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MSC 4TH
SEM UNIVERSITY OF KASHMIR
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BIOREACTORS OR BIOFERMENTERS
A bioreactor is a closed system used for upstream bioprocessing. It is a technology used to
culture cells in a controlled manner to produce biopharmaceuticals. Bioreactors support
applications for the production of vaccines, therapeutics, gene therapies and cell
therapies.Bioreactors are used to grow cells in a specific environment.
The bioreactor provides essential gassing, mixing, temperature control, fluid delivery and
other critical process parameters (CPPs). These CPPs support specific applications, and may
vary depending on the requirements of the process demands. CPPs increase the concentration
of cells, the ratio of living cells (viable cell density) as well as sustain the environmental
conditions required while the cells complete their cellular tasks (e.g. secrete the desired
proteins).
There are many different types of bioreactors including:
1. Traditional multiple-use bioreactors require cleaning after each cell culture run.
Smaller-scale bioreactors are glass systems and can be sterilized in an autoclave. Larger
bioreactors are stainless-steel systems that require additional plumbed-in systems for
sterilization, such as cleaning in place (CIP) and steaming in place (SIP).
2. Single-use bioreactors were introduced into the biopharmaceuticals market around 25
years ago. They are made of single-use closed gamma irradiated biocontainers, fitting
on reusable hardware. Single-use bioreactors are increasingly used for small-scale, mid-
scale, and large-scale production runs given their many benefits.
3. Stirred-tank bioreactors are equipped with an impeller for homogenizing culture
media and a sparger for delivering oxygen to the cells. Stirred-tank reactors (STRs) are
the most widely-used bioreactors. These range in sizes from 15 mL to 2000 L for single-
use and are available in sizes larger than 2000 L for stainless-steel. STRs are primarily
used to scale-up a process from research and development scale to manufacturing scale.
The goal is to ensure that a process at a smaller volume can be representative of larger
volumes. In addition to scale-up capacity, usability and process assurance of the single-
use STR at the manufacturing scale are key elements to consider.
4. Rocker bioreactors are offered as single-use systems. They involve a bag on a moving
platform, relying on a rocking motion for the mixing. Oxygen diffuses through the
headspace via liquid-gas interface, as these bioreactors are not equipped with a sparger.
These bioreactors are typically smaller-scale, ranging from a few liters to a maximum
100 L. They are usually used for small-scale production or for seeding into larger
bioreactors.
5. Air lift bioreactors are less frequently used in the biopharmaceuticals industry due to
them being lesser known with regulatory processes that are largely unexplored. They
rely on air bubbles to aerate and carry the media around the reactor for mixing at the
same time.
6. Fixed-bed bioreactors are used for adherent-cells, involving specialist cells that can
only grow when attached to a surface. They usually have strips of fibers (carriers)
resulting in a high surface area for the cells to adhere to. These carriers are packed
together to make the fixed-bed. Aerated culture medium circulates through it. Adherent
cells can also be cultivated in stirred-tank, rocker and air lift bioreactors, such as
2. 19060119015
MSC 4TH
SEM UNIVERSITY OF KASHMIR
2
suspended cells. However, they need to be attached to 100-micrometre beads (i.e.
microcarriers) put in suspension. Scale-up of this process is much more complex and
time-consuming than the equivalent suspension process or the adherent cells process in
the fixed-bed bioreactors technology.
