This system is fully closed and includes the following key elements:
- Two identical manufacturing lines comprising bioreactors with the volumes of 20, 100, 500 and 3000 liters;
- A system of connecting heat-insulated pipelines, the group of membrane valve that connect the referred bioreactors;
- Stationary CIP/SIP systems for automated cleaning and sterilization of the bioreactors and connecting pipelines;
- Nutrient medium preparation and transfer area;
- Mobile containers with junction points to the CIP/SIP systems.
All bioreactors and other technological equipment are connected with the help of heat-insulated pipelines and the group of aseptic membrane valves.
The group of pneumatically controlled valves is used to ensure the integration of each bioreactor in the technological line.
In each valve is installed position sensor, and in each group of valves is installed vibration sensor for detection of the media presence. Such design of membrane valve group ensures sterile transport of substrate, product and CIP solutions.
The automated control system can be divided into 3 parts:
- Bioreactor and CIP/SIP system local automation unit;
- Central cascade control system;
- Computerized control system SCADA.
Each bioreactor is equipped with a process stand for ensuring the automated fermentation, cleaning, sterilization, heating and cooling processes. Each bioreactor container and process stand is equipped with pneumatic elements, mixer, circulation pump and peristaltic pumps. The bioreactors have in-built рН, рО2, temperature, maximum liquid level, foam level and pressure sensors. All sensors and control elements are connected to a corresponding bioreactor control local system, where the local control is performed from a color touch screen display (with a 7” or 9.6”). In the given example, the bioreactor control systems have Siemens Simatic controllers.
Thus the local control of each particular bioreactor was ensured independently from the rest bioreactors. The central cascade control system (CCCS) ensured interconnection between different bioreactors and the CIP/SIP system, as well as with the computerized SCADA system. For this purpose a more powerful Siemens Simatic controller was used in the system. Actually, the CCCS controls certain groups of valves depending on the selected recipe and the condition of the respective sensors in the bioreactors, as well as in the CIP/SIP system and pipelines (medium presence sensors are held in the vent groups).
The central cascade control system directly controls the following processes in the selected bioreactors or pipelines: CIP cleaning, SIP sterilization, nutrition media feed, biomass transfer from one bioreactor to another, and bioreactor emptying.
The best compliance to the GMP requirements for biopharmaceutical production is ensured by visualization and control software package (SCADA), developed in compliance with the requirements pf 21CFR Part11 (US FDA). In addition to basic control and visualization functions, in this case the SCADA software ensures complying with the requirements for electronic records, authorized system access sign-in and operator activity registration log. The JSC “Biotehniskais centrs” has developed its own russified software SCADA that allows creating an efficient biosynthesis process control system. The software is designed on the basis of the industrial software package in compliance with 21CFR Part 11.
The software (SW) SCADA performs the following key functions:
- Process selection;
- Recipe composition and storage selection;
- Process and device condition control visualization;
- Graphical process and parameter display;
- Control system data archiving;
- Operator activity log;
- Alarm signal log;
- Ensured several access levels to SCADA SW;
- Remote access to the system via Internet.
Such an automated process structure in the biopharmaceutical production is simple and easy for work. Combining the local control in separate bioreactors with the central cascade control system of the entire process line enables fast access to separate devices, without losing control over interrelated processes in the whole system. As a result, the operator mistake risk is minimized and automated management of the process is ensured together with documentation in compliance with the up-to-date GMP requirements.