We have experience in application of complex bioreactor lines for biotechnological production. We develop technical requirements, project and qualification documents, manufacture equipment and provide the delivery/ montage/ starting up.

We have experience in application of bioreactor for the manufacturing of following products:

The technical solutions are customized depending on requirements of a concrete production process.

1. Production of substances for remediation of soil from oil pollution

The application of this fermentation system is remediation of soil, contaminated with oil over a long period. In this system bacteria consortium have been cultivated, which has been isolated from oil-contaminated soil.

Fermentation system consists of 30, 100 and 800 liter bioreactors. Another 800 liter reactor is used for storage of a substrate. In every bioreactor is temperature, pH, pO2, foam and level control, as well as time profiles of automatic substrate feeding rate can be adjusted. The sterilization possibility of all fermentation system including pipelines is ensured.

2. Production of ferments for dairy industry

This system is used for the production of ferments for dairy industry, using the following microorganisms: Lactococcuslactis, Streptococcus thermophilus and Candida strains.

The line consists of seeding-fermenter with working volume of 10 and 100 liters and one production fermenter with working volume of 1000 liters; 100, 150 and 1000 l vessels intended for medium preparation, as well as aseptic technological solution and product storage. All fermenters are connected in a technological line via pipelines to ensure cleaning and sterilization with CIP/SIP equipment. Technological line cleaning is performed with two mobile CIP devices. Data collection, processing and documentation is performed with a help of SCADA software, which can be installed on a user’s computer.

3. Production of vaccines for animals

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.

4. Biotechnological processing of whey to gain products with high added value;

Nowadays the processing technology of whey is being mastered for obtainment of high added value products, e.g. whey protein. During the processing of whey, as a side product accrues whey lactose. The utilization of this product, without polluting the environment, is problematic. Therefore this unresolved issue allows developing technology of whey processing with sufficient profitableness.

Latvian company BALTIC DAIRY BOARD in year 2015 launched factory of whey processing and department of lactose processing. The company along with biotechnologists of Latvia, developed bioprocess for various whey, as well as whey lactose processing, where used yeast strains could efficiently uptake lactose as a substrate. As a result, yeasts for food industry were obtained. The given technology is successfully introduced in practice, and as the experts of the field admits, it is unique and gives an opportunity to obtain high added value product.

For the run of production fermentation process, technological line is used. It consists of bioreactors with volume of 35, 350, 4000 liters and two bioreactors with volume of 15 000 l. In all bioreactors, a novel type magnetic mixer (even in 15 000 liter bioreactor!) was used. Above mentioned system is fully closed and automated, the connections between bioreactors are provided by pipeline system and 4 membrane valve group. The system with membrane valve group provides sterile nutrition media and product transport, as well as pipeline and reactor cleaning and sterilizing.

Each individual bioreactor is equipped with a technological stand, to ensure automatic fermentation, cleaning, sterilizing, heating and cooling process. Local control of each bioreactor occurs via color touch screen display (9.6”). In this bioreactor control system Siemens Simatic S7-300 (ET200) controllers are used. Thereby the local control of each individual bioreactor is provided, apart from rest of the bioreactors.

Central cascade control system (CCCS) ensures connection between different bioreactors and CIP/SIP systems, as well as with computerized software SCADA. For this purpose more powerful Siemens Simatic S7-300 (S7-317) was used. 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 system CIP/SIP and pipelines (medium presence sensors are installed 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 (e.g. inoculum) transfer from one bioreactor to another, and bioreactor emptying. Before starting the process, new recipe must be selected or prepared. In each recipe, the movement rout of substrate, product, CIP solution and SIP steam is detected.

5. Biotechnological production of soil fertility increasing cultures (soil supplements)

Two bioreactor lines are installed to manufacture biological products that increase soil fertility, restore its natural balance and increase plant productivity. The main products consist of bacteria that fix nitrogen, release phosphorus, increase potassium absorption and restrict plant diseases that are caused by fungi.

First line consists of 50, 500 and 5000 liter bioreactors, but second line consists of 50, 500, 5000 and 20000 liter bioreactors. In all bioreactors are installed novel magnetic drive mixers (also in 20 000 liter bioreactor!) The systems are fully closed and all operation between bioreactors, CIP, SIP and mixing vessels is completely automated.

6. Bioreactors for bioleaching

Bioleaching is the extraction of metals from their ores with a help of the living microorganisms. This method can be applied for example, to recover copper, zinc, lead, arsenic, antimony, nickel, molybdenum, gold, silver, cobalt.

We have developed and manufactured laboratory and pilot scale systems of bioreactors for bioleaching according to the following configuration:

  1. Two 6 liter bioreactors for preparing of inoculant AND four 6 liter bioreactors with feeding reactor connected in sequence by peristaltic pumps. All inside parts of bioreactors are from glass, PTFE or covered with special chemical resistant coating.
  2. Three30 and 80 liter bioreactors with 80 liter feed reactor connected in sequence according to two options: by peristaltic pumps or gravity. All inside surfaces are covered with special chemical resistant coating.

The systems of bioreactors can be applied for development of bioleaching technologies. The configuration of bioreactors can be customized.

All equipment was constructed for EU project, in cooperation between JSC “Biotehniskais centrs”, Mining and Metallurgy Institute “Bor” (Serbia) and “Mintek” (South Africa).

The technical solutions are customized depending on requirements of a concrete production process.