Abstract:
A container for storing a biopharmaceutical drug product is disclosed. The container includes two surface area planar walls. A plurality of smaller side walls circumscribing each, of the planar walls. The container may also include a plurality of members extending between the first planar surface and the second planar surface and located at spaced apart locations on each of the first and second planar surfaces. A method of freezing at least one biopharmaceutical product in the container is also disclosed.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to a container that is used to contain biopharmaceutical material that is intended to be frozen for storage and shipping. 
       BACKGROUND OF THE INVENTION 
       [0002]    Biopharmaceutical drugs are manufactured in bulk amounts in order to lower the cost per unit of the drug. Often, the drugs are manufactured in a liquid form, with drug and other solutes being homogeneously dissolved and distributed within the solution. In order to enhance the stability and shelf life of the drug, the drug solution is frozen in a container. It is advantageous if the container is also suitable for transport. 
         [0003]    It is well known that solutes in bulk liquid solutions are subject to a stress force induced by the advancement of the ice front during the freezing process. Depending on the ice front velocity, solutes can be either trapped in the solid phase or pushed away from the ice-liquid interface into the bulk liquid region. The migration of the solutes results in a heterogeneous solute distribution in the frozen material. Testing of such migration has indicated that the change in percentage of solute in the solution vary significantly, e.g., from 60% to 300% of the initial (pre-freezing) value. One solution to limit this migration is to reduce the time required to freeze the solution. 
         [0004]    The heat transfer process during freezing is well characterized by the Stefan solution equation, which correlates the thickness of the ice formed after a period of time, when the temperature of the cold surface, as well as, the ice conductivity and heat of fusion are known. The equation indicates that the time required to freeze liquid in a container is a function of the square of the distance that heat travels from the liquid. Therefore, a reduction in the time required to freeze the liquid requires a reduction in the distance that the heat must travel to be removed from the liquid. 
         [0005]    It would be beneficial to develop a container in which a liquid drug may be stored and frozen, such that the container geometry that reduces the time required to freeze the drug solution, thus limiting the migration of solute, and hence variability of solute distribution, during the freezing process. 
       SUMMARY OF THE INVENTION 
       [0006]    Briefly, the present invention provides a container for storing a biopharmaceutical drug product. The term “biopharmaceutical” means, for example, medical drugs produced using biotechnology. Such biopharmaceuticals comprise proteins (including peptides and antibodies), nucleic acids (DNA, RNA or antisense oligonucleotides) used for therapeutic or in vivo diagnostic purposes and sub-fractions (fragments) and multimers (multiple copies) of all of the above mentioned types of molecules. The container includes two side surface walls, typically planar, and a plurality of smaller side walls, which circumscribe and connect the surface area planar walls and define the interior of the container. The container may also include a plurality of members extending from the first side surface to the second side surface and located at spaced apart locations on each of the first and second side surfaces. 
         [0007]    In one embodiment, the invention relates to a container for storing a biopharmaceutical drug product comprising two relatively large surface area planar surfaces extending opposite to one another. For example, a first and second planar surface can be intersecting, non-parallel, or parallel to each other. In addition, one embodiment also includes a plurality of relatively small surface area side walls circumscribing each of the first and second planar surfaces, wherein the plurality of side walls connect the first and second relatively large surface area surfaces, all of said surfaces collectively defining the interior of the container. 
         [0008]    In another embodiment, the first and second relatively large surface area planar surfaces are parallel surfaces. 
         [0009]    In yet another embodiment of the invention, one of the plurality of side walls extends at an oblique angle relative to an adjacent of the plurality of side walls. In another embodiment, the remaining side walls each define at least a portion of a side of a rectangle. 
         [0010]    In another embodiment, the container further comprises an opening formed within one of the plurality of side walls. In another embodiment, container further comprises a nipple formed around the opening and extending outwardly from the one of the plurality of side walls. In yet another embodiment, the container has a nipple that extends within the rectangle. 
         [0011]    In another embodiment of the invention, the container&#39;s second planar surface is spaced from the first planar surface by a distance of between about 5 to 11 centimeters. In another embodiment, the second planar surface is spaced from the first planar surface by a distance of about 8 centimeters. 
         [0012]    In a further embodiment, the container&#39;s first planar surface is spaced from the second planar surface by a distance, and wherein a maximum dimension of each of the first and second planar surface is no more than ten times that of the distance. 
         [0013]    In another embodiment of the invention, the container&#39;s first and second planar surface and the plurality of side walls all have a thickness of between about 0.1 to 0.95 centimeters. 
         [0014]    Additionally, the present invention includes a method of freezing a biopharmaceutical product. The method comprises the step of providing a container, as described above. The method further includes the steps of inserting the biopharmaceutical product into the container; subjecting the container to freezing conditions; and freezing the biopharmaceutical product within the container while maintaining a generally homogenous solution. 
         [0015]    In another embodiment of the invention, the specification discloses a method of freezing a biopharmaceutical product comprising the steps of providing a container having two relatively large surface area planar walls extending opposite to one another and a plurality of relatively small surface area side walls circumscribing each of the first and second planar surfaces, wherein the plurality of side walls connect the first and second planar surfaces, all of said surfaces collectively defining the interior of the container. The method also includes, inserting the biopharmaceutical product into the container, subjecting the container to freezing conditions, and freezing the biopharmaceutical product within the container while maintaining a generally homogenous solution. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS  
         [0016]    The foregoing summary, as well as the following detailed description of desired embodiments of the invention, will be better understood when read in conjunction with the appended drawings, which are incorporated. herein and constitute part of this specification. For the purposes of illustrating the invention, there are shown in the drawings an embodiment that is presently desired. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities shown. In the drawings, the same reference numerals are employed for designating the same elements throughout the several figures. In the drawings: 
           [0017]      FIG. 1  is a perspective view of a container according to one embodiment of the present invention; 
           [0018]      FIG. 2  is a sectional view of the container of  FIG. 1 ; 
           [0019]      FIG. 3  is a sectional view of the container taken along lines  3 - 3  of  FIG. 2 . 
           [0020]      FIG. 4  is a perspective view of a container stand; and 
           [0021]      FIG. 5  is a perspective view of a container stand and the container of  FIG. 4 . 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0022]    Certain terminology is used herein for convenience only and is not to be taken as a limitation on the present invention. The terminology includes the words specifically mentioned, derivatives thereof and words of similar import. The following describes a desired embodiment of the invention. However, it should be understood based on this disclosure, that the invention is not limited by the desired embodiment of the invention. 
         [0023]    Referring generally to the figures, a container  100  for receiving, freezing, and storing a biopharmaceutical product  102  is shown. The container  100  may also include a plurality of structural support members  160  that extend through the container  100  to help, amongst other things, maintain a desired shape of the container  100 , and also provide a sufficient rate of freezing and/or thawing of the biopharmaceutical product  102  in the container  100 . The structural support members  160  also serve to enhance heat transfer through the container  100 . 
         [0024]    Referring specifically to  FIGS. 1 and 2 , the container  100  includes a first generally planar wall  110  and a second generally planar wall  112 . In one embodiment, the first and second planar walls  110  and  112  are generally parallel to each other and are spaced apart from each other by a distance. The “distance” that separates the first and second planar walls  110  and  112  is determined by the width of the smaller side walls. In another embodiment of the invention, the dimensions of the container mentioned herein are the outside dimension/measurements of the container. For example, the distance between the first and second planar walls  110  and  112  can be 8 cm if the width of the smaller side walls  120 ,  122 ,  124 ,  126 , and  128  are all 8 cm wide. In another embodiment, the first and. second. side planar walls  110  and  112  may be spaced. apart from each other by about 5 to about 11 centimeters in order to provide a sufficient rate of freezing of the biopharmaceutical product  102  in the container  100 , while still providing acceptable height and length dimension of the container  100  to retain a desired fluid volume. 
         [0025]    The time, t, required to fully freeze a solution in such a container is determined by the Stephan Equations (below), which calculate freezing time in a container as a function of distance. The Stephan equations are as follows: 
         [0000]    
       
         
           
             
               
                 
                   t 
                   = 
                   
                     
                       
                         
                           ρ 
                           s 
                         
                          
                         
                           λ 
                           ′ 
                         
                       
                       
                         2 
                          
                         
                             
                         
                          
                         
                           
                             k 
                             s 
                           
                            
                           
                             ( 
                             
                               
                                 T 
                                 f 
                               
                               - 
                               
                                 T 
                                 w 
                               
                             
                             ) 
                           
                         
                       
                     
                      
                     
                       δ 
                       2 
                     
                   
                 
               
               
                 
                   Equation 
                    
                   
                       
                   
                    
                   1 
                 
               
             
           
         
       
     
         [0000]      λ′=+ Cp   L ( T   i   −T   f )   Equation 2 
         [0026]    where: 
         [0027]    δ=heat transfer length (m) 
         [0028]    λ=latent heat of fusion (J/kg) ρ s =density of ice (kg/m 3 ) 
         [0029]    Cp L =heat capacity of the solution (J/kg.°K) 
         [0030]    k s =heat conductivity of ice (W/m. °K) 
         [0031]    T i =initial temperature of the solution (°K) 
         [0032]    T f =freezing temperature of the solution (°K) T w =freezer wall temperature (°K) 
         [0033]    t=time (s) 
         [0034]    Different solutions, which represent solutions that may be stored in the container  100 , were analyzed to determine freeze rates for different container sizes. The solutions tested were distilled water, 0.5 M NaCl solution, and formulation buffers comprising 12% and 18% sucrose. The freezing times were about the same for these solutions, with the note that the freezing temperature of the 0.5 M NaCl and the formulation buffers was −1.5±0.5 degrees Celsius, as opposed to 0 degrees Celsius for the water. 
         [0035]    Using equations 1 and 2, and the aforementioned baseline solutions, with the distance between the planar walls  110  and  112  of the container  100  being 5 cm, which corresponds to a heat transfer length of 2.5 cm since the heat is removed from both sides of the container  100 , freezing time was calculated to be about 12.6 minutes. Thus, the average ice front velocity is about 119 mm/hr. Similarly, the average ice front velocity of the container  100  with a distance δ of 11 cm, which corresponds to a heat transfer length of 5.5 cm, is about 54 mm/hr. Freezing time was calculated to be about 61.1 minutes. 
         [0036]    In one embodiment, in order to minimize solute re-distribution in the container  100  during freezing, the freezing velocity is to be at least 50 mm/hr or faster, corresponding to a maximum surface area planar wall spacing of about 11 cm. Further, in another embodiment, a minimum planar wall spacing of the container  100  is about 5 cm. Otherwise, the container  100  to be used for large bulk material, for example about 5 to about 50 liters would necessarily have to be very thin and very tall in order to contain a sufficient volume of solution. An increase in the height of the container  100  would be required to obtain a desired internal volume, but would raise the center of gravity of the container  100 , allowing the container  100  to flip over easily. In one embodiment, a maximum dimension of each of the first and second planar walls  110  and  112  is no more than ten times that of the distance between the first and second planar walls  110  and  112 . In one embodiment, the “dimensions” of each of the first and second planar walls are the height and width of  110  and  112 . For example, if the distance between  110  and  112  is 6 cm, then the height and width of  110  and  112  should not exceed 60 cm. In another embodiment, the outside dimensions of the container arc only limited in size and shape by the size and shape of the freezer used to store the containers. 
         [0037]    Generally, in one embodiment of the invention, the planar interwall spacing is about midway between the limits of 5 cm and 11 cm (about 8 cm) to cover a range of conditions of materials to be contained. In another embodiment, planar interwall spacing is about 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, or 11 cm to cover a range of conditions of materials to be contained. However, an interplanar wall distance from about 5 cm to about 11 cm should provide a desired freezing time for a wide range of materials and should keep any common solute redistribution within an acceptable limit. For different solutions with different thermodynamic properties, the rate of freezing will likely vary slightly, but it is believed by the inventor(s) that the distilled water, 0.5 M NaCl solution, and formulation buffers discussed above are representative of the thermodynamic properties of the types of solutions that may be stored within the container  100 . 
         [0038]    While the interplanar wall spacing may be from 5 to 11 cm and is generally to be about 8 cm in one embodiment, the height and width of each of the first planar wall  110  and the second planar wall  112  may be varied, depending upon the size of the freezer (not shown) into which the container  100  is intended to be placed to freeze the biopharmaceutical product  102  in the container  100 , or by the desired interior volume of the container  100 . For example, for the container  100  having a volume of 8 liters, either a length of about 300 millimeters and a height of about 500 millimeters or a length of about 400 millimeters and a height of about 400 millimeters provides the desired volume of the container  100 . 
         [0039]    A plurality of side walls circumscribe each of the first planar wall  110  and the second planar wall  112 . As can be seen in  FIG. 2 , five side walls  120 ,  122 ,  124 ,  126 ,  128  connect the first planar wall  110  and, the second planar wall  112 , forming an interior volume within which the biopharmaceutical product  102  is contained. Four of the side walls  120 ,  122 ,  124 ,  126  are orthogonal to an adjacent side wall  120 ,  122 ,  124 ,  126 , while the fifth side wall  128  extends at an oblique angle relative to at least one of its adjacent side walls  120 ,  126 . The side walls  120 ,  122 ,  124 ,  126 ,  128  all fit within an area defined by an imaginary rectangle  130 , with the side walls  122 ,  124  forming the entire corresponding side walls of the rectangle  130  and side walls  120 ,  126  forming a portion of the remaining side walls of the rectangle  130 . In another embodiment, the the side walls  120 ,  122 ,  124 ,  126 ,  128  all fit within an area defined by an imaginary square (not shown). 
         [0040]    The first and second planar walls  110 ,  112  and the side walls  120 ,  122 ,  124 ,  126 ,  128  also serve to enhance heat transfer between the biopharmaceutical product  102  in the container  100  and the environment external to the container  100 . In one embodiment, the first and second planar walls  110 ,  112  and the side walls  120 ,  122 ,  124 ,  126 ,  128  all have a thickness of between about 0.1 and 0.95 centimeters. In another embodiment, the first and second planar walls  110 ,  112  and the side walls  120 ,  122 ,  124 ,  126 ,  128  all have a thickness of between about 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, or 0.95 cm. The walls  110 ,  112 ,  120 ,  122 ,  124 ,  126 ,  128  are of such thickness to enhance heat transfer through the walls  110 ,  112 ,  120 ,  122 ,  124 ,  126 ,  128  during freezing of the biopharmaceutical product  102  within the container  100 . 
         [0041]    The side wall  128  includes a circular opening  132  formed therein. The opening  132  allows the biopharmaceutical product  102  to be poured into and out of the container  100 . In one embodiment, the circular opening  132  is sealed with a plug (not shown) that provides adequate sealing of the opening  132  and containment of the biopharmaceutical product  102 . In another embodiment, a nipple  134  having external threads  136  is formed around the opening  132  and extends outwardly from the side wall  128 . The nipple  134  is sized such that the nipple  134  remains within the rectangle  130 . The nipple  134  remains within the rectangle  130  to accommodate the entire container  100  when the container  100  is placed into a larger container, such as a freezer, with minimal wasted space between the container  100  and the freezer. 
         [0042]    A removable cap  138  is releasably connectable to the nipple  134 . In one embodiment, the cap  138  includes internal threads (not shown) that engage with the external threads  136  of the nipple  134  for a threaded fit. In another embodiment, the cap  138  includes a seal (not shown) that is located on the underside of the cap  138  to provide adequate sealing of the cap  138  with the nipple  134 . In a further embodiment, the exterior circumference of the cap  138  comprises a plurality of ribs  138   a  to engage with a removable locking mechanism  168  as illustrated in  FIG. 1  and. discussed further below. 
         [0043]    In another embodiment, a first and second handle wings  140 ,  142  extend outwardly from the side wall  128 , with the first handle wing  140  on one side of the nipple  134  and the second handle wing  142  extending from an opposing side of the nipple  134 . Each handle wing  140 ,  142  includes a generally circular opening  140   a ,  142   a , respectively, that is sized to receive a hook portion of a handle  150 , shown in  FIG. 1 . Each handle wing  140 ,  142  may further include an extension portion  140   b ,  142   b , respectively, that extends inwardly towards the nipple  134 . The extension portions  140   b ,  142   b  may further include indentions  140   c ,  142   c , respectively, for receiving a spring loaded mechanism for holding the locking mechanism  168  in place. As shown in  FIG. 2 , the handle wings  140 ,  142  are sized and shaped to remain within the imaginary rectangle  130 . 
         [0044]    In a further embodiment, a removable locking mechanism  168  positively locks the cap  138  to first and second handle wings  140 ,  142  using the ribs  138   a  on cap  138  to prevent movement of the cap  138  during the freezing and/or thawing process. In this embodiment, the removable locking mechanism  168  comprises an oblong configuration having a generally circular opening  168   a  and further configured to slidably engage the ribs  138   a  of the removable cap  138 . Locking mechanism  168  further comprises a first end  168   b  that extends from one side of the generally circular opening  168   a  and a second end  168   c  extending from an opposing side of the generally circular opening  168   a . Each end  168   b ,  168   c  further comprises a double prong configured to receive extension portions  140   b ,  142   b , of the handle wings  140 ,  142 , respectively. 
         [0045]    In various embodiments, the locking mechanism  168  is constructed from high density polyethylene or another material compatible with the container  100  for example, glass, metal or other biocompatible plastics, etc. One embodiment of the invention is that the material used to construct the locking mechanism  168  should be rigid enough to maintain its structure or shape during its use and under freezing and thawing conditions. 
         [0046]    The double prong portion of the locking mechanism  168  may further comprise a spring loaded mechanism  168   d , such as a pin. The spring loaded mechanism may comprise any material that will withstand gamma radiation, for example, plastic or stainless steel type material. The spring loaded mechanism  168   d  engages the indentions  140   c ,  142   c  to hold the locking mechanism  168  in place. 
         [0047]    In a further embodiment, a handle  150  includes an elongated, generally cylindrical handle portion  152 . Hook portions  154 ,  156  extend from each end of the handle  150 . Each hook portion  154 ,  156  include a curved hook  154   a ,  156   a  that is sized to be inserted into a respective circular opening  140   a ,  142   a . The hooks  154   a ,  156   a  are spaced from each other sufficiently so that the hook  154   a  may be inserted in the opening  140   a  as the hook  156   a  is being inserted in the opening  142   a.    
         [0048]    The handle  150  is removable from the container  100  in order to conserve space within the freezer into which the container  100  is intended to be placed to freeze the biopharmaceutical product  102  within the container  100 . If the handle  150  were not removable, the handle  150  would extend beyond the imaginary rectangle  130 , forcing the container  100  to be made smaller to fit within the freezer, or requiring a larger freezer, thus wasting freezer space. 
         [0049]    In another embodiment, a container stand  200  for stabilizing the container  100  is shown in  FIGS. 4 and 5 . The container stand may comprise a base portion  202  and an upwardly extending cradle portion  204  sized to receive the container  100 . In one embodiment, the cradle portion  204  comprises a set of openings  206  to receive screws (not shown) to attach the cradle portion  204  to the base portion  202 . The base portion  202  further comprises a set of threaded holes (not shown) to receive the screws through the bottom of the cradle portion  204 . 
         [0050]    In one embodiment, the cradle portion  204  as illustrated in  FIG. 4  comprises generally planar wall  208 , generally planar wall  210  extending from and adjacent to both wall  208  and a generally planar wall  212  that opposes wall  208 . The cradle walls  208 ,  210 , and  212  are oriented to substantially conform to the outside dimension/measurements of the container  100  to enable a snug fit to provide stabilizing support to the container  100 . In another embodiment, the height of walls  208 ,  210  and  212  may be adjusted to provide adequate support while minimizing an insulating effect on the container  100 . Preferably, the maximum height of walls  208 ,  210  and  212  does not obscure open passageways  166  of container  100  to aid in freezing/thawing and further to prevent an insulating effect on container  100 . 
         [0051]    In various embodiments, the internal dimensions of the cradle  204  may be adjusted according to the size and. shape of the container  100 . In one embodiment, for example, where the distance (as discussed above) between the walls  110  and  112  of the container  100  is 8 cm, the internal dimensions of the cradle  204  may be adjusted to accommodate a distance of 8 cm such that the external surface of the container  100  substantially abuts the interior surface of the cradle  204 . In another embodiment, the internal dimensions of the cradle  204  may be adjusted to accommodate a container  100  having the walls  110  and  112  spaced apart from each other by about 5 to about 11 centimeters. In another embodiment, the interior size and shape of the cradle  204  is designed to complement the size and shape of the container  100  that it will hold as illustrated in  FIG. 5 . 
         [0052]    In a further embodiment, to maintain a sterile environment and help prevent migration of liquid between the base portion  202  and the cradle  204 , the base portion  202  may comprise an overhang that slopes downward from the cradle  204  and further extends outwardly beyond the dimensions of the cradle  204 . The wider base portion  202  may be adjusted to further provide additional stability to the container stand  200 . 
         [0053]    Referring to  FIG. 5 , in one embodiment, an open side  214  may facilitate sliding the container  100  into the cradle  204 . 
         [0054]    In one embodiment, the cradle  204  is constructed from high density polyethylene or another biocompatible material such as, glass, metal, other biocompatible plastics, etc. The cradle material should be rigid enough to maintain its structure and shape in order to provide support to the container  100 . In another embodiment, the base portion  202  is comprised of black anodized aluminum to help maintain a sterile environment. In alternate embodiments, the base portion  202  may further be comprised of another type of biocompatible material having sufficient structure and rigidity to provide base support to the cradle  204  and the container  100 . 
         [0055]    Referring to  FIGS. 1 and 2 , a plurality of structural support members  160  extend through the container  100  between the first planar wall  110  and the second planar wall  112 . In one embodiment, each support member  160  is generally tubular in shape, with a first open end  162  at the first planar surface  110  and a second open end  164  at the second planar surface  112 . An open passageway  166  extends between the first open end  162  and the second open end  164 . In a further embodiment, each open passageway has a diameter of about 0.8 cm. The structural support members  160  serve to prevent the first and second planar walls  110 , and  112  from buckling during the freezing process. The support members  160  allow the first and second planar walls  110 ,  112  to be relatively thin to support heat transfer, yet still be able to maintain structural integrity during and after the freezing process. 
         [0056]    The structural support members  160  also serve to enhance heat transfer between the biopharmaceutical product  102  in the container  100  and the environment external to the container  100 . The open passageways  166  allow cooling fluid to engage the surface area of the support members  160 , enlarging the external surface area of the container  100  as a whole. Additionally, the location of the passageways  166  along the volume between the first and second planar walls  110 ,  112  enhances ice formation from the support members  160  to the internal portion of the container  100 , thus speeding up the ice formation, deterring the formation of a planar ice-form from moving from the planar walls  110 ,  112  inward, and reducing the possibility of solutes being driven from the solution during the freezing process. 
         [0057]    While  FIGS. 1 and 2  show the support members  160  arranged generally in a 3×3 square pattern, those skilled in the art will recognize that a different number of support members  160  may be provided in a different arrangement and still remain within the scope of the present invention. Therefore, the term “plurality of structural support members” extending from the first side surface to the second side surface means that one skilled in the art would recognize that the number of members used can be based on, for example, the size of the container, material used to construct the container, and/or the rate at which the to biopharmaceutical product is to be frozen and/or thawed. 
         [0058]    In one embodiment, the container  100  is constructed from high density polyethylene (HDPE), because it is known that HDPE is biocompatible with the types of biopharmaceutical product  102  that is intended to be stored within the container  100 . However, those skilled in the art will recognize that other biocompatible materials may be used for the container  100  as well. For example, glass, metal, other biocompatible plastics, etc. One embodiment of the invention is that the material used to construct the container  100  should be rigid enough to maintain its structure or shape during its use and under freezing conditions. Furthermore, the material should be able to sustain the handling at a temperature ranged between +20° C. and −70° C. 
         [0059]    In use, the cap  138  is removed from the nipple  134  and the biopharmaceutical product  102  is placed, transferred, or poured into the interior of the container  100 . After the container  100  is filled with a desired amount of the biopharmaceutical product  102 , the cap  138  is replaced over the nipple  134 , sealing the container  100 . A handle  150  is connected to the container  100  by inserting the hooks  154   a ,  156   a  into their respective handle wing openings  140   a , and  142   a . The container  100  may now be transported to a freezer for freezing of the biopharmaceutical product  102 . When the container  100  is placed in a desired location within the freezer, the handle  150  may be removed from the container  100 . The container  100  is subjected to a heat transfer process by which heat contained in the container  100  and in the biopharmaceutical product  102  being stored within the container  100  is absorbed by the lower temperature of the exterior environment of the freezer surrounding the container  100 . The relatively large surface areas of the first and second planar walls  110 ,  112 , as well as the surface areas of the passageways  166  in the structural supports  160 , allow the biopharmaceutical product  102  to freeze while maintaining a generally homogeneous concentration of solute within the frozen solution. In another embodiment, the biopharmaceutical product  102  may be a mixture of at least one biopharmaceutical product, such as monoclonal antibodies, DNA, DNA vaccines, peptides, and other protein molecules. 
         [0060]    Optionally, to further enhance heat transfer through the passageways  166 , rods  170  (shown in  FIG. 3 ), constructed from a material of relatively high heat conductivity, such as steel or copper, may be inserted into each passageway  166  to improve heat transfer through the walls of the passageways  166 . 
         [0061]    In still another embodiment, the structural support members  160  may be solid cylinders, with a high heat conductive material formed within the cylinder. Such an arrangement may further contribute to the support that the structural support members  160  provide to the container  100 , allowing the structural support members  160  to be formed with a smaller diameter. This embodiment may result in a larger internal volume within the container  100  for the same external dimensions. 
         [0062]    Further, in another embodiment, the present invention is directed to a container that is used to remove heat from within the container over a reduced period of time to reduce the formation of a heterogeneous solution within the container, those skilled in the art will recognize that the container may also be used to add heat to material within the container over a reduced period of time and with reduced localized temperature differentiation, if so desired. 
         [0063]    Although the invention is illustrated and described herein with reference to specific embodiments, the invention is not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims and without departing from the invention.