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1. CASE STUDY
TITER CAPACITY
ANALYSIS
To understand the impact of increasin g titer on the
throu ghput of a lar ge manufacturin g facility .
• Analysis for large Biotech manufacturer with large fixed plant.
• As titer increased, the downstream purification facility became a
bottleneck for production.
• Working in conjunction with Process Engineers, Bio-G evaluated a
number of different processing strategies and plant modifications.
• The strategy suggested by Bio-G showed a 15% higher throughput than
alternative strategies.
• ROI of over $200 M over four years.
As our understanding of the systems behind protein expression develops,
biotech companies are increasing the titer (or concentration) of new and
existing products at a remarkable rate. Intense efforts to optimize production
processes and improve efficiency have resulted in titers doubling every three
years for almost twenty years.
8
4
2
1
2005
Projected
2008
YEAR
TITER
GOAL
high level
summary
THE BRIEF
Historical Industry Average:
Titer over Time
The challenge to many manufacturers is that their existing manufacturing
capacity assumes a fixed titer. While many manufacturers can express
titers of 2 grams per liter and above, the ability of existing purification
equipment to process that quantity of protein in one run is strictly limited.
With downstream purification as the bottleneck, the benefits of research into
higher titers cannot be realized.
The key challenge for one large biotech manufacturer was to retrofit their
current production plant to allow much higher titers to be processed.
Bioproduction Group’s brief was to evaluate the different retrofit options and
determine the optimal strategy to maximize return on investment.
© Bioproduction Group. All Rights Reserved. 1

2. How We Did It
“Establishing a credible
estimate based on physical
plant capability is the key
to understanding value.”
David Zhang, Principal
Results
Bio -G Results:
10-15% impro vement
over proposed scenario
MORE INFORMATION
BIOPRODUCTION GROUP
CONTACT@BIO-G.COM
www.bio-g.com
Bioproduction Group’s methodology was to firstly understand the impact
of high titer on plant throughput. “The key question to ask is not about cost,
but about runs per week,” comments Principal David Zhang. “Establishing
a credible estimate based on physical plant capability is the key to
understanding value.”
Working with engineers in process development, Bio-G established a detailed
simulation baseline that included all downstream main operations, buffer
preparation steps, cleaning activities and support steps. The simulation
was based directly from historical plant data and validated using process
engineers on the shop floor.
From this detailed simulation model, Bio-G built a number of scenarios
representing the different ways in which the plant could process the additional
protein product. One Engineer commented: “We needed someone who’d get
down and dirty. Bio-G worked to deliver hard answers to hard questions.”
Bio-G’s recommendations were to pursue a processing strategy based on
the effect of variability on one key bottleneck step in downstream operations.
This single processing step was shown to dominate the overall processing
time and value of the scenario. Based on this recommendation, the plant was
able to increase their overall plant throughput by 10-15% compared to the
next best high titer scenario.
TIME (hours)
6000
5000
4000
3000
2000
1000
20 40 60 80 100 120
NUMBER
OF OUTPUT
BATCHES
The strategy allowed the company to minimize additional investment in
infrastructure, while nearly doubling effective plant throughput. The ROI of
the scenario was over $200 M in a period of four years.
© Bioproduction Group. All Rights Reserved. 2