WO1994027645A1 - System for packaging and delivering of a sterile powder medium - Google Patents

System for packaging and delivering of a sterile powder medium Download PDF

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Publication number
WO1994027645A1
WO1994027645A1 PCT/US1993/005175 US9305175W WO9427645A1 WO 1994027645 A1 WO1994027645 A1 WO 1994027645A1 US 9305175 W US9305175 W US 9305175W WO 9427645 A1 WO9427645 A1 WO 9427645A1
Authority
WO
WIPO (PCT)
Prior art keywords
sterilized
powdered
sterile
cartridge
powder
Prior art date
Application number
PCT/US1993/005175
Other languages
French (fr)
Inventor
Diane E. Wyatt
Douglas R. Purtle
Original Assignee
Porton International Plc
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 Porton International Plc filed Critical Porton International Plc
Priority to PCT/US1993/005175 priority Critical patent/WO1994027645A1/en
Priority to AU43996/93A priority patent/AU4399693A/en
Publication of WO1994027645A1 publication Critical patent/WO1994027645A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/26—Conditioning fluids entering or exiting the reaction vessel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0029—Radiation
    • A61L2/0035—Gamma radiation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M37/00—Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination

Definitions

  • the invention relates to techniques for the sterile delivery of products for biological uses, and specifically to an apparatus and method for providing sterile delivery of biological products without the need for passing the medium through a filter or sterilizing membrane filter.
  • the methodology currently employed to prepare certain of these reagents involves the use powdered ingredients.
  • these powdered reagents are not sterile when received by the end user, who converts these powdered ingredients into a solution using purified water. Since the solution is not sterile, as the powdered ingredients were not, the solution is then passed through a sterilizing membrane filter and transferred aseptically to a sterile container or culturing vessel.
  • the disadvantage of the above method is that such handling greatly increases the chances of biological contamination and loss or alteration of the product, contamination due to environmental or human exposures, loss due to transfer, and alteration due to removal of certain components during membrane sterilization.
  • the powder medium is stored in a cartridge or bag, which is then subject to gamma irradiation for sterilization. This results in delivering a powdered product to the end user in a sterile state.
  • the cartridge or bag is designed so that the solution can be generated within the unit, eliminating potential opportunities for contamination. Since this invention eliminates the need for post-mixing sterilization, it reduces the potential for loss of product or components, thereby increasing batch-to-batch consistency.
  • Fig. 1 is a view of a powder delivery cartridge of the present invention.
  • Fig. 2 is a view of the reconstituting apparatus for the powder delivery cartridge of the present invention.
  • Fig. 3 is a view of a powder delivery bag of the present invention.
  • Fig. 4 is a view of the reconstituting apparatus for the powder delivery bag of the present invention.
  • the present invention is directed to a method and apparatus for sterile delivery of cell culture products in solution.
  • a method and apparatus for sterile delivery of cell culture products in solution To facilitate the distribution and transport of biological products used in cell cultures, it is desirable when and where possible to reduce the products to a stable powder form.
  • the powder is combined with sterile purified water to generate a liquid solution, which then may be transferred to the cell culture vessel or vessels.
  • Fig. 1 shows the apparatus used in a first embodiment of the present invention, where a powdered medium is contained within a cartridge.
  • Cartridge 1 comprises a hollow cartridge barrel 2 (which may be, but is not limited to, a suitable IV blood filter cartridge), and has end caps 3, tubing 4, tubing connectors 5, and tubing clamps 6 connected at each end.
  • the procedure for assembly and filling of the cartridge 1 involves first connecting tubing connectors 5 to tubing 4, by coating tubing connectors 5 with solvent and inserting them into tubing 4. Tubing clamps 6 are then clamped onto both pieces of tubing 4. Next, tubing 4 is connected to end caps 3 by first applying solvent to end caps 3 and then inserting end cap 3 end into tubing 4 end. One end cap 3 is then attached to barrel 2 by coating the outside edge of the end cap 3 with solvent and connecting it to barrel 2 end. The cartridge 1 is then filled from the other end of barrel 2 with the appropriate amount of powdered medium. Powder should not be present on the inside edge of barrel 2. Finally, the other end cap 3 is attached to the open end of barrel 2, using the procedure outlined above, and the cartridge 1 is labelled to indicate the type and quantity of powdered medium therein.
  • the cartridge is then stored with a desiccant, at a temperature between 2-
  • Fig. 2 The configuration for a suggested apparatus for reconstitution by an end user of medium stored in a cartridge is illustrated in Fig. 2.
  • Reconstitution of the powdered medium is accomplished by connecting cartridge 1 to a reconstituting apparatus 7.
  • Reconstituting apparatus 7 contains an inlet tube 8 which is connected to a source (not shown) of water, preferably WFI-grade water. Water is pumped from its source by a peristaltic pump 9, of any known type for accurate delivery of liquids.
  • the outlet of peristaltic pump 9 is connected to a filter unit 10, preferably containing a sterile 0.2 ⁇ m filter.
  • sodium bicarbonate cartridge 11 Connected in series with filter unit 10 is a sodium bicarbonate cartridge 11, which has at one end tubing 12 which may be connected to the tubing connector 5 on cartridge 1.
  • Sodium bicarbonate is necessary in the reconstitution process to act as a buffer for the powdered medium, but must be packaged separately due to potential problems of carbon dioxide generation.
  • sodium bicarbonate is shown in Fig. 2 as added to the water through cartridge 11, it could, alternatively, be added to the water upstream of the peristaltic pump 9 at the water source, thus eliminating the need for sodium bicarbonate cartridge 11.
  • sodium bicarbonate cartridge 11 should be gamma irradiated for sterilization.
  • the cartridge 1 is connected to tubing 12 on reconstituting apparatus 7 by means of tubing connector 5.
  • sodium bicarbonate cartridge (if necessary) and filter 10 have been connected to peristaltic pump 9 to complete reconstituting apparatus 7.
  • Clamp 6 on cartridge 1 adjacent tubing 12 is then undamped.
  • the unconnected tubing connector 5 on cartridge 1 is then aseptically joined to a sterilized receiving vessel 13.
  • clamp 6 on cartridge 1 adjacent sterilized receiving vessel 13 is undamped.
  • Peristaltic pump 9 is then activated. Liquid flows from its source, through peristaltic pump 9, filter unit 10, sodium bicarbonate cartridge 11, powder cartridge 1 and (as solution) into sterilized receiving vessel 13.
  • Solution is therefore generated and placed into vessel 13 without need for handling or filtering of the solution itself.
  • the solution is sterile due to pre-cartridge filtering of the water and the previous gamma irradiation of the powder medium and sodium bicarbonate.
  • Peristaltic pump 9 is run until the volume of solution generated in vessel 13 is of a desired quantity. Solution in vessel 13 may thereafter be transferred to specific cell culture devices.
  • Fig. 3 shows a second embodiment of the present invention, utilizing a powder delivery bag 14.
  • Powder delivery bag 14, of appropriate manufacture so that it is compatible with cell culture usage generally contains three ports: septum port 15, filling port 16, and dispensing port 17.
  • Filling port 16 and dispensing port 17 consist of flexible tubing (as were the inlets and outlets to cartridge 1) to which are attached tubing clamps 18. During filling, the tubing clamps 18 are undamped, and powder is dispensed into bag 14 through filling port 16. After filling is completed, tubing clamps 18 are clamped to both filling port 16 and dispensing port 17. The bag is then stored with a desiccant, at a temperature between 2-8° C.
  • the contents of the bag are then sterilized using gamma irradiation, generally between 0.5 and 3.0 megaRad. Finally, the bag is shipped, with a desiccant and at a temperature between 2-8° C, to the end user. The end user reconstitutes the powder using the apparatus shown in Fig. 4.
  • the apparatus for reconstitution in powder bag 14 is similar to that used to reconstitute powder in powder cartridge 1.
  • tubing connector 5 is connected between tubing 12 and filling port 16.
  • Dispensing port 17 is connected to sterilized receiving vessel 13.
  • Clamps 18 are then undamped, and peristaltic pump 9 is activated.
  • Liquid flows through pump 9, filter 10, sodium bicarbonate cartridge 11 (if necessary), bag 14, and (as solution) into vessel 13. Accordingly, as in cartridge 1, solution is dispensed into sterile receiving vessel 13 without the need to handle the powder and without the need to filter the solution.
  • Bag 14 may be used for storage of the material for a prescribed period of time.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Apparatus For Disinfection Or Sterilisation (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

A method and apparatus are disclosed for improved transfer and delivery of biological media used in tissue cell cultures. The media are reduced to powdered form, and then placed inside a cartridge or bag (1). The media are then sterilized within the bag (1) by the use of gamma irradiation. The cartridge or bag (1) is shipped to an end user, who reconstitutes the powder into solution. Sterilized water is pumped through the cartridge or bag (1), and solution exits from an outlet in the cartridge or bag (1) to a sterilized vessel (13). The solution can then be added to a tissue culture. The method is advantageous in that it does not require the solution to be filtered to be sterile, thus eliminating product losses during the filtering process. The method is also advantageous in that there is no direct handling of the powder after sterilization, thus greatly reducing the chance that the solution will be contaminated.

Description

System for Packaging and Delivering of a Sterile Powder Medium
Background of the Invention
The invention relates to techniques for the sterile delivery of products for biological uses, and specifically to an apparatus and method for providing sterile delivery of biological products without the need for passing the medium through a filter or sterilizing membrane filter.
In the generation of large-scale ceil growth for the production of vaccines and biologicals, difficulties are encountered in attempting to prevent or eliminate contamination of a culture. The process of production will require the introduction of reagents, such as cell culture media, salts, sera, antibiotics, and proteins to stimulate the desired growth. These reagents must be prepared, and must remain-, sterile so that they do not contaminate the culture when introduced into a culture vessel.
The methodology currently employed to prepare certain of these reagents involves the use powdered ingredients. Typically, these powdered reagents are not sterile when received by the end user, who converts these powdered ingredients into a solution using purified water. Since the solution is not sterile, as the powdered ingredients were not, the solution is then passed through a sterilizing membrane filter and transferred aseptically to a sterile container or culturing vessel. The disadvantage of the above method is that such handling greatly increases the chances of biological contamination and loss or alteration of the product, contamination due to environmental or human exposures, loss due to transfer, and alteration due to removal of certain components during membrane sterilization.
Summary of the Invention
The drawbacks of the above system and apparatus are overcome by the method and apparatus of the invention.
In the present invention, the powder medium is stored in a cartridge or bag, which is then subject to gamma irradiation for sterilization. This results in delivering a powdered product to the end user in a sterile state. The cartridge or bag is designed so that the solution can be generated within the unit, eliminating potential opportunities for contamination. Since this invention eliminates the need for post-mixing sterilization, it reduces the potential for loss of product or components, thereby increasing batch-to-batch consistency.
Brief Description of the Drawings
Fig. 1 is a view of a powder delivery cartridge of the present invention.
Fig. 2 is a view of the reconstituting apparatus for the powder delivery cartridge of the present invention. Fig. 3 is a view of a powder delivery bag of the present invention.
Fig. 4 is a view of the reconstituting apparatus for the powder delivery bag of the present invention.
Detailed Description
The present invention is directed to a method and apparatus for sterile delivery of cell culture products in solution. To facilitate the distribution and transport of biological products used in cell cultures, it is desirable when and where possible to reduce the products to a stable powder form. At the point of use of the products, the powder is combined with sterile purified water to generate a liquid solution, which then may be transferred to the cell culture vessel or vessels.
In the system and apparatus of the present invention, powdered products are sealed in a container at the point of manufacture. The container is made of a material that is non-cytotoxic, impermeable to gas exchange, and sterilizable by gamma irradiation. Fig. 1 shows the apparatus used in a first embodiment of the present invention, where a powdered medium is contained within a cartridge. Cartridge 1 comprises a hollow cartridge barrel 2 (which may be, but is not limited to, a suitable IV blood filter cartridge), and has end caps 3, tubing 4, tubing connectors 5, and tubing clamps 6 connected at each end.
The procedure for assembly and filling of the cartridge 1 involves first connecting tubing connectors 5 to tubing 4, by coating tubing connectors 5 with solvent and inserting them into tubing 4. Tubing clamps 6 are then clamped onto both pieces of tubing 4. Next, tubing 4 is connected to end caps 3 by first applying solvent to end caps 3 and then inserting end cap 3 end into tubing 4 end. One end cap 3 is then attached to barrel 2 by coating the outside edge of the end cap 3 with solvent and connecting it to barrel 2 end. The cartridge 1 is then filled from the other end of barrel 2 with the appropriate amount of powdered medium. Powder should not be present on the inside edge of barrel 2. Finally, the other end cap 3 is attached to the open end of barrel 2, using the procedure outlined above, and the cartridge 1 is labelled to indicate the type and quantity of powdered medium therein.
The cartridge is then stored with a desiccant, at a temperature between 2-
8° C. The contents of the cartridge are next sterilized using gamma irradiation, generally between 0.5 and 3.0 megaRad. Finally, the cartridge is shipped, with a desiccant and at a temperature between 2-8° C, to the end user. The configuration for a suggested apparatus for reconstitution by an end user of medium stored in a cartridge is illustrated in Fig. 2.
Reconstitution of the powdered medium is accomplished by connecting cartridge 1 to a reconstituting apparatus 7. Reconstituting apparatus 7 contains an inlet tube 8 which is connected to a source (not shown) of water, preferably WFI-grade water. Water is pumped from its source by a peristaltic pump 9, of any known type for accurate delivery of liquids. The outlet of peristaltic pump 9 is connected to a filter unit 10, preferably containing a sterile 0.2 μm filter.
Connected in series with filter unit 10 is a sodium bicarbonate cartridge 11, which has at one end tubing 12 which may be connected to the tubing connector 5 on cartridge 1. Sodium bicarbonate is necessary in the reconstitution process to act as a buffer for the powdered medium, but must be packaged separately due to potential problems of carbon dioxide generation. Although sodium bicarbonate is shown in Fig. 2 as added to the water through cartridge 11, it could, alternatively, be added to the water upstream of the peristaltic pump 9 at the water source, thus eliminating the need for sodium bicarbonate cartridge 11. Generally, sodium bicarbonate cartridge 11 should be gamma irradiated for sterilization.
In operation, the cartridge 1 is connected to tubing 12 on reconstituting apparatus 7 by means of tubing connector 5. Previously, sodium bicarbonate cartridge (if necessary) and filter 10 have been connected to peristaltic pump 9 to complete reconstituting apparatus 7. Clamp 6 on cartridge 1 adjacent tubing 12 is then undamped. The unconnected tubing connector 5 on cartridge 1 is then aseptically joined to a sterilized receiving vessel 13. Next, clamp 6 on cartridge 1 adjacent sterilized receiving vessel 13 is undamped. Peristaltic pump 9 is then activated. Liquid flows from its source, through peristaltic pump 9, filter unit 10, sodium bicarbonate cartridge 11, powder cartridge 1 and (as solution) into sterilized receiving vessel 13. Solution is therefore generated and placed into vessel 13 without need for handling or filtering of the solution itself. The solution is sterile due to pre-cartridge filtering of the water and the previous gamma irradiation of the powder medium and sodium bicarbonate. Peristaltic pump 9 is run until the volume of solution generated in vessel 13 is of a desired quantity. Solution in vessel 13 may thereafter be transferred to specific cell culture devices.
Fig. 3 shows a second embodiment of the present invention, utilizing a powder delivery bag 14. Powder delivery bag 14, of appropriate manufacture so that it is compatible with cell culture usage, generally contains three ports: septum port 15, filling port 16, and dispensing port 17. Filling port 16 and dispensing port 17 consist of flexible tubing (as were the inlets and outlets to cartridge 1) to which are attached tubing clamps 18. During filling, the tubing clamps 18 are undamped, and powder is dispensed into bag 14 through filling port 16. After filling is completed, tubing clamps 18 are clamped to both filling port 16 and dispensing port 17. The bag is then stored with a desiccant, at a temperature between 2-8° C. The contents of the bag are then sterilized using gamma irradiation, generally between 0.5 and 3.0 megaRad. Finally, the bag is shipped, with a desiccant and at a temperature between 2-8° C, to the end user. The end user reconstitutes the powder using the apparatus shown in Fig. 4.
The apparatus for reconstitution in powder bag 14 is similar to that used to reconstitute powder in powder cartridge 1. To reconstitute the powder, tubing connector 5 is connected between tubing 12 and filling port 16. Dispensing port 17 is connected to sterilized receiving vessel 13. Clamps 18 are then undamped, and peristaltic pump 9 is activated. Liquid flows through pump 9, filter 10, sodium bicarbonate cartridge 11 (if necessary), bag 14, and (as solution) into vessel 13. Accordingly, as in cartridge 1, solution is dispensed into sterile receiving vessel 13 without the need to handle the powder and without the need to filter the solution. Bag 14 may be used for storage of the material for a prescribed period of time. While the invention has been described with reference to specific embodiments, it will be apparent to those skilled in the art that many alternatives, modifications, and variations may be made. Accordingly, it is intended to embrace all such alternatives or modifications that may fall within the spirit and scope of the appended claims.

Claims

WHAT IS CLAIMED IS:
1. A method for delivering sterile biological media or cell culture reagents comprising the steps of: filling a device with a powdered biological product; sealing said powdered biological product in said device; irradiating said device and said powdered biological product with gamma radiation; connecting a source of sterile liquid to said device; delivering said sterile liquid so as to continuously flow through said device; collecting a resulting solution from said device in a sterile container; and transferring a portion of said resulting solution from said sterile container into a receptacle containing a cell culture.
2. The method of claim 1, wherein: said device is a cartridge.
3. The method of claim 1, wherein: said device is a bag.
4. The method of claim 1, wherein: said device and said powder are irradiated at a level between 0.5 and 3.0 megaRad.
5. The method of claim 1, wherein: said device has two tubular conduits connected therewith; said sterile liquid flows into one of said tubular conduits; and said resulting solution flows out of the other of said tubular conduits.
6. The method of claim 1, wherein: said tubular conduits are sealed by clamps between the step of filling the device and the step of connecting the source of sterile liquid to said device.
7. The method of claim 1, wherein: said sterile liquid is sterilized as it flows to said device.
8. The method of claim 7, wherein: said sterile liquid is sterilized using a filter through which the liquid flows as it moves towards said device.
9. A method for packaging a sterile powder of biological products comprising the steps of: filling a rigid cartridge with a powder of biological products; sealing the rigid cartridge; subjecting the rigid cartridge and the powder to gamma irradiation.
10. The method of claim 9, wherein: said device is filled with powder through a tubular conduit, which is sealed after filling by a clamp.
11. The method of claim 9, wherein: said device and said powder are irradiated at a level between 0.5 and 3.0 megaRad.
12. An apparatus for reconstituting a powdered biological medium comprising: a source of a reconstituting liquid; a flow line through which said reconstituting liquid flows; a sterilizer in said flow line which sterilizes said liquid as it flows through said flow line; a buffering device in said flow line containing a buffering medium which is added to said liquid as it flows through said flow line; and a connecting member connected to said flow line downstream of said sterilizer and said buffering device, said connecting member arranged to be connected to a device containing sterilized powdered biological medium.
13. The apparatus of claim i2, further comprising: a device containing said sterilized powdered biological medium, said device being connected to said connecting member.
14. The apparatus of claim 13, wherein: said device has two conduits, one of said conduits connected to said connecting member and the other of said conduits connected to a sterilized vessel.
15. The apparatus of claim 13, wherein: said sterilized powdered biological medium has been sterilized within the device by gamma irradiation.
16. The apparatus of claim 12, wherein: said sterilizer is a filter.
17. The apparatus of claim 14, wherein: said other of said conduits contains no sterilizing means.
18. An apparatus for transporting and delivering biological products comprising: a rigid cartridge constructed of a gamma radiation permeable material; at least two conduits leading to the interior of said device; and a powdered biological medium contained within said device; wherein said at least two conduits are sealed after introduction of said powdered biological medium into said device, and said powdered biological medium is subjected to gamma irradiation after said at least two conduits are sealed.
19. The method of claim 1, further comprising the step of: buffering said sterile liquid before it is delivered into said device.
20. The method of claim 19, wherein: the step of buffering said sterile liquid comprises the steps of: connecting a second device containing a sterilized, powdered buffer material to said source of sterile liquid; delivering said sterile liquid into said second device.
21. The method of claim 20, wherein: said sterilized, powdered buffer material is sterilized by gamma irradiation.
22. The method of claim 20, wherein: said sterilized, powdered buffer material is sodium bicarbonate.
PCT/US1993/005175 1993-05-28 1993-05-28 System for packaging and delivering of a sterile powder medium WO1994027645A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/US1993/005175 WO1994027645A1 (en) 1993-05-28 1993-05-28 System for packaging and delivering of a sterile powder medium
AU43996/93A AU4399693A (en) 1993-05-28 1993-05-28 System for packaging and delivering of a sterile powder medium

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1993/005175 WO1994027645A1 (en) 1993-05-28 1993-05-28 System for packaging and delivering of a sterile powder medium

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WO1994027645A1 true WO1994027645A1 (en) 1994-12-08

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2112753A1 (en) * 1995-04-28 1998-04-01 Campo Robles Juan Luis E Del Disposal bacteriological control device and process for manufacturing it
WO1999009838A1 (en) * 1997-08-25 1999-03-04 Chr. Hansen A/S Dairy starter culture delivery system and use hereof
US6383810B2 (en) * 1997-02-14 2002-05-07 Invitrogen Corporation Dry powder cells and cell culture reagents and methods of production thereof
WO2002036735A3 (en) * 2000-11-06 2002-06-20 Invitrogen Corp Dry powder cells and cell culture reagents and methods of production thereof
US6627426B2 (en) 1997-02-14 2003-09-30 Invitrogen Corporation Methods for reducing adventitious agents and toxins and cell culture reagents produced thereby
WO2018130674A3 (en) * 2017-01-16 2018-10-04 Merck Patent Gmbh System and apparatus for discharging sterile media

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4282863A (en) * 1978-07-20 1981-08-11 Beigler Myron A Methods of preparing and using intravenous nutrient compositions
US4784495A (en) * 1987-02-06 1988-11-15 Gambro Ab System for preparing a fluid intended for a medical procedure by mixing at least one concentrate in powder form with water
US5116575A (en) * 1986-02-06 1992-05-26 Steris Corporation Powdered anti-microbial composition

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4282863A (en) * 1978-07-20 1981-08-11 Beigler Myron A Methods of preparing and using intravenous nutrient compositions
US5116575A (en) * 1986-02-06 1992-05-26 Steris Corporation Powdered anti-microbial composition
US4784495A (en) * 1987-02-06 1988-11-15 Gambro Ab System for preparing a fluid intended for a medical procedure by mixing at least one concentrate in powder form with water

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2112753A1 (en) * 1995-04-28 1998-04-01 Campo Robles Juan Luis E Del Disposal bacteriological control device and process for manufacturing it
US6383810B2 (en) * 1997-02-14 2002-05-07 Invitrogen Corporation Dry powder cells and cell culture reagents and methods of production thereof
US6627426B2 (en) 1997-02-14 2003-09-30 Invitrogen Corporation Methods for reducing adventitious agents and toxins and cell culture reagents produced thereby
EP1702978A3 (en) * 1997-02-14 2006-10-04 Invitrogen Corporation Dry powder cells and cell culture reagents and methods of production thereof
US7572632B2 (en) 1997-02-14 2009-08-11 Life Technologies Corporation Dry powder cells and cell culture reagents and methods of production thereof
WO1999009838A1 (en) * 1997-08-25 1999-03-04 Chr. Hansen A/S Dairy starter culture delivery system and use hereof
US6335040B1 (en) 1997-08-25 2002-01-01 Chr. Hansen A/S Dairy starter culture delivery system and method thereof
US6548089B2 (en) 1997-08-25 2003-04-15 Chr. Hansen A/S Dairy starter culture delivery system and use hereof
WO2002036735A3 (en) * 2000-11-06 2002-06-20 Invitrogen Corp Dry powder cells and cell culture reagents and methods of production thereof
WO2018130674A3 (en) * 2017-01-16 2018-10-04 Merck Patent Gmbh System and apparatus for discharging sterile media
US11434465B2 (en) 2017-01-16 2022-09-06 Merck Patent Gmbh System and apparatus for discharging sterile media

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Publication number Publication date
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