Cambridge Healthtech Institute’s 5th Annual
Process Characterization and Control
A Best Practices Forum for the Translation of Process Understanding into Control Strategies for Maintaining Quality Throughout the Product Lifecycle
August 15-16, 2019
With the recent publication of process validation guidances from both US and European regulators, the demonstration of process understanding, identification of critical quality attributes and the implementation of well-validated control strategies must
now become a routine part of biologics manufacturing operations. But significant ambiguities remain in the specific steps that must be taken in the production of legacy and new products, by companies of different scale and resources and for
specific product formats. Process Characterization and Control offers a forum for the sharing of strategies and best practices from a wide range of industry companies working to implement these complex new standards.
Thursday, August 15
11:30 am Registration Open
12:15 pm Enjoy Lunch on Your Own
1:15 Ice Cream Social in the Exhibit Hall with Last Chance for Poster Viewing
1:55 Chairperson’s Remarks
George Bou-Assaf, PhD, Scientist, Biogen
2:00 KEYNOTE PRESENTATION: Process Control as an Enabling Technology for Continuous Vaccine Production
Richard D. Braatz,
PhD, Professor, Chemical Engineering, Massachusetts Institute of Technology
Continuous manufacturing has the potential to significantly improve efficiency, boost production, and reduce the cost of vaccine manufacturing. The presence of defective interfering particles has been shown to result in large periodic variations in virus
titers, limiting overall production rates. This talk describes the design of process control systems that simultaneously remove process oscillations and increase the overall production rate.
2:45 NEW: Biopharm Product’s Structure-Function Relationship (SFR), Rationale for Accelerating Analytical Development and Process Characterization
Wasfi AlAzzam, PhD, CSO, TechnoPharmaSphere (TPS)
SFR aims to measure structural attributes impact on product’s activity and safety profiles, this practice stands true for most pharmaceutics. SFR from in vitro and
in vivoprovides in-depth understanding of product’s QA and determine CQA, which help accelerate analytical methods development, acceptance criteria, and product’s specs. SFR results are used to accelerate process characterization,
process control strategy, and establishing QBD principles for manufacturing process. SFR is keystone for justifying analytical development acceleration and process characterization & control.
3:15 Process Characterization Planning & Execution for an Effective Product Lifecycle Management
Naveen Pathak, Director,
Pharmaceutical Science, Takeda
Process Characterization is a time and resource-intensive activity to enable process understanding as described in ICH Q8. The presentation will discuss strategies and efficient execution of characterization studies related to determination of control
strategy, successful completion of technology transfer, and lifecycle management. A system for knowledge management of the acquired process understanding over the product lifecycle will be highlighted.
3:45 Featured Poster Presentation: Development of a Rapid Peptide Mapping Method, Using Scaled Down Gradient, to Support Biologics Development
Nandu Madayiputhiya, PhD, Senior Scientist, Celgene
Peptide mapping is extensively used to monitor attributes however, LCMS based peptide mapping is typically a complex, time consuming process and this precludes rapid turnaround time expected for supporting process development. Here we present a simlpe
way for scaling down peptide map gradient for rapid analysis by simply changing the time.100 minute gradient was scaled down to 25 and 12.5 min without compromising the senstivity and accuracy of PTM quantification.
4:00 Refreshment Break
4:15 Process Characterization for Cell and Gene Therapies; Contrast with Protein Therapeutics
Bou-Assaf, PhD, Scientist, Protein & Gene Therapy Biophysical Characterization, Biogen
Gene therapy products comprise a capsid of proteins and a nucleic acid packaged inside. Given the complex structural assembly, advanced analytical tools are indispensable for process characterization. We describe how several analytical tools traditionally
employed for protein therapeutics can be applied as is or adapted to gene therapy products. In addition, we describe challenges uniquely associated with gene therapy products and how they were overcome with new methods and instrumentation.
4:45 Application of High Throughput Chromatography for mAb Downstream Process Characterization
Rowicki, Biologics Process Research and Development, Merck Research Laboratories
High throughput process development (HTPD) approaches are becoming the preferred development approach over traditional lab scale column studies. Key advantages of HTPD include enhanced process understanding and decreases in time and material requirements.
This approach has been utilized to effectively identify operating parameters that significantly impact product attributes and accelerate commercial process development and characterization. A case study describes the strategies, successes, and challenges
of implementing these tools into process characterization.
5:15 End of Day
Friday, August 16
7:30 am Registration Open
7:30 Small-Group Breakout Discussions with Continental Breakfast
This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations
or commiserate about persistent challenges.
8:30 Chairperson’s Remarks
Marina Kirkitadze, PhD, Head, Analytical Process Support & PAT Platform, Analytical Sciences, Sanofi Pasteur, Canada
8:35 Phase Appropriate Approach to Analytical Comparability for Innovator Biotherapeutics: How Much is Enough?
Sonia Taktak, PhD,
Principal Scientist, BioTherapeutics Pharmaceutical Sciences, Pfizer, Inc.
As drug candidates move though development, manufacturing process improvements and formulation changes can impact product quality attributes. The goal of a comparability exercise is to ensure that these changes have no adverse impact on the quality, safety
and efficacy of the drug. In this presentation, we will review key components of a successful analytical comparability strategy based on product-specific considerations, phase of development (early, late) and nature of the change(s).
9:05 Update on BioPhorum’s Roadmap for Inline Monitoring and Real-Time Release
PhD, Associate Director, Bristol-Myers Squibb
Real time monitoring and in-time release of product attributes create a demand to move testing of CPP and CQA from off-line analysis to the manufacturing shop floor (in-line, on-line or at-line monitoring) for reducing speed, cost and maximizing quality
of product. The presentation will focus on the advance in implementation of BioPhorum’s ILM-RTR roadmap strategy related to Business case development and URS completion for a prioritized list of desired CQA’s and CPP, due to be published
as part of a White Paper in 2019.
9:35 Characterization of Drug Excipients Related Impurities from Oxime Chemistry: Is PS80 the Scapegoat?
Puneet Gupta, Associate Scientist, Bristol-Myers Squibb
Fatty acid is linked to the drug via oxime chemistry through a peptide linker to facilitate drug delivery. To gain process and product understanding, the multiple peaks which could be associated with fatty acid were characterized. We used RP-UPLC method
to verify the impurity from derivatized fatty acid under stress conditions and evaluated the source of the products in the formulation buffer and characterized the impurity peaks using LC-MS/MS.
10:05 Networking Coffee Break
10:30 Development, Validation and Implementation of a SEUHPLC Method Based of USP <129>
Wen-Li Chung, Quality
Control Scientist, Genentech
USP <129> was published in 2016 which provides detailed instructions regarding how to perform SEC with a generic USP reference solution as a system suitability method control. Size-exclusion ultra high-performance liquid chromatography, an alternative
method was developed based on this USP <129> SEC method and then validated according USP <1225> with various molecular weight ranging from Fab to bispecifc proteins. Results of the study demonstrated equivalency of these two methods.
11:00 Innovative AI Tools Applicable for Process Control and Automated Device Integration
PhD, Principal Scientist and Digitalization Lead, Large Molecule Research, Roche, Germany
Therapeutic proteins development becomes more challenging due to the complexity of the diverse molecule formats. Drug development and particular process development use more and more high throughput systems which require sampling for controlling and
generate a huge amount of data. Therefore, we developed a new soft sensor, as non-invasive sensor application. The new approach, based on artificial neural network, processed the common online signals of the bioreactors to estimate the cell growth
and key metabolites during cultivation time.
11:30 Cross-Functional Data Harmonization for Predictive Pharmaceutical Development
Data Scientist, AbbVie, Germany
Modern drug development is highly resource-intensive and new highly-engineered protein-based variants are entering the pharmaceutical development pipelines. AbbVie invested in miniaturized automated high-throughput screening. The aim is to collect
standardized data sets to apply machine learning to support formulation design space. How can in silico methods guide liquid formulation development? Prior knowledge from multiple departments and homology models
can provide predictive descriptors for protein stability.
12:00 pm Late-Breaking Presentation
12:30 Enjoy Lunch on Your Own
1:15 Session Break
1:25 Chairperson’s Remarks
Wei Xue, PhD, Senior Process Scientist, Regeneron Pharmaceuticals, Inc.
1:30 Inline Probes for Process Monitoring and Product Characterization
Kirkitadze, PhD, MBA, Head, Analytical Process Support & PAT Platform, Analytical Sciences, Sanofi Pasteur, Canada
Interaction between antigen and adjuvant or adsorption of antigen to adjuvant is critical for the effective adsorption. Particle size distribution of aluminum phosphate and adsorbed protein were examined by Laser diffraction and Focused Beam Reflectance
Measurement at line and inline respectively. Compositional analysis of aluminum phosphate was performed at line using FTIR and Raman spectroscopy, and inline ATR probe were used to examine adsorbed protein suspension.
2:00 Oxygen Uptake Rate (OUR) Measurement of Mammalian Cells with a Real-Time Off-Gas Analyzer
Wei Xue, PhD, Senior Process Scientist,
Regeneron Pharmaceuticals, Inc.
Oxygen uptake rate (OUR) is one of the most important measurable indicators used to reveal cell status and intensity of cellular metabolic activities. At Regeneron, the Sartorius BioPat® Xgas off-gas analyzer was evaluated for its potential to
measure on-line OUR with example small-scale processes. In the evaluation, it was clearly demonstrated that OUR shows strong correlation with cell growth and glucose consumption.
2:30 Development of High-Resolution Isoelectric Chromatofocusing for In-Process Monitoring of Monoclonal Antibody Charge Variants
Helen Zhao, Associate
Scientist, Process Development Analytics, Bristol-Myers Squibb
The development of an at-line isoelectric chromatofocusing (ICF) method for the analysis of monoclonal antibody charge variants is presented here. This method shows comparability to conventional imaged capillary isoelectric focusing for protein charge
analysis. This ICF technique implements a linear pH gradient on strong anion exchange media and was applied on an at-line UPLC system to monitor the charge variant profile of an ion exchange process eluent in real time.
3:00 When Good Intentions Go Awry: The Use of Analytical Characterization to Detect Unexpected Chemical Modifications Formed during Cell Culture
Chris M. Chumsae, PhD, Senior Scientist, Protein Analytics, AbbVie Bioresearch Center
3:30 Close of Conference