Claims for Patent: 3,951,184

Summary for Patent: 3,951,184

Title:	Method of filling, sampling and sealing an aseptic tank with sterile product without destroying asepsis of either the sterile product or the tank and its associated valves and fittings
Abstract:	The method of this invention includes aseptically sealing an empty sterilized tank while maintaining asepsis of the tank, and thereafter connecting a product line to an opening in the tank, sterilizing the product line while so connected, and filling the tank with sterile product from the product line, all without destroying the aseptic condition of the tank. In addition, the method includes sampling the product in the product line during the tank filling operation while maintaining asepsis of both the product line and the tank. Finally, the method includes sealing the tank when full of sterile product, removing samples of sterile product from the tank subsequent to its filling and resealing the tank after each such sampling operation. Asepsis is maintained during each of the tank sealing, tank sampling and tank re-sampling operations.
Inventor(s):	Rechtsteiner; Steve A. (Cincinnati, OH), Nelson; Philip E. (West Lafayette, IN), Heron; John R. (West Lafayette, IN)
Assignee:	Purdue Research Foundation (West Lafayette, IN)
Application Number:	05/496,654
Patent Claims:	1. A method of aseptically sealing, sampling and filling an aseptic storage tank with sterile product comprising the steps of: closing the first valve to seal the tank interior from the cavity of the first valve to which the tank opening is connected, filling with liquid chemical sterilant valve-closure cavities of first and second aseptic valves which are connected in series with an opening in an aseptic tank to sterilize and establish first and second aseptic barriers between the tank opening and the environment, the second valve having at least one additional port not directly connected to said first valve, closing the second valve to seal the second valve cavity from the first valve cavity, to establish an aseptic chemical block between the environment and said tank, sealing said at least one additional port of said second valve to seal said second valve cavity from the environment, disconnecting the second valve from the first valve and allowing the first cavity to drain of chemical sterilant, connecting a third aseptic valve having a valve-closure cavity to said first valve and a fourth aseptic valve having a valve-closure cavity to said third valve, filling the first, third and fourth valve-closure cavities of said first, third and fourth valves with liquid chemical sterilant to sterilize said valve cavities, closing said third valve to seal the first valve cavity to establish a sealed chemical sterilant barrier between said tank opening and the environment, connecting a fifth aseptic valve to said fourth valve via a sample port in said fifth valve which is normally sealed by said fourth valve, said fifth valve having a valve closure element establishing alternate liquid flow paths including (a) a first path between the environment and said sample port connecting to the fourth valve cavity, and (b) a second path between a sample container and the sample port connecting to said fourth valve cavity, introducing liquid chemical sterilant into the first flow path of said fifth valve to sterilize the sample port connecting to said fourth valve cavity, feeding sterile product into said third cavity, opening said third valve to permit said tank to fill with product via said first valve and tank opening, operating the valve closure of said fifth valve to establish said second flow path, and opening said fourth valve, which normally seals said fourth valve cavity from said fifth valve flow paths, to permit product to flow into said sample container via said second flow path, whereby a product sample is obtained while the previously sealed and empty aseptic tank is being filled. 2. The method of claim 1 further including the step of purging said third and fourth cavities of sterilant, prior to feeding sterile product into said third valve cavity, by introducing sterile water into said third and fourth valve cavities. 3. The method of claim 2 further including the step of purging said sample port of said fifth valve of sterilant, prior to opening said fourth valve to permit product flow into said sample container via said second flow path, by opening said fourth valve to permit product flow from said fourth valve cavity to the environment via said first flow path. 4. The method of claim 1 further including the steps of: closing said fourth valve to terminate product flow to said sample container, operating said fifth valve to establish said first flow path to seal said sample container, disconnecting said fifth valve from said fourth valve while said fifth valve and sample container are still connected and substituting therefor a replacement fifth valve and sample container, with said replacement fifth valve connected to said fourth valve, introducing chemical sterilant into the first flow path of said replacement fifth valve to sterilize the sample port connecting to said fourth valve cavity, opening said fourth valve to permit product flow from said fourth valve cavity to the environment via said first flow path, closing said fourth valve to terminate product flow to said environment via said first flow path, operating the valve closure of said fifth valve to establish said second flow path, and opening said fourth valve to permit product to flow into said sample container via said second flow path, whereby a second product sample is obtained while the tank is being filled. 5. The method of claim 1 further comprising the steps of: disconnecting said third valve from said first valve, reconnecting said second valve in series with said tank opening and said first valve, filling with liquid chemical sterilant the valve-closure cavities of said first and second valves while said first valve is closed and said second valve is open to sterilize and establish first and second aseptic barriers between the tank opening and the environment, closing the second valve to seal the second valve cavity from the first valve cavity to establish an aseptic chemical block between said tank and environment, and sealing the remaining prots of said second valve to seal said second valve cavity from the environment, whereby the tank is resealed following filling with sterile product and dual aseptic chemical blocks are established in series between said tank and the environment. 6. The method of claim 5 further comprising the steps of: unsealing a first port of said second valve, connecting a replacement fifth aseptic valve to said unsealed port of said second valve via the sample port in said fifth valve, said replacement fifth valve having a valve closure element establishing alternate fluid flow paths including (a) a first flow path between the environment and said sample port connecting to the second valve cavity, and (b) a second flow path between a sample container and the sample port connecting to said second valve cavity, introducing liquid chemical sterilant into the first fluid flow path of said replacement fifth valve to sterilize the second valve cavity and the sample port connecting to said second valve cavity, and opening said first and second valves and operating said replacement fifth valve to establish said second flow path, to permit product stored in said tank to enter said sample container via said first and second valve cavities and said second flow path, whereby a product sample is extracted from the previously filled and sealed tank. 7. The method of claim 6 further including the step of purging said first and second valve cavities and said replacement fifth valve ports of sterilant, prior to operating said replacement fifth valve to establish said second flow path, by opening said first and second valves to permit product flow from said tank into said first and second valve cavities and said first flow path. 8. The method of claim 6 further comprising the steps of: closing said first valve to terminate flow of product into said sample container, operating said replacement valve to establish said first flow path, after filling said container with sample product from said tank, to seal said sample container, filling said first and second valve cavities with liquid chemical sterilant to sterilize and establish first and second aseptic barriers between the tank opening and the environment, and closing the second valve to seal the second valve cavity from the first valve cavity, and sealing the first port to seal the second valve cavity from the environment, whereby the tank is re-sealed and the dual aseptic barriers are re-established after a product sample is removed from the previously filled and sealed tank.

Details for Patent 3,951,184

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		2039-09-23