Claims for Patent: 4,610,790

Summary for Patent: 4,610,790

Title:	Process and system for producing sterile water and sterile aqueous solutions
Abstract:	Water substantially free of pyrogens and microorganisms that meets the requirements of United States Pharmacopoeia Standard USP XX Water for Injection is produced by processing drinking quality water through a filtration step adapted to remove organic contaminants and impurities that degrade downstream seperation membranes, a reverse osmosis step to remove dissolved solids, pyrogens, microorganisms and chemical contamination, a deionization step to further remove dissolved solids, and an ultrafiltration step to remove pyrogens. A sterile filter to remove microorganisms increases the water quality to USP XX Sterile Water for Injection. Means are provided to periodically remove accumulated chemical contaminants, pyrogens and microorganisms from the reverse osmosis apparatus, the deionization apparatus and the ultrafiltration apparatus. The sterile water can be admixed with a sterile concentrate composition to produce a sterile dilute solution that can be packaged under sterile conditions.
Inventor(s):	Reti; Adrian R. (Belmont, MA), Benn; James A. (Lexington, MA)
Assignee:	Sterimatics Company Limited Partnership (Bedford, MA)
Application Number:	06/578,950
Patent Claims:	1. A process for producing water substantially free of pyrogens to produce USP XX grade water for injection or irrigation solutions which comprises passing drinking quality water through a water purification system comprising: (a) a filtration step to remove organic impurities; (b) a reverse osmosis separation step to remove dissolved solids or ions, pyrogens and microorganisms from said water; (c) a deionization step to remove ions from said water and to increase the electrical resistance of said water; (d) an ultrafiltration step downstream of steps (a), (b) and (c) thereby to remove pyrogens from said water; and (e) periodically washing ion exchange means in the deionization step for removing ions from said water and a membrane utilized in the ultrafiltration step with water heated to a temperature to sterilize microorganisms in said deionization and ultrafiltration steps and to remove impurities accumulated in said deionization step and said ultrafiltration step while avoiding washing steps (a) and (b) with said heated water. 2. A process for producing water substantially free of pyrogens and microorganisms to produce sterile USP XX grade sterile water for injection which comprises passing drinking quality water through a water purification system comprising: (a) a filtration step to remove organic impurities; (b) a reverse osmosis separation step to remove dissolved solids or ions, pyrogens and microorganisms from said water; (c) a deionization step to remove ions from said water and to increase the resistance of said water; (d) an ultrafiltration step subsequent to steps (a), (b) and (c) thereby to remove pyrogens from said water; (e) a membrane filter step capable of retaining microorganisms; and (f) periodically washing ion exchange means in the deionization step for removing ions from said water and a membrane utilized in the ultrafiltration step with water heated to a temperature to sterilize microorganisms in said deionization and ultrafiltration steps and to remove impurities accumulated in said deionization step and said ultrafiltration step while avoiding washing steps (a) and (b) with said heated water. 3. The process of claim 1 wherein the drinking quality water is passed sequentially through steps (a), (b), (c) and (d). 4. The process of claim 2 wherein the drinking quality water is passed sequentially through steps (a), (b), (c), (d), and (e). 5. The process of any one of claims 1, 2, 3 or 4 wherein membranes in the reverse osmosis step, the deionization step and the ultrafiltration step are cleaned periodically by being flushed with water in said system. 6. A process for preparing a sterile package containing a sterile dilute aqueous solution formed from sterile USP XX grade water for injection water and irrigation and adapted to be administered to a patient which comprises passing drinking grade water through a water purification system comprising: (a) a filtration step to remove organic impurities; (b) a reverse osmosis separation step to remove dissolved solids or ions, pyrogens and microorganisms from said water; (c) a deionization step to remove ions from said water and to increase the resistance of said water; (d) an ultrafiltration step subsequent to steps (a), (b) and (c) thereby to remove pyrogens from said water and produce USP XX grade water for injection or irrigation; (e) mixing said sterile water with a sterilized liquid concentrate composition thereby to produce said sterile dilute solution; (f) passing said dilute solution through a filter adapted to retain microorganisms into a sterile container; and (g) periodically washing ion exchange means in the deionization step for removing ions from said water and a membrane utilized in the ultrafiltration step with water heated to a temperature to sterilize microorganisms in said deionization and ultrafiltration steps and to remove impurities accumulated in the deionization and ultrafiltration steps while avoiding steps (a) and (b) with said heated water. 7. The process of claim 6 wherein the drinking water is passed sequentially through steps (a), (b), (c), (d), (e) and (f). 8. The process of any one of claims 6 or 7 wherein said dilute solution is passed through filtration means adapted to retain microorganisms and then into a plurality of sterile containers. 9. The process of any one of claims 6 or 7 wherein said sterile containers are transparent flexible containers. 10. The process of any one of claims 6 or 7 wherein said filled packages are sealed from the atmosphere after being filled. 11. The process of any one of claims 6 or 7 wherein said sterile containers are transparent flexible containers and the filled packages are sealed from the atmosphere after being filled. 12. A system for producing USP XX grade sterile water for injection from drinking water which comprises (a) a filtration means adapted to remove organic impurities from water; (b) a reverse osmosis separation means adapted to remove dissolved solids, microorganisms and pyrogens from water; (c) deionization means adapted to remove dissolved solids from water; (d) ultrafiltration means downstream of steps (a), (b) and (c) adapted to remove pyrogens and microorganisms from water; (e) means for passing the drinking grade water through said first filtration means, said reverse osmosis separation means, said deionization means and said ultrafiltration means; (f) means for passing heated water periodically through said deionization means and said ultrafiltration means thereby to remove accumulated pyrogens and microorganisms from said system while avoiding washing means (a) and (b) with said heated water; and (g) means for passing pressurized water across membranes in said reverse osmosis means to remove accumulated microorganisms from said system. 13. The system of claim 12 wherein said drinking water is passed sequentially through means (a), (b), (c) and (d). 14. A system for preparing a package containing a sterile dilute aqueous solution adapted to be administered to a patient said solution being formed from USP XX grade water for injection or irrigation which comprises (a) a filtration means adapted to remove organic impurities from water; (b) a reverse osmosis separation means adapted to remove dissolved solids, microorganisms and pyrogens from water; (c) deionization means adapted to remove dissolved solids from water; (d) ultrafiltration means downstream of steps (a), (b) and (c) adapted to remove pyrogens and microorganisms from water; (e) means for passing the drinking grade water through said first filtration means, said reverse osmosis separation means, said deionization means and said ultrafiltration means; (f) means for passing heated water periodically through said deionization means and said ultrafiltration means thereby to remove accumulated pyrogens and microorganisms from said system while avoiding washing means (a) and (b) with said heated water; and (g) means for passing pressurized water across membranes in said reverse osmosis means to remove accumulated microorganisms from said system. 15. The system of claim 14 wherein said drinking grade water is passed sequentially through means (a), (b), (c) and (d). 16. The system of any one of claims 14 or 15 wherein said dilute solution is passed into a plurality of sterile packages under sterile conditions. 17. The system of any one of claims 14 or 15 wherein said sterile packages are transparent flexible containers. 18. The system of any one of claims 14 or 15 including means for sealing said packages containing said dilute solutions from the atmosphere under sterile conditions. 19. The system of any one of claims 14 or 15 wherein said sterile packages are transparent flexible packages and means are included for sealing said packages containing said dilute solution from the atmosphere under sterile conditions. 20. A process for producing water substantially free of pyrogens to produce USP XX grade water for injection or irrigation solutions which comprises passing drinking quality water through a water purification system comprising: (a) a filtration step to remove organic impurities; (b) a reverse osmosis separation step to remove dissolved solids or ions, pyrogens and microorganisms from said water; (c) a deionization step to remove ions from said water and to increase the electrical resistance of said water; (d) an ultrafiltration step downstream of steps (a), (b) and (c) thereby to remove pyrogens from said water; and (e) periodically washing a membrane utilized in the ultrafiltration step with water heated to a temperature to sterilize microorganisms in said systems and to remove impurities accumulated on said membrane while avoiding washing steps (a) and (b) with said heated water. 21. A process for producing water substantially free of pyrogens and microorganisms to produce sterile USP XX grade sterile water for injection which comprises passing drinking quality water through a water purification system comprising: (a) a filtration step to remove organic impurities; (b) a reverse osmosis separation step to remove dissolved solids or ions, pyrogens and microorganisms from said water; (c) a deionization step to remove ions from said water and to increase the resistance of said water; (d) an ultrafiltration step subsequent to steps (a), (b) and (c) thereby to remove pyrogens from said water; (e) a membrane filter step capable of retaining microorganisms; and (f) periodically washing a membrane utilized in the ultrafiltration step with water heated to a temperature to sterilize microorganisms in said systems and to remove impurities accumulated on said membrane while avoiding washing steps (a) and (b) with said heated water. 22. The process of claim 20 wherein the drinking quality water is passed sequentially through steps (a), (b), (c) and (d). 23. The process of claim 21 wherein the drinking quality water is passed sequentially through steps (a), (b), (c), (d), and (e). 24. The process of any one of claims 20, 21, 22 or 23 wherein membranes in the reverse osmosis step, the deionization step and the ultrafiltration step are cleaned periodically by being flushed with water in said system. 25. A process for preparing a sterile package containing a sterile dilute aqueous solution formed from sterile USP XX grade water for injection water and irrigation and adapted to be administered to a patient which comprises passing drinking grade water through a water purification system comprising: (a) a filtration step to remove organic impurities; (b) a reverse osmosis separation step to remove dissolved solids or ions, pyrogens and microorganisms from said water; (c) a deionization step to remove ions from said water and to increase the resistance of said water; (d) an ultrafiltration step subsequent to steps (a), (b) and (c) thereby to remove pyrogens from said water and produce USP XX grade water for injection or irrigation; (e) mixing said sterile water with a sterilized liquid concentrate composition thereby to produce said sterile dilute solution; (f) passing said dilute solution through a filter adapted to retain microorganisms into a sterile container; and (g) periodically washing ion exchange means in the ultrafiltration step with water heated to a temperature to sterilize microorganisms in said system and to remove impurities accumulated on said membrane while avoiding steps (a) and (b) with said heated water. 26. The process of claim 25 wherein the drinking water is passed sequentially through steps (a), (b), (c), (d), (e) and (f). 27. The process of any one of claims 25 or 26 wherein said dilute solution is passed through filtration means adapted to retain microorganisms and then into a plurality of sterile containers. 28. The process of any one of claims 25 or 26 wherein said sterile containers are transparent flexible containers. 29. The process of any one of claims 25 or 26 wherein said filled packages are sealed from the atmosphere after being filled. 30. The process of any one of claims 25 or 26 wherein said sterile containers are transparent flexible containers and the filled packages are sealed from the atmosphere after being filled.

Details for Patent 4,610,790

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