I am Pouria Motevalian and I am scientist
in Bioprocess Research and Development in Pfizer.
Today, we will talk about characterization and scale up
of microfiltration processes for biotechnology application.
Here is the outline for today's talk.
First, we review the background on application of
membrane filtration for manufacturing biotechnology products,
then we focus on microfiltration and
review microfiltration devices and membrane chemistries.
Next, our focus shifts toward a sterile filtration as one of
the most commonly used form of
microfiltration and review sterile filtration membrane fouling.
Then we talk about the scale up of a sterile filtration processes
and membrane sizing for a sterile filtration application and finish with a summary.
Membranes are extensively used in production,
purification, and formulation of biotechnology products.
From size and application perspective,
membrane filtration can be categorized into four categories: microfiltration,
ultrafiltration, virus filtration, and nanofiltration.
Microfiltration membranes typically retain bacteria, cell debris,
and intact cells by passing colloids,
viruses, proteins, and salts.
The approximate pore size for microfiltration membranes spans from 50 nanometer
to 10 micron which makes them suitable for multiple upstream and downstream applications.
Upstream applications of microfiltration
include a sterile filtration of fermentation media,
pH control solutions, and gases.
Tangential flow microfiltration is used for medium exchange, perfusion, and harvest.
Downstream applications of microfiltration include
a sterile filtration of buffer products and gases,
which are typically air and nitrogen.
In upstream, virus filtration may be used to protect
cell culture from introduction of viral contaminants in media raw material.
Virus filters are often used in
the downstream processing of cell culture dry product to ensure
removal of both viruses that may enter into
the cell through contaminated raw material or virus particles.
The approximate pore size for virus filters is 20 nanometer to 70 nanometer and
these filters are designed to retain viruses
while allowing protein and buffer components to pass through.
Ultrafiltration membranes typically retain proteins while allowing amino acids,
anti-foam, and buffer components to pass through.
The approximate pore size for ultrafiltration membranes is one nanometer to 20 nanometer
and these membranes are widely used in
downstream to concentrate and buffer exchange the product pool.
It is also used for final formulation of bulk products.
Finally, nanofiltration is used for retaining multi-valent salt,
sugar, amino acids, and antibiotics.
Nanofilters have pore size in the range of 0.1-1 nanometer.