Claims for Patent: 8,852,437

Summary for Patent: 8,852,437

Title:	Method and production plant for producing sterile water
Abstract:	A method of producing sterile water from raw water during a production cycle in a production plant P, including adding a disinfectant to the produced sterile water during the production cycle to permanently monitor the condition of the sterile water and/or the production plant, and determining and evaluating a reduction of concentration of the disinfectant directly in the production stream. In a production plant suited for carrying out the method, a sterile sensor is provided directly in the production stream through which the reduction of concentration of the disinfectant added to the produced sterile water can be permanently measured and evaluated to provide a sterility evidence.
Inventor(s):	Zacharias; Jorg (Koefering, DE)
Assignee:	Krones AG (Neutraubling, DE)
Application Number:	13/249,556
Patent Claims:	1. Method of producing a product stream of sterile water from raw water during a production cycle by ultrafiltration in at least one membrane unit in a production plant, the method comprising: continuously adding a disinfectant to the product stream of the sterile water downstream of the at least one membrane unit during the production cycle to determine whether the production plant is working properly during the production cycle, the continuously adding comprising adding, at a region of a beginning of a residence time section provided in the product stream, a known concentration of the disinfectant to the product stream; measuring a reduction of concentration of the disinfectant in the product stream between a first position downstream of the residence time section and one or more second positions downstream of the membrane unit and upstream of the residence time section and/or in a beginning portion of the residence time section; evaluating the known concentration of the disinfectant and the measured concentration of the disinfectant to permanently detect a concentration difference measurement indicative of the concentration reduction of the added disinfectant; and determining, based on the concentration difference measurement, whether the production plant is working properly during the production cycle, wherein the determining comprises determining that the production plant is working properly during the production cycle when the detected concentration difference measurement is less than or equal to a predetermined concentration difference measurement representative of a predetermined sterility of the product stream, and wherein the determining comprises determining that the production plant is not working properly during the production cycle when the detected concentration difference measurement exceeds the predetermined concentration difference measurement. 2. The method according to claim 1, wherein continuously adding the disinfectant comprises adding ozone, chlorine dioxide, hydrogen peroxide, singlet oxygen, or a combination thereof. 3. The method according to claim 1, wherein the measuring and the evaluating are carried out, during the production cycle, with a sterile sensor that is arranged downstream of the at least one membrane unit of the product plant in the product stream. 4. The method according to claim 1, further comprising: continuing the production cycle when it is determined that the production plant is working properly during the production cycle and when it is determined that the production plant is not working properly during the production cycle; increasing the known concentration of the disinfectant added to the product stream when the detected concentration difference measurement exceeds the predetermined concentration difference measurement, the increasing performed until the detected concentration measurement difference is less than or equal to the predetermined concentration difference measurement; and cancelling the production cycle when the known concentration of the disinfectant added to the product stream cannot be increased such that the detected concentration measurement difference is less than or equal to the predetermined concentration difference measurement. 5. The method according to claim 4, wherein the increasing comprises increasing the known concentration of the disinfectant in stages. 6. The method according to claim 1, wherein the evaluating comprises evaluating a half-life reduction of the disinfectant in the product stream. 7. The method according to claim 1, further comprising removing disinfectant residues before the product stream is released for use, the removing performed until a level of the disinfectant residues falls below a limiting value. 8. The method according to claim 1, wherein the adding comprises adding ozone one of inline, in a bypass flow, and in a circular flow. 9. The method according to claim 1, further comprising cancelling the production cycle when it is determined that the production plant is not working properly during the production cycle. 10. Production plant for producing a product stream of sterile water, the production plant comprising: at least one ultrafiltration membrane unit; a residence time section for the product stream, the residence time section being downstream of the at least one ultrafiltration membrane unit; a disinfectant adding device for continuously adding a known concentration of at least one disinfectant to the product stream in a region of a beginning of the residence time section; a sterile sensor for permanently measuring a concentration of the disinfectant in the product stream at a position downstream of the residence time section, the sterile sensor configured to evaluate the known concentration of the at least one disinfectant added to the product stream and the measured concentration of the disinfectant to permanently detect a concentration difference measurement indicative of a concentration reduction of the added disinfectant, and the sterile sensor further configured to determine, based on the concentration difference measurement, whether the production plant is working properly during the production cycle, wherein the production plant is working properly during the production cycle when the detected concentration difference measurement is less than or equal to a predetermined concentration difference measurement representative of a predetermined sterility of the product stream, and wherein the production plant is not working properly during the production cycle when the detected concentration difference measurement exceeds the predetermined concentration difference measurement, the sterile sensor comprising a first component downstream of the residence time section and one or more second components downstream of the at least one ultrafiltration membrane unit and upstream of the residence time section and/or in a beginning portion of the residence time section. 11. The production plant according to claim 10, wherein the sterile sensor comprises a disinfectant final concentration sensor downstream of the residence time section, and wherein the disinfectant adding device comprises a disinfectant dosing device configured to produce the known concentration of the at least one disinfectant or the sterile sensor comprises a disinfectant initial concentration sensor in the region of the beginning of the residence time section configured to measure an initial concentration of the at least one disinfectant added to the product stream, the known concentration being the initial concentration. 12. The production plant according to claim 11, further comprising a volume flow rate measuring device placed upstream of the disinfectant final concentration sensor. 13. The production plant according to claim 11, wherein the disinfectant final concentration sensor and the disinfectant initial concentration sensor are each operable (i) utilizing a measuring principle of an electrochemical reaction through a membrane with an electrolyte and a pair of electrodes at one side of the membrane, or (ii) as an inline UV process photometer. 14. The production plant according to claim 11, wherein the adding device comprises an ozone generator. 15. The production plant according to claim 11, wherein the residence time section comprises a pipe section with a defined pipe cross-section that is larger than cross-sections of other product stream pipelines of the production plant. 16. The production plant according to claim 15, wherein the pipe section of the residence time section is larger than a cross-section of a pipe section of at least each of the disinfectant final concentration sensor and the disinfectant initial concentration sensor. 17. The production plant according to claim 10, further comprising a sensor for detecting an original condition of the sterile water in the product stream, the sensor disposed upstream of the residence time section and upstream of the disinfectant adding device. 18. The production plant according to claim 10, wherein the sterile sensor is disposed directly in the product stream.

Details for Patent 8,852,437

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		2030-09-30