Automated integrated continuous system and bioprocess for producing therapeutic protein

An automated integrated continuous bioprocess system (100) for producing therapeutic protein comprising:

• a bioreactor (103) to culture mammalian cells capable of producing the therapeutic protein in culture medium, the bioreactor (103) comprises alternating tangential flow (ATF) filter (109) to collect a harvest comprising the therapeutic protein secreted into the culture medium;
• a first chromatography system (119) comprising one or more affinity chromatography column(s) connected to the ATF filter (109) without any intermediate hold vessel to purify the harvest comprising the therapeutic protein and provide protein A eluate;
• a viral inactivation system (126) including a viral inactivation vessel (128) with a pH probe connected to a transmitter for measuring the pH of the protein A elute connected to the first chromatography system (119) to collect the protein A eluate and inactivate viruses that may be present in the protein A eluate, and the viral inactivation vessel (128) configured to automatically adjust pH of the protein A eluate to obtain a virus inactivated, neutralized, and filtered protein A eluate;
• a collection vessel (136) connected with the viral inactivation vessel (128) through one or more filters to receive the virus inactivated, neutralized, and filtered protein A eluate, wherein said one or more filter(s) (224) and (226) are configured to remove impurities as precipitates from the virus inactivated, neutralized, and filtered protein A eluate received from the viral inactivation vessel;
• a second chromatography system (137) comprising one or more multimodal anion exchange column(s) and one or more cation exchange column(s) connected with the collection vessel (136) to receive the virus inactivated, neutralized, and filtered protein A eluate from the collection vessel (136) and to provide purified protein;
• one or more of solenoid or pneumatic pinch valves (114), sensors, air bubble sensors, pressure sensors and load cell sensors for creating a feedback loop in order to maintain fluid flow using tubes between various components of the system, avoid formation of air bubbles and regulate flow of liquid;
• cleaning in place (CIP) system (120) comprising a plurality of reservoirs of cleaning solutions and a plurality of valves for periodic cleaning of the first chromatography system and/or second chromatography system, viral inactivation vessel, collection vessel, and tubes;
• one or more control systems selected from supervisory control and data acquisition (SCADA) control system (110), proportional integral derivative (PID);
• programmable logic circuit (PLC), Industrial PC (IPC), distributed control system (DCS);
• Input-Output Modules or IO Boxes (130) and (132) operably connected with the first chromatography system (119);
• the viral inactivating system (126);
• the collection vessel (136);
• and the second chromatography system (137).