Container System and Method for Freezing and Thawing a Liquid Product

Abstract

Container system and method for freezing (and subsequently thawing) a liquid such as a drug substance, such that all containers in a set have a uniform width, hence uniform freeze-path length, in the widthwise direction and perpendicular to major walls of the containers, irrespective of the particular length, height, and volumetric capacity of the various containers in the set. This leads to uniform freezing performance and thereby reduces cryoconcentration. The system also eliminates or reduces ice-bridging, and the potential for containers rupturing during freezing and thawing operations.

1 . A set of containers for storing therein a liquid substance which is to be frozen and thawed, with each of the containers in the set having an essentially parallelepiped configuration with a substance-receiving cavity defined therein by the walls of the container;
 wherein each of the containers in the set has a pair of major walls on opposite sides of the container that define a length and a height of the respective container, the major walls of each of the containers being spaced apart by a distance that defines a width of the respective container;   wherein the substance-receiving cavity of at least one of the containers in the set has a first volume and the substance-receiving cavity of at least another one of the containers in the set has a second volume, which is different from the first volume;   wherein all of the containers in the set have the same width, such that a freeze-path length associated with each of the containers in the set is essentially the same; and   wherein the dimensions and/or geometry of each of the containers in the set are selected so that liquid tends to freeze within the containers along the walls of the containers at a significantly faster rate than the liquid tends to freeze at an upper, air/liquid interface surface thereof, whereby the occurrence of ice-bridging is suppressed.   
     
     
         2 . (canceled) 
     
     
         3 . The set of containers according to  claim 1 , wherein the dimensions of each of the containers in the set are selected so that, for a given predetermined cooling medium and a given predetermined liquid to be frozen, an ice bridging number (IBN) is less than about 0.6. 
     
     
         4 . The set of containers according to  claim 3 , wherein the dimensions of each of the containers in the set are selected so that, for the given predetermined cooling medium and the given predetermined liquid to be frozen, the ice bridging number is greater than about 0.1 and less than about 0.6. 
     
     
         5 . A system for storing, freezing, transporting, and thawing a liquid substance, comprising:
 a set of containers each having an essentially parallelepiped configuration with a substance-receiving cavity defined by the walls of the container, the walls of each container in the set including a pair of major walls on opposite sides of the container that define a length and a height of the respective container and the major walls of each of the containers in the set being spaced apart by a distance that defines a width of the container; with the substance-receiving cavity of at least one of the containers in the set having a first volume and the substance-receiving cavity of at least another one of the containers in the set having a second volume, which is different from the first volume; and with all of the containers in the set having the same width such that a freeze-path length associated with each of the containers in the set is essentially the same; and   a container-support platform including a plurality of formations that define a plurality of container-receiving spaces, with each of the container-receiving spaces being essentially equal in width to the width of the containers and with groups of the formations being positioned so as to support a plurality of said containers on the container-support platform, received within respective container-receiving spaces, equally spaced from each other.   
     
     
         6 . The system according to  claim 5 , wherein the dimensions and/or geometry of each of the containers in the set are selected so that liquid tends to freeze within the containers along the walls of the containers at a significantly faster rate than the liquid tends to freeze at an upper, air/liquid interface surface thereof, whereby the occurrence of ice-bridging is suppressed. 
     
     
         7 . The system according to  claim 5 , wherein the dimensions of each of the containers in the set are selected so that, for a given predetermined cooling medium and a given predetermined liquid to be frozen, an ice bridging number (IBN) is less than about 0.6. 
     
     
         8 . The system according to  claim 7 , wherein the dimensions of each of the containers in the set are selected so that, for the given predetermined cooling medium and the given predetermined liquid to be frozen, the ice bridging number is greater than about 0.1 and less than about 0.6. 
     
     
         9 . A method for storing and freezing a liquid substance, comprising:
 introducing said liquid substance into a plurality of containers selected from a set of containers, wherein
 each of the containers in the set has an essentially parallelepiped configuration with a substance-receiving cavity defined therein by the walls of the container; 
 each of the containers in the set has a pair of major walls on opposite sides of the container that define a length and a height of the respective container, the major walls of each of the containers being spaced apart by a distance that defines a width of the respective container; 
 the substance-receiving cavity of at least one of the containers in the set has a first volume and the substance-receiving cavity of at least another one of the containers in the set has a second volume; and 
 all of the containers in the set have the same width, such that a freeze-path length associated with each of the containers in the set is essentially the same; 
   disposing the containers into which the liquid substance has been introduced on a container-support platform, with the liquid-containing containers equally spaced from each other; and   causing the liquid substance contained within the liquid-containing containers to freeze, with generally uniform progression of the freeze front or freeze fronts within each of the liquid-containing containers, by flowing a cooling medium through spaces between adjacent containers.   
     
     
         10 . The method of  claim 9 , further comprising insulating headspace disposed above the upper surface of the liquid in each of the containers while causing the liquid to freeze. 
     
     
         11 . The method of  claim 9 , wherein liquid-containing containers with the same volumetric capacities are disposed on the same container-support platform and subjected to freezing simultaneously. 
     
     
         12 . The method of  claim 9 , wherein liquid-containing containers with different volumetric capacities are disposed on the same container-support platform and subjected to freezing simultaneously. 
     
     
         13 . The method of  claim 12 , wherein multiple containers each having a given volumetric storage capacity are assembled together to form a cassette of containers that is disposed on the container-support platform, which cassette of containers has an overall length and height that is essentially the same as the length and height of a single container having a greater volumetric storage capacity than the volumetric storage capacity of each of said multiple containers. 
     
     
         14 .- 16 . (canceled) 
     
     
         17 . A system for storing, freezing, transporting, and thawing a liquid substance, comprising:
 a set of containers each having an essentially parallelepiped configuration with a substance-receiving cavity defined by the walls of the container, the walls of each container in the set including a pair of major walls on opposite sides of the container that define a length and a height of the respective container and the major walls of each of the containers in the set being spaced apart by a distance that defines a width of the container, with all of the containers in the set having the same width such that a freeze-path length associated with each of the containers in the set is essentially the same; and   a container-support platform including a plurality of formations that define a plurality of container-receiving spaces, with each of the container-receiving spaces being essentially equal in width to the width of the containers and with groups of the formations being positioned so as to support a plurality of said containers on the container-support platform, received within respective container-receiving spaces, equally spaced from each other.   
     
     
         18 . The system according to  claim 17 , wherein the dimensions and/or geometry of each of the containers in the set are selected so that liquid tends to freeze within the containers along the walls of the containers at a significantly faster rate than the liquid tends to freeze at an upper, air/liquid interface surface thereof, whereby the occurrence of ice-bridging is suppressed. 
     
     
         19 . The system according to  claim 17 , wherein the dimensions of each of the containers in the set are selected so that, for a given predetermined cooling medium and a given predetermined liquid to be frozen, an ice bridging number (IBN) is less than about 0.6. 
     
     
         20 . The system according to  claim 19 , wherein the dimensions of each of the containers in the set are selected so that, for the given predetermined cooling medium and the given predetermined liquid to be frozen, the ice bridging number is greater than about 0.1 and less than about 0.6. 
     
     
         21 . A method for storing and freezing a liquid substance, comprising:
 introducing said liquid substance into a plurality of containers selected from a set of containers, wherein
 each of the containers in the set has an essentially parallelepiped configuration with a substance-receiving cavity defined therein by the walls of the container; 
 each of the containers in the set has a pair of major walls on opposite sides of the container that define a length and a height of the respective container, the major walls of each of the containers being spaced apart by a distance that defines a width of the respective container; and 
 all of the containers in the set have the same width, such that a freeze-path length associated with each of the containers in the set is essentially the same; 
   disposing the containers into which the liquid substance has been introduced on a container-support platform, with the liquid-containing containers equally spaced from each other; and   causing the liquid substance contained within the liquid-containing containers to freeze, with generally uniform progression of the freeze front or freeze fronts within each of the liquid-containing containers, by flowing a cooling medium through spaces between adjacent containers.   
     
     
         22 . The method of  claim 21 , further comprising insulating headspace disposed above the upper surface of the liquid in each of the containers while causing the liquid to freeze. 
     
     
         23 . The method of  claim 21 , wherein liquid-containing containers with the same volumetric capacities are disposed on the same container-support platform and subjected to freezing simultaneously. 
     
     
         24 . The method of  claim 21 , wherein liquid-containing containers with different volumetric capacities are disposed on the same container-support platform and subjected to freezing simultaneously. 
     
     
         25 . The method of  claim 24 , wherein multiple containers each having a given volumetric storage capacity are assembled together to form a cassette of containers that is disposed on the container-support platform, which cassette of containers has an overall length and height that is essentially the same as the length and height of a single container having a greater volumetric storage capacity than the volumetric storage capacity of each of said multiple containers. 
     
     
         26 .- 28 . (canceled) 
     
     
         29 . A method for thawing a frozen liquid substance, comprising:
 disposing on a container-support platform a plurality of containers containing therein an amount of said frozen liquid substance, with the containers equally spaced from each other; and   causing the frozen liquid substance contained within the containers to thaw, with generally uniform progression of the thaw front or thaw fronts within each of the containers, by flowing a warming medium through spaces between adjacent containers;   wherein each of the containers has an essentially parallelepiped configuration, with frozen liquid substance contained within a substance-receiving cavity defined by the walls of the container;   each of the containers has a pair of major walls on opposite sides of the container that define a length and a height of the respective container, the major walls of each of the containers being spaced apart by a distance that defines a width of the respective container;   the substance-receiving cavity of at least one of the containers has a first volume and the substance-receiving cavity of at least another one of the containers set has a second volume; and   all of the containers have the same width to promote uniformity of thawing.   
     
     
         30 . The method of  claim 29 , further comprising mechanically agitating the substance while it is thawing. 
     
     
         31 . The method of  claim 30 , wherein the substance is mechanically agitated by rocking the liquid-containing containers in a longitudinal direction so that liquid container therein moves back and forth, from one end of each container to the opposite end of each container. 
     
     
         32 .- 34 . (canceled)