment of the present invention is shown. The vacuum dryer 100 generally extends between a first end 102 (or inlet) and a second end 104 (or outlet) and includes a plurality of chambers arranged adjacent to each other. Proceeding from the first end 102 toward the second end 104, the vacuum dryer 100 includes a loading chamber 110, a drying chamber 112, and an unloading chamber 114. The vacuum dryer 100 also includes a microwave chamber 116. In this example, the loading chamber, drying chamber, and unloading chamber are aligned along a central axis, the drying chamber 112 is disposed between the other two chambers, and the microwave chamber 116 is disposed below the drying chamber.

[0048] from Figure 12 As best seen, a plurality of vacuum pumps 146 may be in communication with loading chamber 110, drying chamber 112, and unloading chamber 114. In at least some examples, each of the three chambers may have a designated vacuum pump 146a-c in communication with it via a hose or conduit (e.g., vacuum pump 146a is in communication with loading chamber 110, vacuum pump 146b is in communication with drying chamber 112 via a condenser, and vacuum pump 146c is in communication with unloading chamber 114).

[0049] like Figure 2 As best shown, loading chamber 110 and unloading chamber 114 each have a pair of airlocks 121, 122 and 123, 124. These airlocks allow containers containing products to be loaded into and unloaded from these chambers while maintaining them under reduced pressure required for the dehydration process. Specifically, a first airlock 121 isolates loading chamber 110 from the external environment, while a second airlock 122 isolates loading chamber 110 from drying chamber 112. Similarly, a third airlock 123 isolates drying chamber 112 from unloading chamber 114, and a fourth airlock 124 isolates unloading chamber 114 from the environment. Each of these airlocks can be manually or automatically actuated to allow communication or establish a pathway between a chamber and an adjacent chamber or between a chamber and the environment. In at least some examples, the second and third airlocks are synchronized, such that they open and / or close simultaneously. When gates 121-124 are open, a single continuous passage 125 is formed from the first end 102 to the second end 104, as shown by the dashed line. Certain elements of the passage 125 adjacent to the gate positions are shown in detail “A”, which correspond to… Figure 8 The photo.

[0050] Each chamber can typically include stainless steel, other metals, or suitable materials that can block the microwave path. Figure 8 These are photographs showing some details of the chambers. Each of the unloading chamber, drying chamber, and loading chamber may include a sealing element between them, such as an outer gasket 126 serving as a microwave seal to prevent microwave leakage and thus protect the operator. An inner gasket 127 may also be included adjacent to the outer gasket 126; the inner gasket is a vacuum-grade gasket to provide a sterile boundary.

[0051] Back to Figure 3Microwave chamber 116 may be disposed below drying chamber 112 and may include a plurality of magnetrons 130. The plurality of magnetrons 130 may be arranged in an array within microwave chamber 116, below drying chamber 112, and along the length of drying chamber 112. This magnetron array may include one row / group or several rows / groups (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or more rows of magnetrons), and each row may include a single magnetron 130 (e.g., one, two, three, or more magnetrons per row). In at least some examples, the magnetrons 130 may be arranged in a matrix of rows and columns below the drying chamber. Based on their position along the length of the drying chamber, each of the plurality of magnetrons may be set to a predetermined power setting (e.g., between 50 watts and 900 watts, between 50 watts and 500 watts, or between 100 watts and 500 watts). Alternatively, each magnetron within a specific row can be set to a predetermined power. Furthermore, each magnetron can be programmed to turn on or off at specific time periods during the process to improve the uniformity of product drying.

[0052] As noted, in some examples, microwave chamber 116 is positioned below drying chamber 112, and microwaves are generated in microwave chamber 116 below drying chamber. Microwaves can reach drying chamber via traveling waveguides. In these examples, microwaves then pass through drying chamber 112 to a water circulation system 117 located above drying chamber. Water circulation system 117 may include wave-permeable conduits (e.g., plastic pipes or tubing) in which cold water is recirculated. The conduits may be arranged in a serpentine path parallel to the drying surface. This prevents reflections of waves and standing waves and allows one-way microwaves. The bottom and top plates of drying chamber may be formed of plastic or other wave-permeable materials to allow microwaves to pass through. At least one side of drying chamber (e.g., sidewall, bottom plate, or top plate) may include a port for process monitoring. In at least some examples, this port is used for thermal imaging probes or fiber optic probes, which are needed because they allow monitoring without disrupting the sterile boundary. For example, port 118 is located on the top plate of drying chamber 112 (see...). Figure 3 In some examples, adding traveling waveguides, magnetron arrays, water circulation systems 117, and other features can provide uniformity in drying.

[0053] The microwave vacuum dryer 100 may further include a condenser 132, which is connected to the drying chamber 112 via a delivery pipe or conduit 133. The condenser is configured to receive sublimated vapors from the dehydrated product and trap them as ice on a cold coil. Alternatively, a removable microwave barrier 134 may be placed between the condenser and the drying chamber to prevent microwaves from entering the condenser 132. Figure 9Vacuum pump 146 can evacuate the condenser, and cooler 139 is configured to adjust the temperature of the condenser by means of coolant and cool it to an appropriate temperature. Figure 12 In at least some examples, cooler 139 is configured to maintain the condenser at a temperature between -60 degrees Celsius and -80 degrees Celsius or lower. Alternatively, two or more condensers can be used to allow continuous operation, such that one condenser can be emptied while another continues to operate.

[0054] exist Figure 3 In this configuration, conveyor belt system "B" runs through the drying chamber to provide a movement mechanism for moving products from one side of the drying chamber 112 to the other. Because conveyor belt systems can generate particulate matter, this configuration is not preferred for use in current Good Manufacturing Practice (cGMP) environments. Alternatively, an oscillating ratchet system with movable walls can move trays through the drying chamber. In another embodiment, such as... Figures 10 to 11 As shown, a smooth guide channel 135 with rails 136 can be used. Channel 135 may include two walls and a base plate 137 defining two parallel inner edges, which include removable tray rails that can be removed for cleaning and reinserted into channel 135. In some examples, rails 136 are positioned within a trough that slopes towards a lower discharge channel. Channel 135 has no actuating components; instead, it relies on a tray delivery assembly to move the tray "T" through the chamber.

[0055] like Figure 3 As best shown, in addition to conveyor systems, ratchet systems, or smooth aisles, pallet conveying assemblies can be used. Pallet conveying assemblies include a pallet loader shown as pallet pusher 142 and a pallet unloader shown as pallet puller 144. In some examples, pallet pusher 142 includes one or more arms positioned in a first position within loading chamber 110 and configured and arranged to move to a second position within the drying chamber to drive a pallet from loading chamber 110 into drying chamber 112 and retract to its initial position. In other examples, this process may be repeated two or more times to gradually push the pallet into the drying chamber. In some examples, pallet puller 144 includes one or more arms positioned in a first position within unloading chamber 114 and configured and arranged to move to a second position within the drying chamber to collect a pallet from drying chamber 112 into unloading chamber 114 and retract to its initial position. In other examples, this process may be repeated two or more times to gradually pull the pallet into the unloading chamber (e.g., the pallet puller 144 may be actuated two or more times to fully pull the pallet into the unloading chamber).

[0056] Alternatively, the drying chamber 112 may include a lid 150 configured to be opened or closed. Figures 6 to 7 In one example, the lid 150 is connected to the drying chamber via one or more hinges 152, allowing the lid to be opened to allow cleaning of the interior of the drying chamber. The lid 150 may accommodate a water circulation system 117.

[0057] Alternatively, the loading chamber 110, drying chamber 112, unloading chamber 114, and condenser 132 can be configured to be sterilized using an external VHP generator system via vaporized hydrogen peroxide (VHP). Typically, VHP utilizes vaporized hydrogen peroxide as a broad-spectrum antimicrobial agent and is effective against bacteria, yeast, viruses, and bacterial spores, thus targeting biopharmaceutical purification systems. The dryer can be configured by the operator to achieve optimal sterilization cycles through VHP circulation. VHP ports can be used as inlets or outlets and can be located on the loading chamber 110, unloading chamber 114, and / or condenser 132. The system can be configured to allow for a single inlet and a single outlet, or multiple inlets and / or outlets (e.g., two inlets and one outlet, or two outlets and one inlet). The inner surface of the vacuum dryer 100 can be made of a material that does not react with VHP, such as stainless steel, aluminum, acrylonitrile butadiene styrene (ABS), or polyvinyl chloride (PVC). In at least some examples, the tray pusher 142, the tray puller 144, the second gate 122 and / or the third gate 123 are circulated during VHP to ensure that their surfaces are also sterilized.

[0058] In use, the vacuum dryer 100 can operate in one of two modes: a semi-continuous mode or a batch mode. Each of these modes will now be described in more detail. It should be understood that the same microwave vacuum dryer can operate in either mode, and the mode can be selected by connecting the vacuum dryer to a computer, laptop, tablet, or telephone via a wired or wireless connection, or via an embedded computer with memory, a processor, and an interface. In at least some examples, the vacuum dryer 100 may have a controller "C" with a processor and memory, capable of monitoring, regulating, or adjusting the vacuum pump 146, magnetron 130, cooler 139, condenser 132, and / or water circulation system 117. Figure 12 ).

[0059] Semi-continuous mode

[0060] In semi-continuous mode, a vacuum pump evacuates the condenser 132 and drying chamber 112, while gates 122 and 123 remain closed. Cooler 139 cools the condenser 132 to the desired temperature. Alternatively, cooler 139 may also be used to cool a cooling platform or cooling plate disposed on the base plate of loading chamber 110. The cooling plate ensures that the frozen product does not exceed its glass transition temperature (Tg). The glass transition temperature is the temperature at which an amorphous material transitions from a rigid glass to a viscous solid. By keeping the product below its glass transition temperature during loading, the product is protected from damage, and bulk materials are protected from collapse. Vaccines and biological agents can have glass transition temperatures ranging from -28°C to -41°C, therefore it is desirable to keep them frozen below their respective glass transition temperatures before the drying process begins.

[0061] Once the target vacuum in drying chamber 112 and the target temperature in condenser 132 are reached, magnetron 130 in microwave chamber 116 is switched on to generate a microwave field. Water is recirculated through water circulation system 117 to remove excess microwaves from the drying chamber. Frozen products placed in containers (e.g., vials, beads, double-chamber cylinders, bottles, or bulk materials in trays) can be placed on trays and manually loaded into loading chamber 110. The frozen products themselves may include any one or more of live viral vaccines, enveloped and non-enveloped viruses, adjuvants, subunit vaccines, proteins, peptides, antibody-drug conjugates (ADCs), bispecific fusion proteins, and / or small molecule drugs. Gate 121 is then closed, and a second vacuum pump evacuates loading chamber 110. If enabled, a cooling platform in loading chamber 110 is used to keep the product frozen during evacuation.

[0062] Once loading chamber 110 is balanced with drying chamber 112, second gate 122 opens automatically (or manually), and tray pushing mechanism pushes product trays into drying chamber 112. Optionally, position sensors can be added to either the drying chamber or loading chamber to monitor tray position. Tray pusher 142 can then retract and optionally provide a follow-up push to fully load the tray into the drying chamber. After the final push, tray pusher 142 can then retract and second gate 122 can close. Drying of the first tray can then begin in drying chamber 112. At any point during the drying process, the operator can load the second tray into loading chamber 110. Specifically, the vacuum in loading chamber 110 is released and first gate 121 is opened. Next, the operator can load the tray with the frozen product as described above. First gate 121 can then be closed, and loading chamber 110 can be evacuated and held within loading chamber 110 for a calculated time. In some examples, the calculated time is determined by dividing the desired total drying time by the number of positions in drying chamber 112. Once the calculation time has elapsed, the second tray is pushed into the drying chamber 112 as described above. As the second tray moves into the drying chamber 112, it contacts and pushes the adjacent first tray further in a straight line within the drying chamber 112. In this way, each tray pushed by the tray pusher 142 is used to advance within the drying chamber 112 without generating particles.

[0063] This process can be repeated at timed intervals until all drying positions in the drying chamber 112 are filled. Throughout the process, the product trays are dehydrated, and their water vapor is collected at the condenser 132. At any given time, each tray is at a different point in its dehydration curve. Therefore, the magnetrons 130 can be programmed, configured, and arranged to be activated at different power settings based on their position within the drying chamber 112 and / or the heat required for that portion of the dehydration cycle.

[0064] At the second end 104 of the vacuum dryer 100, the trays are unloaded in the same order as the loading trays. Once the first tray has spent the appropriate time in its final dried position in the drying chamber 112, the unloading process begins. A vacuum is drawn into the unloading chamber 114 by a third vacuum pump. When the unloading chamber 114 is balanced with the drying chamber 112, the third gate 123 opens automatically. The tray puller 144 extends into the drying chamber 112 and retracts the tray into the unloading chamber 114. Optionally, the tray puller 144 can perform multiple extension / retraction steps to gradually unload the tray. After complete retraction, the third gate 123 can close. For partially clogged vials, optional gas backfilling can be performed to provide a partial vacuum within the vial. The gas can be selected from nitrogen, argon, or a suitable gas, and backfilling can be performed at a pressure between 200 and 750 Torr, between 450 and 700 Torr, or 540 Torr or approximately 540 Torr. A stopper plate compresses the vial to secure it. The stopper plate can be driven by a hydraulic, pneumatic, or electric motor from the external environment, which is connected to the stopper plate via a bellows shaft to maintain the sterility of the unloading chamber 114. The stopper plate can be configured to be compressed multiple times with programmable force and residence time. Afterward, the vacuum is released and the operator manually unloads the tray from the fourth gate 124.

[0065] As the tray is removed from the unloading chamber 114, the fourth gate 124 closes and a vacuum is drawn again into the unloading chamber 114. The unloading process is repeated as described above until the final tray is removed. Because the movement of the tray through the drying chamber 112 depends on the introduction of a new tray through the loading chamber 110, an "empty tray" containing no product but having a similar weight to the product tray must be loaded until the final product tray is unloaded. Alternatively, a weight equal to the loaded vials can be added to the "empty tray".

[0066] Batch mode

[0067] A similar method can be used for batch processing, but with some differences. After the drying chamber 112 is evacuated, but before the magnetron 130 is turned on, product pallets can be loaded into the loading chamber 110. The pallets are loaded using the same loading process as described above, but there is no holding time between pallet loading actions. Once the drying chamber 112 is loaded using the pallet pusher 142, the magnetron 130 is turned on. The power of the magnetron 130 varies over time, rather than having a different power setting based on its position within the drying chamber 112. After a sufficient drying time (e.g., between 3 and 24 hours), the magnetron 130 is turned off. The pallets are then unloaded from the unloading chamber 114 one pallet at a time, as described above.

[0068] It should be understood that the embodiments described herein are merely illustrative examples of the principles and applications of the invention. Furthermore, certain components are optional, and the invention contemplates various configurations and combinations of the elements disclosed herein. Therefore, it should be understood that various modifications can be made to the exemplary embodiments, and other arrangements can be designed, without departing from the spirit and scope of the invention as defined by the appended claims.

[0069] It should be understood that the various dependent claims and the features set forth therein may be combined in ways different from those presented in the initial claims. It should also be understood that features described in conjunction with a single embodiment may be shared with other described embodiments.

Claims

1. A microwave vacuum dryer, comprising: A loading chamber and a first vacuum pump connected to the loading chamber; A first gate separates the loading chamber from the external environment; A drying chamber adjacent to the loading chamber, a second vacuum pump communicating with the drying chamber, and a condenser communicating with the drying chamber; A second gate separates the loading chamber from the drying chamber; An unloading chamber adjacent to the drying chamber and a third vacuum pump connected to the unloading chamber; A third gate separates the drying chamber from the unloading chamber; The fourth gate separates the unloading chamber from the external environment; as well as A microwave chamber having multiple magnetrons, the microwave chamber being located on a different plane from the loading chamber and the unloading chamber and adjacent to the drying chamber. Each of the unloading chamber, the drying chamber, and the loading chamber includes an outer gasket and an inner gasket adjacent to the outer gasket, the outer gasket serving as a microwave seal when one of the chamber's gates is closed, and the inner gasket providing a sterile boundary when one of the chamber's gates is closed.

2. The microwave vacuum dryer according to claim 1, wherein, The microwave chamber is located below the drying chamber.

3. The microwave vacuum dryer according to claim 1, wherein, The drying chamber has a base plate defining two internal parallel edges and at least two walls, the two edges including removable tray rails.

4. The microwave vacuum dryer according to claim 1, wherein, The loading chamber, the drying chamber, and the unloading chamber are each aligned along their central axis.

5. The microwave vacuum dryer according to claim 1, wherein, The first gate and the fourth gate are manually operable.

6. The microwave vacuum dryer according to claim 1, wherein, The second gate and the third gate are automatically operable and allow the second gate and the third gate to move simultaneously.

7. The microwave vacuum dryer according to claim 1, wherein, The plurality of magnetrons are arranged in an array along the length of the drying chamber located between the second gate and the third gate.

8. The microwave vacuum dryer according to claim 7, wherein, The array of magnetrons is arranged in rows.

9. The microwave vacuum dryer according to claim 8, wherein, The row includes six rows of magnetrons.

10. The microwave vacuum dryer according to claim 9, wherein, Each of the six rows of magnetrons includes three individual magnetrons.

11. The microwave vacuum dryer according to claim 7, wherein, Each of the plurality of magnetrons has a predetermined power setting based on its position along the length of the drying chamber.

12. The microwave vacuum dryer according to claim 1, wherein, The drying chamber includes multiple ports for monitoring the drying of containers holding the freezing solution.

13. The microwave vacuum dryer according to claim 1, further comprising a tray unloader housed in the unloading chamber and a tray loader housed in the loading chamber.

14. The microwave vacuum dryer according to claim 1, wherein, The unloading chamber includes a shut-off valve for partially backfilling the unloading chamber with inert gas, and a plug mechanism for closing a partially blocked container.

15. A method for drying a product, comprising: A microwave vacuum dryer is provided, the microwave vacuum dryer having Loading chamber and a first vacuum pump connected to said loading chamber, A first gate separates the loading chamber from the external environment. A drying chamber adjacent to the loading chamber, a second vacuum pump communicating with the drying chamber, and a condenser communicating with the drying chamber via vapor. A second gate separates the loading chamber from the drying chamber. An unloading chamber adjacent to the drying chamber and a third vacuum pump connected to the unloading chamber, A third gate separates the drying chamber from the unloading chamber. A fourth gate, which separates the unloading chamber from the external environment, and a microwave chamber having multiple magnetrons, the microwave chamber being located on a different plane from the loading chamber and the unloading chamber and adjacent to the drying chamber; The second vacuum pump is used to evacuate air from the drying chamber; as well as At least one of the plurality of magnetrons is activated to generate a microwave field in the drying chamber, wherein each of the unloading chamber, the drying chamber, and the loading chamber includes an outer gasket located therebetween and an inner gasket adjacent to the outer gasket, the outer gasket serving as a microwave seal and the inner gasket providing a sterile boundary.

16. The method of claim 15, further comprising the step of: The water adjacent to the drying chamber is recirculated to remove excess microwaves from the drying chamber.

17. The method of claim 15, further comprising the step of: The first gate is opened, a first tray carrying one or more containers containing a freezing solution is loaded into the loading chamber, the first gate is closed, and air is evacuated from the loading chamber to balance the environment of the loading chamber with that of the drying chamber.

18. The method of claim 17, further comprising the step of: The second gate is opened, the first pallet of the container is pushed into the drying chamber using a pallet loader housed in the loading chamber, and the second gate is closed.

19. The method of claim 18, further comprising the steps of: loading an additional pallet into the loading chamber, closing the first gate, and evacuating air from the loading chamber to balance the environment of the loading chamber with that of the drying chamber.

20. The method according to claim 19, wherein, The additional tray carries one or more containers containing a freezing solution, or the additional tray may be empty.

21. The method of claim 19, further comprising the step of: using a pallet loader housed in the loading chamber to push the additional pallet into the drying chamber, thereby further pushing the first pallet into the drying chamber with the additional pallet.

22. The method of claim 21, further comprising the step of: Repeatedly load the additional pallet into the loading chamber and push the pallet in front of the additional pallet through the drying chamber until the drying chamber is full of pallets.

23. The method according to claim 22, wherein, The plurality of magnetrons are arranged in an array along the length of the drying chamber located between the second gate and the third gate, and wherein the magnetrons in different portions of the array are activated at different power levels before the first tray of the container is pushed into the drying chamber.

24. The method according to claim 22, wherein, The plurality of magnetrons are arranged in an array along the length of the drying chamber located between the second gate and the third gate, and wherein the plurality of magnetrons are activated to one or more predetermined power levels, and wherein the plurality of magnetrons are activated after the drying chamber is filled with a tray.

25. The method of claim 22, further comprising the step of: The third gate is opened, and the first pallet is pushed into the unloading chamber using a pallet unloader housed within the unloading chamber.

26. The method of claim 25, further comprising the step of: All the trays are pushed from the drying chamber into the unloading chamber in sequence.

27. The method of claim 25, further comprising the step of: Remove the first tray from the unloading chamber.

28. The method according to claim 15, wherein, The drying chamber has a base plate defining two internal parallel edges and at least two walls, the two edges including removable tray rails.

29. The method of claim 15, further comprising operating the microwave vacuum dryer in a semi-continuous mode by sequentially performing the following steps: (i) evacuating air from the drying chamber using the second vacuum pump, (ii) recirculating water in a water chamber above the drying chamber, (iii) generating a microwave field in the drying chamber, (iv) loading a first tray containing a container of freezing solution into the loading chamber and closing the first gate, (v) evacuating air from the loading chamber to equilibrate the environment of the loading chamber with the environment of the drying chamber, and (vi) drying the freezing solution in the container of the first tray in the drying chamber.

30. The method of claim 15, further comprising operating the microwave vacuum dryer in batch mode by sequentially performing the following steps: (i) evacuating air from the drying chamber using the second vacuum pump, (ii) loading a plurality of trays containing containers of freezing solution into the drying chamber through the loading chamber, (iii) recirculating water in a water chamber above the drying chamber, (iv) generating a microwave field in the drying chamber, and (v) drying the freezing solution in the containers within the drying chamber.

31. The method according to claim 15, wherein, The unloading chamber includes a shut-off valve for partially backfilling the unloading chamber with inert gas, and a plug mechanism for closing a partially blocked container.

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