Bioreactors: the central element of bioprocesses

If there is a word that has been on everyone’s lips in recent years, it is biotechnology. At Klinea, we are aware that biotechnology is destined to revolutionize the pharma sector, especially its processes. And although biotechnology has many variants and offers an enormous range of possibilities, in many cases the production of a medicine will revolve around a bioreactor.

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

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

All of these attributes aim to maintain a series of critical conditions in the reactor environment. These conditions are: pH, temperature, 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, among which the most notable are:

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

The main types of bioreactors are:

  • Stirred tank reactor: can operate in continuous or batch mode. It is agitated by blades and, ideally, the conditions of the medium are the same at any point in the bioreactor.
  • Bubble column reactor: this type of reactor does not have a mechanical stirring method. Homogeneity is achieved by injecting gas through the bottom using a perforated disc. The gas moving through the liquid will mix the contents of the medium
  • Air lift type reactor: in this case there is no mechanical agitation either. The reactor has two concentric cylinders and a gas outlet at the bottom. The gas injected between the two cylinders circulates through the channel that is formed in an upward direction and exits at the top. The heavier liquid (without air bubbles) will move down 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 to which the substrate can reach so that the reaction can occur and the product can be obtained. Within this type we find plug flow reactors, in which the conditions are maintained over time (steady state), but change depending on the position inside 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: consists of the 2D rocking movement of bioreactors, which create a wave or cause the formation of eddies on the wall, causing the suction of air in the liquid phase. It provides comparatively higher gas mass transfer rates than in stirred tank bioreactors, while mechanical shear forces are considerably lower. This leads to altered micromorphology and subsequently different growth rates and product synthesis.

As a general rule, the reactors required for the production of biopharmaceutical products are not usually too large (<2000L), but they can reach several thousand L, especially outside the pharma sector.

Bio processes are increasingly common in the pharmaceutical industry, and good engineering is essential for the production of any medicine. An adequate bioreactor that fits well into the process design will be key to avoiding problems and ending up achieving a quality product.

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