Year: 2015-16

Company: Boehringer Ingelheim

Liaison(s): Raquel Orozco

Boehringer Ingelheim (BI), founded in 1885 by Albert
Boehringer in Ingelheim Germany, is a privately owned
global enterprise, employing over 44,000 people across
50 countries, and bringing in €13.3 billion in global net
sales in 2014. BI has a wide corporate profile including
biopharmaceuticals and prescription drugs, consumer
health, animal health, and industrial manufacturing.
BI’s focus is primarily in the therapeutic areas of
cardiovascular disease, respiratory disease, diseases of
the central nervous system, metabolic disease, virology,
and oncology.
The Process Development team at BI’s Fremont,
California, location is currently working towards
developing a robust platform based on continuous
bioprocessing. Continuous bioprocessing has
numerous advantages: reduced capital costs,
increased productivity and product quality. One of
the most challenging unit operations is low pH viral
inactivation. This involves lowering the pH of the
product solution and incubating the liquid for 60
minutes to achieve up to six logs of clearance of non-
enveloped virus such X-MULV. A major challenge
in continuous viral inactivation is understanding the
fluid dynamics that allow for minimal dispersion in
the product stream as it flows through the incubation
chamber.
The BI Viral Inactivation team initially carried out
an extensive literature review to gather a set of
governing equations and principles to support the fluid
dynamic characterization of the incubation system.
Using this information, the team developed a novel
configuration for the viral inactivation chamber and
characterized the flow through the chamber. The team
then used these metrics to gain insight on how axial
dispersion is affected by variables such as flow rate and
incubation chamber design. Thereafter, the team used
computational fluid dynamics models to characterize
the flow patterns in several configurations. Based on
the empirical results and models’ outputs, the team
selected an optimized incubation chamber design for
further characterization. Upon completion of this
project, the Boehringer Ingelheim TMP team will have
developed a 3D printed prototype chamber for viral
inactivation for a set of flow rates that pertain to a
100L perfusion bioreactor scale. The results have been
communicated to BI through regular presentations and
will be drafted into manuscripts for publication and
conference presentations