Data Processing at the Speed of Thought: Using High Speed Data Visualization to Answer Complex Performance Challenges
T. Barreira (Merrimack Pharmaceuticals, Inc.), L. Graham (Alkemy Innovation, Inc.)
B. Crandall (Seeq Corporation)
Approach/Strategy
Abstract
Upstream
Bioreactor development and scale up strategies rely heavily on classic engineering principles alongside biological growth and metabolism data. When challenges arise it becomes necessary to couple these data, often in multiple iterations, to better understand the complex bioreactor dynamics. Upstream Process Operation and Data Flow
• 6 Bioreactors, • 3 chromatography skids,
• 14 individual sample points, • 5-­‐6 offline pieces of analytical equipment,
• thousands of online trending data points With high speed, high throughput analytics, there is a need for high speed data processing and visualization, yet most processing is still done in basic spreadsheets with highly manual inputs and operations. This poster describes a new cross functional data visualization platform in the context of troubleshooting typical bioreactor and scale up challenges. Beckman
Coulter
Vi-CELL
+ Downstream
Problem Statement/Background
The Approach: The Challenge: Protein degradation observed at production scale (1000L). Scale-­‐up Observations (1000L)
Required: A more effective way to analyze data across all bioreactors and downstream operations to support 1) rapid problem-­‐solving, 2) small-­‐scale model verification, and 3) future process development.
Leverage the Seeq® application Exploration
alongside lab-­‐scale and pilot-­‐scale Creation
Reflection
experimentation to rapidly gather, Implementation
analyze, and visualize data.
From manual, time-­‐
consuming incomplete analysis…
Upstream Process Train
1.5L Bioreactor
=
Results
…to rapid, real time data investigation and analysis at the “speed of thought”…
Upstream
100L (n-­‐1)
Bioreactor
Product Quality Attributes
Nova
BioProfile
Flex
F
1000L Production Bioreactor
Cell Line Characteristics
,
Bioreactor Environment
+
Downstream
Processing Environment
100L
100L
O2 Flow
3L
à Cell-­‐specific oxygen uptake rates
3L
IVCD
3L
Physical Situation
• Rapid investigation into the complex bioreactor dynamics of multiple scales of equipment…all in the same environment
+ Downstream
• Rapid evaluation of chromatography curves using pattern recognition features to easily visualize downstream processing data, right alongside other process data.
… to a “holistic” molecule view.
Conclusions
To get the most value out of high speed, high throughput analytics, there is a need for high speed data processing and visualization. It is important to stop the manual processing efforts historically made in basic spreadsheets with highly manual inputs and operations. Better data analysis and visualization applications, within the right data strategy framework, can support the analysis across many aspects of biotherapeutic development, including the following:
• Cell Line Selection and Development Methodology
Viable Cell Density
VCD (e6 vc/ml)
• Heterogeneity in Cell Line Screening and Selection • Optimized Media Composition and Feed Strategies
• Understanding the Science of Scale for mAb Production Across the Scale-­‐up Train
• Process Investigations, Development and Optimization Protocols
Days in Culture
Titer by HPLC (mg/L)
HPLC Titer
Minus light chain Intact
In this case study, this approach to data management, analysis, visualization and reporting • uncovered important issues related to bioreactor scale-­‐up, including quick comparisons of key process steps across multiple batches,
• quickly calculated and compared durations of sensitive periods during the process (e.g. during an intensive cell growth phase), and
• enabled analysis of related downstream process operations. provided an environment perfectly aligned with the need for a fast way to evaluate multiple unit operations together in a single place (e.g., bioreactor with downstream chromatography). Acknowledgements
Days in Culture
The authors wish to thank their technical teams for their contribution to the project.