Container for lyophilizing biological products

• US 6,517,526 B1
• Filed: 01/02/2002
• Issued: 02/11/2003
• Est. Priority Date: 12/29/2000
• Status: Expired due to Fees

• Current Assignee: Yehuda Tamari
• Original Assignee: Yehuda Tamari
• Inventors: Tamari, Yehuda
• Primary Examiner(s): Michalsky, Gerald A.
• Application Number:
  US10/038,688
• Time in Patent Office: 405 Days
• Field of Search: 604/403, 604/408, 604/410
• US Class Current: 604/403
• CPC Class Codes: A01N 1/0236 Mechanical aspects
• CPC Class Codes: A01N 1/0252 Temperature controlling refrigerating apparatus, i.e. devices used to actively control the temperature of a designated internal volume, e.g. refrigerators, freeze-drying apparatus or liquid nitrogen baths
• CPC Class Codes: A01N 1/0263 Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
• CPC Class Codes: A61J 1/05 for collecting, storing or administering blood, plasma or medical fluids multiple bags systems for separating or storing blood components A61M1/0209; Infusion or perfusion containers
• CPC Class Codes: A61L 2/26 Accessories or devices or components used for biocidal treatment
• CPC Class Codes: A61L 2202/181 Flexible packaging means, e.g. permeable membranes, paper
• CPC Class Codes: A61L 2202/21 Pharmaceuticals, e.g. medicaments, artificial body parts
• CPC Class Codes: A61L 2202/22 Blood or products thereof
• CPC Class Codes: A61M 1/0277 Frames constraining or supporting bags, e.g. during freezing
• CPC Class Codes: F26B 5/06 the process involving freezing

Abstract

The invention is an improved container for collecting, freeze-drying, storing, reconstituting, and administering biological solutions and, in particular, blood products. The container features a pliable bottom wall providing intimate thermal contact with the cooling/heating shelf of the lyophilizer; a top wall incorporating a hydrophobic membrane providing a path for water vapor and a bacterial barrier; and side walls sufficiently stiff to support the ceiling but preferably also sufficiently flexible to collapse and minimize storage space especially once lyophilization is complete. The walls incorporate sealable ports that can be used to load the solution for processing and/or adding reconstituting liquids and/or administering the reconstituted solution to a patient. The top wall may incorporate a removable cover that protects the membrane before freeze-drying takes place. A secondary pouch encloses the container immediately post-lyophilization and may incorporate means to evacuate its inner space thereby reducing space and limiting the gas volume the final product is exposed to during storage.

Claims

1. A container for lyophilizing a biological solution in a lyophilization chamber, said chamber having a shelf to receive said container while freezing and lyophilizing said solution said container comprising

a) a tray having a solution side compatible with said solution, said tray defining;

i) a floor having a first inside periphery, an inside surface contacting said solution, and an underside surface contacting said shelf;

said floor formed of a pliable material that easily conforms to said shelf;

ii) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery, and a landing extending from said second upper periphery;

b) a roof, said roof incorporating a hydrophobic membrane, said membrane providing vapor communication with said chamber while retaining said solution within said chamber, said floor, vertical walls and roof joined to form a solution sealed product chamber for containing said solution;

c) at least one port in fluid communication with said solution chamber said port used to introduce into said chamber and or remove from said chamber said solution;

d) said floor being sufficiently pliable that said floor conforms, by the weight of said solution in the container, to the surface of said shelf thereby assuring the intimate contact between the two surfaces necessary for the most efficient thermal transfer between said shelf and said solution via said floor.

2. A container for lyophilizing biological solutions as claimed in claim 1 wherein said floor, said vertical wall and said landing are formed from a single thermoformed plastic film.

3. A container for lyophilizing biological solutions as claimed in claim 2, said container further including a first frame, said first frame having a footprint which corresponds to said landing, said landing and said frame securing said hydrophobic membrane to said landing.

4. A container for lyophilizing biological solutions as claimed in claim 3 wherein said first frame is stiffer than said landing to thereby limit flexure of said landing from said hydrophobic membrane.

5. A container for lyophilizing biological solutions as claimed in claim 3 wherein said port is incorporated into said frame, said port facing upwards at an angle from said roof.

6. A container for lyophilizing biological solutions as claimed in claim 5 wherein said angle is between 30°

and 90°

.

7. A container for lyophilizing biological solutions as claimed in claim 5 wherein said port has a first inside diameter between ⅜

″ and

1″

, said port being closed with a removable cap, said cap incorporating a hydrophobic membrane to reduce blockage of vapor flow across said cap.

8. A container for lyophilizing biological solutions as claimed in claim 2 wherein said roof is stiffer than said hydrophobic membrane film to limit sagging of said hydrophobic membrane to limit contact of said hydrophobic membrane with said solution.

9. A container for lyophilizing biological solutions as claimed in claim 1 wherein said port is incorporated in said vertical wall.

10. A container for lyophilizing biological solutions as claimed in claim 9 wherein said port is directed upward relative to said floor at a first angle, thereby assuring that any solution entering said port will drip by gravity into said chamber when said floor is horizontal on said shelf.

11. A container for lyophilizing biological solutions as claimed in claim 10 wherein said first angle is at least 10°

.

12. A container for lyophilizing biological solutions as claimed in claim 1 wherein said port is incorporated into said container by sandwiching said port between said roof and said landing, said port being directed upward relative to floor at a first angle, thereby assuring that any liquid product entering said port would drip by gravity into said chamber when said floor is horizontal on said shelf.

13. A container for lyophilizing biological solutions as claimed in claim 12 wherein said first angle is at least 10°

.

14. A container for lyophilizing biological solutions as claimed in claim 1 wherein said landing extends outward from said second upper periphery.

15. A container for lyophilizing biological solutions as claimed in claim 1 wherein said landing extends inward from said second upper periphery.

16. A container for lyophilizing biological solutions as claimed in claim 1 wherein said container for lyophilizing is sealed within an external pouch that preserves the lyophilized product and protects the lyophilizing container.

17. A container for lyophilizing biological solutions as claimed in claim 16 wherein said pouch is evacuated.

18. A container for lyophilizing biological solutions as claimed in claim 17 wherein said pouch incorporates means that facilitate said container to have a geometry having a rectangular footprint and a uniform thickness with said thickness being thinner than that of said lyophilization container prior to the evacuation of said pouch.

19. A container for lyophilizing biological solutions as claimed in claim 1 wherein said vertical wall is more rigid than said floor of said tray.

20. A container for lyophilizing biological solutions as claimed in claim 19 wherein said vertical wall incorporate means that allow the volume of said chamber for lyophilizing biological solutions to be minimized for storage post-lyophilization.

21. A container for lyophilizing biological solutions as claimed in claim 20 wherein said means are bendable hinges.

22. A system for lyophilizing biological solutions in a lyophilization chamber, said chamber having a shelf to receive said system while freezing and lyophilizing said solution, said system comprising:

a) a disposable container, said container having;

(i) a tray having a solution side compatible with said solution, said tray defining

(1) a floor having a first inside periphery, an inside surface contacting said solution, and an underside surface contacting said shelf, said floor formed of a pliable material that easily conforms to said shelf;

(2) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery, and a landing extending from said upper periphery;

(ii) a roof having a third inside periphery, said roof incorporating a hydrophobic membrane, said membrane providing vapor communication with said chamber while retaining said solution within said chamber, said floor, vertical walls and roof joined to form a solution sealed product chamber for containing said solution;

(iii) at least one port in fluid communication with said solution chamber said port used to introduce into said chamber and or remove from said chamber said solution;

b) a rigid supporting tray adapted to be placed on said lyophilization shelf, said supporting tray used to support and facilitate handling of said lyophilization container prior to and during a lyophilization process;

wherein said floor of said container is sufficiently pliable that said floor conforms, by the weight of said solution in the container, to the surface of said lyophilization shelf thereby assuring the intimate contact between the two surfaces necessary for the most efficient thermal transfer between said shelf and said solution via said floor.

23. A system for lyophilizing biological solutions in a lyophilization chamber as claimed in claim 22 wherein said supporting tray is thermally conductive and further defines at least one cavity having a cavity floor and a depth that accommodates said lyophilization container in a manner that assures that said floor of said container makes sufficient contact with the floor of said cavity to further assure efficient thermal conductance between said product in said container through said cavity floor and said lyophilization shelf.

24. A system for lyophilizing biological solutions in a lyophilization chamber as claimed in claim 23 wherein said landing extending outward from said second upper periphery and said system further includes a rigid mating flange which overlays said supporting tray cooperates therewith to secure said landing of said lyophilization container during lyophilization of the biological solution.

25. A system for lyophilizing biological solutions in a lyophilization chamber as claimed in claim 24 wherein said system further includes a securing means on said lyophilization container, said securing means and said port being secured between said support tray and said rigid mating flange to support said lyophilization container during lyophilization of the product therein.

26. A system for lyophilizing biological solutions in a lyophilization chamber as claimed in claim 23 wherein cavity has a depth of H-y where “

H”

equals the height of the vertical wall of the lyophilization container, and “

y”

equals a fraction of said “

H”

, said fraction being between 0 and 50% of said vertical wall of the lyophilization container, so that said first vertical wall sags when the container is filled with product to assure that the floor of the container makes complete contact with the floor of the cavity defined by the supporting tray.

27. A system for lyophilizing biological solutions in a lyophilization chamber as claimed in claim 23 wherein said cavity floor incorporates channels that form fluid communication with said lyophilizer thereby allowing vacuum to be applied to said floor of said container to further enhance said intimate contact and said thermal transfer between said shelf and said solution via said floor.

28. A system for lyophilizing biological solutions in a lyophilization chamber as claimed in claim 22 wherein said supporting tray defines a support surface for engaging and supporting the landing defined by said tray.

29. A system for lyophilizing biological solutions in a lyophilization chamber as claimed in claim 22 wherein said rigid supporting tray includes a plurality of legs which support the landing at a height of H-y where “

H”

equals the height of the vertical wall of the lyophilization container, and “

y”

equals a fraction of said “

H”

, said fraction being between 0 and 50% of said vertical wall of the lyophilization container, so that said first vertical wall sags when the container is filled with product to assure that the floor of the container makes complete contact with the shelf of the lyophilization chamber.

30. A system for lyophilizing biological solutions in a lyophilization chamber as claimed in claim 22 which further includes a securing means on said lyophilization container which engages a support element formed on an upper surface of said supporting tray to facilitate support of said lyophilization container during lyophilization of the product therein.

31. A container for desiccating a biological solution in a desiccating chamber, said chamber having a shelf to receive said container while drying said solution, said container comprising

a) a tray having a solution side compatible with said solution, said tray defining;

(i) a floor having a first inside periphery, an inside surface contacting said solution, and an underside surface contacting said shelf, said floor formed of a pliable material that easily conforms to said shelf;

(ii) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery and a landing extending from said upper periphery;

b) a roof having a third inside periphery, said roof incorporating a hydrophobic membrane, said membrane providing vapor communication with said chamber while retaining said solution within said chamber, said floor, vertical walls and roofjoined to form a solution sealed product chamber for containing said solution;

c) at least one port in fluid communication with said solution chamber said port used to introduce into said chamber and or remove from said chamber said solution;

d) wherein said floor is sufficiently pliable that said floor conforms, by the weight of said solution in the container, to the surface of said shelf thereby assuring the intimate contact between the two surfaces necessary for the most efficient thermal transfer between said shelf and said solution via said floor.

32. A container for lyophilizing a biological solution in a lyophilization chamber, said chamber having a shelf to receive said container while freezing and lyophilizing said solution, said container comprising

a) a tray having a solution side compatible with said solution, said tray defining;

i) a floor having a first inside periphery, an inside surface contacting said solution, and an underside surface contacting said shelf;

ii) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery;

b) a roof having a third inside periphery, said roof incorporating a hydrophobic membrane having a fourth outside periphery that is at least as large as said third inside periphery of said roof, said membrane providing vapor communication with said chamber while retaining said solution within said chamber, said floor, vertical walls and roofjoined to form a solution sealed product chamber for containing said solution;

b) at least one port in fluid communication with said solution chamber said port used to introduce into said chamber and or remove from said chamber said solution;

c) a thermal plate placed between said underside surface of said floor of said container and said shelf of said lyophilization chamber;

wherein said thermal plate assures intimate thermal contact between said floor of said container and said shelf of said lyophilization chamber.

33. A container for lyophilizing a biological solution in a lyophilization chamber, said chamber having a shelf to receive said container while freezing and lyophilizing said solution, said container comprising

a) a tray having a solution side compatible with said solution, said tray defining;

i) a floor having a first inside periphery, an inside surface contacting said solution, and an underside surface contacting said shelf,

ii) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery;

b) a roof, said roof incorporating a hydrophobic membrane, said membrane providing a vapor path with said chamber while retaining said solution within said chamber, said floor, vertical walls and roof joined to form a solution sealed product chamber for containing said solution;

c) at least one port in fluid communication with said solution chamber said port used to introduce into said chamber and or remove from said chamber said solution;

d) a mating flange having an opening said opening, having a third periphery, said opening corresponding to said hydrophobic membrane;

wherein when said matching flange tops said container, the weight of said flange providing an additional force that enhances the thermal contact between said underside of said floor and said shelf of said lyophilizer without obstructing said vapor path.

34. A container for lyophilizing a biological solution in a lyophilization chamber, said chamber having a shelf to receive said container while freezing and lyophilizing said solution, said container comprising

a) a tray having a solution side compatible with said solution, said tray defining;

i) a floor having a first inside periphery, an inside surface contacting said solution, and an underside surface contacting said shelf;

ii) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery;

b) a roof, said roof incorporating a hydrophobic membrane having a third outside periphery, said membrane providing vapor communication with said chamber while retaining said solution within said chamber, said floor, vertical walls and roofjoined to form a solution sealed product chamber for containing said solution;

c) a removable, impermeable cover having a fourth outside periphery said fourth periphery being at least as large as said third inside periphery of said membrane;

wherein said impermeable cover seals and protects said membrane.

35. A container for lyophilizing biological solutions as claimed in claim 34 wherein said impermeable cover is removed prior to the lyophilization process.

36. A container for lyophilizing biological solutions as claimed in claim 34 wherein said impermeable