Claims for Patent: 4,336,329

Summary for Patent: 4,336,329

Title:	Method and apparatus for treatment of biological substances, particularly for cultivation of biological cells and tissues, or of microorganisms
Abstract:	To establish predetermined humidity levels within a sterile treatment chamber, and maintain sterility, water, preferably deionized, is conducted to an evaporator outside of a container defining the treatment chamber, to be there heated to superheated steam, for example in the order of 300.degree. C., and conducted to a bypass duct (1) in atmospheric communication with the treatment chamber (10), for mixing with the atmosphere within the treatment chamber. Preferably, the treatment chamber is surrounded by heat exchanger elements, such as electrical heating wires and/or cooling coils, the heaters being controlled to rapidly heat the treatment chamber to a temperature in the order of 180.degree. C. during pauses of treatment for sterilizing the interior of the container, and/or maintaining temperature levels at a desired treatment level in operation. Additional gases to establish controlled atmospheres can be admitted to the interior of the treatment chamber, preferably after having passed through a heat exchanger for establishment of a desired temperature level.
Inventor(s):	Hesse; Peter (Bruchkobel, DE), Schinle; Friedbert (Hanau am Main, DE), Loscher; Helmut (Nidderau, DE)
Assignee:	W. C. Heraeus GmbH (Hanau am Main, DE)
Application Number:	06/160,230
Patent Claims:	1. Method of treating biological materials comprising positioning the materials in a container; providing a housing structure (11) defining a treatment chamber (10) and a bypass duct (1); introducing at least one container with the materials therein into the chamber; maintaining the temperature within the chamber at a predetermined temperature level; selectively introducing gas components into the chamber; humidifying the atmosphere within the chamber to provide a predetermined humidity level within the chamber, wherein the step of providing the predetermined humidity level comprises generating sterile water vapor; cooling the water vapor to a desired temperature; controllably introducing the cooled water vapor into the bypass duct (1); mixing the cooled water vapor with the gas component; and circulating the atmosphere within the treatment chamber and the bypass duct to provide for uniformity of atmosphere and gaseous and vapor mixtures within the chamber and the bypass duct, and mixing of the components of the atmosphere and the vapor by turbulence. 2. Method according to claim 1, wherein the step of generating the sterile vapor comprises heating water to above the boiling point and generating steam; superheating the steam; and cooling the steam. 3. Method according to claim 2, wherein the step of heating the water comprises heating the steam to sterilizing temperature and thereby drying the steam. 4. Method according to claim 1, further including the step of sterilizating the interior of the chamber and the bypass by heating the atmosphere therein prior to introduction of the materials therein to a sterilizing temperature. 5. Method according to claim 1, wherein wherein the steps of introducing the gas components into the chamber and introducing the water vapor into the chamber comprises mixing the gas components and the water vapor before admitting the mixture into the treatment chamber; and the step of removing the condensate arising upon cooling of the steam is carried out in said bypass duct. 6. Method according to claim 1, further including the step of controlling the temperature of the interior of the treatment chamber and said bypass duct by circulating a fluid of controlled temperature within a surrounding jacket. 7. Method according to claim 6, wherein the chamber is surrounded by a jacket having cooling coils retaining a cooling fluid therein; further including the step of draining the cooling fluid from the cooling coils prior to heating the interior of the chamber to a sterilizing temperature. 8. Method according to claim 6, wherein the step of controlling the temperature level of the atmosphere in the chamber comprises the step of reducing the temperature thereof to a level within the range of about 5.degree. C. and 50.degree. C. 9. Method according to claim 8, wherein the temperature reduction step comprises reducing the temperature of the steam to a level of between 20.degree. C. and 37.degree. C. 10. Apparatus for treatment of biological materials comprising a housing (11) defining a chamber (1, 10) therein and having a door (11c) selectively closing the chamber in gas-tight manner; subdividing means in said housing for dividing said chamber into a main treatment chamber (10) and a bypass (1), said bypass being in atmospheric communication with the main treatment chamber; humidity sensing means (4, 16, 17, 17a) positioned within the bypass; gas supply means (AIR, CO.sub.2, N.sub.2, O.sub.2) connected to the housing for supplying a predetermined gas under controlled conditions; temperature control means (13, 14) in thermal transfer relation with the inner walls of the housing surrounding the chamber for maintaining the chamber at a predetermined temperature; an evaporator (20) positioned outside of the housing and furnishing a supply of sterilized steam; means (7) for cooling and conducting said steam into the chamber; means (5) for cooling the steam to obtain sterilized water vapor positioned within said bypass (1) condensate collection means (5b) positioned within the bypass for conducting condensate to the outside of said housing; and means (6b) for supplying said sterlized water vapor to the space defining the chamber. 11. Apparatus according to claim 10, further including water supply means (19), and means (15) for controllably conducting water from said water supply means (19) to the evaporator (20), said controllable water conducting means being controlled by the humidity sensing means for selectively supplying water to the evaporator to maintain the humidity within the treatment chamber at a predetermined level. 12. Apparatus according to claim 11, further including gas circulating means for circulating the gas components forming the atmosphere within the chamber through the main treatment chamber and the bypass, said gas circulating means providing for uniformity of composition of the atmosphere within the main treatment chamber and for turbulence of the components thereof as they pass through the bypass to provide for intimate mixing of the components. 13. Apparatus according to claim 10, wherein the housing has a double wall, the outer wall thereof being heat-insulated and being gas and vapor-tight; the temperature control means includes heating means and cooling means forming a heat exchanger positioned within the double walls of the housing, said double walls forming, therebetween, open spaces permitting circulation of fluid therethrough; and forced circulating means (12) are provided located in the space between said double walls to circulate said fluid and provide for uniformity of heat transfer to the inner walls of the housing surrounding said chamber essentially throughout the extent thereof. 14. Apparatus according to claim 13, wherein the fluid within the space defined by the double walls is air. 15. Apparatus according to claim 10, further including heater elements located in heat transfer relationship with at least portions of the inner walls of the housing and heatable to prevent formation of condensation thereon. 16. Apparatus according to claim 15, wherein the heater elements are positioned, in part, in heat transfer relation with the door. 17. Apparatus according to claim 10, wherein the housing (11) comprises a double-wall structure having heat insulation at the outside thereof; and a preheater-cooler forming a heat exchange element (9) is positioned within the double walls forming the housing and of the treatment chamber in heat transfer relation with the gas supply means at a location immediately in advance of admission of the gases into the chamber (10) defining the housing to selectively preheat or precool the gases being supplied to the chamber and to provide for said controlled conditions. 18. Apparatus according to claim 10, including forced gas circulation means (6) positioned in the bypass for circulating the gas components forming the atmosphere within the chamber through the main treatment chamber and the bypass, generating turbulence, and intimately mixing the gas components and the sterilized water vapor. 19. Apparatus according to claim 18, wherein the means (5) for cooling treatment atmosphere are located in the bypass. 20. Apparatus according to claim 18, further including atmospheric condition sensing means (2, 3, 4) positioned within said bypass. 21. Apparatus according to claim 20, wherein the temperature control means (13, 14) includes heating means for heating both the treatment chamber and the bypass; said heating means being capable of heating the treatment chamber and the bypass to a temperature in the order of about 180.degree. C. to sterilize the entire chamber. 22. Apparatus according to claim 21, wherein the temperature control means includes cooling coils retaining a cooling fluid; and means (35) connected to and interlocked with the heating means to drain cooling fluid from the cooling coils when the heating means are energized to heat the interior of the chamber to a sterilizing temperature. 23. Apparatus according to claim 10, further including a sterility filter (8g) connected downstream in the gas supply means and in advance of the chamber to sterilize gases from the gas supply means. 24. Apparatus according to claim 10, wherein the evaporator (20) is capable of heating water supplied thereto to steam at a sterilizing temperature; and the cooling means is connected to receive the steam and provide water vapor at a lower temperature level into said chamber. 25. Apparatus according to claim 24, wherein said range is between about 20.degree. C. and 37.degree. C. 26. Apparatus according to claim 10, wherein said evaporator is a superheater for superheating water supplied thereto to dry steam at sterilizing temperature to provide sterilized steam to said cooling means (5) connected thereto and with the chamber. 27. Apparatus according to claim 10, wherein said door (11c) is a double door having an inner glass portion and an outer heatable opaque portion. 28. Apparatus according to claim 10, further including subdivision means (37) subdividing the main treatment chamber (10) into compartments, and support means 40 located within the respective compartments to support at least one of: dishes, containers, plates; for the biological materials therein. 29. Apparatus according to claim 10, further comprising semi-permeable containers for the biological materials within said main treatment chamber (10). 30. Apparatus according to claim 10, further comprising dish containers for the biological materials within said main treatment chamber (10). 31. Apparatus according to claim 10, further including driven movable holder means (38) positioned within said main treatment chamber (10) to hold and retain said biological materials. 32. Apparatus according to claim 10, further including electrical connection means (39) positioned within said main treatment chamber (10) to permit attachment of electrical connections to electrical apparatus (30, 31, 38) therein.

Details for Patent 4,336,329

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		1999-06-22