Titer capacity analysis
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A biotech manufacturer wanted to increase production by processing higher titers but their purification facility was a bottleneck. Bio-G evaluated different retrofit strategies through simulation and determined that focusing on variability in a key purification step could increase throughput by 10-15% with the highest ROI over 4 years.
Titer capacity analysis
- 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