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.

Final Agenda

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 


Harborview 2

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

Braatz_RichardRichard 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

Pathak_NaveenNaveen 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

Madayiputhiy_NandakumarNandu 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_GeorgeGeorge 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_PatriciaPatricia 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.


Harborview 2

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?

Taktak_SoniaSonia 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

Aich_UdayanathUdayanath Aich, 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?

Gupta_PuneetPuneet 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>

Cheung_Wen-LiWen-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.


Harborview 2

11:00 Innovative AI Tools Applicable for Process Control and Automated Device Integration

Paul_WolfgangWolfgang Paul, 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

Wilbertz_AxelAxel Wilbertz, 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


Harborview 2

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_MarinaMarina 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

Xue_WeiWei 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

Zhao_HelenHelen 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

Chumsae_ChrisChris M. Chumsae, PhD, Senior Scientist, Protein Analytics, AbbVie Bioresearch Center

3:30 Close of Conference