Pharmacy
and Biotechnology
Fermenters with volumes of 30L, 300L, and 3000L, a 1000L nutrient solution tank, pH correction tanks, and a pipeline connecting the fermenters to the feed tank and CIP cleaning station
In response to the increasing demand for microbial products as alternatives to mineral fertilizers and crop protection agents in agriculture, the client has chosen to invest in a biotechnology production line. This investment aims to boost current production, enhance efficiency, and help the company maintain competitive product pricing.
THE ROLE OF BIOSTIMULANTS IN AGRICULTURE
WHAT BENEFITS DOES SUCH A PRODUCT BRING?
Reduced chemical use: Due to their organic nature, biostimulants can partially replace traditional mineral fertilizers and chemical pesticides. This results in fewer chemicals being introduced into the environment, leading to healthier and more natural agricultural products.
Improved soil quality: Biological products positively impact soil structure and composition, enhancing soil fertility and water retention capacity. This makes plants more resilient to drought and extreme weather conditions.
Lower CO2 emissions and increased organic carbon: By promoting healthy vegetation and improving soil structure, these products aid in capturing and storing carbon, reducing CO2 emissions, and contributing to better air quality.
Shorter supply chains: As certain bioproducts do not rely on importing raw materials from third-party countries, their production and use help shorten supply chains, increasing independence and operational security.
BIOREACTOR LINE
The project was based on the development of a bioreactor line consisting of three fermenters with capacities of 30 L, 300 L, and 3,000 L, each specifically adapted for the cultivation of various fungal species. The system enables semi-continuous fermentation under controlled microbial growth conditions.
Automated systems continuously monitor and regulate key parameters such as pH, temperature, and oxygenation, ensuring optimal conditions for microbial development. The entire facility is equipped with a failure and error monitoring system, allowing for quick responses to any irregularities in the production process. An added benefit is the ability to remotely monitor and control the system’s operating parameters.
One of the key strengths of this solution is its comprehensiveness. We provided prefabricated skids containing the bioreactors, along with support for installation and commissioning. This approach facilitated the rapid deployment of the technology and optimization of the production processes.
Additionally, the project incorporates advanced cleaning and sterilization methods to ensure hygienic production conditions. A CIP (Clean-in-Place) cleaning station and the ability to perform steam sterilization (SIP) are crucial for maintaining cleanliness and safety throughout the production cycle.
PROCESS
The production process is based on semi-continuous fermentation, where ingredients are either added or products removed during the process. There are three types of fermentation: batch (discontinuous), semi-continuous, and continuous. In batch fermentation, all ingredients are introduced at the start, and products are collected at the end. Continuous fermentation involves simultaneous input and output of materials while maintaining a constant reactor volume. Semi-continuous fermentation, used in this plant, involves either the addition of ingredients without simultaneous product removal or vice versa.
The installation consists of three bioreactors with volumes of 30 L, 300 L, and 3,000 L, as well as a 1,000 L nutrient tank. The nutrient solution is prepared and sterilized in the 1,000 L tank, which serves as the feed tank for the bioreactors. The nutrient solution, typically glucose-based, is adjusted according to the needs of the microorganisms.
The production cycle begins with a thorough cleaning and sterilization of the plant. The nutrient solution is prepared and sterilized before being pumped into the bioreactors in specific proportions, tailored to each reactor’s process requirements. In the lab, a concentrated “inoculum” of microorganisms is prepared, which is added to the smallest bioreactor, and the fermentation process begins. Initially, fermentation starts in small volumes and is gradually scaled up to larger bioreactors, as direct large-scale cultivation would not allow optimal microbial growth.
The bioreactor’s contents are continuously stirred and aerated with sterile compressed air if required by the specific microorganisms. A CIP (Clean-in-Place) station enables automated cleaning and sterilization of all components after each production cycle. Process control systems monitor and regulate key parameters, including pH, temperature, and oxygenation (via an O2 sensor), ensuring optimal conditions for fungal growth and product formation.
Heating is controlled using a TCU (Temperature Control Unit) equipped with a steam-to-water heat exchanger, maintaining stable conditions typically around 37°C. Critical parameters such as pH are adjusted via an automated pH control system, which delivers precise amounts of diluted acid or base from 200 L tanks. Adjustments are made through a pressurized loop to avoid microbial stress.
The entire process is managed by an integrated automation system with a large HMI touch panel for real-time visualization, program selection, and fault notifications. Remote monitoring is also available via mobile devices, ensuring continuous oversight even when staff are not on-site.
The fermentation process, lasting several days, is monitored around the clock. Automated systems control airflow, stirrer speeds, and nutrient dosing based on process demands. Notifications of potential issues are sent directly to mobile devices, and shift workers are responsible for decision-making during operations.
The anti-foaming agent is dosed as needed, both at the start of fermentation and during mixing, based on signals from foam sensors. Samples can be taken at any time using a test valve. Transfers between bioreactors are done by pressure to avoid damaging the microorganisms.
As the process scales up, the contents move from the smaller to the larger bioreactors without the need for additional inoculum, as the culture grows naturally in the larger vessels. Continuous monitoring and control ensure that microbial growth and product yield are optimized throughout the process.
MAIN FEATURES
Additional Features of the Bioreactor System Include:
WEIGH-BASED TANK FILL MEASUREMENT:
Each of the four tanks is mounted on strain gauge scales, enabling precise determination of the fill level. This ensures high accuracy in weighing and measurement, which is critical for maintaining consistency in the process.
INDIRECT STEAM HEATING VIA HEAT EXCHANGER:
The bioreactor is heated indirectly through a heat exchanger, preventing steam from being fed directly into the jacket. This eliminates rapid temperature fluctuations that could harm the microorganisms, ensuring even temperature control, which is essential in fermentation processes.
BIOREACTOR CONTENT STERILIZATION:
The system offers the capability to sterilize bioreactor contents by injecting steam directly into the jacket. This allows the contents to be sterilized at the appropriate temperature (around 121°C) for the required duration, meeting the customer’s sterilization needs.
CLEAN-IN-PLACE (CIP) SYSTEM:
The plant includes a CIP station for automated cleaning of all components, including process tanks, transfer pipelines, and tanks for cleaning agents (acid and alkali). This ensures thorough cleaning and disinfection after each production cycle.
RINSE RECIRCULATION:
The system is equipped with a rinse recirculation feature that collects and reuses rinse water, conserving water and reducing overall consumption by employing it in subsequent cleaning cycles.
STEAM-IN-PLACE (SIP) STERILIZATION:
The entire plant is designed for SIP sterilization, a standard practice in biotechnology facilities, ensuring that all components can be steam-sterilized to maintain hygienic conditions.
These additional features enhance process control and operational efficiency across the plant, fully meeting customer requirements and industry standards. Furthermore, the system is optimized for energy and water conservation, contributing to the sustainability of the operation.
CUSTOMER BENEFITS
Scaling up production: The system allows for increased production of fertilizers and other additives, contributing directly to the customer’s business growth.
Automation and reduced production time: The process has been automated, significantly shortening production time and enhancing operational efficiency.
Testing larger volumes: The installation supports scaling up to higher production volumes, facilitating the production of new strains and products, which bolsters the customer’s research and development efforts.
Process optimization: The ability to transfer the contents from the 300 L bioreactor directly to the centrifuge and spray dryer, bypassing the 3000 L bioreactor, enhances flexibility and optimizes the overall production process.
Standard cleaning and sterilization procedures: After each production cycle, the plant undergoes automatic cleaning and sterilization, ensuring adherence to high hygienic standards.
Technical innovations: The 3000 L nutrient solution and bioreactor tanks are equipped with a Pillow Plate heating/cooling jacket, improving heat transfer efficiency. Additionally, various access mechanisms, such as inspection hatches, automatic lid lifting, and a service platform, simplify operation and maintenance.
Clean Steam: A purification filter is included, which converts technical steam into clean steam, maintaining cleanliness and process quality without the need for expensive clean steam generators.
These benefits not only enhance productivity and production efficiency but also ensure high hygienic standards and provide flexibility to adapt to changing needs and market conditions
