Bioreactors
Veenbrink RVS bioreactors use a fermentation process. This is a biological process in which microorganisms are introduced into an ideal environment. By very precisely controlling the conditions in the reactor, such as pH value, temperature, pressure and oxygen content, the growth and activity of the micro-organisms are optimised. The cells provide for the production of nutrients for the finished product.
The desired environment is created under highly sterile conditions to prevent contamination and cell loss. In this way, oxygen is evenly supplied over the cell solution through a special sparger pipe. Stirring the liquid helps distribute and disperse the added oxygen. The agitator also ensures that the cells are kept moving homogeneously, without damaging the cells.
The life cycles of fermentation batches are often uniform. Cells exposed to the controlled conditions at the beginning of the process must first acclimate to the new environment. Once the cells become accustomed, they begin to double at a consistent rate. When cells secrete a certain amount of waste, cell growth stagnates: the number of cells that die increases and the number of cells that double decreases.
ISF model (Internal Spin Filter) and ATF model (Alternating Tangential Flow)
Once the fermentation process is at its peak, the harvest takes place. Harvesting can be done in different ways: • ISF (Internal Spin Filter) harvesting • ATF (Alternating Tangential Flow) harvesting With an ISF (Internal Spin Filter) the harvest is obtained by using a spin filter inside the reactor: a harvest tube collects all cell-free media present in the spin filter. Because the filter has a specific mesh size, it ensures that cells remain outside the filter and the harvesting zone and can continue to grow as long as conditions are right. With an ATF (Alternating Tangential Flow), the cell suspension (retentate) is removed from the bioreactor using vacuum techniques. Cell-free harvest is recovered and collected by pumping the suspension back into the bioreactor through the filter housing.
Upstream processing
Within biopharmaceuticals, a distinction is often made between upstream processing and downstream processing. Both phases also consist of a number of process steps. The upstream process essentially consists of:
• Media preparation, which involves making products that feed the microorganisms in the fermentation phase to grow.
• Cell culture, in which cells are cultivated by carefully controlling variables such as pH, temperature, pressure and oxygen content to optimise cell growth.
• Fermentation, where the culture broth is transformed within the bioreactor into a valuable raw material that serves as the basis for the end product.
• Harvesting, where cell growth has reached a peak and different techniques are used to separate the cells from the culture broth, such as using an ISF (Internal Spin Filter) or ATF (Alternating Tangential Flow).
The entire fermentation process is therefore also seen as an upstream process within biotechnology. Process equipment within the media preparation is often cleaned locally by means of CIP and/or SIP. The fermenters and bioreactors, on the other hand, are often cleaned by autoclaving.