Patent Application
20240375840
The present disclosure generally relates to lyophilization, and more specifically, to containers and structures for lyophilization, and also to methods of using and making the same.
This section provides background information related to the present disclosure which is not necessarily prior art.
Lyophilization (also referred to as freeze drying) includes processes used to preserve materials (including, for example, biological materials and/or foods and/or pharmaceuticals) to increase shelf life of the materials and also to improve transport and safe handling of the materials. Lyophilization commonly occurs by freezing the materials (the material is commonly a liquid at room temperature and pressure) to form solid materials and subjecting the solid materials to a low-pressure and low-temperature environment that is sufficient to take the solid material below its triple point. In the instance of water, for example, the triple point is the temperature (for example, about 0.01° C.) and pressure (for example, about 0.00603 atm) at which all three phases (i.e., vapor, liquid, and ice) of water can exist in equilibrium. Lyophilization is carried out below the triple point to enable conversion of ice into vapor without entering the liquid phase. This conversion from ice to vapor is known as sublimation.
Lyophilization of a fluid often occurs using a lyophilizer that includes a shelf system (for example, a hydraulic shelf system) configured to receive containers loaded with the fluid. In at least one example embodiment, the shelf system may be configured to receive a generally flexible lyophilization structure (e.g., bag) that defines the lyophilization container. In other example embodiments, the shelf system may be configured to receive a generally rigid, outer box (or fixture or structure) that is configured to receive and/or hold at least a portion of the generally flexible lyophilization structure (e.g., bag). The rigid, outer box and the generally flexible lyophilization structure may together define the lyophilization container. In still other example embodiments, the shelf system may be configured to receive a generally rigid frame that is configured to receive and/or hold at least a portion of the generally flexible lyophilization structure (e.g., bag). The rigid frame and the generally flexible lyophilization structure may together define the lyophilization container. The rigid frame may differ from the outer box in that the frame has a greater total surface area compared to the rigid outer box. It should be appreciated that, in various example embodiments, the rigid outer box and the rigid frame may be interchangeable.
In each instance, lyophilization of the fluid can be accelerated if the fluid is frozen into a relatively thin solid layer or layers (which may, in certain instances, also be referred to as an ice layer or ice layers) in the respective lyophilization container with notable headspace above the formed thin solid layers. The headspace allows vapor (for example, water vapor) to move freely away from the surface of the solid layers and towards and out of a sterile barrier vent during the sublimation process. In the instance where the lyophilization container includes a generally rigid, outer box and a generally flexible lyophilization structure, the desired geometry of the thin solid layers/ice layers is often achieved by introducing gas pressure causing the generally flexible lyophilization structure to inflate/stretch and conform to the outer, rigid box. Induced stress in the flexible films, which can be caused, for example, by the applied pressure, often causes various failure modes, including in a peel seal often used to separate and/or distinguish and/or temporarily occlude sections of the generally flexible lyophilization structure. Accordingly, it would be desirable to develop improved materials, processes, and means for freeze drying/lyophilizing fluids.
This section provides a general summary of the disclosure and is not a comprehensive disclosure of its full scope or all of its features.
In various aspects, the present disclosure provides an example lyophilization container.
In at least one example embodiment, the lyophilization container may include a first section that include a first layer, a second layer aligned with the first layer, and a cavity defined by the alignment of the first and second layers, where at least one of the first and second layers may be preformed to have a three-dimensional shape.
In at least one example embodiment, the selected three-dimensional shape may include a planar surface and side angled away from the planar surface.
In at least one example embodiment, the sides may be substantially perpendicular to the planar surface.
In at least one example embodiment, the three-dimensional shape may have an open-box configuration.
In at least one example embodiment, the planar surface may be a first planar surface, the first layer may include the three-dimensional shape, and the second layer may include a second planar surface, where the second planar surface may be coupled to the sides of the three-dimensional shape to define the cavity.
In at least one example embodiment, the three-dimensional shape may be a first three-dimensional shape, the first layer may include the first three-dimensional shape, and the second layer may include a second three-dimensional shape.
In at least one example embodiment, the first and second three-dimensional shapes may be the same.
In at least one example embodiment, the first three-dimensional shape may include a first planar surface and first sides angled away from the first planar surface, and the second three-dimensional shape may include a second planar surface and second sides angled away from the second planar surface. The first and second planar may be substantially parallel. The first and second sides may be coupled together to define the cavity.
In at least one example embodiment, the first and second layers may be different parts of a continuous sheet.
In at least one example embodiment, the cavity may be a first cavity, and the lyophilization container may further include a second section that includes a third layer, a fourth layer aligned with the third layer, and a second cavity defined by the alignment of the third and fourth layers, where at least one of the third and fourth layers includes a breathable membrane.
In at least one example embodiment, the third and fourth layers may be different parts of a continuous sheet.
In at least one example embodiment, one of the first and second sections of the lyophilization container may include one or more apertures for securing the lyophilization container to a lyophilization fixture.
In at least one example embodiment, the lyophilization fixture may include a first portion configured to support the first portion of the lyophilization container and a second portion configured to support the second portion of the lyophilization container, where the first portion includes a base and a movable lid that together define a housing that receives the first portion of the lyophilization container.
In at least one example embodiment, the lyophilization container may further include an occluding section disposed between the first section and the second section, where the occluding section may be movable between a first configuration and a second configuration. The occluding section in the first configuration may prevent liquid movement between the first and second cavities. The occluding section in the second configuration may allow for liquid movement between the first and second cavities.
In various aspects, the present disclosure provides an example method for forming a lyophilization container.
In at least one example embodiment, the method may include heating a sheet to a pliable temperature, disposing the sheet on or near a surface of a mold structure including a portion shaped to mold the sheet to form a layer having an open box configuration, and cooling the layer to form the lyophilization container, where the open box configuration may include a planar surface and sides angled away from the planar surface.
In at least one example embodiment, the layer may be a first layer, the portion may be a first portion, the mold structure may further include a second portion shaped to mold the sheet to form a second layer continuous with the first layer, and the method may further include aligning the second layer with the first layer to define a cavity.
In at least one example embodiment, the open box configuration may be a first open box configuration, the planar surface may be first planar surface, the sides may be first sides, the second layer may have a second open box configuration, the second open box configuration may include a second planar surface and second sides angled away from the second planar surface, and the method may further include joining together the first and second sides together to enclose the cavity.
In at least one example embodiment, the method may include using a vacuum to mold the sheet to form the layer having the open box configuration.
In at least one example embodiment, the sheet may be a first sheet, the pliable temperature may be a first pliable temperature, the mold may be a first mold, the layer may be a first layer, the open box configuration may be a first open box configuration, the planar surface may be a first planar surface, the sides may be first sides, and the method may further include heating a second sheet to a second pliable temperature, disposing the second sheet on or near a surface of a second mold structure including a portion shaped to mold the sheet to form a second layer having a second open box configuration, and joining together the first and second sides together to enclose the cavity. The second open box configuration may include a second planar surface and second sides angled away from the second planar surface.
In various aspects, the present disclosure provides an example method of using a lyophilization container.
In at least one example embodiment, the method may include obtaining a lyophilization container, the lyophilization container including a first section and a second section. The first section of the lyophilization container may include a first layer, a second layer aligned with the first layer, and a cavity defined by the alignment of the first and second layers, where at least one of the first and second layers may be preformed to have a three-dimensional shape. The second section of the lyophilization container may include a third layer, a fourth layer aligned with the third layer, and a second cavity defined by the alignment of the third and fourth layers, where at least one of the third and fourth layers may include a breathable membrane. The method may further include disposing the lyophilization container in a lyophilization fixture. The lyophilization fixture may include a first portion configured to support the first portion of the lyophilization container and a second portion configured to support the second portion of the lyophilization container. The first portion may include a base and a movable lid that together define a housing that receives the first portion of the lyophilization container.
In various aspects, the present disclosure provides an example lyophilization fixture.
In at least one example embodiment, the lyophilization fixture may include a base member and a lid member. The lid member may be movable between a first position and a second position relative to the base member. The base member and lid member may together define a housing that receives at least a portion of a lyophilization container.
In at least one example embodiment, the lid member may include two or more lid coupling members, and the base member may include two or more base coupling members. Each of the two or more base coupling members may include slots configured to receive at least a portion of the corresponding lid coupling member.
In at least one example embodiment, the two or more lid coupling members may include a first pair of lid coupling members and a second pair of lid coupling members, the first pair of lid coupling members may be disposed on a first side of the lid, and the second pair of lid coupling members may be disposed on a second side of the lid.
In at least one example embodiment, the two or more base coupling members may include a first pair of base coupling members and a second pair of base coupling members. The first pair of base coupling members may be disposed on a first side of the base member and configured to receive at least a portion of the first pair of lid coupling members. The second pair of lid coupling members may be disposed on a second side of the base member and configured to receive at least a portion of the second pair of lid coupling members.
In at least one example embodiment, the first pair of base coupling members and the first pair of lid coupling members may define a hinge that allows for movement of the lid member between the first position and the second position.
In at least one example embodiment, the hinge may be a first hinge, and the second pair of base coupling members and the second pair of lid coupling members may together define a second hinge that allows for movement of the lid member between the first position and a third position.
In at least one example embodiment, the base member and the lid member may together define a first portion of the lyophilization fixture, the portion of the lyophilization container may be a first portion of the lyophilization container, and the lyophilization fixture may further include a second portion. The second portion may include a frame member configured to support a second portion of the lyophilization container.
In at least one example embodiment, the frame member may include a first section having a first major plane and a second section having a second major plane that is separated from the first major plane.
In at least one example embodiment, the frame member may further include a third section that joins together the first section and the second section.
In at least one example embodiment, the second member may be continuous with the base member of the first portion.
In at least one example embodiment, the second portion may further include one or more couplers for engaging the lyophilization container.
In at least one example embodiment, the two or more couplers may be disposed at a distal portion of the second portion away from the first portion.
In at least one example embodiment, the lyophilization container may include a first section to be received by the first portion of the lyophilization fixture and a second section to be received by the second portion of the lyophilization fixture. The first section of the lyophilization container may include a first layer, a second layer aligned with the first layer, and a cavity defined by the alignment of the first and second layers, where at least one of the first and second layers may be preformed to have a three-dimensional shape. The second section of the lyophilization container may include a third layer, a fourth layer aligned with the third layer, and a second cavity defined by the alignment of the third and fourth layers, where at least one of the third and fourth layers may include a breathable membrane.
In various aspects, the present disclosure provides another example lyophilization fixture.
In at least one example embodiment, the lyophilization fixture may include a first portion and a second portion. The first portion may include a base member and a lid member removable from and couplable to the base member. The lid member may be movable between a first position and a second position. The base member and lid member may together define a housing that receives a non-breathable portion of a lyophilization container. The second portion may include a frame member configured to support a breathable portion of the lyophilization container. The frame member may include a first section continuous with the base member and a second section separated therefrom.
In at least one example embodiment, the lid member may include two or more lid coupling members and the base member includes two or more base coupling members. Each of the two or more base coupling members may include slots configured to receive at least a portion of the corresponding lid coupling member.
In at least one example embodiment, the two or more lid coupling members may include a first pair of lid coupling members and a second pair of lid coupling members. The first pair of lid coupling members may be disposed on a first side of the lid, and the second pair of lid coupling members may be disposed on a second side of the lid.
In at least one example embodiment, the two or more base coupling members may include a first pair of base coupling members and a second pair of base coupling members. The first pair of base coupling members may be disposed on a first side of the base member and configured to receive at least a portion of the first pair of lid coupling members, and the second pair of lid coupling members may be disposed on a second side of the base member and configured to receive at least a portion of the second pair of lid coupling members.
In at least one example embodiment, the first pair of base coupling members and the first pair of lid coupling members may define a hinge allowing for movement of the lid member between the first position and the second position.
In at least one example embodiment, the hinge may be a first hinge, and the second pair of base coupling members and the second pair of lid coupling members may define a second hinge allowing for movement of the lid member between the first position and a third position.
In at least one example embodiment, the frame member may further include a third section that joins together the first section and the second section.
In various aspects, the present disclosure provides a method of using a lyophilization fixture.
In at least one example embodiment, the method may include aligning a first portion of a lyophilization container with a first portion of the lyophilization fixture and aligning a second portion of the lyophilization container with a second portion of the lyophilization fixture. The first portion of the lyophilization fixture may include a base member and a lid member removable from and couplable to the base member. The lid member may be movable between a first position and a second position. The base member and lid member may together define a housing that receives a non-breathable portion of a lyophilization container. The second portion of the lyophilization fixture may include a frame member configured to support a breathable portion of the lyophilization container. The frame member may include a first section continuous with the base member and a second section separated therefrom.
Further areas of applicability will become apparent from the description provided herein. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.
The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations and are not intended to limit the scope of the present disclosure.
Corresponding reference numerals indicate corresponding parts throughout the several views of the drawings.
Example embodiments will now be described more fully with reference to the accompanying drawings.
Example embodiments are provided so that this disclosure will be thorough and will fully convey the scope to those who are skilled in the art. Numerous specific details are set forth such as examples of specific components, devices, and methods, to provide a thorough understanding of embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be employed, that example embodiments may be embodied in many different forms and that neither should be construed to limit the scope of the disclosure. In some example embodiments, well-known processes, well-known device structures, and well-known technologies are not described in detail.
The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting. As used herein, the singular forms “a,” “an,” and “the” may be intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms “comprises,” “comprising,” “including,” and “having” are inclusive and therefore specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. It is also to be understood that additional or alternative steps may be employed.
When an element or layer is referred to as being “on,” “engaged to,” “connected to,” or “coupled to” another element or layer, it may be directly on, engaged, connected, or coupled to the other element or layer, or intervening elements or layers may be present. In contrast, when an element is referred to as being “directly on,” “directly engaged to,” “directly connected to,” or “directly coupled to” another element or layer, there may be no intervening elements or layers present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” etc.). As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items.
Although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers, and/or sections, these elements, components, regions, layers, and/or sections should not be limited by these terms. These terms may be only used to distinguish one element, component, region, layer or section from another region, layer, or section. Terms such as “first,” “second,” and other numerical terms when used herein do not imply a sequence or order unless clearly indicated by the context. Thus, a first element, component, region, layer, or section discussed below could be termed a second element, component, region, layer, or section without departing from the teachings of the example embodiments.
Spatially relative terms, such as “inner,” “outer,” “beneath,” “below,” “lower,” “above,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. Spatially relative terms may be intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the example term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
Various components are referred to herein as “operably associated.” As used herein, “operably associated” refers to components that are linked together in operable fashion and encompasses embodiments in which components are linked directly, as well as embodiments in which additional components are placed between the linked components. “Operably associated” components can be “fluidly associated.” “Fluidly associated” refers to components that are linked together such that fluid can be transported between them. “Fluidly associated” encompasses embodiments in which additional components are disposed between the two fluidly associated components, as well as components that are directly connected. Fluidly associated components can include components that do not contact fluid but contact other components to manipulate the system (e.g., a peristaltic pump that pumps fluids through flexible tubing by compressing the exterior of the tube).
In this application, including the definitions below, the term “module” or the term “controller” may be replaced with the term “circuit.” The term “module” may refer to, be part of, or include: an Application Specific Integrated Circuit (ASIC); a digital, analog, or mixed analog/digital discrete circuit; a digital, analog, or mixed analog/digital integrated circuit; a combinational logic circuit; a field programmable gate array (FPGA); a processor circuit (shared, dedicated, or group) that executes code; a memory circuit (shared, dedicated, or group) that stores code executed by the processor circuit; other suitable hardware components that provide the described functionality; or a combination of some or all of the above, such as in a system-on-chip.
The module may include one or more interface circuits. In some example embodiments, the interface circuits may include wired or wireless interfaces that are connected to a local area network (LAN), the Internet, a wide area network (WAN), or combinations thereof. The functionality of any given module of the present disclosure may be distributed among multiple modules that are connected via interface circuits. For example, multiple modules may allow load balancing. In a further example, a server (also known as remote, or cloud) module may accomplish some functionality on behalf of a client module.
The term code, as used above, may include software, firmware, and/or microcode, and may refer to programs, routines, functions, classes, data structures, and/or objects. The term shared processor circuit encompasses a single processor circuit that executes some or all code from multiple modules. The term group processor circuit encompasses a processor circuit that, in combination with additional processor circuits, executes some or all code from one or more modules. References to multiple processor circuits encompass multiple processor circuits on discrete dies, multiple processor circuits on a single die, multiple cores of a single processor circuit, multiple threads of a single processor circuit, or a combination of the above. The term shared memory circuit encompasses a single memory circuit that stores some or all code from multiple modules. The term group memory circuit encompasses a memory circuit that, in combination with additional memories, stores some or all code from one or more modules.
The term memory circuit is a subset of the term computer-readable medium. The term computer-readable medium, as used herein, does not encompass transitory electrical or electromagnetic signals propagating through a medium (such as on a carrier wave); the term computer-readable medium may therefore be considered tangible and non-transitory. Non-limiting examples of a non-transitory, tangible computer-readable medium are nonvolatile memory circuits (such as a flash memory circuit, an erasable programmable read-only memory circuit, or a mask read-only memory circuit), volatile memory circuits (such as a static random access memory circuit or a dynamic random access memory circuit), magnetic storage media (such as an analog or digital magnetic tape or a hard disk drive), and optical storage media (such as a CD, a DVD, or a Blu-ray Disc).
The apparatuses and methods described in this application may be partially or fully implemented by a special purpose computer created by configuring a general-purpose computer to execute one or more particular functions embodied in computer programs. The functional blocks, flowchart components, and other elements described above serve as software specifications, which can be translated into the computer programs by the routine work of a skilled technician or programmer.
The computer programs include processor-executable instructions that are stored on at least one non-transitory, tangible computer-readable medium. The computer programs may also include or rely on stored data. The computer programs may encompass a basic input/output system (BIOS) that interacts with hardware of the special purpose computer, device drivers that interact with particular devices of the special purpose computer, one or more operating systems, user applications, background services, background applications, etc.
The computer programs may include: (i) descriptive text to be parsed, such as HTML (hypertext markup language), XML (extensible markup language), or JSON (JavaScript Object Notation) (ii) assembly code, (iii) object code generated from source code by a compiler, (iv) source code for execution by an interpreter, (v) source code for compilation and execution by a just-in-time compiler, etc. As examples only, source code may be written using syntax from languages including C, C++, C#, Objective-C, Swift, Haskell, Go, SQL, R, Lisp, Java®, Fortran, Perl, Pascal, Curl, OCaml, Javascript®, HTML5 (Hypertext Markup Language 5th revision), Ada, ASP (Active Server Pages), PHP (PHP: Hypertext Preprocessor), Scala, Eiffel, Smalltalk, Erlang, Ruby, Flash®, Visual Basic®, Lua, MATLAB, SIMULINK, and Python®.
Example embodiments will now be described more fully with reference to the accompanying drawings.
The apparatus 100 includes a chamber 104 encompassing a shelfing structure (which may also be referred to as a shelfing system) 112 configured to hold the materials to be lyophilized and a housing 108 in communication with the chamber. The housing 108 may include, for example, at least one of a vacuum system (not shown) configured to create a low-pressure environment in the chamber 104, a temperature control system (not shown) configured to control the temperature of the shelfing structure 112, a vapor condensing system (not shown) configured to collect and hold sublimating vapor leaving the chamber 104, and a control system (not shown) including, for example, a computer system having one or more processors for controlling various functions of the apparatus. The housing 108 may include, for example, a user interface 116. The user interface 116 may be configured to allow an operator to input data, parameters, and other information to control certain functions of the apparatus 100. For example, the user interface 116 may permit the operator to communicate with the control system to create and execute custom processes for lyophilizing different materials, including multi-step programmable cycles.
The material to be lyophilized may be placed onto the different shelves of the shelfing structure 112. The temperature control system disposed in the housing 108 and configured to alter the temperature of the shelfing structure 112 may then be used to first freeze the material to be lyophilized and then to further reduce the temperature of the frozen material to a predetermined level which may be, for example, the temperature to be maintained during the sublimation phase of the lyophilization cycle. For example, in the instance of water sublimation, the temperature may be selected to be below the triple point so as to help preserve materials suspended or dissolved in the aqueous solution. For example, in at least one example embodiment, the predetermined level may include temperatures greater than or equal to about −30° C. to less than or equal to about −20° C.
After the material to be lyophilized is frozen and is further cooled to the predetermined temperature, the vacuum system disposed in the housing 108 and configured to alter the pressure within the chamber 104 may be used to bring the environment in the chamber 104 to a pressure that is lower than atmospheric pressure. For example, in at least one example embodiment, the pressure might be lowered to and maintained below an absolute pressure of less than about 100 milli-Torr for a duration of a sublimation period. The sublimation phase or period includes the time lapse between the start of sublimation and the end of sublimation. Sublimation begins as the pressure and temperature in chamber 104 create a chamber environment that is lower than the triple point. Sublimation ends when all ice has been removed from the material to be lyophilized. The sublimation period may vary depending on the material to be lyophilized, quantity of the material to be lyophilized, and the shape, for example, the thickness, of the material to be lyophilized.
In at least one example embodiment, the vacuum system may work in cooperation with the vapor condenser system to maintain an environment within the chamber 104 at a pressure that is the lower than atmospheric pressure. As sublimation takes place at the low chamber pressure, the escaping vapor can carry heat energy away from the material to be lyophilized. The escaping vapor may then be captured onto the vapor condenser system contained within housing 108. The continuous capture of sublimating vapors by the vapor condenser system can help to maintain the low chamber pressure within the sublimating chamber 104. The control system contained within housing 108 may be programmed to control temperature of the shelving structure 112 such that the escaping heat energy is replaced, and the shelving structure may be maintained at a temperature sufficient to sustain sublimation until all volatile substances have been removed from the material to be lyophilized. Following sublimation of essentially all volatile material components and/or other material component(s) (i.e., end of the sublimation period), an increased shelf temperature may be set and maintained for an additional period of time to desorb one or more other material components from the material to be lyophilized. The one or more other material may have been previously absorbed or absorbed by the material. Once desorption is complete, pressure within the chamber may be returned to atmospheric pressure and the now completely dried product may be harvested.
The containers 328 may be like those described in U.S. Pat. No. 11,747,082 titled MULTI-PART LYOPHILIZATION CONTAINER AND METHOD OF USE, issued Sep. 5, 2023, and listing Kestas P. Parakininkas, Eric T. Hansen, Kirk L. Weimer, Nathaniel T. Johnson, and Dennis J. Hlavinka as co-inventors and/or U.S. Pat. No. 11,609,042 titled MULTI-PART LYOPHILIZATION CONTAINER AND METHODS OF USE, issued Mar. 21, 2023, and listing Kestas P. Parakininkas, Eric T. Hansen, Kirk L. Weimer, Nathaniel T. Johnson, and Dennis J. Hlavinka as co-inventors and/or U.S. Pat. No. 10,793,327 titled LYOPHILIZATION CONTAINER AND METHOD OF USING THE SAME, issued on Oct. 6, 2022, and listing Kirk L. Weimer, Nate T. Johnson, Dennis J. Hlavinka, and Kestas P. Parakininkas as co-inventors and/or U.S. Pat. No. 11,634,257 titled LYOPHILIZATION CONTAINER AND METHOD OF USING SAME, issued Apr. 25, 2023 and listing Kirk L. Weimer, Nate T. Johnson, Dennis J. Hlavinka, and Kestas P. Parakininkas as co-inventors and/or U.S. Pat. No. 11,609,043, titled LYOPHILIZATION CONTAINER FILL FIXTURE, SYSTEM AND METHOD OF USE, issued on Mar. 21, 2023 and listing Nathaniel T. Johnson, Rylan A. Summit, Dennis A. Bridges, Dennis J. Hlavinka, Kestas P. Parakininkas, Kirk L. Weimer, Michael Lawrence Glover, Alexander Du Nguyen, and Margaret V. Kwiat as co-inventors, the entire disclosures of which are hereby incorporated by reference.
For example, in at least one example embodiment, the containers 328 may be generally flexible containers, including, for example, bags and/or trays. In other example embodiments, the containers 328 may include generally rigid fixtures (or structures or frames or boxes) configured to receive at least a portion of a bag (or another generally flexible structure) that carries (or holds) the material to be lyophilized. In such instances, the generally rigid fixture may be sized to receive, contain, and confine the bag throughout the lyophilization process. In at least one example embodiment, the fixture may include one or more sealing structures configured to retain the bag within the fixture. In at least one example embodiment, the fixture may be configured to receive an empty bag and once positioned the material to be lyophilized may be added to the bag. Gas, including, for example, air or nitrogen, may then be introduced into the bag to ensure that the bag conforms to the dimensions of the fixture. The generally ridged fixture may include, or be formed, as detailed, for example, in U.S. Pat. No. 11,609,043, titled LYOPHILIZATION CONTAINER FILL FIXTURE, SYSTEM AND METHOD OF USE, issued on Mar. 21, 2023 and listing Nathaniel T. Johnson, Rylan A. Summit, Dennis A. Bridges, Dennis J. Hlavinka, Kestas P. Parakininkas, Kirk L. Weimer, Michael Lawrence Glover, Alexander Du Nguyen, and Margaret V. Kwiat as co-inventors, the entire disclosure of which is hereby incorporated by reference. The assembly (including the generally rigid fixture and the bag including the material to be lyophilized) may undergo a lyophilization cycle as detailed above
With renewed reference to
The shelfing structure 320 may also include a thermal fluid system 316 that may be configured to circulate a thermal fluid through and/or around at least a portion of the plurality of plates 304. For example, in at least one example embodiment, the thermal fluid system 316 may be removably coupled to the plates 304 using any appropriate connections, including, for example, connectors, tubings, fittings, pipes, adapters, or any combination thereof. In each instance, the movement of the thermal fluid may be used to remove and/or add energy to at least a portion of the plurality of plates 304. For example, the movement of the thermal fluid may be used to control the temperature of one or more of the plurality of plates and the materials for lyophilization disposed on the plates.
At least some example embodiments of the present disclosure provides lyophilization containers, for example, for use with the example lyophilizers illustrated in
The breathable membrane 512 of the second section 508 may include (or be formed from) a microbial barrier porous material that allows the passage of small molecules, such as water vapor, nitrogen, carbon dioxide, or any combination thereof. In contrast, the first section 502 may include (or be formed from) a polymeric film that has no discernable pore structure to allow vapor transfer. In at least one example embodiment, the microbial barrier porous material may have an average pore size greater than or equal to about 0.15 micrometers to less than or equal to about 0.5 micrometers (e.g., optionally about 0.22 micrometers or optionally about 0.45 micrometers). In at least one example embodiment, the microbial barrier porous material may include polytetrafluoroethylene (PTFE), polypropylene, polyethylene, polyester, or any combination thereof.
In at least one example embodiment, the top (or front) 550A of the lyophilization container 500 (for example, as illustrated in
In at least one example embodiment, the first section 502 includes a first sheet (or layer or film) 516 that overlaps with and may be parallel to a second sheet (or layer or film) 518, where one or more portions of the first and second sheets 516, 518 are connected or sealed (for example, heat welded and/or radio frequency welded) to define a first perimeter 520 and also the first enclosed cavity 504. Although two, separate sheets (or layers or films) are discussed, it should be appreciated that, in at least one example embodiment, the first section 502 may include (or be formed from) a continuous sheet (or layer or film) that may be folded along one or more portions to define the first cavity 504 and also parallel first and second portions corresponding with the herein described first and second sheets 516, 518.
In at least one example embodiment, at least one of the first and second sheets 516, 518 may be preformed to have a selected three-dimensional shape, such that at least one surface of the lyophilization container 500 has, for example, improved contact with a shelfing structure (for example, such as the shelfing structure 112 illustrated in
In at least one example embodiment, the first sheet 516 may have a first three-dimensional shape. As best illustrated, for example, in
In at least one example embodiment, the second sheet 518 may have a first three-dimensional shape. As best illustrated, for example, in
In at least one example embodiment, the first and second ends 524, 526 of the first substantially planar surface 522 may be joined to the respective portions of the corresponding second sheet 518 (e.g., the first and second ends 562, 564). In at least one example embodiment, first and second sides 528, 530 of the first substantially planar surface 522 may be joined to the respective portions of the corresponding second sheet 518 (e.g., the first and second sides 566, 568).
As discussed above, the first and second sheets 516, 518 may include non-breathable, polymeric sheets (or layers or film). In at least one example embodiment, the first and second sheets 516, 518 may include (or be formed of), for example, polyvinyl chloride (PVC), ethylene-vinyl acetate (EVA), polyethylene (PE), polypropylene (PP), thermoplastic elastomers (TPE), or other flexible polymeric film. The first and second sheets 516, 518 may be preformed using, for example, a thermoformed process, such as illustrated in
With renewed reference to
In at least one example embodiment, one of the fluidic ports 534, 536, 538 may include (or be defined by) a spike port. In at least one example embodiment, one of the fluidic ports 534, 536, 538 may include (or be defined) by a docking port. In at least one example embodiment, one of the fluidic ports 534, 536, 538 may include (or be defined by) a reconstitution port. In at least one example embodiment, a first fluidic port of the one or more fluidic ports 534, 546, 538 may include a spike port and a second fluidic port of the one or more fluidic ports 534, 546, 538 may include a docking port. In at least one example embodiment, a first fluidic port of the one or more fluidic ports 534, 546, 538 may include a spike port and a second fluidic port of the one or more fluidic ports 534, 546, 538 may include a reconstitution port. In at least one example embodiment, a first fluidic port of the one or more fluidic ports 534, 546, 538 may include a docking port and a second fluidic port of the one or more fluidic ports 534, 546, 538 may include a reconstitution port. In at least one example embodiment, a first fluidic port of the one or more fluidic ports 534, 546, 538 may include a spike port, a second fluidic port of the one or more fluidic ports 534, 546, 538 may include a docking port, and a third fluidic port of the one or more fluidic ports 534, 546, 538 may include a reconstitution port.
In at least one example embodiment, a spike port may help to facilitate reinfusion of a reconstituted product (for example, a reconstituted blood product) into a subject (or patient or source). In at least one example embodiment, a docking port may help to facilitate connection between the lyophilization container 500 and another container, such as a blood pooling container or a pooling container set or a single unit of blood product. Additionally, or alternatively, the docking port may help to facilitate the introduction of air and/or gases into the lyophilization container 500. In at least one example embodiment, a reconstitution port may help to facilitate allow for an inflow of a reconstitution fluid into the lyophilization container 500. In at least one example embodiment, the reconstitution port may include one or more one-way valves and/or other methods to prevent contamination and to ensure proper connection.
In at least one example embodiment, the second section 508 includes a first sheet (or layer or film) 540 that overlaps with and may be substantially parallel to a second sheet (or layer or film) 542, where one or more portions of the first and second sheets 540, 542 are sealed (for example, heat welded) to define a second perimeter 544 and also the second enclosed cavity 508. Although two separate sheets or layers or films are discussed, it should be appreciated that, in at least one example embodiment, the second section 508 may include a continuous sheet (or layer or film) that may be folded along one or more portions to define the second cavity 510 and also parallel first and second portions corresponding with the herein described first and second sheets 540, 542.
The second section 508 includes a breathable region. In at least one example embodiment, at least one of the first and second sheets 540, 542 includes a breathable membrane 512 that may be embedded within, or joined to, a non-breathable, polymeric sheet (or layer or film) 552. For example, as illustrated, the first sheet 540 may include a first breathable membrane 512A and a first non-breathable, polymeric region 552A encompassing at least a portion of the first breathable membrane 512A, and the second sheet 542 may include a second breathable membrane 512B and a second non-breathable, polymeric region 552B encompassing at least a portion of the second breathable membrane 512B. In at least one example embodiment, the non-breathable, polymeric sheets 552 may include, for example, polyvinyl chloride (PVC), ethylene-vinyl acetate (EVA), polyethylene (PE), polypropylene (PP), or another flexible polymeric film. In at least one example embodiment, the breathable membrane 512 may include, for example, expanded polytetrafluoroethylene (PTFE), medical paper like that used in packaging, spun bonded polyolefin, or the like.
Although the first non-breathable, polymeric region 552A is illustrated as substantially surrounding the first breathable membrane 512A, it should be appreciated that, in other example embodiments, the first non-breathable, polymeric region 552A may surround only a portion of the first breathable membrane 512A, and further still, in other example embodiments, the first non-breathable, polymeric region 552A may be only disposed adjacent to the first breathable membrane 512A. Similarly, although the second non-breathable, polymeric region 552B is illustrated as substantially surrounding the second breathable membrane 512B it should be appreciated that, in other example embodiments, the second non-breathable, polymeric region 552B may surround only a portion of the second breathable membrane 512B, and further still, in other example embodiments, the second non-breathable, polymeric region 552B may be only disposed adjacent to the second breathable membrane 512B. Further, although not illustrated, it should be appreciated that, in still another example embodiment, only one of the first and second sheets 540, 542 includes a breathable region. Further, although not illustrated, it should be appreciated that, in still other example embodiments, the first and second sheets 540, 542 may be formed from a breathable membrane. Further still, although not illustrated, it should be appreciated, that in still other example embodiments, a breathable region may extend from the first sheet 540 to the second sheet 542.
In at least one example embodiment, the second perimeter 544 of the second section 508 may be joined to the first perimeter 520 of the first section 502 or formed integrally therewith to define an outer perimeter 546 of the lyophilization container 500. The outer perimeter 546 may have, for example, an average width greater than or equal to about 2 millimeters to less than or equal about 12 millimeters (e.g., optionally about 7 millimeters). In at least one example embodiment, as illustrated, the outer perimeter 546 (including the first perimeter 520 and/or the second perimeter 544) may include one or more apertures 548 configured, for example, for hanging the lyophilization container 500 and/or positioning (or securing) the lyophilization container 500 within a rigid, outer box or fixture or structure, as further discussed below.
In at least one example embodiment, the lyophilization container 500 further includes a third section (or region or portion or zone) (which may also be referred to as the peelable section or region and/or occluding section (or region or portion or zone)) 514 that extends between and joins the first and second sections 502, 508. The third section 514 may be adapted to facilitate the evolution of the lyophilization container 500 throughout its life cycle. For example, occlusion of the lyophilization container 500 in the third region 514, either initially by an intact peelable seal, or by subsequent occlusion (for example, using clamps) creates a temporary impermeable, or substantially impermeable seal, eliminating fluid communication between the first second 502 and the second section 508. Both prior to, and after, the sublimation and removal of vapor during lyophilization, the first and second sections 502, 508 should be isolated from one another.
In at least one example embodiment, the third section 514 may include a temporary peelable seal that when intact creates an initial occlusion that separates and isolates the first and second cavities 504, 510, for example, prior to and during the introduction of fluid via one or more of the fluidic ports 534, 536, 538. Once the fluid is frozen to form a frozen structure (which may also be referred to as a solid layer), a pressure differential may be generated, for example, by the application of a vacuum in a lyophilization chamber (like chamber 104 illustrated in
In at least one example embodiment, the third section 514 may include a stent (or batten) 515. The stent 515 may be rigid enough to aid with holding the temporary peelable seal in the open state but also flexible enough to yield and flatten when the shelves of shelfing structure of a lyophilizers (e.g., the lyophilizers 100, 200 illustrated in
The ability of the lyophilization container 500 to continually evolve in form and function ensures that no contact occurs between the fluid and the breathable region of the second section 508 by causing the subject liquid to be isolated and frozen in only the first (non-breathable) section 502 and allowing the vapor flow from sublimation and desorption to flow into the breathable region of the second section 508 and exit the lyophilization container 500 through the breathable region. The lyophilization container 500 may be configured to create a physical separation between the subject fluid and the breathable region of the second region 510. The first section 502 may be adapted to accommodate any of a solid, a liquid, or a gas, while the second section 508 may be adapted to accommodate only gas. The third section 514 is further detailed, for example, in U.S. Pat. No. 11,609,042, titled MULTI-PART LYOPHILIZATION CONTAINER AND METHOD OF USE, issued on Mar. 21, 2023 and listing Kestas P. Parakininkas, Eric T. Hansen, Kirk L. Weimer, Nathaniel T. Johnson, and Dennis J. Hlavinka as co-inventors the entire disclosure of which is hereby incorporated by reference.
At least some example embodiments of the present disclosure provides a box (or fixture or structure or frame) that is configured to receive and/or hold at least a portion of a generally flexible lyophilization structure, for example, for use with the example lyophilizers illustrated in
In at least one example embodiment, the first portion 710 of the lyophilization fixture 700 includes a chassis (or base or base member) 712 and a lid (or lid member) 714 movable between a first (or opened) position as illustrated in
The chassis 712 also includes one or more coupling members for engaging the lid 714 to define a cavity (or housing) 718 that holds and secures the first section of the lyophilization container (like the first section 502 of the lyophilization container 500 illustrated in
In at least one example embodiment, the one or more coupling members may include a second set (or pair) of couplers 754A, 754B also configured to engage or secure the first portion of the lyophilization container away from the second section of the lyophilization container. As best illustrated, for example, in
In at least one example embodiment, the one or more coupling members may include a third set (or pair) of couplers (or coupling bodies or coupling members) 756A, 756B configured to engage or secure a second portion (or section) of the first portion of the lyophilization container nearer to the second portion of the lyophilization container. As best illustrated, for example, in
In at least one example embodiment, the lid 714 may include a surface 760 that corresponds with the surface 716 of the chassis 712. The surface 760 of the lid 714 may be similarly substantially planar to aid in the production of thin and substantially uniform ice structures, for example, as detailed below in the instance of
In at least one example embodiment, the second portion 720 of the lyophilization fixture 700 includes a frame (or supporting member or frame member) 722 for receiving (or supporting or holding) the second section of the lyophilization container (like the second section 508 of the lyophilization container 500 illustrated in
The frame 722 also includes one or more coupling means for joining the frame 722 to the second section of the lyophilization container (like the second section 508 of the lyophilization container 500 illustrated in
In at least one example embodiment, as illustrated, the one or more coupling means may include a second set (or pair) of couplers 726A, 726B configured to also engage with and secure the first portion of the second section of the lyophilization container away from the first section of the lyophilization container. As best illustrated, for example, in
In at least one example embodiment, as illustrated, the one or more coupling means may include a third set (or pair) of couplers 728A, 728B configured to engage with and secure a second portion of the second section of the lyophilization container nearer to the first section of the lyophilization container. As best illustrated, for example, in
In various aspects, the present disclosure provides methods (or processes) for lyophilization. For example,
The method 800 may include securing a lyophilization container (like the lyophilization container 500 illustrated in
The method 800 may include, additionally or alternatively, loading 812 the lyophilization container into a lyophilizer. The method 800 may include, additionally or alternatively, freezing 814 the fluid to create a thin, frozen structure having a substantially uniformed thickness. The method 800 may include, additionally or alternatively, removing 816 an occlusion between the non-breathable section of the lyophilization container and a breathable section of the lyophilization container (such as, the second section 508 of the lyophilization container 500 illustrated in
The method 800 may include, additionally or alternatively, occluding 822 the lyophilization container (for example, the third section 514 of the lyophilization container 500 illustrated in
The foregoing description of the embodiments has been provided for purposes of illustration and description. It is not intended to be exhaustive or to limit the disclosure. Individual elements or features of a particular embodiment are generally not limited to that particular embodiment, but, where applicable, are interchangeable and can be used in a selected embodiment, even if not specifically shown or described. The same may also be varied in many ways. Such variations are not to be regarded as a departure from the disclosure, and all such modifications are intended to be included within the scope of the disclosure.
| Number | Date | Country | |
|---|---|---|---|
| 63431134 | Dec 2022 | US |
