Bioreactors: the central element in bioprocesses

If there is a word that has been on everyone’s mouth in recent years, that is biotechnology. At Klinea, we are aware that biotech is destined to revolutionize the pharma sector, especially its processes. And although biotechnology has many variations and offers a huge range of possibilities, in many cases the production of a medicine will depend on a bioreactor.

A bioreactor is a container in which there are controlled conditions that allow the a reaction to run using living organisms or biochemically active substances. The diversity of processes implies that there are several types of bioreactors and that they can be classified in different ways. Although they always include the following attributes:

• Jacket to control temperature

• Acid and base input for pH control
  • Inlet of sterile gases. These gases can be air, O2, CO2, N2, among others
  • Aseptic entry for the inoculum, the medium or specific nutrients
  • Ventilation filter. It is usually a 0.2µm hydrophobic membrane that avoids external contamination and the emission of cells into the environment.
  • There is a lot of variability of the type and number of blades depending on the conditions of the crop
  • Probes for parameter analysis (O₂ concentration, pH …)
  • Aseptic input for sampling and parameter analysis

All these attributes aim to maintain a whole series of critical conditions in the reactor environment. These conditions are: pH, temperature, concentration of nutrients and dissolved oxygen.

Depending on the growth kinetics of the microorganism (if it is a microorganism) that we have in the bioreactor, there will be several modes of operation. The main ones are:

• Batch: the microorganisms are inoculated in a fixed volume and the nutrients will be progressively consumed while the product is generated.
• Fed-Batch: it is a variation of the batch, in which microorganisms are inoculated and nutrients are added as time passes. This mode is especially interesting when there is substrate inhibition
• Continuous: in this operation, medium is added to the bioreactor continuously, while medium with cells and product is extracted. Usually, part of the extracted medium is recirculated towards the entrance

The main types of bioreactors are:

• Stirred tank reactor: can operate in continuous or discontinuous mode. It is shaken by paddles and, ideally, the conditions of the medium are the same anywhere in the bioreactor
• Bubble column reactor: this type of reactor does not have a mechanical agitation method. Homogeneity is achieved by injecting gas at the bottom using a perforated disc. The gas moving through the liquid will mix the content of the medium
• Airlift reactor: in this case there is also no mechanical agitation. The reactor has two concentric cylinders and a gas outlet at the bottom. The gas injected between the two cylinders circulates through the formed channel upwards. The heavier liquid (without air bubbles) will go down across the outside of the cylinders. In this way, a flow of fluids will be generated that will allow homogeneity
• Packed bed reactor: the biological agent (cell or enzyme) is attached to a support that the substrate can reach to run the reaction and obtain the product. Within this type we find piston flow reactors, in which the conditions are maintained over time (steady state), but change depending on the position within the reactor.
• Fluidized bed reactor: the biocatalyst is attached to some type of support, but the support is suspended in the medium. High flows are required to achieve good fluidization of the biocatalyst particles
• Reactor with WAVE system: the 2D balancing motion of bioreactors, creates a wave or cause eddies to form on the wall, causing air to suction in the liquid phase. It provides comparatively higher gas mass transfer rates than stirred tank bioreactors, while mechanical shear forces are considerably lower. This leads to an altered micromorphology and, subsequently, different growth rates and product synthesis.

As a general rule, reactors required for the elaboration of biopharmaceutical products are not too large (<2000L). But they can be up to several thousands of L, especially outside the pharma sector.

Bioprocesses are becoming more common in the pharmaceutical industry, and good engineering is essential for the production of any medicine. A suitable bioreactor that fits well into the design of the process will be key to avoid problems and end up achieving a quality product.

If you are interested in learning more about bioreactors, biotechnology and how we can help you, contact us: klinea@klinea.es