Sartorius AG · XETR:SRT
Sartorius — Technical Presentation (October 2015)
43 slides from Sartorius's technical presentation, October 2015
Slide 1: BioPAT Chemometrics Toolbox
BioPAT® Chemometrics Toolbox for efficient bioprocess development and robust manufacturing turning science into solutions
Slide 2: Contents
Contents 1 Sartorius PAT Solutions at a Glance 2 DoE - The Efficient Way of Bioprocess Optimization 3 MVDA – Discover Hidden Process Information 4 Summary
Slide 3: Objectives for PAT Implementation
PAT Solutions Objectives for PAT Implementation Process Optimization & Process Understanding Process SCADA MVDA Analytics DoE Sensors Yields & Titers Critical Process Parameters CoGs | R&D costs Design Space Tech Transfer | Time to Market Ease of Process Changes Page 2
Slide 4: PAT Toolbox for Enhanced Process Understanding and Process Automation
PAT Solutions PAT Toolbox for Enhanced Process Understanding and Process Automation Technology Selected Sartorius products Application Electrochemical sensors SU PH sensor, MU PH sensor, MU redox sensor Mixing | Fermentation | CC Optical sensors SU Sensors for pH and DO Fermentation | Cell Culture S
Slide 5: PAT Enabling Chemometric Software Solutions
PAT Solutions PAT Enabling Chemometric Software Solutions powered by UMETRICS Design of Experiments #1 Multivariate Data Analysis#2 MVDA-online #3 (DoE) (MVDA) Page 5
Slide 6: Designed to Meet the Needs of PD, Scale-up and Production
PAT Solutions Designed to Meet the Needs of PD, Scale-up and Production Page 6
Slide 7: Contents
Contents 1 Sartorius PAT Solutions at a Glance 2 DoE - The Efficient Way of Bioprocess Optimization 3 MVDA – Discover Hidden Process Information 4 Summary
Slide 8: Motivation for Design of Experiments
Design of Experiments Motivation for Design of Experiments Key technology in Quality by Design (QbD) discussions REGULATORY Speed up development of new therapeutics with less experiments TIME Increase manufacturing efficiency and lower production costs MONEY Improve process understanding wit
Slide 9: Design of Experiments – Definition and Objectives
Design of Experiments Design of Experiments – Definition and Objectives Regression Coefficient 3-D Response Surface 2-D Contour Plot Probability Plot Plot Plot (Design Space) ￭ “A structured, organized method for determining the relationship between factors affecting a process and the output of that
Slide 10: DoE – The Efficient Way of Experimentation
Design of Experiments DoE – The Efficient Way of Experimentation Random Approach Intuitive Approach (COST) Efficient Approach (DoE) Changing all factors Changing One Single factor Changing all factors at the arbitrarily at a Time same time according to a well designed plan High number of exp
Slide 11: Parallel Systems: the Ideal Equipment for DoE
Design of Experiments Parallel Systems: the Ideal Equipment for DoE Although a DoE investigation can be carried out in one vessel, systems designed for parallel operation provide the optimal basis to implement a series of experiments in an economical way. Medium Screening with 15 parameters = 32 e
Slide 12: Integrated DoE for Efficient Setup & Execution of Designed Experiments
Design of Experiments Integrated DoE for Efficient Setup & Execution of Designed Experiments DoE #1 SCADA #2 MFCS DoE Module Quantitative controlled factors Design setup using a simple wizard Automatic S88 recipe configuration Parallel start of multiple experiments Automatic data & design
Slide 13: Current ICH Q8(R2) Guideline Lacks Risk-Based Design Space
Design Space Current ICH Q8(R2) Guideline Lacks Risk-Based Design Space “Regardless of how a design space is developed, it is expected that operation within the design space will result in a product meeting the defined quality. “ [ICH Q8(R2)] “Recent changes in the regulations for pharmaceutical
Slide 14: Design Space Estimation with BioPAT MODDE According to ICH Q8(R2)
Design Space Design Space Estimation with BioPAT® MODDE According to ICH Q8(R2) Design Space Classical Contour Plot Sweet Spot Plot Classical Contour Plot shows point Sweet Spot Plot shows design space prediction response surface visualizing according to current ICH Q8(R2) definition average pro
Slide 15: Novel Approach in BioPAT MODDE for Improved Design Space Estimation
Design Space Novel Approach in BioPAT® MODDE for Improved Design Space Estimation Design Space Probability Contour Plot Sweet Spot Plot Monte Carlo simulation rapidly estimates probability of being in or out of specification Uncertainties in process factors and in the model are considered Desi
Slide 16: FDA Recognizes Uncertainty Analysis as a Powerful Tool
Design Space FDA Recognizes Uncertainty Analysis as a Powerful Tool Kauffmann et al. (2012): Evaluation of Process Models with Monte Carlo Methods, FDA Page 16 Peterson, J.J. (2010): What Your ICH Q8 Design Space Needs: A Multivariate Predictive Distribution, GSK
Slide 17: Optimization of Growth and Production Culture Media
Design of Experiments Optimization of Growth and Production Culture Media PowerCHO® Chemically defined, hydrolysate-free, serum-free and non-animal origin CHO media already optimized for cell growth and protein production ensures high viability (>90%) at high cell densities CHO Therapeutic antibody
Slide 18: Parameter Screening & Optimization for Accelerated Process Development
Design of Experiments Parameter Screening & Optimization for Accelerated Process Development BioPAT® Trace Self-calibrating, smallest online analyzer in the market for simultaneous online monitoring of glucose and lactate CHO Monoclonal antibody Design space identified, operational parameters as Abu
Slide 19: Optimization of Purification Conditions
Design of Experiments Optimization of Purification Conditions Electronic Pipettes The electronic pipettes of Sartorius Biohit are the perfect companion for daily, repetitive liquid handling in laboratories, where accuracy of the results and ergonomics are critical. Recombinant protein yield > 90%, 6
Slide 20: Robustness and Validation Studies of Virus Inactivation
Design of Experiments Robustness and Validation Studies of Virus Inactivation Virosart® Virus filters for robust and efficient removal of small non- enveloped and large enveloped viruses in biopharmaceutical applications. CHO Therapeutic protein Proven acceptable ranges (PAR) defined for Looby et al
Slide 21: Optimization of Freeze and Thaw Rates
Design of Experiments Optimization of Freeze and Thaw Rates Celsius®-Pak Provides uniform and reproducible freeze and thaw processes for biopharmaceuticals in manufacturing and process development Recombinant protein Reduction of undesired dimer content < 1%, optimum Le Saoutet al. (2010) found for
Slide 22: Contents
Contents 1 Sartorius PAT Solutions at a Glance 2 DoE - The Efficient Way of Bioprocess Optimization 3 MVDA – Discover Hidden Process Information 4 Summary
Slide 23: Properties of a Fermentation Process
MVDA Properties of a Fermentation Process Start ????? End Start: Start conditions, set-points according to DoE – how the experiments should run End: End point analysis – results of the experiments Between: In between there are hours, days of activities which are unaccounted for... (...failures
Slide 24: Univariate Batch-to-Batch Comparison Can Be a Challenge
MVDA Univariate Batch-to-Batch Comparison Can Be a Challenge Univariate monitoring and process reviews lead to “cumbersome” troubleshooting Difficult to find key trends, correlations, patterns and relationships from historical data sets Page 24
Slide 25: Multivariate Monitoring Can Reveal Unseen Outliers
MVDA Multivariate Monitoring Can Reveal Unseen Outliers The information is found in the correlation pattern - not in the individual variables! Page 25
Slide 26: Multivariate Control Limits Describe Good Process Conditions Better
MVDA Multivariate Control Limits Describe Good Process Conditions Better Multivariate Control Limits (joint acceptance region) Page 26
Slide 27: Post-Batch MVDA Enables Easy Interpretation
MVDA Post-Batch MVDA Enables Easy Interpretation Post-batch MVDA enables easy interpretation and analysis of large process data sets Principal Component Analysis (PCA) models the behavior of large numbers of key parameters simultaneously and allows batch to batch comparisons Identification of Ou
Slide 28: MVDA - The Art of Compressing and Visualizing Information
MVDA MVDA - The Art of Compressing and Visualizing Information Data Multivariate Modeling Information Univariate monitoring and process reviews lead to “cumbersome” troubleshooting Post-batch MVDA enables easy interpretation and analysis of large process data sets Find key trends, correlations
Slide 29: MFCS/win 3.0 MVDA Module for Efficient Data Analysis
PAT Solutions MFCS/win 3.0 MVDA Module for Efficient Data Analysis MVDA #1 SCADA #2 MVDA Module MFCS/win 3.0 module for offline export of historical process data sets Save up to 50% time for data preparation Faster troubleshooting and analysis Precise and accurate method Page 29
Slide 30: MVDA-online: Multivariate Data Analysis for Continuous Process Verification
MVDA-online Multivariate Data Analysis for Continuous Process Verification File offline DB Model DB MVDA offline MFCS Model Generation Historical DB MVDA online online DB MFCS Data Interpretation Real-time Build offline model to find key trends, correlations, patterns and relationships from MFCS/w
Slide 31: MFCS/win 3.0 OPC HDA for Full Connectivity to SIMCA-online
PAT Solutions MFCS/win 3.0 OPC HDA for Full Connectivity to SIMCA-online MVDA-online #1 SCADA #2 OPC HDA Server MFCS/win 3.0 module for online export of current and historical process data sets 100 % compliance with full functionality (e.g. Repredict, Catch-up, Extraction) Easy implementation in
Slide 32: What makes BioPAT SIMCA-online so powerful?
MVDA-online What makes BioPAT® SIMCA-online so powerful? Data from all relevant process parameters are concentrated to a few highly informative graphs Process trajectories for Real-Time Multivariate Statistical Process Monitoring (RT-MSPM) Enhanced process safety by easy understandable graphic
Slide 33: Early Detection of Process Deviations with Guiding to Potential Root Cause
MVDA-online Early Detection of Process Deviations with Guiding to Potential Root Cause Faster troubleshooting reduces the risk for costly shutdown periods Control and assurance of overall process and product quality Page 33
Slide 34: Early Detection of Process Deviations with Guiding to Potential Root Cause
MVDA-online Early Detection of Process Deviations with Guiding to Potential Root Cause Early fault detection SIMCA-online technology is acknowledged for its ability to detect process issues before they become critical Project dashboard Full drill-down to raw data for cause analysis Knowledge bui
Slide 35: Management Support – Make the Tool Available
MVDA-online Management Support – Make the Tool Available Manufacturing shift-change discussion biogen idec, Inc. is a biotechnology company specializing in drugs for neurological Daily reinforcement at the morning plant meeting disorders, autoimmune disorders and cancer. On-floor and off-floor
Slide 36: Shorten the Timelines for a Seamless Scale-Up
MVDA Shorten the Timelines for a Seamless Scale-Up BioPAT®-Xgas Measure key standard parameters for scale-up , such as oxygen uptake rate (OUR), carbon dioxide production rate (CPR) or respiratory quotient (RQ) PER.C6 Causes for batch deviations identified, process differences revealed between Merci
Slide 37: Learn from History and Improve Future
MVDA Learn from History and Improve Future Training & Services In cooperation with our partner UMETRICS we provide a range of training and consulting services in addition to support. Vaccine Robustness demonstrated for two different production Thomassenet al. (2010) scales (700 L, 1500 L), outliers
Slide 38: Monitor Design Space Online and Save Batches by Early Fault Detection
MVDA-online Monitor Design Space Online and Save Batches by Early Fault Detection Quality Compliance BioPAT® SIMCA-online is developed according to GAMP5 and extensively tested and validated. It is compliant with CFR 21 Part 11 and OPC certified. CHO Deviations in real-time charts detected for low v
Slide 39: New Opportunities for Innovative Downstream Operations
MVDA-online & DoE New Opportunities for Innovative Downstream Operations FlexAct® UD For SU processing the FlexAct® UD is supplied with a unique gamma sterilized bag loop with a pre-flushed Hydrosart self contained Sartocube®. Yeast Flux improvement in the range between 89.32% and Jokić et al. (2010
Slide 40: Contents
Contents 1 Sartorius PAT Solutions at a Glance 2 DoE - The Efficient Way of Bioprocess Optimization 3 MVDA – Discover Hidden Process Information 4 Summary
Slide 41: Numerous applications in upstream...
Summary Numerous applications in upstream... Page 41
Slide 42: ... and in downstream
Summary ... and in downstream Page 42
Slide 43: The Unique BioPAT Chemometrics Toolbox
Summary The Unique BioPAT® Chemometrics Toolbox Page 43