Source: https://patents.google.com/patent/US7137261
Timestamp: 2018-03-24 23:57:44
Document Index: 85697092

Matched Legal Cases: ['Application No. 60', 'Application No. 60', 'art 290', 'art 290', 'art 290', 'art 290', 'art 290']

US7137261B2 - Systems and methods for freezing, mixing and thawing biopharmaceutical material - Google Patents
US7137261B2
US7137261B2 US11085314 US8531405A US7137261B2 US 7137261 B2 US7137261 B2 US 7137261B2 US 11085314 US11085314 US 11085314 US 8531405 A US8531405 A US 8531405A US 7137261 B2 US7137261 B2 US 7137261B2
US11085314
US20050180998A1 (en )
This application is a Continuation of U.S. patent application Ser. No. 10/455,222, filed Jun. 4, 2003, which is a Continuation-In-Part of U.S. application Ser. No. 10/254,036 filed on Sep. 23, 2002 (now U.S. Pat. No. 6,698,213, granted Mar. 2, 2004) and titled “Systems and Methods for Freezing, Storing and Thawing Biopharmaceutical Material” which claims the benefit of U.S. Provisional Application No. 60/334,622, filed Nov. 1, 2001, all of which are incorporated herein by reference. U.S. application Ser. No. 10/453,222, filed on Jun. 4, 2003 was also a Continuation-In-Part of U.S. application Ser. No. 10/254,025 filed on Sep. 23, 2002 (now U.S. Pat. No. 6,684,646, granted Feb. 3, 2004) and titled “Systems and Methods for Freezing, Storing, and Thawing Biopharmaceutical Material”, which claims the benefit of Provisional Application No. 60/334,622, filed on Nov. 1, 2001, all of which are incorporated herein by reference. U.S. Pat. Nos. 6,684,646 and 6,698,213 are also Continuation-In-Parts of U.S. Pat. No. 6,453,683, filed on Jul. 13, 2001, and granted on Sep. 24, 2002, which is a Continuation-In-Part of U.S. Pat. No. 6,635,414, filed on May 22, 2001, and granted on Oct. 21, 2003, both of which are incorporated herein by reference.
In an exemplary embodiment depicted in FIGS. 1–7, portions of a system for cooling, freezing, preserving, processing, thawing, and/or mixing biopharmaceutical materials are shown. The system may include a temperature control unit 20 (e.g., a freeze-thaw module) configured to receive a sterile container, such as a flexible container 10 adapted to contain the biopharmaceutical materials. Further, temperature control unit 20 may be configured to receive a supporting structure, such as a frame 15, for supporting container 10.
Temperature control unit 20 is configured to control the temperature of a cavity or an interior 26 thereof, which may include one or more slots 25 as depicted in FIGS. 1–3. Also, temperature control unit 20 may include therein, or may be coupled to, a controller portion 21 and/or a sensor (e.g. a temperature sensor 18) to allow a user to control the heating, cooling, freezing, agitating, thawing, or mixing, for example, of the biopharmaceutical materials in flexible container 10, when it is inserted into interior 26 of temperature control unit 20. Heating, cooling, freezing or thawing of the contents of flexible containers 10 placed inside temperature control unit 20 may be controlled by blowing a continuous stream of cold or warm air, by direct contact of the containers with cold or warm surfaces, or by spraying cooling fluid thereon (e.g., liquid nitrogen), for example.
Also, one or more of plates 28 may be moveable to allow compression of flexible container 10, when flexible container 10 is received in frame 15 and frame 15 is received in slot 25 of interior 26 of temperature control unit 20, as depicted in FIGS. 2–3. Further, plates 28 could be stationary and temperature control unit 20 may include one or more non-temperature controlled moveable plates, surfaces, or walls (not shown) configured to compress flexible container 10, when flexible container 10 and frame 15 are received in slot 25. In one example, such non-temperature controlled movable plates may compress a container while the container is cooled by blast freezing, or other means of controlling a temperature of the container without contacting heat transfer plates therewith, e.g., via convective cooling. Alternatively, plates 28 may control the temperature of the container and may be movable along with such additional non-temperature controlled movable plates, surfaces, or walls.
Flexible container 10 may be formed of a laminated film which includes a plurality of layers and may have an interior volume ranging from 0.01–100 liters, for example. Further, flexible container 10 could be available in a variety of sizes to accommodate different uses, for example, 8.3 and 16.6 liter flexible containers may be utilized. Also a biocompatible product-contacting layer of the interior of flexible container 10 may be formed of a low density polyethylene, very low density polyethylene ethylene vinyl acetate copolymer, polyester, polyamide, polyvinylchloride, polypropylene, polyfluoroethylene, polyvinylidenefluoride, polyurethane or fluoroethylenepropylene, for example. A gas and water vapor barrier layer may also be formed of an ethylene/vinyl alcohol copolymer mixture within a polyamide or an ethylene vinyl acetate copolymer. Further, flexible container 10 may include a layer with high mechanical strength (e.g. a polyamide), and an external layer with insulating effect to heat welding, for example, polyester. The layers may be compatible with warm and cold conditions and may be able to withstand ionizing irradiation for sterilization purposes. Also, flexible container 10 may have a large surface area to volume ratio, and a relatively thin wall thus promoting heat transfer therethrough when received in temperature control unit 20. One example of materials useful for formulation of flexible container 10 is described in U.S. Pat. No. 5,988,422 to Vallot, the entire subject matter of which is hereby incorporated herein by reference. Also, flexible container 10 may be disposable, thus promoting ease of use and preventing cross-contamination of the interior of flexible container 10 which might result when reusing other types of containers.
Sterile, flexible container 10 may be configured to be received in frame 15 for supporting flexible container 10. For example, flexible container 10 may include an outwardly-extending flange 100 adapted to be received in a channel 200 of frame 15, as depicted in FIGS. 4–6. For example, flange 100 could be a plastic reinforcement rod dimensioned to be received in channel 200. Thus, flange 100, and therefore flexible container 10, may be inserted vertically downward or removed vertically upward, but may not be moved laterally or in directions other than up and down due to the engagement of flange 100 with channel 200. Thus, flange 100 serves to support the flexible container 10 laterally, retain a shape of flexible container 10 during filling thereof, reduce sagging of container 10 and ensure dimensional stability of flexible container 10 by spreading a load placed thereon along three different sides of flexible container 10, i.e., both sides and the bottom thereof.
Frame 15 may be formed to receive and support flexible container 10 to provide additional rigidity and support to flexible container 10, thus facilitating handling, storage, and/or temperature control thereof. Frame 15 may include a first opening 210 and a second opening 211 (FIGS. 2–3 and 5–6) on an opposite side of frame 15 from opening 210. These openings expose a large surface area of flexible container 10 to interior 26 of temperature control unit 20, when received therein. Through these openings, flexible container 10 may contact heat transfer surfaces such as plates 28 (FIGS. 2–3), air at a controlled temperature, or liquid cooling spray within temperature control unit 20. For example, a first side 12 of flexible container 10 may contact a heat transfer surface (e.g., one of plates 28) of interior 26 of temperature control unit 20 (FIG. 1) through opening 210 to control the temperature of the biopharmaceutical material in flexible container 10. Alternatively, side 12 of flexible container 10 may be exposed to a still or circulating air within the temperature control unit 20. For example, the biopharmaceutical material may be frozen or thawed while in flexible container 10, when flexible container 10 is received in frame 15 and frame 15 is received in temperature control unit 20.
Also, as described above, plates 28 (FIGS. 2–3) of temperature control unit 20 may be configured to contact and compress flexible container 10, when substantially filled with the biopharmaceutical material, and flexible container 10 and frame 15 are received in slot 25 of interior 26 of temperature control unit 20, as depicted in FIGS. 2–3. Further, as depicted in FIG. 3, the contents of flexible container 10 may be frozen or solidified while plates 28 are compressing it in temperature control unit 20 to cause flexible container 10 to have a dimension or width 115 in a direction between first opening 210 and second opening 211 (FIG. 4) of frame 15, which is less than or equal to a dimension or width 230 of an interior 240 of frame 15 in the same direction as width 115. Thus, flexible container 10 having the biopharmaceutical material frozen therein may be confined within an envelope or thickness defined by frame 15. By compressing flexible container 10 in frame 15, a substantially rectangular cross-sectional profile is created of flexible container 10 having the biopharmaceutical material therein. Such a cross-sectional profile promotes contact between flexible container 10 and heat transfer plates 28 as depicted in FIG. 3. This is particularly true in the corners of flexible container 10, thus allowing freezing to proceed in a uniform manner in a direction normal to plates 28. Further, the compression of flexible container 10 may force the biopharmaceutical material in flexible container 10 to occupy any voids or spaces between plates 28 and flexible container 10. By reducing or minimizing such voids or spaces, contact of plates 28 with flexible container 10 may be more uniform and thus cause more uniform cooling of the biopharmaceutical material contained in flexible container 10. Alternatively, the biopharmaceutical material may be heated or thawed in temperature control unit 20 through such contact with plates 28.
Another example of a temperature control unit 400 configured to receive flexible container 10 supported by frame 15 is depicted in FIGS. 10–13. Frame 15 may be received on a receiving frame 401 having a first rail 402 and a second rail 403 in a cavity or an interior 415 of temperature control unit 400. Heat transfer plates 428 are movable toward each other and may compress and control a temperature of biopharmaceutical material held in flexible container 10. Heat transfer fluids may be sent to and received from plates 428 by heat transfer conduits 410. Movement of plates 428 may be operatively caused by a linear actuator or piston 405 which may extend and contract as manually actuated or controlled by a computing unit (not shown). The contraction of piston 405 (depicted in phantom in FIG. 10) may cause movement of plates 428 toward each other while the extension of piston 405 (depicted in FIG. 10) may cause movement of plates 428 away from one another.
Also, it will be understood by those skilled in the art that the movement (e.g., reciprocation) of receiving frame 401 in interior 415 may be caused by any means for moving receiving frame 401. For example, such movement may be caused mechanically, such as by an electric motor with a gear box and a cam with an arm. Other examples include an electromagnetic solenoid, a hydraulic or pneumatic piston, and return by a spring. Further examples include electromechanical devices such as a crank shaft coupled to a motor or other electromechanical means. Additionally, it is evident from FIGS. 10–13 that temperature control unit 400 may be moved and/or reciprocated on wheels 560. Moreover, receiving frame 401 may be stationary relative to cavity 415 or receiving frame 401 may be moved within interior 415 simultaneously to temperature control unit 400 as a whole being moved on wheels 560. Such movement of receiving frame 401 may occur in a same direction or a different direction from temperature control unit 400 on wheels 560. Further, temperature control unit 400 may be moved by any means for causing movement, as described for receiving frame 401 and temperature control unit 20. In another unillustrated example, an interior or cavity of a temperature control unit may be moveable with a support or frame supporting a flexible container therein without the temperature control unit as a whole being moved.
FIG. 14 depicts temperature control unit 400 coupled to a temperature regulator or chiller 411 configured to provide heat transfer fluid to plates 428 (FIGS. 10–13) to control the temperature of biopharmaceutical material held in flexible container 10 in interior 415 (FIGS. 10–13). Further, FIG. 15 depicts a temperature control unit 413 identical to temperature control unit 400 except that it includes an interior 416 having multiple slots 417 for receiving multiple frames 15 holding multiple flexible containers 10. Each of slots 417 may include plates 428 coupled to temperature regulator and/or chiller 411 to control the temperature of biopharmaceutical material held therein. The temperature of the biopharmaceutical material may be controlled and/or monitored by temperature sensors and/or controllers located within the temperature control unit, as previously described herein, thermally coupled to the chiller. Temperatures determined by the sensors and/or controllers may be processed by a computing unit to control the temperature of the heat transfer fluid provided by the chiller to the temperature control unit. Further, each of slots 417 may be moveable on multiple receiving frames 401 to allow the agitation of biopharmaceutical material held in flexible container 10 held in each of slots 417. Transportation cart 290 may be located adjacent temperature control unit 413 for transferring frame 15 into one or more of slots 417.
A further example of a temperature control unit 600 configured to receive flexible container 10 supported by frame 15 is depicted in FIGS. 16–19. Frame 15 may be received on a receiving frame 601 in an interior 615 of temperature control unit 600. Heat transfer plates 628 are movable toward and may compress and control a temperature of biopharmaceutical material held in flexible container 10. Heat transfer fluids may be sent to and received from plates 628 by heat transfer conduits 610. Movement of plates 628 may be operatively caused by linear actuators or pistons 605 which may extend and contract as manually actuated or controlled by a computing unit (not shown). The extension of pistons 605, as depicted in FIGS. 16–19 may cause movement of plates 628 toward each other while the contraction of pistons 605 may cause movement of plates 628 away from one another. Thus, pistons 605 may be extended toward flexible container 10 when it is desired to compress and/or freeze the biopharmaceutical material held in flexible container 10. Accordingly, pistons 605 may be contracted to allow frame 15 to be inserted on receiving frame 601 or removed therefrom. Pistons 605 are mounted on an outer surface 610 of temperature control unit 600. In another example, depicted in FIGS. 20–23, pistons 705 are mounted on an interior frame 707 of a temperature control unit 700 and may cause movement of plates 728 toward one another to promote freezing and/or compressing of biopharmaceutical materials held in flexible container 10 supported by frame 15 on a receiving frame 701. Thus, it will be understood by those skilled in the art that heat transfer plates (e.g., plates 28, plates 428, plates 628, and plates 728) may be moved toward or away from each other using various means.
A typical process for processing and/or preserving a biopharmaceutical material is described as follows. Flexible container 10 is inserted into frame 15, as depicted in FIGS. 5–6. Also, frame 15 may be placed in transportation cart 290 (FIG. 1) and transported to a filling station (not shown). Biopharmaceutical material, for example liquid biopharmaceutical material, is inserted through conduit 120 into flexible container 10. In one example, frame 15 may be slid from transportation cart 290 to scale supporting rails (not shown) of a scale (not shown). Flexible container 10 may then be filled to a certain weight determined by the scale. In another example, cart 290 may be moved onto a scale (not shown), which does not include scale rails and which is configured to receive cart 290, and flexible container 10 may be filled thereon.
US11085314 2001-05-22 2005-03-21 Systems and methods for freezing, mixing and thawing biopharmaceutical material Active US7137261B2 (en)
US10455222 Continuation US6945056B2 (en) 2001-05-22 2003-06-04 Systems and methods for freezing, mixing and thawing biopharmaceutical material
US20050180998A1 true US20050180998A1 (en) 2005-08-18
US7137261B2 true US7137261B2 (en) 2006-11-21
US10455222 Active 2022-10-31 US6945056B2 (en) 2001-05-22 2003-06-04 Systems and methods for freezing, mixing and thawing biopharmaceutical material
US11085314 Active US7137261B2 (en) 2001-05-22 2005-03-21 Systems and methods for freezing, mixing and thawing biopharmaceutical material
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