Bacteriostatic filter system for antibody drugs production process, and method of operating same
The present invention relates to a bacteriostatic filter system for an antibody drug production process, and to a method of operating same, in which devices are configured and the system is designed so as to enable, through a control unit, the in-lining of a bacteriostatic filter cartridge and in-situ integrity testing of a bacteriostatic filter, wherein according to a result value of the integrity testing, media or buffer are transferred to a storage tank from a preparation tank, or the media or buffer transferred to the storage tank are transferred back to the preparation tank. Accordingly, the present invention can reduce the time required for filter cartridge replacement and integrity testing and implement a system having automated the transferring and backfeeding of media and buffers as well as processing liquids, and can thus reduce the amount of labor needed and shorten the processing time.
1 . A sterilization filter system for a process of manufacturing an antibody pharmaceutical, comprising:
a preparation tank for preparing one selected from a medium and a buffer;
a storage tank for storing the medium or buffer received from the preparation tank;
a transfer pipeline configured to flow the medium or buffer stream discharged from the preparation tank into the storage tank;
a process liquid storage tank for storing a process liquid in the intermediate stage of purification and culture processes;
a process liquid transfer pipeline configured to flow the process liquid into the process liquid storage tank;
a sterilization filter cartridge disposed on one or more selected from the transfer pipeline and the process liquid transfer pipeline; and
a control unit,
wherein the sterilization filter cartridge comprises, for a washing and filter test process including one or more selected from filter sterilization, filter wetting, flushing, filter integrity test, air ballasting and barrier integrity testing, a first pipeline entering the sterilization filter cartridge, and a second pipeline exiting the sterilization filter cartridge,
wherein the first pipeline and the second pipeline are separate from the transfer pipeline and the process liquid transfer pipeline,
wherein the first pipeline and the second pipeline are configured to supply and discharge a test fluid for performing the washing and filter test process, and
wherein the washing and filter test process is performed while the sterilization filter cartridge remains disposed on the transfer pipeline or the process liquid transfer pipeline.
2 . The system of claim 1 , wherein an integrity tester is provided on the first pipeline entering the sterilization filter cartridge.
3 . The system of claim 1 , wherein the control unit automatically transfers a medium or buffer from the preparation tank to the storage tank or reversely transfers the medium or buffer transferred to the storage tank to the preparation tank, depending on a filter integrity test result value.
4 . The system of claim 1 , wherein the control unit automatically transfers the process liquid to the process liquid storage tank or reversely transfers the process liquid transferred to the process liquid storage tank along the process liquid transfer pipeline, depending on a filter integrity test result value.
5 . The system of claim 1 , wherein the sterilization filter system is applied to transfer one or more of a medium, a buffer and a process liquid in the process of manufacturing one or more antibody pharmaceuticals selected from the group consisting of abagovomab, abciximab, adalimumab, adecatumumab, alemtuzumab, altumomab, altumomab pentetate, anatumomab, anatumomab mafenatox, arcitumomab, atlizumab, basiliximab, bectumomab, bectumomab, belimumab, benralizumab, bevacizumab, brentuximab, canakinumab, capromab, capromab pendetide, catumaxomab, certolizumab, clivatuzumab tetraxetan, daclizumab, denosumab, eculizumab, edrecolomab, efalizumab, etaracizumab, ertumaxomab, fanolesomab, fontolizumab, gemtuzumab, girentuximab, golimumab, ibritumomab, igovomab, infliximab, ipilimumab, labetuzumab, mepolizumab, muromonab, muromonab-CD3, natalizumab, necitumumab, nimotuzumab, ofatumumab, omalizumab, oregovomab, palivizumab, panitumumab, ranibizumab, rituximab, satumomab, sulesomab, ibritumomab, ibritumomab tiuxetan, tocilizumab, tositumomab, trastuzumab, ustekinumab, visilizumab, votumumab, zalutumumab, brodalumab, anrukinzumab, bapineuzumab, dalotuzumab, demcizumab, ganitumab, inotuzumab, mavrilimumab, moxetumomab pasudotox, rilotumumab, sifalimumab, tanezumab, tralokinumab, tremelimumab, urelumab, adornase alfa, Rebif, becaplermin, alteplase, laronidase, alefacept, aflibercept, raxibacumab, darbepoetin alfa, becaplermin concentrate, interferon beta-1b, botulinum toxin type A, rasburicase, asparaginase, epoetin alfa, etanercept, agalsidase beta, interferon alfacon-1, interferon alfa-2a, anakinra, botulinum toxin type B, pegfilgrastim, oprelvekin, filgrastim, denileukin diftitox, peginterferon alfa-2a, aldesleukin, dornase alfa, interferon beta-1a, becaplermin, reteplase, interferon alfa-2, tenecteplase, drotrecogin alfa, rilonacept, romiplostim, methoxypolyethylene glycol-epoetin beta, a C1 esterase inhibitor, idursulfase, alglucosidase alfa, abatacept, galsulfase, palifermin and interferon gamma-1b.
6 . A method of operating the sterilization filter system of claim 1 , comprising:
sequentially performing filter sterilization, filter wetting, flushing, a first filter integrity test, air ballasting and a barrier integrity test, transferring one or more selected from a medium, a buffer and a process liquid using an automatic valve, and
following the completion of the transfer of one or more selected from a medium, a buffer and a process liquid, sequentially performing filter wetting, flushing, a second filter integrity test, using an automatic valve, along the first pipeline, filter cartridge and second pipeline.
7 . The method of claim 6 , wherein the filter integrity test comprises one or more tests selected from a forward flow integrity test (FFIT), a bubble point test (BPT), and a pressure hold test (PHT).
8 . The method of claim 6 , wherein the control unit automatically transfers a medium or a buffer from the preparation tank to the storage tank when the first filter integrity test result value satisfies a preset reference value, and sends a sterilization filter replacement alarm when the first filter integrity test result value does not satisfy the preset reference value.
9 . The method of claim 6 , wherein the control unit continues the washing and filter test process when the second filter integrity test result value satisfies a preset reference value, and reversely transfers the medium or buffer transferred to the storage tank to the preparation tank when the second filter integrity test result value does not satisfy the preset reference value.
10 . The method of claim 6 , wherein the control unit automatically transfers a process liquid to the process liquid storage tank along the process liquid transfer pipeline when the first filter integrity test result value satisfies a preset reference value, and sends a sterilization filter replacement alarm when the first filter integrity test result value does not satisfy the preset reference value.
11 . The method of claim 6 , wherein the control unit continues the washing and filter test process when the second filter integrity test result value satisfies a preset reference value, and reversely transfers the process liquid transferred to the process liquid storage tank along the process liquid transfer pipeline when the second filter integrity test result value does not satisfy the preset reference value.
12 . The system of claim 1 ,
wherein the test fluid flows through the sterilization filter cartridge from the first pipeline to the second pipeline independently of a flow of the medium, buffer, or process liquid through the transfer pipeline or the process liquid transfer pipeline.
13 . The system of claim 1 ,
wherein the test fluid is not delivered to the storage tank or the process liquid storage tank.