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WO2001008630A2 - Conditionnement sterile de matiere vivante, dote de caracteristiques ameliorees de stockage - Google Patents

Conditionnement sterile de matiere vivante, dote de caracteristiques ameliorees de stockage Download PDF

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Publication number
WO2001008630A2
WO2001008630A2 PCT/US2000/020739 US0020739W WO0108630A2 WO 2001008630 A2 WO2001008630 A2 WO 2001008630A2 US 0020739 W US0020739 W US 0020739W WO 0108630 A2 WO0108630 A2 WO 0108630A2
Authority
WO
WIPO (PCT)
Prior art keywords
compartment
outer container
labile
fluid
cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2000/020739
Other languages
English (en)
Other versions
WO2001008630A9 (fr
WO2001008630A3 (fr
Inventor
Frank T. Gentile
Antonio P. Melo
James R. Birkhead
Barry D. Weitzner
Mark A. Lotito
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Reprogenesis Inc
Original Assignee
Reprogenesis Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Reprogenesis Inc filed Critical Reprogenesis Inc
Priority to AU66148/00A priority Critical patent/AU6614800A/en
Priority to JP2001513363A priority patent/JP2004500158A/ja
Publication of WO2001008630A2 publication Critical patent/WO2001008630A2/fr
Anticipated expiration legal-status Critical
Publication of WO2001008630A3 publication Critical patent/WO2001008630A3/fr
Publication of WO2001008630A9 publication Critical patent/WO2001008630A9/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2096—Combination of a vial and a syringe for transferring or mixing their contents
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/14—Mechanical aspects of preservation; Apparatus or containers therefor
    • A01N1/146—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/10—Bag-type containers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0095—Packages or dispensers for prostheses or other implants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
    • A61J1/2006—Piercing means
    • A61J1/201—Piercing means having one piercing end
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
    • A61J1/2079—Filtering means
    • A61J1/2086—Filtering means for fluid filtration

Definitions

  • This invention relates generally to the field of storing and using living material therapeutically. More particularly, the invention relates to sterile packaging of live material with improved storage characteristics.
  • Non-living material can be sterilized after being placed into a container, but living materials are adversely affected by the sterilization process and thus have to be treated differently.
  • Living material can be introduced in a sterile environment, although it is difficult.
  • An example of sterile surgical use of living material is blood transfusion bags.
  • Apparatuses and methods of sterilely using blood bag systems are known in the art, such as disclosed in United States Patent No. 3,942,529, to Waage, herein incorporated by reference. Waage discloses a package and method for storing blood. While blood bags are sterile before they are filled, after filled they are no longer sterile and extreme precaution has to be used once the bags are brought into a sterile environment.
  • Aseptic transfer is an alternative method for introducing living material into a sterile operating room.
  • the living material is aseptically packed in a vial
  • the outside of the vial is typically clean, but is not ste ⁇ le Therefore, to use the living mate ⁇ al m the vial in the operating room, a non- sterile assistant has to open the vial and hold it for the ste ⁇ le operator The ste ⁇ le operator would then draw the cells via a straw or other tube into a ste ⁇ le sy ⁇ nge. Only then can the living mate ⁇ al be used in the ste ⁇ le environment.
  • ste ⁇ le packaging of live mate ⁇ al with improved storage characte ⁇ stics is disclosed It is an object of this invention to allow living mate ⁇ al to be aseptically introduced into a ste ⁇ le field
  • the invention provides a storage package comp ⁇ smg an outer container, a second outer container completely enclosing the outer container, an access portal transiting the outer container, a cell containing compartment, a stabilizing bath compartment, wherein the stabilizing bath compartment is connected to the cell containing compartment through a semi- permeable bar ⁇ er, wherein the semi-permeable bar ⁇ er permits passage of molecular species but does not permit passage of living cells, and further wherein the semi- permeable bar ⁇ er forms at least a portion of the bar ⁇ er between the stabilizing bath compartment and the cell containing compartment, and wherein the outer container completely encloses the cell containing compartment and the stabilizing bath compartment, means for removing the second outer container, and means for removing the outer container
  • the invention provides an inner container and an outer container completely enclosing the inner container An access portal transits the outer container and is operative to introduce a labile fluid or solid from outside the outer container into
  • the invention discloses a method for providing a fluid to a ste ⁇ le field
  • the method involves ste ⁇ lizing a storage package, the storage package comp ⁇ sing an outer container that completely encloses an inner container and a fluid-conducting conduit that transits the outer container, with the outer container being removable
  • the method further involves inserting a fluid from outside the outer container into the sterilized mnei container through the fluid-conducting conduit such that the fluid does not breach the ste ⁇ hty of the outer container
  • the fluid typically comp ⁇ ses mate ⁇ al which is labile to sterilization, such as desired living cells suspended therein and the fluid is usually substantially free of contaminant cells other than the desired living cells
  • This method provides for opening the outer container in proximity to a ste ⁇ le field, and dispensing the fluid from the inner container
  • the package is not subject to further gross ste ⁇ hzation
  • the invention discloses a method for sto ⁇ ng a labile fluid or solid
  • the method involves sterilizing a storage package comp ⁇ sing an outer container that completely encloses an inner container where a sealable access portal transits the outer container
  • the outer container is removably sealed about the inner container
  • the method subsequently involves inserting a labile fluid or solid from outside the outer container into the inner container through the access portal, such that the labile fluid or solid does not breach the ste ⁇ hty of the outer container
  • the package and the labile fluid or solid are not subject to terminal ste ⁇ hzation subsequent to inserting the labile fluid or solid
  • the invention discloses a method for sterilely dispensing a labile fluid or solid.
  • the method involves providing a storage package that comprises an outer container completely enclosing an inner container having a labile fluid or solid therein, with the inner container being detachably connected to an access portal that transits the outer container.
  • the outer container is removable.
  • the method also involves opening the outer container in proximity to a sterile environment and then dispensing the labile fluid or solid from the inner container.
  • the invention discloses a storage package having an outer container; a labile material containing compartment; and a stabilizing bath compartment.
  • the stabilizing bath compartment encloses at least a portion of the labile material containing compartment through a semi-permeable barrier.
  • the semi-permeable barrier forms at least a portion of the barrier between the stabilizing bath compartment and the labile material containing compartment.
  • the outer container completely encloses the stabilizing bath compartment.
  • the storage apparatus may comprise a means for evacuating the labile material from said storage apparatus. Further, the storage may comprise a means for evacuating said stabilizing bath from said storage apparatus.
  • a storage apparatus having an outer container, a stabilizing bath and labile material compartment for containing stabilizing material and labile material. At least a portion of the stabilizing bath and labile material compartment is enclosed by the outer container. A means is provided for separating at least a portion of the stabilizing material from the labile material.
  • the storage apparatus has a semi- permeable barrier enclosing at least a portion of the stabilizing bath and labile material compartment not enclosed by the outer container.
  • the means for separating at least a portion of the stabilizing material from the labile material may be a plunger, connected to the semi-permeable barrier, that when depressed decreases a volume of the stabilizing bath and labile material compartment.
  • the means for evacuating the stabilizing material is a syringe ba ⁇ el enclosing a remaining portion of the stabilizing bath and labile material compartment not enclosed by the outer container.
  • the syringe ba ⁇ el has a first and second end, wherein the first end is an open end connected to the stabilizing bath and labile material compartment allowing the barrel to communicate with the stabilizing bath and labile material compartment, and the second end has a movable plunger.
  • the syringe barrel is rigidly connected to the semi-permeable barrier, both of which slidably engage inside the outer container to decrease a volume of the stabilizing bath and labile material compartment when the syringe ba ⁇ el is depressed.
  • the stabilizing bath to filter through the semi-permeable barrier and separate from the labile material.
  • the storage package of this invention permits a sterile operator to easily handle and use living material in a sterile environment while not risking contamination of the material, the sterile environment, or the sterile operator.
  • the storage package of this invention is well suited for containing and presenting implants and cell-containing compositions used in tissue engineering.
  • Fig. 1A is a top perspective of a storage package according to one embodiment of the invention.
  • Fig. IB is a side perspective of a storage package according to one embodiment of the invention.
  • Fig. 1C is an end perspective of a storage package according to one embodiment of the invention.
  • Fig. 2 illustrates a storage package with multiple inner containers according to another embodiment of the invention.
  • Fig. 3 illustrates a storage package with a thermoformed rigid tray outer container according to another embodiment of the invention.
  • Fig. 4 illustrates a storage package with a flexible package outside an inner container according to another embodiment of the invention.
  • Fig. 5 illustrates a storage package with multiple outer containers according to another embodiment of the invention.
  • Fig. 6 is a perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 7 illustrates an example of the storage package of Fig. 6 in use.
  • Fig. 8 illustrates another example of the storage package of Fig. 6 in use.
  • Fig. 9 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 10 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 11 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 12 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 13 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 14 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 15 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 16 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 17A is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 17B is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 18 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 19 is perspective representation of a storage package accordingo another embodiment of the invention.
  • Fig. 20 is perspective representation of a storage package accordingo another embodiment of the invention.
  • Fig. 21 is perspective representation of a storage package accordingo another embodiment of the invention.
  • Fig. 22 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 23 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 24 is perspective representation of a storage package according to another embodiment of the invention.
  • Fig. 25 is perspective representation of a storage package according to another embodiment of the invention
  • Fig. 26 is perspective representation of a storage package according to another embodiment of the invention.
  • the invention encompasses a method and apparatus for providing a living mate ⁇ al to a ste ⁇ le environment in a faster, easier, and improved manner
  • the apparatus includes a ste ⁇ le inner container that is enclosed by an outer container which can be handled by a non-ste ⁇ le operator or assistant without comp ⁇ sing the ste ⁇ hty of the inner container
  • the inner container is aseptically filled with a living material in an aseptic manner
  • the apparatus is transported to a non-ste ⁇ le environment and handled by the non-ste ⁇ le assistant
  • the non-ste ⁇ le assistant The non-ste ⁇ le assistant
  • the invention is particularly beneficial for handling a labile fluid or solid, i.e., a material that undergoes detrimental chemical, physical, or biological changes or breakdown under sterilizing conditions.
  • the labile fluid or solid of the various embodiments disclosed herein may be many things.
  • it may be cells, a cell-containing composition, blood, lymph, or an aqueous suspension containing a heat-denaturable material such as a therapeutic protein in an aqueous solution.
  • the labile material may also be a solid, semi-solid, liquid, sheet (thin or thick), block, other three-dimensional structure, gel, or hydrogel such as particularly or completely hardened alginate.
  • the labile material will have cells distributed on the surface and/or throughout all or a portion of the material.
  • the labile fluid or solid may also be cells by themselves, such as a block or sheet of living tissue.
  • the labile fluid or solid will be a cell-containing composition.
  • the storage package of this invention is used to contain cell-containing compositions for implantation or tissue engineering as described in European Patent Publication Nos. 0299010 and 0469070; International Patent Publication No. WO 94/25080; or United States Patent No. 5,667,778, all herein incorporated by reference.
  • a material that could be used, especially in the embodiment depicted in Fig. 10 could be the composition depicted in United States Patent No. 5,567,612, herein incorporated by reference.
  • the inner container may contain a fluid composed of living or non- living material. Typically, such material will be labile to the sterilization method used to sterilize the storage package. Further, the storage package disclosed in these embodiments can be used whether sterilized or non-sterilized.
  • FIG. 1A there is shown a storage package according a first embodiment of the invention.
  • the storage package indicated generally at 10, comprises an inner container 20 which is completely enclosed by an outer container 22.
  • Outer container 22 has an end that contains a peelable element 32.
  • the other three sides of outer container 22 are sealed at sealed edges 31.
  • a fluid-conducting conduit 24 transits outer container 22.
  • fluid-conducting conduit 24 allows something outside of outer container 22 to enter inside of outer container 22 without opening outer container 22.
  • Fluid-conducting conduit 24 has an end 30 which is typically closed by a removable closure.
  • the closure at end 30 can include a luer connector, an opening, a cap, or a septum.
  • Fluid-conducting conduit 24 is detachably connected to inner container 20 at connection point 26. Because inner container 20 is detachably connected, inner container 20 can easily be removed from fluid-conducting conduit 24.
  • the detachable connection may be, for example, a friction fit or luer connector.
  • a labile fluid or cell-containing composition may be inserted into fluid-conducting conduit 24 at end 30 of fluid-conducting conduit 24 such that the labile fluid or cell- containing composition does not result in a breach of outer container 22 that would compromise sterility; the labile fluid or cell-containing composition originating from outside of outer container 22 ends up substantially inside of inner container 20, with little or preferably none of the cell-containing composition of fluid between the outside of inner container 20 and the inside of outer container 22. Thus, introduction of the labile fluid or cell-containing composition does not cause a breach of sterility inside of outer container 22. Further, the labile fluid or cell- containing composition is introduced into inner container 20 without otherwise opening outer container 22.
  • peelable element 32 can be removed to expose inner container 20.
  • Peelable-element 32 can be formed of any material that facilitates easy removal.
  • peelable element 32 can be made of TYVEK® (100% high density polyethylene sheet formed from flash-spun plexifilaments), paper, nylon, or foil. Peelable element 32 can also be a breathable or nonbreathable material. Nonbreathable peelable material is usually made from a plastic.
  • Nonbreathable peelable element is typically two layers coated with an adhesive suitable for separation of the two layers of the peelable element to facilitate removal.
  • Breathable peelable material can either be coated or non-coated.
  • a non-coated peelable material typically generates a stronger seal, but is harder to open.
  • peelable element 32 may be integrally connected to one or more of the upper and lower layers 34 and 36 such that opening peelable element 32 leads to peeling apart the upper and lower layers 34 and 36 at peelable sealed edges 31, shown in Figure 1A.
  • peelable element 32 may be a tear strip, as described in United States Patent No. 4,367,816, to Wilkes, herein incorporated by reference.
  • peelable element 32 may be a sealed edge that can be easily ripped or cut.
  • fluid-conducting conduit 24 provides access to inner container 20 without breaching the seal of outer container 22 at 38.
  • the seal at 38 forms a strong seal around fluid-conducting conduit 24, to prevent leakage, such that access to inner container 20 is blocked from the outside of outer container 22, except for fluid-conducting conduit 24.
  • Fluid-conducting conduit 24 may be, for example, a septum port or a tube.
  • fluid-conducting conduit 24 is made from polyethylene.
  • fluid-conducting conduit 24 can be made of any material that can be sealed to outer container 22.
  • such materials are, but not limited to, polyethylene terephthalate glycol, polyvinyl chloride, polystyrene, polyethylene terephthalate, polyethylene, polyester (such as MYLAR®), SCLAIR® (linear low density polyethylene), TYVEK®, paper, nylon, or foil.
  • fluid-conducting conduit 24 may be substituted by an access portal to facilitate the introduction of a labile fluid or solid comprising larger particles into inner container 20.
  • FIG. 1C an end view of storage package 10 is depicted. Lower layer 34 and upper layer 36 are shown to connect at sealing element 32.
  • End 30 of fluid-conducting conduit 24 is depicted, where a labile fluid or cell-containing composition would be introduced.
  • a luer fitting could be fitted onto end 30 to facilitate easy connection to a syringe or some other device for introducing the labile fluid or cell-containing composition.
  • end 30 could be a septum for inserting a needle into fluid-conducting conduit 24 or an access conduit that can allow the labile fluid or cell-containing composition to be introduced aseptically.
  • End 30 of fluid-conducting conduit 24 is ordinarily sealed to prevent leakage and maintain the sterility of inner container 20.
  • Means for sealing end 30 of fluid-conducting conduit 24 can include any method of sealing end 30 such that a barrier exists between fluid-conducting conduit 24 and the environment of outside outer container 22.
  • sealing means may include a heat seal of end 30 to completely seal end 30, a clasp that clamps shut end 30, a cap for end 30, a fluid seal that seals end 30, or a valve to seal end 30.
  • inner container 20 is a syringe; however, inner container 20 can be any containing device.
  • Inner container 20 may be made of any suitable rigid material, such as metal, glass, polypropylene, polycarbonate, or polyethylene.
  • inner container 20 will be constructed to facilitate dispensing the labile fluid or cell-containing composition on demand.
  • inner container 20 can be a bag made of any flexible material, and the contents dispensed by squeezing the bag. Any of the components of storage package 10 can be substituted for any of the like components described with respect to the other embodiments disclosed herein.
  • a storage package 110 containing multiple inner containers is depicted.
  • a second inner container 140 is also completely enclosed by outer container 122.
  • Inner container 120 has an end 142 and inner container 140 has an end 144. Ends 142 and 144 can be alternatively connected to end 126 of fluid-conducting conduit 124.
  • Additional inner containers can be introduced into outer container 122. Further, additional elements can be enclosed within outer container 122, such as needles, cannulae, dispensing valves, bottles, wash fluid, fittings such as a stopcock, connectors, or delivery catheters and mechanisms.
  • elements that are to be used in the sterile field in conjunction with administration of the labile fluid or cell-containing composition may be enclosed within outer container 122, where they are maintained in sterile condition and readily available at the time the labile fluid or cell-containing composition is dispensed.
  • a tray 146 can be used as a frame inside of outer container 122 to hold inner containers 120 and 140. Tray 146 is molded to the shape of inner container 120 and 140 to hold inner containers 120 and 140.
  • tray 146 not only keeps inner containers 120 and 140 from being jostled during transit, but also provides an easy method of removing inner containers 120 and 140.
  • tray 146 may be bendably distortable so that when outer container 122 is removed, tray 146 can be contorted to force out inner containers 120 and 140 successively or simultaneously without directly touching inner containers 120 and 140. While tray 146, as depicted, can maintain one or two inner containers, the structure of tray 146 can be altered to maintain any number of inner containers.
  • Tray 146 can be made of any rigid material, for example polyethylene terephthalate glycol, polyvinyl chloride, polystyrene, polyethylene terephthalate, or polyethylene, and preferably tray 146 is elastically distortable.
  • a storage package 210 is depicted including an outer container 250 comprising a thermoformed tray 252 and a peelable element 232.
  • Thermoformed tray 252 provides a sturdy outer container to protect inner container 220 and maintain the sterility of inner container 220.
  • Peelable element 232 can be easily removed to expose inner container 220. To remove peelable element 232, a user needs only to grasp thermoformed tray 252 and pull outward on peelable element 232. This will separate peelable element 232 from thermoformed tray 252, exposing inner container 220.
  • thermoformed tray 252 can be shaped to hold inner container 220, with a tray analogous to tray 146.
  • Thermoformed tray 252 can be made of any sturdy material, including but not limited to polyethylene terephthalate glycol, polyvinyl chloride, polystyrene, polyethylene terephthalate, or polyethylene.
  • Peelable element 232 can be formed of any material that facilitates easy removal.
  • peelable element 232 may be made of TYVEK®, paper, nylon, or foil.
  • thermoformed tray 252 may be substituted by a sheet of flexible mate ⁇ al, mentioned herein, sealed to peelable element 232 to form outer container 250. Va ⁇ ations on these structures using combinations of flexible and ⁇ gid mate ⁇ al will be readily apparent to those skilled in the art, and are within the contemplation of this invention (see, e ⁇ g_, Fig. 4).
  • a hermetic seal 238 forms a strong seal around fluid-conducting conduit 224.
  • End 230 allows entry of mate ⁇ al from outside outer container 250 to inside of inner container 220 via fluid-conducting conduit 224.
  • end 230 can be a check valve or stopcock
  • each of the components of storage package 210 can be substituted for any of the like components desc ⁇ bed with respect to the other embodiments
  • a storage package 310 includes an optional flexible package 362 su ⁇ ounding an inner container 364
  • Inner container 364 is analogous to outer containers 22, 122, and 250 of Figs. 1-3 and surrounds inner container 320
  • Inner container 364 has a built-in ⁇ gid member 366 supporting a fluid-conducting conduit 324
  • Flexible package 362 provides a flexible container that protects inner container 364 and inner container 320 and helps maintains the ste ⁇ hty of inner container 364 and inner container 320
  • storage package 310 is ste ⁇ hzed
  • flexible package 362 can be removed and inner container 320 can be filled with a labile fluid or cell-containing composition This leaves the ste ⁇ le inner container 320 filled with the labile fluid or cell-containing composition su ⁇ ounded by inner container 364
  • Inner container 364 covers inner container 320 and holds ⁇ gid member 366.
  • Flexible package 362 and inner container 364 can be made of any flexible mate ⁇ al, for example, polyethylene, polyester (such as MYLAR®), SCLAIR®, TYVEK®, paper, nylon, or foil
  • Inner container 364 and flexible package 362 can each include a peelable element to facilitate easy opening
  • Rigid member 366 can be made of any ⁇ gid mate ⁇ al mentioned herein Rigid member 366 assists in forming a strong seal around fluid-conducting conduit 324.
  • End 330 allows entry of mate ⁇ al from outside inner container 364 via fluid-conducting conduit 324
  • End 330 can be a can be covered with an end cap 390 or other capping or sealing mechanism
  • inner container 320 has an optional connector 396 that couples septum 392 to inner container 320
  • a user can manipulate inner container 320, with septum 392 at its end, from outside of inner container 364 to fit into needle housing 398 so that needle 394 penetrates septum 392.
  • a labile fluid or cell-contammg composition may be inserted through fluid-conducting conduit 324 into inner container 320.
  • Inner container 320 could also be entirely disassembled from connectors, such that a user could assemble inner container 320 and connectors as needed Additionally, multiple connectors and fittings, preferably having male/female luer connectors, could be used to facilitate connection between inner container 320 and fluid-conducting conduit 324. Moreover, each of the components of storage package 310 can be substituted for any of the like components desc ⁇ bed with respect to the other embodiments. Further, storage package 310 could be surrounded by a ⁇ gid exte ⁇ or tray, such as tray 146 depicted in Fig.
  • inner container 364 enclosing inner container 320 could be held into place by the ⁇ gid tray
  • storage package 310 before flexible package 362 has been removed, could be inserted into a ⁇ gid exte ⁇ or tray Using a ⁇ gid exte ⁇ or tray could assist m the shipping, mechanical manipulation, or protecting of inner container 364 and inner container 320
  • FIG. 5 a storage package 410 with multiple outer containers is depicted.
  • a first outer container 470 is similar to outer container 250
  • First outer container 470 includes a thermoformed tray 472 and a peelable element 474, that are similar to thermoformed tray 252 and peelable element 232, respectively.
  • a second outer container 480 completely encloses first outer container 470
  • Second outer container 480 includes a thermoformed tray 482 and a peelable element 484, that are similar to thermoformed tray 252 and peelable element 232, respectively
  • fluid-conducting conduit 424 extends through the multiple outer containers to the outside of second outer container 480, allowing a labile fluid or cell-containing composition to be introduced from outside of second outer container 480 into inner container 420.
  • Storage package 410 can have any number of outer containers as long as fluid-conducting conduit 424 extends through the outermost outer container. In fact, any of the components of storage package 410 can be substituted for any of the like components desc ⁇ bed with respect to the other embodiments.
  • FIG. 6 storage package 510 according to another embodiment of the present invention is depicted Outer container 522 completely encloses inner container 520, and tray 546 holds inner container 520 in place While storage package 510 is similar to storage package 10, a significant difference between the two embodiments is that outer container 522 has opening 556 that provides controlled access to the mte ⁇ or of outer container 522 Typically opening 556 will be sealed before and after filling of inner container 520 with a labile fluid or cell- contammg composition
  • End 542 of inner container 520 can be lined up with opening 556 for the filling operation
  • End 542 can include an opening, a septum, a luer connector, or a stopper
  • end 542 can be made of cork, rubber, or plastic
  • fluid-conducting conduit 524 is a hollow needle connected to a sy ⁇ nge 590, which is part of the filling apparatus Sy ⁇ nge 590 can be filled with a suitable fluid which may be a cell-contammg
  • an outer ste ⁇ le bamer 564 can be enclosed entirely around outer container 522 as shown in Fig. 8.
  • Outer ste ⁇ le bar ⁇ er 564 can be, for example, made of any mate ⁇ al that can maintain the ste ⁇ hty of outer container 522 and inner container 520.
  • polyethylene, low density polyethylene, polyester (such as MYLAR®), SCLAIR®, TYVEK®, paper, nylon, or foil can be used.
  • outer ste ⁇ le barrier 564 can be ⁇ gid or flexible, thus, for example, polyethylene terephthalate glycol, polyvinyl chlo ⁇ de, polystyrene, or polyethylene terephthalate, could also be used.
  • package 510 would be ste ⁇ hzed with bar ⁇ er 564 m place, and bar ⁇ er 564 would be removed immediately p ⁇ or to filling inner container 520 with mate ⁇ al that is labile to ste ⁇ hzation.
  • the storage package of all the embodiments function similarly
  • the storage package is ste ⁇ hzed by a known ste ⁇ hzation means.
  • the storage package is filled aseptically using a ste ⁇ le filling apparatus, preferably involving a biosafety cabinet
  • a labile fluid or solid is inserted from outside of the outer container into the inner container through an access portal, which may be a fluid-conducting conduit
  • the access portal allows the labile fluid or solid to be introduced into the inner container without otherwise opening the outer container.
  • the labile fluid or solid does not breach the ste ⁇ hty inside of the outer container
  • the labile fluid or solid does not substantially enter the area between the outside of the inner container and the inside of the outer container
  • the labile fluid or solid may or may not be ste ⁇ le
  • the labile solid or fluid contains a desired population of living cells, but otherwise is substantially free of contaminant cells other than those living cells, the only non- ste ⁇ le mate ⁇ al in the ste ⁇ le storage package would be those desired living cells. If, however, the labile solid or fluid does not contain living cells, but rather non-living labile mate ⁇ al, then everything in the storage package may be ste ⁇ le.
  • any excess labile fluid or solid left in the access portal or fluid-conducting conduit can be pushed into the inner container by using some means to remove the excess labile fluid or solid Any means for purging the access portal or fluid- conductmg conduit of excess labile fluid or solid is acceptable
  • the excess mate ⁇ al can be pushed using a rod, by forcefully blowing air into the access portal or fluid-conducting conduit, or by tapping the access portal or fluid- conducting conduit.
  • the end of the access portal or fluid-conducting conduit may then be closed. Any sealing means may be used as long as a good seal is created that keeps the inner container sterile.
  • the storage package may then be translocated to a sterile field, such as an operating room.
  • the storage package once filled with the labile fluid or solid, is not further subjected to terminal sterilization. Terminal sterilization would kill everything living in the storage package. Because the labile fluid or solid preferably contains living material or other materials labile under sterilizing conditions, terminal sterilization would adversely affect the labile fluid or solid. Therefore, gross sterilization of the package is only performed prior to insertion of the labile fluid or solid.
  • a non-sterile operator or assistant may then take the storage package and bring it into the operating room or adjacent to a sterile field.
  • the non-sterile assistant can remove the outer container of the storage package.
  • the non-sterile operator might simply peel off the peelable element of the outer container, tear or rip open the outer container, or cut the outer container.
  • a sterile operator can grasp the inner container (or one of them if there are several) and disconnect it from the access portal or fluid-conducting conduit, if it is attached.
  • the non-sterile assistant can bend the tray such that an inner container pops out into the sterile field or the sterile operator's hand.
  • the non-sterile assistant can dump the inner containers out of the outer container, once the outer container has been opened.
  • the inner container is a container
  • the sterile operator can grasp the container.
  • the non-sterile assistant can open the inner container and let the sterile operator grasp the sample.
  • the sterile operator could open the inner container and remove the sample.
  • the solidified sample will be a cell-containing composition or material, such as a preformed implant; however, it is within the contemplation of this invention that the preformed implant contain material labile to sterilizing conditions, such as a therapeutic protein, but no cells.
  • the outer container according to this invention can be removed or opened such that inner container is not contaminated and the inner container is not exposed to any non-sterile surface.
  • the sterile operator can dispense the labile fluid or solid. If the inner container is a syringe, the syringe plunger can be pushed to dispense the contents. If the inner container is a container, the inner container can be squeezed to release the desired labile fluid or solid.
  • End 30 of fluid-conducting conduit 24 reversibly is sealed.
  • Means to seal end 30 include, for example, heat sealing the end, a cap, a fluid valve, a value, or clamping shut end 30.
  • Storage package 10, with end 30 sealed, is then sterilized to kill substantially all contaminating organisms in storage package 10.
  • residual contamination will be at or below the level acceptable under good manufacturing practices for medical devices.
  • Storage package 10 could be sterilized with any suitable method, for example, by steam, ethylene oxide, gamma i ⁇ adiation, electron beam irradiation, or with ultraviolet light. After being subjected to sterilization by a suitable means, inner container 20 is filled aseptically. In one example, storage package 10 is transported to a biosafety cabinet, such as a class 100 sterilization hood. Once inside of the biosafety cabinet, the removable seal on end 30 of fluid-conducting conduit 24 is removed. The labile fluid or cell-containing composition is then inserted into inner container 20 of storage package 10. The labile fluid or cell-containing composition may be inserted by any one of numerous methods.
  • a sterile filling syringe with a luer lock is connected to end 30 of fluid-conducting conduit 24.
  • This filling syringe can be connected manually or mechanically, such that sterility in the interior of the biosafety cabinet is not breached.
  • the filling syringe is then emptied into fluid-conducting conduit 24 and the labile fluid or cell-containing composition is forced into inner container 20. After filling inner container 20, the filling syringe is removed.
  • any excess labile fluid or cell-containing composition left m fluid-conducting conduit 24 can be pushed into inner container 20 by using any means for purging fluid-conducting conduit 24 of excess fluid, for example by using a rod to push the excess fluid into inner container 20, by forcefully blowing air into fluid-conducting conduit 24, or by tapping fluid-conducting conduit 24
  • end 30 of fluid-conducting conduit 24 is then sealed again with any of the above methods
  • End 30 can even be permanently sealed with heat
  • storage package 10 is not subsequently subjected to terminal ste ⁇ lization that would affect the labile fluid or cell-contammg composition
  • Terminal ste ⁇ lization is a final ste ⁇ lization that substantially kills all living things p ⁇ or to shipment of a ste ⁇ le product Accordingly, terminal ste ⁇ hzation would adversely affect the labile fluid or cell-containing composition after inner container 20 of storage package 10 has been filled However, so long as the
  • Storage package 10 is then typically transported to the point of use, which may be an operating room with a ste ⁇ le environment
  • the inside of outer container 22 and the outside of inner container 20 will be ste ⁇ le (l e , substantially free of contaminating organisms)
  • the mside of inner container 20 will be ste ⁇ le, except for the desired labile fluid or cell-containing composition
  • a non-ste ⁇ le assistant in the operation room can peel open outer container 22, exposing inner container 20 without contaminating it
  • a ste ⁇ le operator can then grasp inner container 20 and twist inner container 20 free from the luer connector
  • the non-ste ⁇ le assistant could remove outer container 22 and push inner container 20 free from the tray 46 by indirect pressure without contaminating the outside of inner container 20, allowing inner container 20 to fall either into the sterile environment or the sterile operator's hand.
  • outer container 22 could be removed by the non-sterile assistant without touching inner container 20 directly, and the sterile operator could either grasp inner container 20 or let it fall out of outer container 22 into the sterile field.
  • the sterile operator can use inner container 20 to dispense the labile fluid or cell-containing composition.
  • inner container 20 is a syringe
  • the labile fluid or cell-containing composition can be dispensed through the syringe.
  • inner container 20 is a flexible bag
  • inner container 20 can depressed to squeeze or squirt out the labile fluid or cell-containing composition.
  • outer container 22 everything contained within outer container 22 and translocated to the sterile environment will typically be in sterilized and in clean condition, previously untouched until grasped by the sterile operator.
  • inner container 20 is a syringe or a bag, then only the exterior of inner container 20 would be touched by the sterile operator.
  • the needle, cell-containing composition, or fluid would typically be entirely untouched by any operator.
  • the labile fluid or cell-containing composition is aseptically introduced to the sterile field or patient.
  • a storage package 610 according to another embodiment of the present invention is depicted.
  • An outer container 622 completely encloses an inner container 620, and a tray 646 holds inner container 620 in place.
  • storage package 610 is similar to storage package 510, the significant difference between the two embodiments is that outer container 622 has a flap 664.
  • Flap 664 includes an access portal 624.
  • Access portal 624 can be aligned with an end 642 of inner container 620.
  • Access portal 624 allows a labile fluid or solid, to enter from outside of outer container 622 and into inner container 620.
  • any or all of the components of storage package 610 can be substituted for any of the like components desc ⁇ bed with respect to the other embodiments
  • storage package 610 may operate as follows End 642 of inner container 620 is not o ⁇ ginally connected to access portal 624, but rather inner container 620 is free floating withm outer container 622 Storage package 610 is ste ⁇ hzed and then translocated to a filling station, for example a biosafety cabinet While in the biosafety cabinet, end 642 can be connected to access portal 624 End 642 can be connected using any known connecting means
  • outer container 622 is a flexible mate ⁇ al which may be manipulated to align end 642 with access portal 624 After ste ⁇ lizing storage package 610 and connecting end 642 to access portal 624, a labile fluid or solid is inserted from outside of outer container 622 to inside of inner container 620 After inserting the labile fluid or solid, end 642 is disconnected from access portal 624 and access portal 624 is closed Access portal 624 can be sealed by heating outer container at the area marked 668, or fusing closed access portal 624 Alternatively, it can be sealed with any method that provides
  • Storage package 610 is then translocated to a location adjacent to a ste ⁇ le environment or field
  • a non- ste ⁇ le assistant can remove outer container 622
  • One such method could be to cut, tear, or ⁇ p along dotted line 676, removing flap portion 668
  • outer container 622 can be removed in any conventional manner as long as the non-ste ⁇ le assistant does not come into substantial contact with inner container 620
  • a ste ⁇ le operator can grasp inner container 620, if inner container 620 has a graspable portion that is easily grasped, or can allow inner container 620 to fall out from outer container 622
  • inner container 620 can be sterilely removed by any suitable means. The labile fluid or solid can then be sterilely dispensed.
  • Storage package 710 is well suited to handle solid materials, including tissues such as a living skin sample, but would also function well with any other labile fluid or cell-containing material, for example in the form of sheets (thin or thick), blocks, or other three dimensional structures.
  • the solid material will be a cell-containing material, such as a preformed tissue implant; however, it is within the contemplation of this invention that the solid be a matrix containing material labile to sterilizing conditions, such as a therapeutic protein, but no cells.
  • Inner container 720 may resemble a container for storage and distribution of a skin wound dressing container disclosed in Tubo et al., U.S. Patent No.
  • access portal 724 extends into inner container 720.
  • inner container 720 includes thermoformed tray 772 and an peelable element 774.
  • Outer container 722 completely encloses inner container 720, and access portal 724 also transits outer container 722.
  • access portal 724 can be a joining point of inner container 720 and outer container 722, as depicted in Figure 10.
  • Outer container 722 can alternatively be made of a flexible material, as previously disclosed. Additionally, any or all of the components of storage package 710, can be substituted for any of the like components described with respect to the other embodiments.
  • a sample 790 could be sterilely inserted through access portal 724 in a sterile hood or other environment suited for aseptic filing, and into inner container 720.
  • access portal 724 may be sealed by any sealable means, including the previously mentioned means.
  • storage package 710 may be translocated to a sterile field.
  • a non-sterile assistant can remove outer container 722 by any of the fore-mentioned means, including separating peelable element 784. Then a sterile operator can remove sterile peelable element 774 and remove sample 790.
  • inner container 720 could be a molded shape.
  • a cell- contammg composition or other labile fluid could be inserted into inner container 720 such that once inside, the cell-containing composition or other labile fluid solidifies into the shape of the molded inner container 720.
  • outer container 722 and inner container 720 could be removed, exposing the molded sample to manipulation by the ste ⁇ le operator.
  • a seedable substrate could be placed in inner container 720, either before or after the storage package 710 has been ste ⁇ lized. If the substrate is placed in inner container 720 before the storage package 710 is ste ⁇ lized, the storage package 710 should be ste ⁇ hzed before living cells are introduced to the inner container 720. Cells or some other cell-contammg composition may then be ste ⁇ lely introduced to the inner container, as desc ⁇ bed above, to seed the substrate with cells or other cell-contammg composition. When the cells, that have now been seeded by the substrate, are to be removed, they may be removed as desc ⁇ bed above.
  • Fig. 11 shows an embodiment of a storage package according to this invention.
  • a cell containing compartment 807 is enclosed by a stabilizing bath compartment 809; stabilizing bath compartment 809 is enclosed by an outer ste ⁇ le container 804; and outer ste ⁇ le container 804 is optionally enclosed by an second outer container 801
  • Cell containing compartment 807 and stabilizing bath compartment 809 comp ⁇ se releasable container 832.
  • releasable container 832 is freely removable from the storage package upon opening outer ste ⁇ le container 804
  • Molded conduit 803 is integrally incorporated into outer ste ⁇ le container 804.
  • Channel 812 transits molded conduit 803.
  • channel 812 integrally includes fluid transporter 805.
  • Fluid transporter 805 can be inserted into cell containing compartment 807 through access portal 810 of stabilizing bath compartment 809.
  • fluid transporter 805 allows access from outside of outer ste ⁇ le container 804 to the mside of cell compartment 807, without opening outer ste ⁇ le container 804.
  • the storage package is treated to make it ste ⁇ le and then a fluid composition containing living cells is introduced into cell containing compartment 807 through fluid transporter 805.
  • cell containing compartment 807 retains labile material, such as cell containing composition 811.
  • Cell containing compartment 807 provides liquid/liquid contact of cell stabilization material 808 and cell containing composition 811, while preventing release of cell containing composition 811 into cell stabilizing material 808.
  • the walls of cell containing compartment 807 are constructed to facilitate the exchange of certain components between cell stabilization material 808 and cell containing composition 811.
  • the pore size of the walls of cell containing compartment 807 permits transfer of desired components, but does not permit transfer of cells.
  • the pore size of the walls of cell compartment 807 is 0.1 to 0.4 microns.
  • the walls of cell containing compartment 807 may be made of any suitable micro-porous material.
  • the walls of cell containing compartment 807 may be made of any suitable porous material, such as, Gortex, PTFE, polycarbonate, polyacrylonitrile, porous polyethylene, PDMS, PET, nylon, a co-polymer of polyacrylonitrile and vinyl chloride, or any suitable porous silicon- based material.
  • the walls of cell containing compartment 807 may be flexible or rigid.
  • a suitable matrix which entraps labile material, particularly cells, and permits transfer of desired components, but does not permit transfer of cells, may be used in place of the cell containing compartment.
  • the shape of cell containing compartment 807 is designed to maximize the exchange of desired components between cell stabilization material 808 and cell containing composition 811. Maximizing the surface area to volume ratio of cell containing compartment 807, for example, with a flatly-shaped cell containing compartment 807, maximizes desired component exchange.
  • Cell containing compartment 807 is fixed to access portal 810 with a suitable attachment mechanism, such as an adhesive.
  • Cell containing compartment 807 is enclosed by stabilizing bath compartment 809.
  • the surface area of the wall of cell compartment 807 is maximized, commensurate with the desired volume ratio between cell stabilization material 8 and cell containing composition 811.
  • Cell stabilization material 808 comprises soluble components to support and stabilize cell containing composition 811 contained inside of cell containing compartment 807.
  • Cell stabilization material 808 is contained within stabilizing bath compartment 809, which includes access portal 810, and bounded by cell containing compartment 807.
  • Preferably, cell stabilization material 808 substantially surrounds cell containing compartment 807 for maximum solute transfer.
  • Cell stabilization material 808 comprises a solution capable of providing support and stabilization to cell containing composition 811.
  • the support may be a medium which includes nutrients for cells in cell containing composition 811, such as cell culture nutrient media, M199, RPMI, or DMEM, or may be any isotonic solution, such as isotonic saline.
  • Cell stabilization material 808 may also contain serum, or can be serum-free, may also contain buffer, or can be buffer-free.
  • the most common material for use as a cell stabilization material 808 is cell culture media, but the skilled worker will recognize that references to media below are only exemplary of any solution that contains solutes which can serve to stabilize cells for storage.
  • the volume of cell stabilization medium 808 is typically sufficient to provide that cell containing composition 811 does not experience significant changes in environment over time, for example, due to changes in cell containing composition 811 resulting from cellular metabolism. Generally, maintaining a suitable cell environment requires a larger volume of cell stabilization medium 808 than the volume of cell containing composition 811.
  • the volume ratio of cell stabilization medium 808 to cell containing composition 811 is in the range from 5: 1 to 200:1. If longer storage times are desired, a higher ratio may be used.
  • the cell stabilizing medium 808 may be introduced into the stabilizing bath compartment 809 in any of a variety of ways. For example, if the cell stabilizing medium 808 is stable to the sterilization procedure (e.g., heat sterilization for isotonic saline or gamma i ⁇ adiation for cell culture medium), the cell stabilizing medium 808 may be sealed into in the stabilizing bath compartment 809 before the package is sterilized. This procedure obviates the need for a separate port for introduction of the cell stabilizing medium. Alternatively, as shown in Fig. 12, cell stabilizing medium 908 may be inserted into the stabilizing bath compartment 909 after sterilization of the package via an access port 920 in the stabilizing bath compartment 909.
  • the sterilization procedure e.g., heat sterilization for isotonic saline or gamma i ⁇ adiation for cell culture medium
  • Cell stabilizing medium 908 may be filter sterilized by, for example, passing the cell stabilizing medium 908 through a 0.2 micron filter before introducing it into the stabilizing bath compartment 909.
  • the cells 811 in contact with the cell stabilizing medium 808 may be stored under suitable storage conditions.
  • cells will be stored at temperatures between 1°C and 40°C, and the gaseous atmosphere surrounding the storage system may include 5% CO 2 , depending on whether the walls of the storage system are gas permeable and whether CO 2 atmospheres are beneficial for the particular cell type.
  • Cell storage times are contemplated ranging from hours to days or weeks. In a prefe ⁇ ed embodiment, the cells are stored for 14 days while a formal USP sterility test (which involves a 14 day incubation period), may be performed to confirm sterility of the package.
  • the volume and type of cell stabilizing medium 808 may vary are depending on the desired shelf life for the cells. Variations in the storage temperature, cell density, and cell type will also affect shelf life of the stored cells. The skilled worker will optimize all of these parameters to optimize the packaging for the desired shelf life. For example, increasing the medium-to-cell ratio will tend to prolong shelf life at the expense of increasing the weight of the package and possibly degrading its handling characteristics. Alternatively, for some embodiments of the storage system of this invention, aged medium may be withdrawn and replaced with fresh medium periodically to lengthen shelf life of the cells without increasing the weight of the package. Similarly, shelf life for most cell types can be extended by reducing storage temperature, permitting lower medium- to-cell ratios and lower package weight for comparable storage times.
  • Stabilizing bath compartment 809 retains cell stabilization medium 808 in a compact and manipulable form. Stabilizing bath compartment 809 retains cell stabilization medium 808 inside its walls, allowing the exchange of desired components between cell stabilization medium 808 and cell containing composition 811. Stabilizing bath compartment 809, containing access portal 810, substantially encloses cell stabilization medium 808 and cell containing compartment 807. Stabilizing bath compartment 809 is heat-sealed or otherwise connected to access portal 810. Stabilizing bath compartment 809 is made of a material suitable for retaining cell stabilization medium 808 and suitable for connection to access portal 810. Stabilizing bath compartment 809 is preferably made of polyethylene if access portal 810 is also made of polyethylene to facilitate heat sealing of these two components.
  • Stabilizing bath compartment 809 may also be made of any flexible mate ⁇ al, for example, polyester (such as MYLAR® (E.I. duPont de Nemours and Company)), SCLAIR®, TYVEK® (E.I. duPont de Nemours and Company), paper, or foil.
  • Access portal 810 is made of a mate ⁇ al suitable for connection to stabilizing bath compartment 809, such as polyethylene if stabilizing bath compartment 809 is also made of polyethylene.
  • the mate ⁇ als capable of contacting cell containing solution 811 or cell stabilization medium 808, including stabilizing bath compartment 809, access portal 810, cell compartment 807, injection site 806, and fluid transporter 805, are typically made of a biocompatible mate ⁇ al.
  • Access portal 810 allows fluid transporter 805 to insert cell containing composition 811 into cell containing compartment 807 from outside of outer ste ⁇ le container 804
  • Access portal 810 is connected to cell containing compartment 807, and to stabilizing bath compartment 809.
  • access portal 810 is connected to injection site 806
  • Injection site 806 may be fixed to access portal 810 and to stabilizing bath compartment 809.
  • Injection site 806 maintains the ste ⁇ hty of cell containing composition 811, by preventing matter other than mate ⁇ als which can penetrate injection site 806, such as fluid transporter 805 and its contents, from passing through injection site 806
  • Injection site 806 is made of mate ⁇ al that may be resealed after a penetrating object is removed
  • injection site 806 can be made of rubber and polycarbonate
  • Injection site 806 may also be made of a biocompatible mate ⁇ al suitable for connection to stabilizing bath compartment 809, such as polyethylene, if stabilizing bath compartment 809 is also made of polyethylene.
  • Channel 812 transits molded conduit 803.
  • Channel 812 is capable of being capped, for example by deadender plug 802
  • channel 812 integrally includes fluid transporter 805
  • Fluid transporter 805 is capable of introducing cell containing composition 811 from outside of outer ste ⁇ le container 804 to the mside of cell containing compartment 807, without opening outer ste ⁇ le container 804.
  • Fluid transporter 805 is capable of transiting molded conduit 803, access portal 810, and injection site 806
  • Fluid transporter 805 is any object capable of allowing fluid that is inserted into one end of fluid transporter 805 to exit from an opposite end of fluid transporter 805.
  • fluid transporter 805 may be a KLEEN-NEEDLE® (Tri-State Hospital Supply Corporation) described in references U.S. Patent No.
  • Deadender plug 802 may cap the fluid transporter 805.
  • fluid transporter 5 may be completely removable and deadender plug 802 would cap molded conduit 3.
  • Outer sterile container 804 prevents contamination of cell containing composition 811.
  • Outer sterile container 804 substantially encloses cell containing compartment 807 and stabilizing bath compartment 809.
  • Outer sterile container 804 is enclosed by and connected to molded conduit 803 to block undesired mass transfer inside outer sterile container 804 from outside of outer sterile container 804.
  • Outer sterile container 804 and molded conduit 803 are made of materials suitable for connection to one another, such as polyethylene.
  • suitable fixture processes include heat sealing and use of a suitable adhesive.
  • Outer sterile container 804 may also be made of any flexible material, for example, polyester (such as MYLAR®), SCLAIR®, TYVEK®, paper, or foil.
  • Outer sterile container 804 can be handled by a non-sterile operator or assistant without comprising the sterility of stabilizing bath compartment 809.
  • Outer sterile container 804 can be made of a material suitable to maintain the sterility of stabilizing bath compartment 809, such as polyethylene or TYVEK®.
  • Outer sterile container 804 may also be made of any flexible material, for example, polyester (such as MYLAR®), SCLAIR®, TYVEK®, paper, or foil.
  • Outer sterile container 804 has an end that contains a peelable element 825. Peelable element 825 can be removed to expose stabilizing bath compartment 809. Peelable-element 825 can be formed of any material that facilitates easy removal.
  • peelable element 825 can be made of TYVEK®, paper, nylon, or foil. Peelable element 825 can also be a breathable or nonbreathable material. Nonbreathable peelable material is usually made from a plastic. Nonbreathable peelable element is typically two layers coated with an adhesive suitable for separation of the two layers of the peelable element to facilitate removal. Breathable peelable material can either be coated or non-coated. A non-coated peelable material typically generates a stronger seal, but is harder to open. Alternatively, peelable element 825 may be integrally connected to one or more of the upper and lower layers such that opening peelable element 825 leads to peeling apart the upper and lower layers. Further, peelable element 825 may be a tear strip, as described in United States Patent No.
  • peelable element 825 may be a sealed edge that can be easily ripped or cut.
  • releasable container can be readily removed from the storage package.
  • sterile container 804 is handled by a non-sterile operator and opened in such a way that releasable container 832 is provided to a sterile operator without compromising the sterility of the sterile operator or releasable container 832.
  • second outer container 801 completely encloses outer sterile container 804 during sterilization of the storage package, and may contain a peelable element or tear strip as previously mentioned. To permit easy opening of second outer container 801 for filing cell containing compartment 807.
  • both the cell containing compartment 807 and the stabilizing bath compartment 809, together comprising releasable container 832, will be released from the package into the sterile field.
  • the cell containing compartment 807 is a syringe ba ⁇ el
  • cells may be dispensed manually by pushing the plunger, and suitable cannulae may be attached to the syringe.
  • Cell containing compartment 807 is a flexible tube
  • Cell containing composition 811 contained inside of cell containing compartment 807 can be transfe ⁇ ed to another item, for example, a syringe.
  • cells from the cell containing tube may be extruded into a syringe barrel or taken up into a syringe, and subsequently injected into the desired location.
  • a storage package 910 including access portal 920 which is connected to stabilizing bath compartment 909, but is not connected to cell containing compartment 907, is depicted.
  • Access portal 920 allows the introduction of cell stabilization medium 908 into stabilizing bath compartment 909. This embodiment allows for introduction of cell stabilization medium 908, initially and optionally periodically, for periodic insertion of cell stabilization material 908, for example, to increase storage time, or to promote new cell growth of cell containing composition 911.
  • access portal 920 allows fluid transporter 905 to insert cell stabilization medium 908 into stabilizing bath compartment 909 from outside of outer sterile container 904, without opening outer sterile container 904.
  • Fluid transporter 905, which transits channel 912 is a preferred method of introducing cell stabilization medium 908 to the inside of stabilizing bath compartment 909.
  • Access portal 920 is connected to stabilizing bath compartment 909.
  • Access portal 920 is made of a biocompatible material suitable for connection to stabilizing bath compartment 909, such as polyethylene if stabilizing bath compartment 909 is also made of polyethylene.
  • access portal 920 contains injection site 916.
  • Injection site 916 may be fixed to access portal 920 and to stabilizing bath compartment 909.
  • Injection site 906 maintains the sterility of cell stabilization medium 908, by preventing matter other than materials which can penetrate injection site 916, such as fluid transporter 905 and its contents, from passing through injection site 916.
  • Injection site 916 is made of material as previously mentioned.
  • Cell containing compartment 907 and stabilizing bath compartment 909 comprise releasable container 932.
  • Outer sterile container 904 completely encloses stabilizing bath compartment 909 and may contain a peelable element or tear strip as previously mentioned.
  • second outer container 901 completely encloses outer sterile container 904 and may contain a peelable element or tear strip as previously mentioned.
  • an additional channel may also transits molded conduit 903.
  • the additional channel may be capped, for example by a deadender plug.
  • the additional channel is integrally include an additional fluid transporter.
  • the additional fluid transporter 915 introduces cell stabilization mate ⁇ al 908 from outside of outer ste ⁇ le container 904 to the mside of stabilizing bath compartment 909, without opening outer ste ⁇ le container 904.
  • the additional fluid transporter also transits molded conduit 903, outer ste ⁇ le container 904, and access portal 920. If injection site 916 is connected to access portal 920, as preferred, the additional fluid transporter transits injection site 916.
  • the additional fluid transporter is any object capable of allowing fluid that is inserted into one end, to exit from an opposite end.
  • the additional fluid transporter may be a KLEEN-NEEDLE® as previously mentioned.
  • Storage package 1010 is well suited to handle solid mate ⁇ als, such as a solid tissue sample or a polyme ⁇ c mat ⁇ x containing cells or an effective amount of dissociated human cells and a polyme ⁇ c mat ⁇ x suitable for example, to form or to augment breast tissue, but would also function well with any other cell containing mate ⁇ al or fluid
  • solid mate ⁇ als such as a solid tissue sample or a polyme ⁇ c mat ⁇ x containing cells or an effective amount of dissociated human cells and a polyme ⁇ c mat ⁇ x suitable for example, to form or to augment breast tissue, but would also function well with any other cell containing mate ⁇ al or fluid
  • a typical cell- contaming solid withm this embodiment of the present invention is desc ⁇ bed in U.S. Patent No.
  • stabilizing bath compartment 1039 encloses cell containing solid 1037 and cell stabilization medium 1038
  • stabilizing bath compartment 1039 corresponds to the releasable container of Figs. 11 and 12
  • Cell containing solid 1037 is in liquid/liquid contact with cell stabilization medium 1038, permitting diffusion of medium components to cells 1041
  • cell containing solid 1037 may be su ⁇ ounded by a semi permeable membrane analogous to the cell containing compartment wall of Figs. 11 and 12.
  • Stabilizing bath compartment 1039 is typically made of mate ⁇ al as previously mentioned for analogous components of other embodiments.
  • Cell containing solid 1037 may be su ⁇ ounded by porous walls comp ⁇ sed as previously mentioned.
  • Cell stabilization medium 1038 is bound by stabilizing bath compartment 1039.
  • cell stabilization mate ⁇ al 1038 substantially surrounds cell containing solid 1037 for maximum exchange of desired components between cell stabilization mate ⁇ al 1038 and cells 1041.
  • Cell stabilization material 1038 comprises a stabilization medium as previously mentioned.
  • the volume ratio of cell stabilization material 1038 to cell containing solid 1037 should be a ratio as previously mentioned for other embodiments.
  • Outer sterile container 1034 completely encloses stabilizing bath compartment 1039.
  • Second outer container 1031 completely encloses outer sterile container 1034.
  • Outer sterile container 1034 may comprise peelable element 1032 as previously mentioned.
  • Access portal 1040 transits second outer container 1031.
  • access portal 1040 can be a joining point of outer sterile container 1034 and second outer container 1031 as depicted in Fig. 13.
  • Second outer container 1031 and outer sterile container 1034 may be made of a flexible material as previously disclosed.
  • any or all of the components of storage package 1010 can be substituted for any of the like components described with respect to the other embodiments.
  • a cell containing solid 1037 could be sterilely inserted through an access portal 1040 in a sterilization hood or other environment suited for aseptic filling and into outer sterile container 1034.
  • access portal 1040 may be sealed by any sealable means, including the previously mentioned means.
  • cell containing solid 1037 will be placed in stabilizing bath compartment 1039 at or before the time it is placed inside inner sterile compartment 1034.
  • a fluid transporter may transit access port 1040 and a channel through stabilizing bath compartment 1039 to conduct media exchange during storage.
  • a fluid transporter may transit second outer container 1031 and outer sterile container 1034 by portals other than access portal 1040 to conduct media exchange during storage.
  • Jacketed syringe system 1100 may be enclosed inside of the outer sterile container of a storage system, such as the ones embodied in Fig. 11 and Fig. 12. Again referring to Fig. 14, syringe system 1100 jacketed is placed inside the outer sterile container of Figs. 11 and 12 to allow storage of cell containing composition 1111 and, upon opening of the outer sterile container is released to allow a sterile operator to inject cell containing composition 1111 into a desired location.
  • Jacketed syringe system 1100 comprises a syringe 1120 substantially enclosed by jacket 1130.
  • Cell stabilization material 1108 is bound by syringe 1120 and the jacket 1130.
  • the surface area of syringe 1120 that is in contact with cell stabilization medium 1108 is maximized.
  • the surface area of syringe 1120 that is in contact with cell stabilization medium 1108 may be less than maximized.
  • Syringe 1120 is capable of retaining cell containing composition 1111.
  • the walls of syringe 1120 are made of porous material as previously mentioned to allow desired component exchange between cell containing composition 1111 and cell stabilization material 1108.
  • plunger reservoir system 1200 may be enclosed inside of the outer sterile container of a storage system, such as the ones embodied in Fig. 10, 11, 12 and 13. Again referring to Fig. 15, plunger reservoir system 1200 allows storage of cell containing composition 1211 and allows a sterile operator to inject cell containing composition 1211 into a desired location.
  • Plunger reservoir system 1200 comprises barrel 1201 and plunger shaft 1202.
  • Plunger shaft 1202 is typically removable from barrel 1201.
  • Ba ⁇ el 1201 is capable of containing retaining cell containing composition 1211.
  • Plunger shaft 1202 is capable of retaining cell stabilization medium 1208.
  • Plunger shaft 1202 may comprise porous wall 1204.
  • Porous wall 1204 is preferably connected to the end of plunger shaft 1204 opposite plunger handle 1206.
  • Porous wall 1204 is made of porous material as previously mentioned to allow desired component exchange between cell containing composition 1211 and cell stabilization medium 1208.
  • Plunger ba ⁇ el 1201, plunger handle 1206, and plunger shaft 1202, with the exception of the porous wall, are comprised of a suitable impermeable rigid material.
  • plunger reservoir system 1200 may be placed in a storage package according to any embodiment of this invention and sterilized. After sterilization, cell containing composition 1211 is introduced as described herein. Alternatively, syringe ba ⁇ el 1201 and plunger shaft 1202 maybe sterilized separately and the syringe loaded by placing cell containing composition 1211 into barrel 1201, followed by porous wall 1204, cell stabilization material 1208, and plunger shaft 1202. Thus assembled plunger reservoir system 1200 may be placed in the storage package of this invention, e.g., by inserting through access portal 724 of Fig. 10 or access port 1040 of Fig. 13, for storage.
  • media packet system comprising syringe 1300 may be enclosed inside of the outer sterile container of a storage system, such as those embodied in Fig. 10-13 and Fig. 13. Again referring to Fig. 16, media packet system comprising syringe 1300 allows storage of cell containing composition 1311 and allows a sterile operator to inject cell containing composition 1311 into a desired location. Media packet system comprising syringe
  • each media packet 1303 comprises a syringe barrel 1301 capable of retaining cell containing composition 1311 and capable of retaining media packets 1303.
  • Media packets 1303 are capable of retaining cell stabilization material 1308.
  • the walls of media packets 1303 are made of porous material as previously mentioned to allow desired component exchange between cell containing composition 1311 and cell stabilization material 1308.
  • the cross-sectional area of each media packet 1303 at every angle is preferably greater than the cross sectional area of syringe orifice 1307, allowing cell containing composition 1311 to exit syringe orifice 1307, but not allowing media packets 1303 to exit syringe orifice 1307 when syringe plunger 1309 is depressed.
  • syringe plunger 1309 is inserted into syringe ba ⁇ el 1301 for a limited distance.
  • Syringe ba ⁇ el 1301 and syringe plunger are made of rigid, impermeable solids, molded into a desired shape.
  • assembled media packet system syringe 1300 may be sterilized in place inside the outer sterile container and cell containing composition 1311 introduced after sterilization as described herein for other embodiments.
  • presterilized syringe ba ⁇ el presterilized syringe ba ⁇ el
  • storage package system comp ⁇ sing sy ⁇ nge 1405 may be enclosed within ste ⁇ le container 1430.
  • Sy ⁇ nge 1405 comp ⁇ ses plunger 1409, porous sleeve 1418, and container 1412.
  • Ste ⁇ le container 1430 comp ⁇ ses conduit 1424 extending outward, end 1425 connected to conduit 1424, and housing 1470 extending inward.
  • Housing 1470 comp ⁇ ses needle 1420.
  • Sy ⁇ nge 1405 communicates with end 1425 of ste ⁇ le container 1430 via needle 1420.
  • Sy ⁇ nge 1405 may be used to store labile mate ⁇ al, such as a cell containing composition, in a ste ⁇ hzed manner as follows. External sy ⁇ nge 1460 holding cell containing composition 1410 may be connected and used to inject composition 1410 into end 1425 Du ⁇ ng injection, cell containing composition travels through conduit 1424 and needle 1420 into porous sleeve 1418 of sy ⁇ nge 1405. Cell stabilizing medium 1440 may be placed withm sy ⁇ nge 1405 between container 1412 and porous sleeve 1418 p ⁇ or to injection of labile mate ⁇ al.
  • Porous sleeve 1418 made of porous mate ⁇ al as desc ⁇ bed previous embodiments, allows cell stabilizing medium 1440 to contact cell containing composition 1410. However, as shown in Fig. 17B, when plunger 1409 is activated, cell containing composition 1410 is expelled through tip 1480 of sy ⁇ nge 1405 because cell stabilizing medium 1440, and not the cells, will pass through porous sleeve 1418.
  • the above embodiment is applicable to cell containing compositions that are solid products as well as fluid type products.
  • a gellable composition containing cells may be introduced into porous sleeve 1418 in liquid forma and allowed to gel m-situ
  • a sealable transfer tube may be used in place of needle 1420 to insert the solid into the porous sleeve.
  • porous sleeve 1418 and plunger 1409 may be removed from sy ⁇ nge 1405.
  • the drawing on the left shows sy ⁇ nge 1405 after removal from ste ⁇ le container 1430 as embodied in Fig. 17.
  • Container 1412 and cell stabilizing mate ⁇ al 1440 may be removed from sy ⁇ nge 1405, thereby leaving porous sleeve 1418 with cell containing composition 1450, as shown in the center drawing of Fig. 18
  • Porous sleeve 1418, plunger 1409, and cell containing composition 1450 may be placed in empty sy ⁇ nge 1405, as shown in the ⁇ ght drawing
  • syringe 1600 comp ⁇ ses plunger 1610 and valve 1630 Sy ⁇ nge 1600 may hold cell containing composition 1620, in the form of a gel rod, and cell stabilizing mate ⁇ al 1640 Valve 1630 is provided to drain cell stabilizing mate ⁇ al 1640 Valve 1630 may have a porous filter so that only cell stabilizing mate ⁇ al exits valve 1630 and not the labile mate ⁇ al
  • cell containing composition 1720 is extracted from first container 1760 into second container 1750
  • containers 1760 and 1750 are connected along an axis
  • Container 1760 comp ⁇ ses porous sleeve 1770 separating cell containing composition 1720 from cell stabilizing mate ⁇ al 1740, but, allowing liquid/liquid contact between the two Plunger 1710 of container 1750 is pulled upward to extract cell containing composition 1720 into second contamei 1750
  • porous sleeve 1770 allows cell stabilizing mate ⁇ al 1740, but not cell composition 1720, to pass through porous sleeve 1770, only cell containing composition 1720 flows into second container 1750, as shown in the ⁇ ght drawing
  • FIG. 21 a method and system for transfer ⁇ ng cell containing composition 1860 and cell stabilizing mate ⁇ al 1870 into container 1820 with ste ⁇ le container 1830, according to anothei embodiment of the invention is shown
  • the top drawing of Fig 21 depicts connector 1840 for connecting product container 1820, within ste ⁇ le container 1830, to sy ⁇ nge 1825 Sy ⁇ nge 1825 is connected to sy ⁇ nge 1815 via link 1850
  • Plungers 1810 and 1805 are used respectively with sy ⁇ nges 1825 and 1815 Plunger 1810 extends through container 1820 and ste ⁇ le container 1830
  • Cell containing mate ⁇ al 1860 in sy ⁇ nge 1815 is drawn into container 1820 by pulling plunger 1810 away from sy ⁇ nge 1825
  • sy ⁇ nge 1815 may be replaced with a sy ⁇ nge to inject cell stabilizing material 1870 into container 1820 Upon container 1820 receiving both cell stabilizing
  • plunger 2040 has a filter tip to allow cell stabilizing material to pass through and be stored in chamber 2030 when the plunger is activated.
  • labile gel rod 2120 is formed on the end of plunger 2130 and placed inside container 2100 holding cell stabilizing material 2110. Labile gel rod 2120 may be removed from container 2100 by lifting plunger 2130 and placed into empty container 2140, as shown from left to right in the figure.
  • FIG. 25 depicts a storage apparatus according to another embodiment of the invention.
  • Storage apparatus 2200 comprises syringe ba ⁇ el 2208, porous sleeve 2220, plungers 2230 and 2240.
  • Porous sleeve 2220 is enclosed by container 2205.
  • Porous sleeve 2220 allows labile gel rod 2250 inside container 2205 to be in contact with cell stabilizing material 2210, as shown in step 1.
  • Plunger 2230 has a length that when fully depressed, pushes labile gel rod into syringe ba ⁇ el 2208, as shown in step 2.
  • Plunger 2240 has a length that when fully depressed, pushes labile gel rod out of syringe ba ⁇ el 2208 and away from storage apparatus 2200, as shown in step 3.
  • Storage apparatus 2300 comprises syringe 2305 with plungers 2310 and 2320.
  • Plunger 2310 has filtered tip 2340 so that when activated, cell stabilizing material 2325 filters out of syringe 2305 while labile gel 2315 flows into the chamber of plunger 2310.
  • Plunger 2320 may be activated to expel the labile gel from the syringe.
  • the storage aseptic package of this invention has been described in terms of an operating room containing a sterile field, where the package is opened and used by a non-sterile assistant and sterile operator, respectively, those skilled in the art will recognize that the apparatus and methods for its use are easily adapted to other environments with similar requirements, including a sterile manufacturing facility or a sterile field in an outpatient clinic.
  • the non-sterile assistant may be substituted by mechanical means of opening the second outer container, or even by one hand of the sterile operator while preventing contamination of the other hand which remains in the sterile field.
  • Chondrocytes were obtained by cartilage biopsy taken from a normal human volunteer. Chondrocytes were isolated from the biopsy material using a collagenase digestion process as described in Atala, et al. (1994), J. Urol., 152:641 and Klagsbrun (1979), "Large-scale Preparation of Chondrocytes," Meth. Enzymol, 58:560. Isolated chondrocytes were expanded in T-flask and roller bottle cultures over a 4-8 week period.
  • Test samples were prepared by suspending cells from the expanded chondrocyte population in M199 and combining them with 2.2% Pronova UP MVP sodium alginate. Hydrogel aliquots were formed by combining 2.75 mL of cell- alginate suspension with 0.25 mL of M199 containing 6.0 mg of solid CaSO . The final cell concentration in the hydrogel was 30 X 10 6 cells/ml.
  • the survival of cells in these hydrogel aliquots was tested under various storage conditions, and compared to normal cell storage under low cell density conditions (i.e., control cells stored at 3.8 x 10 4 cells/ml).
  • the hydrogel aliquots were stored under sterile conditions with or without a su ⁇ ounding bath of cell culture medium M199 (30 mL of medium per 3 mL of cell-containing hydrogel) at either room temperature or 4°C.
  • the gaseous atmosphere for the room temperature storage chamber containing the sample with a su ⁇ ounding bath of M199 medium contained 5% CO 2 .
  • the viability of the cells stored under the various conditions was measured at 24 and 48 hours by removing a portion of the hydrogel and dissolving it (using chelating agents) and then determining viability of the cells in the resulting solution by trypan blue exclusion.
  • the results are shown in Table 1.
  • chondrocytes in a hydrogel aliquot stored at room temperature with a bath of culture medium su ⁇ ounding the hydrogel will retain cell viability as well as cells stored under normal cell storage conditions (i.e., low cell density or high medium-to-cell ratio). Cell viability decreased faster under all other conditions.

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Abstract

L'invention concerne un conditionnement de stockage comprenant un premier contenant extérieur, un second contenant extérieur enfermant complètement le premier, une ouverture d'accès, traversant le premier contenant extérieur, un compartiment contenant une cellule, un compartiment qui contient un bain stabilisateur et est relié au compartiment contenant la cellule par l'intermédiaire d'une barrière semi-perméable, laquelle permet le passage d'espèces moléculaires mais pas celui de cellules vivantes et forme en outre au moins une portion de la barrière située entre le compartiment du bain stabilisateur et le compartiment contenant la cellule, le premier contenant extérieur enfermant complètement ces deux compartiments. Ce conditionnement comporte en outre des moyens d'enlèvement du second contenant extérieur, ainsi que des moyens d'enlèvement du premier contenant extérieur.
PCT/US2000/020739 1999-07-29 2000-07-31 Conditionnement sterile de matiere vivante, dote de caracteristiques ameliorees de stockage Ceased WO2001008630A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU66148/00A AU6614800A (en) 1999-07-29 2000-07-31 Sterile packaging of live material with improved storage characteristics
JP2001513363A JP2004500158A (ja) 1999-07-29 2000-07-31 収納パッケージ

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14596799P 1999-07-29 1999-07-29
US60/145,967 1999-07-29

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WO2001008630A9 WO2001008630A9 (fr) 2013-10-10

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1106065A3 (fr) * 1999-11-26 2004-03-03 CellContol Biomedical Laboratories GmbH Procédé et récipient pour conserver et expédier du tissu, du fluide, ou de la matière cellulaire vivante
EP1504728A1 (fr) * 2003-08-05 2005-02-09 Biomet Manufacturing Corp. Méthode et dispositifs pour l'utilisation d'emballage sous vide de matériel allogreffe
EP1627566A3 (fr) * 2004-07-27 2006-04-05 Haemopharm Industry Ag Pouche de securité pour cryoconservation des cellules souches et des components sanguins similaires
EP2113206A3 (fr) * 2008-05-01 2014-01-01 Covidien LP Emballage pour dispositif médical
WO2014019942A1 (fr) * 2012-07-31 2014-02-06 E3 Cortex Conteneur hermetique et procede d'emballage mettant en oeuvre un tel conteneur
WO2015048003A1 (fr) 2013-09-25 2015-04-02 Saint-Gobain Performance Plastics Corporation Contenant de cryoconservation
US10655120B2 (en) * 2011-03-21 2020-05-19 The University Of Newcastle Upon Tyne Transport of cells in hydrogels
US11051900B2 (en) 2014-04-16 2021-07-06 Viacyte, Inc. Tools and instruments for use with implantable encapsulation devices
US20230026520A1 (en) * 2019-12-11 2023-01-26 Robert Schutte Systems, devices and methods for engineered tissue construct transport and containment
EP4289467A3 (fr) * 2014-04-16 2024-02-21 ViaCyte, Inc. Instruments destinés à être utilisés avec des dispositifs d'encapsulation implantables
US11932843B2 (en) 2016-11-09 2024-03-19 Trizell Ltd. Adherent cell culture substrate sampling device

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JP6725716B2 (ja) * 2019-02-25 2020-07-22 ヴィアサイト インコーポレイテッド 埋め込み可能な封入デバイスと共に使用するツールおよび器具
JP7523622B2 (ja) * 2021-10-28 2024-07-26 ヴィアサイト インコーポレイテッド 埋め込み可能な封入デバイスと共に使用するツールおよび器具

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JPS57206447A (en) * 1981-06-12 1982-12-17 Terumo Corp Plastic container receiving liquid drug pasturized with high pressure steam and production thereof
US4597765A (en) * 1984-12-27 1986-07-01 American Medical Systems, Inc. Method and apparatus for packaging a fluid containing prosthesis
US5040677A (en) * 1990-06-04 1991-08-20 Biosurface Technology, Inc. Container for storage and distribution of a skin wound dressing
US5590778A (en) * 1995-06-06 1997-01-07 Baxter International Inc. Double-sterile package for medical apparatus and method of making
US6033392A (en) * 1996-06-10 2000-03-07 Frey; John W. IV pole bag fabricated from anti-microbial material
US5896989A (en) * 1998-02-20 1999-04-27 Bracco Research Usa Flexible medical container packaging

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1106065A3 (fr) * 1999-11-26 2004-03-03 CellContol Biomedical Laboratories GmbH Procédé et récipient pour conserver et expédier du tissu, du fluide, ou de la matière cellulaire vivante
EP1504728A1 (fr) * 2003-08-05 2005-02-09 Biomet Manufacturing Corp. Méthode et dispositifs pour l'utilisation d'emballage sous vide de matériel allogreffe
US7172071B2 (en) 2003-08-05 2007-02-06 Biomet Manufacturing Corp. Method and apparatus for use of a vacuum package for allograft material
EP1627566A3 (fr) * 2004-07-27 2006-04-05 Haemopharm Industry Ag Pouche de securité pour cryoconservation des cellules souches et des components sanguins similaires
EP2113206A3 (fr) * 2008-05-01 2014-01-01 Covidien LP Emballage pour dispositif médical
US10655120B2 (en) * 2011-03-21 2020-05-19 The University Of Newcastle Upon Tyne Transport of cells in hydrogels
WO2014019942A1 (fr) * 2012-07-31 2014-02-06 E3 Cortex Conteneur hermetique et procede d'emballage mettant en oeuvre un tel conteneur
FR2994163A1 (fr) * 2012-07-31 2014-02-07 E3 Cortex Conteneur hermetique et procede d'emballage mettant en oeuvre un tel conteneur
EP3049044A4 (fr) * 2013-09-25 2017-06-14 Saint-Gobain Performance Plastics Corporation Contenant de cryoconservation
WO2015048003A1 (fr) 2013-09-25 2015-04-02 Saint-Gobain Performance Plastics Corporation Contenant de cryoconservation
US11051900B2 (en) 2014-04-16 2021-07-06 Viacyte, Inc. Tools and instruments for use with implantable encapsulation devices
EP4289467A3 (fr) * 2014-04-16 2024-02-21 ViaCyte, Inc. Instruments destinés à être utilisés avec des dispositifs d'encapsulation implantables
US11925488B2 (en) 2014-04-16 2024-03-12 Viacyte, Inc. Tools and instruments for use with implantable encapsulation devices
US11932843B2 (en) 2016-11-09 2024-03-19 Trizell Ltd. Adherent cell culture substrate sampling device
US12391911B2 (en) 2016-11-09 2025-08-19 Trizell Ltd. Adherent cell culture substrate sampling device
US20230026520A1 (en) * 2019-12-11 2023-01-26 Robert Schutte Systems, devices and methods for engineered tissue construct transport and containment

Also Published As

Publication number Publication date
WO2001008630A9 (fr) 2013-10-10
WO2001008630A3 (fr) 2012-01-12
JP2004500158A (ja) 2004-01-08
AU6614800A (en) 2001-02-19

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