Patent Description:
Aspects of the present disclosure relate to devices, systems, and methods for managing chromatography column bed supports. More specifically, embodiments of the present disclosure relate to devices, systems, and methods for using, reusing, and storing product dedicated chromatography column bed supports.

Column chromatography plays an important role in the production of biologic drug products. Facilities involved in the production of biologic drug products, or more generally involved in performing chromatography operations, may have columns that are equipped to perform a wide variety of such operations. Different chromatography operations often include the use of different materials and methods-e.g., differing stationary and mobile phases, buffers, washes, eluents, etc.-depending on the purpose of each operation.

Due to differences in chromatography operations, and the need to maintain the integrity, cleanliness, and effectiveness of each chromatography column and operation, it may be desirable to dedicate a single physical chromatography column to a particular operation. However, in some instances, a facility that performs column chromatography may have a catalog, inventory, or schedule of chromatography operations that includes more operations than the number of physical chromatography columns available at the facility. For example, a facility may not have a budget or a physical space large enough to accommodate a dedicated chromatography column for every operation the facility performs. Alternatively, or additionally, a schedule of chromatography operations may grow faster than the facility's ability to acquire new columns. Also, the chromatography operations that a facility performs may vary over time based on, for example, fluctuating needs to purify different molecules or manufacture different products, a need to perform several different chromatography operations to purify a single molecule, or a need to test several different types of chromatography operations. Therefore, it may not be practicable to dedicate a chromatography column to each chromatography operation of a plurality of chromatography operations.

<CIT> discloses a method of maintenance of a chromatography column which does not require the use of a hoist or crane for disassembly. The method provides improved operator safety by reducing the need for the operator to work below a suspended or support load within the column. The provision of guide elements which can be reversibly attached to the column facilitates removal or insertion of column components.

The object of the invention is solved by the subject matter of the appended claims. Embodiments not falling under the scope of the appended claims are to be considered merely as examples suitable for understanding the invention.

Some embodiments of the present disclosure are directed to a chromatography column bed support case. The case includes a container having, among other things, a body with an opening, an interior in the body accessible via the opening, and a lid configured to cover the opening. The case further includes two (or more) removable inserts configured to fit inside the interior in a parallel configuration, each insert including a cavity configured to house a chromatography column bed support, and a removable divider disposed between the inserts, wherein the divider is sized and configured to separate the inserts.

In some embodiments, the inserts and the divider may be sized and configured to extend from one end of the interior to an opposite end of the interior. In some embodiments, each of the inserts and the divider may include two symmetrical indentations positioned diametrically opposite from one another. In further embodiments, the case may include a plurality of spacer pads disposed between a side of one insert and the container. Each of the inserts and the divider includes a centrally located through hole, and the through holes are coaxial.

In some embodiments, the cavity in each insert may share at least two dimensions with a chromatography column bed support. In some embodiments, each insert may include a recess located at an edge of the cavity, wherein the recess is deeper than the cavity. In some embodiments, the lid may be removably affixed to the container by a securing mechanism. The securing mechanism may include any suitable mechanism now known or later developed, including, but not limited to, a latch, a clasp, a hook-and-eye closure, a tie closure, an elastic closure, or an adhesive. In some embodiments, the container and the dividers include polyethylene.

The present disclosure also includes storage systems comprising a plurality of chromatography column bed support cases, which are of the same or varying sizes and shapes.

Embodiments of the present disclosure also are directed to a method of storing a chromatography column bed support, the method including placing the chromatography column bed support in a chromatography column bed support case as disclosed herein.

In some embodiments, the container and divider may be made from polyethylene.

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate the disclosed embodiments, and together with the description, serve to explain the principles of the disclosed embodiments. In the drawings:.

It may be beneficial for a facility that performs multiple chromatography operations to dedicate a given chromatography column, or parts of a chromatography column, to a particular chromatography operation. This may aid in, e.g., minimizing contamination between chromatography operations, reducing the amount of time spent cleaning and sterilizing columns and parts of columns, and the like. In some instances, however, it may not be practicable, possible, or preferable to dedicate an entire chromatography column to a single chromatography operation, due to limitations on budget, limitations on space, or other considerations. As an alternate solution, it may be possible to dedicate one or more chromatography column bed support(s) to a particular chromatography operation by, e.g., using them in combination with the rest of a chromatography column for the particular chromatography operation, and removing them from the column and storing them while the column is needed for a different operation. Dedicating column bed supports to a particular operation in this manner may provide several advantages. For example, a column bed support may be difficult to clean, sterilize, and quantify (e.g., in terms of its surface area) in between different chromatography operations, due to porous or mesh-type surfaces on the column bed support providing a high amount of surface area that may not be easily accessible. By dedicating a column bed support to a particular operation, the risk for cross-contamination of, e.g., stationary phases, mobile phases, washes, buffers, etc. between operationes is lessened. Maintaining dedicated column bed supports to a particular operation may be much less wasteful than, e.g., discarding used column bed supports after a particular operation and replacing them with new ones when the column is needed for another operation. Furthermore, in a growing facility, it would be easier to keep a stock of new column bed supports on hand, which may be dedicated to new chromatography operations as they are developed, than it would be to keep or manage a stock of new columns.

Devices, systems, and methods disclosed herein may assist in performing a variety of different chromatography operations using a limited number of chromatography columns. Specifically, devices, systems, and methods disclosed herein may assist in managing, storing, and using dedicated chromatography column bed supports for a plurality of chromatography operations. For example, devices disclosed herein may include cases for storing dedicated column bed supports when they are not in columns. Such devices may be designed and built specifically to ensure efficient, secure storage of column bed supports while minimizing risk of damage or contamination. Systems disclosed herein may include groups of column bed support storage cases, for use in conjunction with a plurality of column bed supports and at least one column. Methods disclosed herein may include performing a particular chromatography operation in a column, removing the column bed supports from the column, storing the column bed supports in a column bed support storage case, and installing another set of column bed supports in the column for another chromatography operation.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this invention belongs. The materials, methods, and examples are illustrative only and not intended to be limiting. One of ordinary skill in the art will appreciate that routine variations on the disclosed materials, methods, and examples are possible without undue experimentation.

As used herein, the terms "comprises," "comprising," "includes," "including," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. The term "exemplary" is used in the sense of "example," rather than "ideal. " For such terms, and for the terms "for example" and "such as," and grammatical equivalences thereof, the phrase "and without limitation" is understood to follow unless explicitly stated otherwise. As used herein, the term "about" and the signifier "-" are meant to account for variations due to experimental error. All measurements reported herein are understood to be modified by the term "about," whether or not the term is explicitly used, unless explicitly stated otherwise. As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Moreover, in the claims, values, limits, and/or other ranges mean the value, limit, and/or range +/- <NUM>%, unless otherwise specified.

As used herein, the term "biologic" may refer to a large molecule (e.g., having a size greater than 30kDa) created in a living system such as a cell. Biologics may include proteins (e.g., antibodies), nucleic acids, large sugars, etc. Unlike small molecules that may have well-defined chemical structures, biologics may have highly complex structures that cannot be easily quantified by laboratory methods. Thus, it may be desirable to achieve purity, consistency, and quality in the manufacturing of biologics to ensure biologic quality, especially when intended for medical use.

As used herein, the term "drug product" may refer to a volume of a formulated drug substance apportioned into a primary packaging component for packaging, transportation, delivery, and/or administration to a patient. Drug products may include any active ingredients, including, e.g., small molecules or biologics.

For example, in some embodiments, drug products may include a vascular endothelial growth factor (VEGF) derivative. In other aspects, drug products may include aflibercept, which is described in one or more of <CIT>, <CIT>, <CIT>, <CIT>, <CIT>,<CIT>, <CIT>, <CIT>,<CIT>, <CIT>, <CIT>, <CIT>, and <CIT>.

In other aspects, drug products may include an antigen-binding molecule. In some aspects, the antigen-binding molecule may be an antibody or antigen-binding fragment. In some aspects, drug products may include alirocumab, which is described in <CIT> and <CIT>. In another aspect, drug products may include sarilumab, which is described in <CIT>, <CIT>, and <CIT>. In another aspect, drug products may include dupilumab, which is described in <CIT>. In another aspect, drug products may include any molecule selected from the group consisting of evolocumab, bevacizumab, ranibizumab, tocilizumab, certolizumab, etanercept, adalimumab, abatacept, infliximab, rituximab, anakinra, trastuzumab, pegfilgrastim, interferon beta-1a, Insulin glargine [rDNA origin] injection, epoetin alpha, darbepoetin, filigrastim, and golimumab.

As used herein, the terms "chromatography" or "column chromatography" may refer to any preparatory or analytical column chromatography method. While much of the present disclosure is provided in the context of preparatory packed-bed chromatography for purification of a biologic, it is contemplated that the systems and methods disclosed herein may apply to a wide variety of chromatography operations. The terms "chromatography operation," "chromatography process" and "chromatography program" refer to a collection of specific steps and materials employed in a method of using a chromatography column.

As used herein, the term "facility" may refer to any place at which chromatography is performed. For example, a facility may include a manufacturing plant for the production of biologic drug products, a research center, a clinical center, or other laboratory environment.

Reference will now be made in detail to the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to same or like parts.

<FIG> depicts, in schematic form, an exemplary chromatography column <NUM> with which various embodiments of the present disclosure may be implemented. Column <NUM> may include a mobile phase supply <NUM>, a material injection supply <NUM>, a column frame <NUM>, a mobile phase conduit <NUM>, a column cover <NUM>, a column body <NUM>, an upper column bed support <NUM>, a lower column bed support <NUM>, and a mobile phase outlet <NUM>.

Column <NUM> may be part of a chromatography system in a facility. Examples of such a chromatography system may include, e.g., Chromaflow (GE Healthcare) and Axichrom (GE Healthcare). In some instances, column <NUM> may be a part of a chromatography skid, which may include additional parts, such as a controller, a display, and supplies of mobile phases, washes, and buffers. Column <NUM> may be configured to perform any of various types of chromatography, such as high performance liquid chromatography (HPLC), ion exchange chromatography, size exclusion chromatography, hydrophobic interaction chromatography (HIC), reverse phase chromatography, mixed-mode chromatography, or affinity chromatography. Column <NUM> may be used, for example, to separate biologics in a raw mixture, isolate and/or purify a single type of biologic, and/or eliminate contaminants from a mixture. In some instances, column <NUM> may be a part of a drug product manufacturing system, such as a system for manufacturing a drug product containing a biologic, such as an antibody.

Mobile phase supply <NUM> may be any suitable supply of a mobile phase to column body <NUM>, via mobile phase conduit <NUM>. Mobile phase supply <NUM> may be connected to one or more reservoirs to hold mobile phase liquid(s) used to drive raw materials injected by material injection supply <NUM> into column body <NUM>. Mobile phase supply <NUM> may include, or be connected to, one or more pumps configured to impart pressure to the mobile phase liquid(s). In some embodiments, pumps connected to mobile phase supply <NUM> may be configured to mix two or more solvents (e.g., from two or more reservoirs) in a desired ratio prior to supplying the combined solution to mobile phase conduit <NUM> via mobile phase supply <NUM>. In some embodiments, mobile phase supply <NUM> may be configured to supply a first mobile phase to column body <NUM> via mobile phase conduit <NUM>, and then supply a second mobile phase to column body <NUM> via mobile phase conduit <NUM> after a desired volume of the first mobile phase has been supplied. Mobile phase supply <NUM> may be controlled by, for example, a process controller, or by human interaction.

Material injection supply <NUM> may include any suitable supply of raw material requiring separation and/or purification in column body <NUM>. In some embodiments, material injection supply <NUM> may include raw materials containing one or more biologics, contaminants, solvents, and/or other materials. In further embodiments, material injection supply <NUM> may include one or more drug products, or one or more materials used in the manufacture of a drug product. In some embodiments, material injection supply <NUM> may include one or more reservoirs to hold materials to be separated and/or purified in column body <NUM>.

Column frame <NUM> may be sized and configured to accommodate and support one or more of mobile phase supply <NUM>, material injection supply <NUM>, mobile phase conduit <NUM>, column cover <NUM>, column body <NUM>, upper column bed support <NUM>, lower column bed support <NUM>, and mobile phase outlet <NUM>. In some embodiments, column frame <NUM> may include a series of adjustable struts arranged in a generally cylindrical manner, forming an open housing around column body <NUM>. Column frame <NUM> may be configured to be assembled and disassembled, either fully or partially, such that other parts of column <NUM> may be removed, cleaned, and/or replaced. Column frame <NUM> may, in some embodiments, include wheels or other mobile attributes to allow for portability.

Mobile phase conduit <NUM> may be fluidly connected to mobile phase supply <NUM>, column body <NUM>, and/or column cover <NUM>, such that fluid provided through mobile phase supply <NUM> may pass through mobile phase conduit to column body <NUM>. Such a fluid connection may include, for example, a coupling (e.g., a threaded coupling), one or more gaskets or other seals, etc. In some embodiments, mobile phase conduit <NUM> may be of adjustable length, to accommodate a variety of column heights in column frame <NUM>.

Column cover <NUM> may cover a top of column body <NUM>, and may include one or more features to close and/or otherwise protect an upper end or upper portion of column body <NUM>. For example, column cover <NUM> may include an adjustable seal, such as a gasket seal, to seal itself to a perimeter of the upper end or upper portion of column body <NUM> when column <NUM> is assembled. Column cover <NUM> may include an opening through which mobile phase conduit <NUM> may deliver mobile phase from mobile phase supply <NUM> to column body <NUM>. In some embodiments, column cover <NUM> may include one or more fixation elements with which to hold upper column bed support <NUM> in place at or near an upper end of column body <NUM>, underneath column cover <NUM>.

Column body <NUM> may be any column body suitable for installation in column frame <NUM>. Column body <NUM> may be configured for assembly together with upper column bed support <NUM> and/or lower column bed support <NUM> in column frame <NUM>, and may be packed with a stationary phase suitable for a chromatography operation. One of ordinary skill in the art will recognize that column body <NUM> may have any of a wide variety of sizes (e.g., diameters ranging from about <NUM> to about <NUM>) and may be packed with any of a wide variety of stationary phases. The size, shape, and pack of column body <NUM> may be chosen in view of various factors, including the composition, volume, chemical properties, mechanical properties, charge, pH, and/or other characteristics of the material in material supply <NUM>, as well as the desired outcome of the chromatography run.

Upper column bed support <NUM> and lower column bed support <NUM> may be sized and configured to fit above and below a pack in column body <NUM>. Upper column bed support <NUM> and lower column bed support <NUM> may have several functions, including containment of the stationary phase, ensuring that the stationary phase moves or shifts minimally, and/or filtration of fluid progressing through column body <NUM>. Both column bed supports may include a porous or mesh component through which fluid (e.g., a mobile phase) may pass. A size of the apertures in the porous or mesh components of both column bed supports may be sufficiently large to allow for passage of a mobile phase, while also being small enough to prevent migration of a stationary phase in a chromatography run. Either or both of the column bed supports may be made of any suitable material, such as a metal, metal alloy, or a polymer. For example, column bed supports may be made from steel, nickel, and/or titanium. Both upper column bed support <NUM> and lower column bed support <NUM> may have dimensions (e.g., a length and width, or a diameter) compatible with column body <NUM>, to aid in maintaining the position and integrity of a stationary phase in column body <NUM>. In some embodiments, upper column bed support <NUM> may be sized and configured to fit snugly within column body <NUM>, and lower column bed support <NUM> may be sized and configured to share a diameter with column body <NUM>, such that it may close a lower end of column body <NUM>. Each column bed support <NUM>, <NUM> may also have a depth or thickness suitable for providing physical support to a packed column, while still allowing for passage of a mobile phase. In some embodiments, upper column bed support <NUM> and lower column bed support <NUM> may be generally disk-shaped. One exemplary brand of column bed supports with which this disclosure may be used is AxiChrom®, distributed by GE Healthcare Life Sciences.

Mobile phase outlet <NUM> may be fluidly connected to an opening at a lower end of column body <NUM>, below lower column bed support <NUM>. While running a chromatography operation, mobile phase outlet <NUM> may also be fluidly connected to, e.g., a collector. In some embodiments, one or more detectors may be positioned so as to detect one or more characteristics of fluid exiting the column.

<FIG> depict, in schematic form, an exemplary column bed support case <NUM>, according to aspects of the present disclosure. <FIG> depicts a top view, <FIG> depicts a first side view, <FIG> depicts a front view, <FIG> depicts a second side view, and <FIG> depicts a bottom view of the case <NUM>. Case <NUM> includes an openable front <NUM>, a case body <NUM>, a plurality of external handles <NUM>, <NUM>, <NUM>, <NUM>, an inset handle <NUM>, latches <NUM>, <NUM>, standoffs <NUM>, <NUM>, reinforcement bands <NUM>, <NUM>, and corner guards <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>.

Case <NUM> may be of any shape or size suitable for housing one or more column bed supports (e.g., upper column bed support <NUM> and/or lower column bed support <NUM>). For example, case <NUM> may be of a size and shape suitable for housing one or more column bed supports having a diameter of between about <NUM> and about <NUM>, such as about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, or about <NUM>. These sizes are exemplary, and case <NUM> may be of a size and shape suitable for housing one or more column bed supports having dimensions smaller than about <NUM> or larger than about <NUM>. In some embodiments, case <NUM> may be a rectangular box having a length, a width, and a depth that is less than the length and the width. As depicted in <FIG>, case <NUM> may have a length and width that form a square, such that an interior of case <NUM> may accommodate disk-shaped column bed supports. Case <NUM> may also include a depth that is less than the length and the width, to correspond with the relatively flat shape of the disk-like column bed supports. In alternative embodiments, case <NUM> may have a length longer than its width or depth, or may have other shapes, such as a cylindrical shape (e.g., with a circular cross-section).

A table of exemplary external dimensions suitable for case <NUM> is presented below.

As can be seen from Table <NUM>, the depth of case <NUM> may not necessarily change along with the compatible column bed support, because a column bed support's thickness may not necessarily increase with its diameter. However, case <NUM>'s length and width may be tailored specifically to fit the case's compatible column bed support size.

Case <NUM> may have an exterior housing divided into an openable front <NUM> and a case body <NUM>. Openable front <NUM> may have a length and a width equivalent to the length and width of the case, such that it includes an entire front side of case <NUM> (e.g., the side depicted in <FIG>). Openable front <NUM> may be affixed to case body <NUM> by a number of methods, such as by latches <NUM>, <NUM> on one side of case <NUM>. In some embodiments, openable front <NUM> and case body <NUM> may be movably affixed to one another by one or more hinges on a side of case <NUM> opposite latches <NUM>, <NUM>. In alternative embodiments, case <NUM> may include an openable side having a length and a width equivalent to the length and depth of the case, such that the openable side of case <NUM> is one of the narrower sides of case <NUM>. In such embodiments, the openable side of case <NUM> and the case body may still be removably and/or movably affixed to one another via latches <NUM>, <NUM> and/or one or more hinges located at a juncture between the openable side and the case body of case <NUM>.

Case <NUM> may be made from any material that is strong and stiff enough to maintain its shape and prevent or reduce damage to the case's contents. For example, case <NUM> may be made from a hard plastic, a metal, or a combination of plastic and metal. In some embodiments, case <NUM> may be made from a waterproof or water-resistant material. In some embodiments, case <NUM> may be made from a material having little or low toxicity, e.g., as determined by a regulatory or manufacturing standard. In some embodiments, the material may be manufactured according to one or more regulatory standards, such as standards set by the United States Pharmacopeia (USP). For example, in some embodiments, the material may be a USP Class VI material. In some embodiments, case <NUM> may be made from a polyethylene material, such as a low density polyethylene material (e.g., LD45). In alternative embodiments, case <NUM> may be made from a metal, such as aluminum, steel, titanium, nickel, and/or an alloy of one or more of these metals. In still further embodiments, case <NUM> may be made from a combination of metal and polyethylene, such as a polyethylene-coated metal.

The housing of case <NUM> (including openable front <NUM> and case body <NUM>) may have an approximately uniform overall thickness. For example, if case <NUM> is made from low-density polyethylene (e.g., LD45), the housing of case <NUM> may have an approximately uniform thickness ranging from about <NUM> to about <NUM>, such as from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>. For example, the housing of case <NUM> may have an approximately uniform thickness of about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, or about <NUM>.

External handles <NUM>, <NUM>, <NUM>, <NUM> may be located on one or more sides of case <NUM>. As depicted, external handles <NUM>, <NUM>, <NUM>, <NUM> may be located in pairs on opposing sides of case <NUM>, and may be sized and configured to allow for a user to pick up and carry case <NUM>. External handles <NUM>, <NUM>, <NUM>, <NUM> may be any handles suitable for carrying, such as square handles, rounded handles, loops, rotatable hinged handles, collapsible handles, and the like. They may be made from any suitably strong material, such as a polymer or a metal material. In some embodiments, they may be made from a low-density polyethylene material. In further embodiments, they made be made from steel, nickel, aluminum, titanium, or an alloy including one or more of these metals. In some embodiments, external handles <NUM>, <NUM>, <NUM>, <NUM> may be reinforced, or covered to allow for comfort while in use. For example, in some embodiments, external handles <NUM>, <NUM>, <NUM>, <NUM> may be made from a metal fully or partially covered in a polymer sleeve or coating.

Inset handle <NUM> may be formed from an aperture at the edge of, e.g., a side of case <NUM>, such as the bottom side of case <NUM> depicted in <FIG>. In alternative embodiments, inset handle <NUM> may be formed at the edge of any side of case <NUM>. Inset handle <NUM> may be sized and configured to allow for a hand to grab and hold case <NUM> and, for example, pull or lift case <NUM>. In some embodiments, inset handle <NUM> may be formed from apertures in two intersecting sides of case <NUM> (e.g., a bottom side of case <NUM>, depicted in <FIG>, and a back side of case <NUM>), to form a cavity in case <NUM>. In some embodiments, a case (e.g., case <NUM>) may include more than one inset handle, e.g., on opposite or adjacent sides of case <NUM>. In some embodiments, edges of inset handle <NUM> may be strengthened and reinforced by an added border of material. Such reinforcing material may be affixed to case <NUM> by, e.g., any suitable material, such as an adhesive (e.g., a glue), one or more screws, grommets, or rivets, a welded connection, or a combination of any of these methods.

Standoffs, such as standoffs <NUM>, <NUM>, may be located on one or more sides of case <NUM>, and may be affixed to case <NUM>, reinforcement bands on case <NUM>, or both. Standoffs <NUM>, <NUM> may be sized and configured to support case <NUM> away from, e.g., a surface on which case <NUM> is resting, or a surface adjacent to case <NUM>. Standoffs <NUM>, <NUM> are depicted as being evenly spaced on an edge of the top side of case <NUM>. In alternative embodiments, standoffs may be placed on any number of sides of case <NUM>, in any number.

Reinforcement bands, such as reinforcement bands <NUM>, <NUM> may be affixed on or around one or more edges of case <NUM>. Such reinforcement bands may serve to enhance the durability of case <NUM> by, for example, protecting the edges and corners of case <NUM> from wear and tear. As depicted in <FIG>, reinforcement bands such as bands <NUM>, <NUM> may be present on every angled edge of cage <NUM>. In alternative embodiments, reinforcement bands may be present only on some edges. in yet further embodiments, reinforcement bands may not be present at all.

Corner guards <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> may be affixed on corners of case <NUM> (e.g., where more than two sides of case <NUM> meet in a point. Such corner guards may assist in protecting case <NUM>, users handling case <NUM>, and environments in which case <NUM> is handled, from damaging and/or being damaged by one another. The corner guards may also facilitate movement of case <NUM> by making it easier to slide case <NUM> along a surface.

As depicted in <FIG>, a side of openable front <NUM> is removably affixed to case body <NUM> by latches <NUM>, <NUM>. Latches <NUM>, <NUM> may be any suitable latches or catches known in the art, such as compression spring latches, twist latches, padlockable latches, draw latches, venting latches, keeper latches, long catch latches, and the like. Openable front <NUM> may be movably affixed to case body <NUM> by one or more hinges on a side of case <NUM> opposite latches <NUM>, <NUM>. In other embodiments, openable front <NUM> may be affixed to case body <NUM> by latches or catches on two or more sides of case <NUM>, in lieu of or in addition to hinges. In further alternative embodiments, openable front <NUM> may be affixed to case body <NUM> by any other suitable method, such as by one or more clips, tie-closures, elastic closures, straps, buckles, clasps, zippers, buttons, and the like.

Elements of case <NUM>, such as some or all of handles <NUM>, <NUM>, <NUM>, <NUM>, latches <NUM>, <NUM>, corner guards <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, reinforcement bands <NUM>, <NUM>, standoffs <NUM>, <NUM>, and the reinforced border of inset handle <NUM>, may be made from any of a variety of suitable materials. Suitable materials may include, for example, metals, such as aluminum, steel, titanium, nickel, or alloys of such metals. Suitable materials may also include polymers and co-polymers of sufficient hardness and strength to maintain their structure and perform their function (e.g., a low density polyethylene, such as LD45). In some embodiments, one or more of these elements may be made from a polymer-covered or polymer-coated metal or metal alloy.

Elements of case <NUM>, such as handles <NUM>, <NUM>, <NUM>, <NUM>, latches <NUM>, <NUM>, corner guards <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, reinforcement bands <NUM>, <NUM>, standoffs <NUM>, <NUM>, and the reinforced edges of inset handle <NUM>, may be affixed to case <NUM> and/or to one another by any suitably strong methods that allows for safe, reusable use of case <NUM>. For example, handles <NUM>, <NUM>, <NUM>, <NUM> may be affixed to case <NUM> by a method that allows for case <NUM> to be carried by the handles. For example, elements on the exterior of case <NUM> may be affixed to case <NUM> by an adhesive (e.g., a glue), one or more screws, rivets, or grommets, a welded connection, or a combination of any of these methods.

While case <NUM> is depicted in <FIG> as having several features, such as handles <NUM>, <NUM>, <NUM>, <NUM>, latches <NUM>, <NUM>, corner guards <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, reinforcement bands <NUM>, <NUM>, standoffs <NUM>, <NUM>, and inset handle <NUM>, it is contemplated that a case according to the present disclosure may not necessarily have one or more of these features. For example, a case according to the present disclosure may not include handles or corner guards. As another example, a case according to the present disclosure may not include reinforcement bands (e.g., reinforcement bands <NUM>, <NUM>), or standoffs (e.g., standoffs <NUM>, <NUM>).

<FIG> depicts a cross-sectional view of an exemplary interior of case <NUM>, according to aspects of the present disclosure. The viewing angle of case <NUM> shown in <FIG> is the same as that shown in <FIG>. As shown in <FIG>, case body <NUM> and openable front <NUM> enclose a plurality of stacked contents, including inserts <NUM>, <NUM> separated by divider <NUM>. Insert <NUM> may be spaced from openable front <NUM> by three spacers <NUM>.

As depicted in <FIG>, case <NUM> is sized and configured to snugly fit one or more inserts and dividers. For example, case <NUM> may be sized and configured to fit approximately square inserts and dividers which are, in turn, sized and configured to house circular disk-shaped column bed supports.

Each of inserts <NUM>, <NUM> is configured to hold a column bed support. Divider <NUM> is configured to provide separation and padding between inserts <NUM>, <NUM>, as well as between the column bed supports that they hold. Spacers <NUM> may be configured to provide separation, padding, and filling between one (or both) of the inserts and the housing of case <NUM>. As shown in <FIG>, a combined depth of these contents of case <NUM> is approximately equal to the depth of the interior of case <NUM>. This snug stacking of contents of case <NUM> may assist in minimizing the potential for damage to column bed supports due to jostling, transportation, or other movement of case <NUM>. While a specific organization of inserts, dividers, and spacers is shown in case <NUM> in <FIG>, it is contemplated that inserts, dividers, and spacers could be arranged in other orders. For example, a divider may be placed in between an insert (e.g., insert <NUM>) and an interior of case <NUM>. In some embodiments, a divider may be placed on each side of each insert, e.g., to provide additional protection to the column bed support housed in each insert. As another example, case <NUM> may be sized and configured to hold only one insert. As a further example, case <NUM> may be sized and configured to hold more than two inserts, e.g., <NUM>, <NUM>, <NUM>, or <NUM> inserts.

Each of the components inside case <NUM>, depicted in <FIG>, is described in further detail below.

<FIG> depict two views of a rectangular spacer (e.g., spacers <NUM>) for use in a column bed support case (e.g., case <NUM>) according to aspects of the present disclosure. As shown, spacer <NUM> may be a block positioned between the interior of a case (e.g., case <NUM>) and an insert (e.g., insert <NUM> or insert <NUM>). Spacer <NUM> may have a smaller length and width than the inserts <NUM>, <NUM> and divider <NUM>. Spacer <NUM> may be removable, or may be affixed to, e.g., an interior of the case (e.g., case <NUM>) by, e.g., an adhesive or any of the other fixation methods disclosed herein. Spacer <NUM> may be specifically sized to fill whatever depth is empty in case <NUM>, so as to prevent inserts <NUM>, <NUM> and divider <NUM> from shifting within case <NUM> and potentially dislodging column bed supports held in inserts <NUM>, <NUM>. Any number of spacers <NUM> may be present inside case <NUM> in order to assist in immobilizing inserts <NUM>, <NUM>. For example, case <NUM> may include two, four, six, or eight spacers <NUM>.

<FIG> depict views of a divider (e.g., divider <NUM>) for a column bed support case according to aspects of the present disclosure. Divider <NUM> may extend across a length and width of an interior of case <NUM>, and may be positioned in between inserts (e.g., inserts <NUM>, <NUM>) in case <NUM>. Divider <NUM> serves to prevent inserts in case <NUM> from shifting, falling, hitting one another or jostling one another. Handle indentations <NUM> may be located on one or more sides of divider <NUM>, and may assist with picking up and moving divider <NUM>. In some embodiments, each side of divider <NUM> may include a handle indentation <NUM>. Divider <NUM> includes a through hole <NUM>. A dowel or other device may be placed into through hole <NUM> in order to prevent divider <NUM> from shifting or moving against, e.g., inserts <NUM>, <NUM>. In some embodiments, divider <NUM> may cover a majority of an area between inserts <NUM>, <NUM>. In other embodiments, divider <NUM> may have a smaller surface area. It is contemplated that divider <NUM> may have any shape or size that will fit in case <NUM> and that will separate two or more inserts from one another, or that will separate an insert from an interior wall of a case (e.g., case <NUM>). For example, divider <NUM> may be circular, X-shaped, cross-shaped, or grid shaped.

Divider <NUM> may be made from any material that is strong and stiff enough to maintain its shape and maintain separation between an insert and other portions or components of case <NUM>. For example, divider <NUM> may be made from a hard plastic, a metal, or a combination of plastic and metal. In some embodiments, divider <NUM> may be made from a waterproof or water-resistant material. In some embodiments, divider <NUM> may be made from a material having little or low toxicity, e.g., as determined by a regulatory or manufacturing standard. In some embodiments, the material may be manufactured according to one or more regulatory standards, such as standards set by the United States Pharmacopeia (USP). For example, in some embodiments, the material may be a USP Class VI material. In some embodiments, divider <NUM> may be made from a polyethylene material, such as a low density polyethylene material (e.g., LD45). In other embodiments, divider <NUM> may be made from one or more other polymers, such as acrylonitrile butadiene styrene (ABS). In alternative embodiments, divider <NUM> may be made from a metal, such as aluminum, steel, titanium, nickel, and/or an alloy of one or more of these metals. In still further embodiments, divider <NUM> may be made from a combination of metal and polymer, such as a polymer-coated metal.

<FIG> depict views of an insert (e.g., insert <NUM>) for a column bed support case according to aspects of the present disclosure. Insert <NUM> includes a cavity <NUM>, one or more recesses <NUM> around a perimeter of cavity <NUM>, a through hole <NUM>, and one or more handle indentations <NUM>. Insert <NUM> is sized and configured to house a particular size and/or type of column bed support in cavity <NUM>. For example, in some embodiments, insert <NUM> may be sized and configured to house one of a pair of column bed supports, such as an upper column bed support (e.g., upper column bed support <NUM> depicted in <FIG>).

<FIG> depict views of a second insert (e.g., insert <NUM>) for a column bed support case, according to aspects of the present disclosure. Like insert <NUM>, insert <NUM> includes a cavity <NUM>, one or more recesses <NUM> around a perimeter of cavity <NUM>, a through hole <NUM>, and one or more handle indentations <NUM>. Insert <NUM> is sized and configured to fit a column bed support that forms a pair with a column bed support to be housed in insert <NUM>. For example, if insert <NUM> is sized and configured to house a top column bed support for a given size of chromatography column, then insert <NUM> may be sized and configured to hold a bottom column bed support for the same size of chromatography column. Insert <NUM> may therefore have a cavity <NUM> that is larger than cavity <NUM> of insert <NUM>. In some embodiments, and as depicted in <FIG>, cavity <NUM> may be large enough to partially extend into handle indentations <NUM>.

Cavities <NUM>, <NUM> may extend partially into inserts <NUM>, <NUM>, and may have dimensions (e.g., a diameter, depth, volume, etc.) tailored to house one column bed support each. As depicted, cavities <NUM>, <NUM> may have generally circular cross-sections and may be generally cylindrical in shape; however, it is contemplated that they may have any shape tailored to house a column bed support. In some embodiments, cavities <NUM>, <NUM> may have dimensions similar to those of the column bed supports that they are intended to house, so that column bed supports stored in cavities <NUM>, <NUM> do not have excessive space to shift, knock against other components inside case <NUM>, and/or become damaged or contaminated.

Recesses <NUM>, <NUM> may be located around the perimeter of cavities <NUM>, <NUM>, respectively. As depicted in <FIG> and <FIG>, recesses <NUM>, <NUM> may extend into inserts <NUM>, <NUM> in the same direction as cavities <NUM>, <NUM>, but may extend slightly further than cavities <NUM>, <NUM>. Recesses <NUM>, <NUM> may be sized and configured to allow for placement and removal of column bed supports into cavities <NUM>, <NUM>. As such, recesses <NUM>, <NUM> may be of any size and configuration suitable for sliding hands, fingers, or other tools next to and underneath column bed supports housed in cavities <NUM>, <NUM>. Although recesses <NUM>, <NUM> are depicted as having general cylindrical shapes with circular cross sections, it is contemplated that recesses <NUM>, <NUM> may have other shapes, such as oblong or rectangular shapes. Although four recess <NUM>, <NUM> are depicted in the figure, those of ordinary skill in the art will readily recognize that a greater or lesser number of recesses may be provided on inserts <NUM>, <NUM>.

Inserts <NUM>, <NUM> include through holes <NUM>, <NUM>. As with through hole <NUM> in divider <NUM>, a dowel or other device may be placed into through holes <NUM>, <NUM> in order to prevent inserts <NUM>, <NUM> from shifting or moving inside case <NUM>. This may be suitable in cases where column bed supports housed in inserts <NUM>, <NUM> also include through holes, such that a single dowel, bar, or other device may be threaded through each of inserts <NUM>, <NUM>, divider <NUM>, and column bed supports housed in inserts <NUM>, <NUM>.

As with handle indentations <NUM> of divider <NUM>, handle indentations <NUM>, <NUM> may be located on one or more sides of each of inserts <NUM>, <NUM>, and may assist with picking up and moving each insert. In some embodiments, each side of an insert <NUM>, <NUM> may include a handle indentation <NUM>, <NUM>, respectively. Although handle indentations <NUM>, <NUM>, <NUM> are depicted as having a generally rectangular shape with curved corners, each handle indentation may have any size and shape suitable for hands, fingers, or tools to grasp and lift each of divider <NUM>, insert <NUM>, and insert <NUM>. As depicted, a cavity (e.g., cavity <NUM>) may extend into a handle indentation (e.g., handle indentation <NUM>) without overly disrupting the structure and/or function of either the cavity or the handle indentation.

Inserts <NUM>, <NUM> may be made from any non toxic material suitable for housing a column bed support. In some embodiments, for example, inserts <NUM>, <NUM> may be made from a material having little or low toxicity, e.g., as determined by a regulatory or manufacturing standard. In some embodiments, the material may be manufactured according to one or more regulatory standards, such as standards set by the United States Pharmacopeia (USP). For example, in some embodiments, the material may be a USP Class VI material. In some embodiments, inserts <NUM>, <NUM> may be made from a polyethylene material, such as a low density polyethylene material (e.g., LD45). In other embodiments, inserts <NUM>, <NUM> may be made from one or more other polymers, such as acrylonitrile butadiene styrene (ABS). In further embodiments, and as depicted in <FIG> and <FIG>, inserts <NUM>, <NUM> may have a body made from one material, with a reinforcing back layer <NUM>, <NUM> of a second material. For example, inserts <NUM>, <NUM> may be made primarily from a low density polyethylene, such as LD45, or other plastic or foam material, and may also include a reinforcing back layer (layers <NUM>, <NUM>, respectively) made from a harder material, such as a hard polymer (e.g., ADS) or metal. In alternative embodiments, some or all of inserts <NUM>, <NUM> may be made from foam, metal (e.g., aluminum, steel, titanium, nickel, and/or an alloy of one or more of these metals), or a combination of metal and polymer, such as a polymer coated metal. In still further embodiments, divider <NUM> may be made from a combination of metal and polymer, such as a polymer-coated metal.

As alluded to above, the dimensions of an interior of case <NUM>, spacers <NUM>, inserts <NUM>, <NUM>, and divider <NUM> may be sized and configured to snugly hold column bed supports of a specific size and shape. Table <NUM> below lists three exemplary sets of dimensions for these components, given each of three column bed support sizes (e.g., an approximate diameter of a column bed support, as identified by the column bed support manufacturer).

Tolerances (e.g., manufacturing tolerances) for the above dimensions may be as follows:.

The above dimensions are only exemplary, and many other combinations of dimensions may be appropriate for a case, such as case <NUM>, or variations thereof, and its components.

<FIG> depicts, in flow chart form, steps in a method <NUM> of managing dedicated column bed supports, according to aspects of the present disclosure. According to step <NUM>, a first chromatography column bed support is installed in a chromatography column. According to step <NUM>, a first operation may be run in the chromatography column, using the first column bed support. According to step <NUM>, the first column bed support may be stored in a first storage case. According to step <NUM>, a second column bed support may be installed in the chromatography column. According to step <NUM>, a second chromatography operation may be run in the chromatography column, using the second chromatography column bed support. According to step <NUM>, the second chromatography column bed support may be stored in a second storage case. Steps <NUM> may be repeated additional times, e.g., with the first operation and first column bed support and the second operation and second column bed support, and/or with third, fourth, fifth, or additional operations, and with third, fourth, fifth, or additional column bed supports.

According to step <NUM>, a first chromatography column bed support is installed in a chromatography column. This may be accomplished according to a number of established practices and procedures. For example a first column bed support <NUM> may be installed in, e.g., column body <NUM>. In some embodiments, the first chromatography column bed support may be a new column bed support. In other embodiments, the first column bed support may have been used previously for, e.g., an established chromatography operation. In some embodiments, a pair of first chromatography column bed supports, such as an upper column bed support <NUM> and a lower column bed support <NUM>, may be installed in a chromatography column.

According to step <NUM>, a first operation may be run in the chromatography column, using the first column bed support (or pair of first column bed supports). The first operation may include, for example, a chromatography operatio requiring the use of the first chromatography column bed support (or a first pair of chromatography column bed supports). The first operation may also require a specific column pack (e.g., a particular stationary phase), a specific mobile phase, and/or a specific series of washes and/or buffers. In some embodiments, the first operation may be configured to be run as a part of a manufacturing process for a drug product. In further embodiments, the first operation may be configured to be run as a part of a testing protocol.

According to step <NUM>, the first column bed support (or pair of column bed supports) may be removed from the chromatography column and stored in a first storage case (e.g., case <NUM>). In some embodiments, this step may include unpacking and cleaning the chromatography column. In some embodiments, for example, this may be performed after one or more iterations of the first chromatography operation is run. In some embodiments, the first column bed support or pair of column bed supports may be cleaned or sterilized prior to being stored in a first storage case. In some embodiments, the first storage case may be labeled or otherwise marked as a dedicated storage case for storing the first column bed support (or pair of column bed supports).

According to step <NUM>, a second column bed support may be installed in the chromatography column. As with the first column bed support, the second column bed support may be a new column bed support. In some embodiments, the second column bed support may have been used previously for, e.g., an established chromatography operation different from the first chromatography operation. In some embodiments, step <NUM> may include installing a pair of second chromatography column bed supports in a chromatography column.

According to step <NUM>, a second chromatography operation may be run in the chromatography column, using the second chromatography column bed support (or pair of second column bed supports). The second operation may include, for example, a specific column pack (e.g., a particular stationary phase), a specific mobile phase, and/or a specific series of washes and/or buffers different from those required in the first chromatography operation. In some embodiments, like the first chromatography operation, the second chromatography operation may be configured to be run as a part of a manufacturing process for a drug product. In such embodiments, the drug product involved in the second chromatography operation may be different from a drug product involved in the first chromatography operation. In further embodiments, the first and second chromatography operations may constitute different steps in the manufacture or purification of the same drug product. In further embodiments, the second operation may be configured to be run as a part of a testing protocol or a research and/or development program different from a testing protocol or research/development program for which the first operation is run.

According to step <NUM>, the second chromatography column bed support may be stored in a second storage case. In some embodiments, this step may include unpacking and cleaning the chromatography column. In some embodiments, for example, this may be performed after one or more iterations of the second chromatography operation is run. In some embodiments, the second column bed support or pair of column bed supports may be cleaned or sterilized prior to being stored in a second storage case. In some embodiments, the second storage case may be labeled or otherwise marked as a dedicated storage case for storing the second column bed support (or pair of column bed supports). The column may then be free for use with the first column bed support (or pair of column bed supports) again, or for use with a third column bed support or pair of column bed supports.

<FIG> depicts a flow chart of steps in a method arranged in one way; however, the present disclosure contemplates that steps may be added, removed, and/or performed out of order in the depicted method. The steps of <FIG> may also be performed multiple times in a repetitive sequence, as a part of one or more purification processes, drug product manufacturing processes, and/or research, development, or testing processes. The steps of <FIG> may be employed as a part of a larger chromatography management system, in which column bed supports and cases for storing column bed supports may be labeled, categorized, and stored in an inventory for regular, intermittent, or infrequent use.

Claim 1:
A chromatography column bed support case (<NUM>), comprising:
a housing having a body with an opening, an interior in the body accessible via the opening, and a lid configured to cover the opening;
two removable inserts (<NUM>, <NUM>) configured to fit inside the interior in a parallel configuration, each insert including a cavity configured to house a chromatography column bed support; and
a removable divider (<NUM>) disposed between the inserts (<NUM>, <NUM>), wherein the divider (<NUM>) is sized and configured to separate the inserts (<NUM>, <NUM>),
wherein each of the inserts (<NUM>, <NUM>) and the divider (<NUM>) includes a centrally located through hole, and
wherein the through holes are coaxial.