Cambridge Healthtech Institute’s 4th 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 16-17, 2018

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 16

11:30 am Registration Open

12:15 pm Enjoy Lunch on Your Own

1:15 Dessert Refreshment Break in the Exhibit Hall with Last Chance for Poster Viewing

1:55 Chairperson’s Remarks

Min Zhang, PhD, Director, Manufacturing Sciences and Technology, AstraZeneca

2:00 KEYNOTE PRESENTATION: ‘Real-Time’ Monitoring of the Structure of a Monoclonal Antibody during Chromatographic Elution from a Protein A Affinity Column

Tim Dafforn, PhD, Professor, Biotechnology, University of Birmingham, United Kingdom

The biopharma industry’s increased familiarization with continuous processing technologies has led to the emergence of facilities operating semi-continuous or continuous production trains. However, for the benefits of continuous processing to be realised, it will be necessary to develop novel process analytical technologies (PAT). In this presentation, we describe the development of an automated high-throughput PAT system combining circular dichroism and fluorescence spectroscopies.


2:45 The Challenges of Deploying a QBD Approach for Accelerated and Breakthrough Status Programs

Naveen_PathakNaveen Pathak, PhD, Director, Process Development, Shire

Deploying QbD for breakthrough and accelerated products presents both a timeline challenge and an enabling opportunity. Product and process understanding, the foundation of Qbd strategy, is time and resource intensive. Strategies will be discussed that allow for acquisition of products and process understanding in a step wise fashion while acceleration of PPQ initiation. The enabling factors for such a strategy and the value proposition will be presented to demonstrate that QbD approach is the optimal approach to secure accelerated approval.

3:15 Cell Culture Media Characterization Strategy and Related Challenges in Commercial Manufacturing

Min_ZhangMin Zhang, PhD, Director, Manufacturing Sciences and Technology, AstraZeneca

In overall upstream process characterization strategy, a well-defined cell culture media characterization plan is deemed crucial and highly desirable to ensure a robust commercial manufacturing process. The media characterization strategy generally considers raw material variability (lot-to-lot, vendor-to-vendor), the optimal media preparation process, acceptable ranges for key scaling parameters, and related media preparation operational variability. This presentation outlines the media characterization strategy at AZ and how it impacts commercial manufacturing.

3:45 Sponsored Presentation (Opportunity Available)

4:00 Refreshment Break

4:15 Mass Spectrometric Monitoring of Critical Quality Attributes to Support ADC Process Characterization

Lintao_WangLintao Wang, PhD, Associate Director, Analytical and Pharmaceutical Development, ImmunoGen, Inc.

Biotherapeutic antibody-drug conjugates (ADCs) are tumor-targeting monoclonal antibodies covalently linked with potent cytotoxic agents. Due to the molecular complexity of ADCs, it is critical to understand, characterize and qualify the conjugation process to deliver quality products. For this purpose, mass spectrometric methods were developed and applied in process characterization studies to gain full understanding of the effects of the process parameters on the quality attributes of an ADC.

4:45 Targeted Profiling: Using NMR beyond Fingerprinting

Marc_AucoinMarc Aucoin, PhD, Associate Professor, Chemical Engineering, University of Waterloo, Canada

Together with a well curated database, an NMR spectra can be deconvoluted to reveal the composition of complex solutions such as cell culture media. In this talk, we will discuss the benefits and pitfalls of this technology in the characterization of insect and CHO cell culture processes. For the former, we have examined the contributions of yeast extract to chemically defined incest cell media, while for the latter, we have tracked compounds such GlutaMAX™ and acetate to better understand nucleotide-sugar precursor feeding for more uniform glycosylation of antibodies.

5:15 End of Day

6:00 - 9:00 Recommended Dinner Short Course*

SC13B: Implementing Phase Appropriate GMP for Manufacturing Biologics and Cell Therapy Products

Instructor: Trevor Deeks, PhD, QA/QC and GMP Consultant, Deeks Pharmaceutical Consulting Services, LLC

* Separate registration required.

Friday, August 17

8:00 am Registration Open and Morning Coffee


8:25 Chairperson’s Remarks

Udayanath Aich, PhD, Principal Scientist, Sanofi Genzyme

8:30 Data-Driven Determination of Potency Critical Quality Attributes for an ADC

Taro_FujimoriTaro Fujimori, PhD, MBA, Associate Director, Protein Analytics, Science and Technology Biologics, AbbVie Bioresearch Center

ADC-123 is an antibody drug conjugate comprised of an antibody (mAb-123: targets Receptor XYZ expressed on tumor cells) conjugated to a cytotoxin. ADC-123 has three activities that might contribute to anti-tumor activity: Delivery of cytotoxin to tumor cells with elevated levels of Receptor XYZ, Inhibition of Receptor XYZ signaling and Fc effector function. The primary mechanism of action for ADC-123 is delivery of the cytotoxin to tumor cells with elevated levels of Receptor XYZ.

9:00 Best Practices for Specification Setting: Regulatory Expectations for Specifications

Darrin_CowleyDarrin Cowley, PhD, Head, Development Quality, Biologics, AstraZeneca

Dr Darrin Cowley is currently Head of Development Quality, Biologics at AstraZeneca/MedImmune. He was previously Executive Director Product Quality at Amgen Inc. Prior to working at Amgen, he was Senior Process Scientist Abbott Laboratories Diagnostic Division. He trained in Genetics and Cell Biology and has a PhD in Biochemistry. Darrin has extensive experience in the development, filing and commercialization of a wide range of synthetic and biological molecules including biosimilars. In addition, he has experience with the development and approval of several types of combination products such as auto-injectors and on body injectors.

9:30 Microchip Electrophoresis-MS for Rapid Product Quality Determination and Control

Seth_MadrenSeth Madren, PhD, Scientist, Biogen

Therapeutic mAbs are highly heterogeneous, and Critical Quality Attributes (CQAs) of monoclonal antibodies need to be monitored or characterized to assure product safety and efficacy. In this talk, we present a high-throughput CE-MS method that enables not only near-real time CQA monitoring during cell culture process, but also fault detection as a result of wrong feed or contaminant. Potentially reducing failed batches and permitting possible corrective actions.

10:00 Networking Coffee Break


10:30 Real Time Online Chromatography Monitoring of Product Quality Attributes for Biologics Continuous Manufacturing Process

Gang_XueGang Xue, PhD, Scientific Director, Amgen

The ever-diversifying therapeutic modalities drive for modular and flexible bio-manufacturing. Process Analytics evolve as critical enabling element of the CM process. For the first time, we leverage a multi-functional automation system to directly take samples from the different stage of bio-process, purify, denature, derivatize and digest the samples before injecting onto the UHPLC and UHPLC/MS systems, one for online intact protein analysis, the other for Multiple Attribute Method (MAM) analysis for critical PTM PQAs.

11:00 Roadmap of In-Line Monitoring and Real Time Release (ILM-RTR): A Collaboration Effort by Biomanufacturers, Suppliers and Regional Research Hubs

Udayanath_AichUdayanath Aich, PhD, Principal Scientist, Sanofi Genzyme

The presentation describes a roadmap strategy published by BPOG in July 2017 with active collaboration of Biopharma industry and supply partners. The roadmap implementation is focused on the development of a user requirement strategy (URS) to prioritize the most relevant critical quality attributes (CQA) and critical process parameters (CPP) focusing on the critical control points and future short-, mid- and long-term goals to develop and apply innovative technologies for real time release.

11:30 Late Stage Cell Culture Concept – From Risk Assessments to Process Characterization

Eugen_ProbstEugen Probst, Senior Scientist, Late Stage Upstream Development, Boehringer Ingelheim, Germany
For the commercialization of the upstream process a comprehensive late stage development concept is required. The process knowledge gained during development and clinical manufacturing runs is compiled and utilized in a series of risk assessments to define the process characterization studies. The presentation summarizes the requirements and challenges for knowledge-based risk assessments, establishment of scale-down models and extensive process characterization.

12:00 pm Profiling and Monitoring of Quality Attributes in Biopharmaceutical Characterization, Process Development and QC

John Gebler, PhD, Director, Biopharma Business Development, Pharmaceutical Business, Waters Corporation

Aiming to support QbD, gaining greater understanding of biotherapeutics, an increasing trend of moving MS into lab settings traditionally associated with optical-based assays has been observed. This has facilitated the introduction of LCMS-based Multi Attribute Monitoring methods to increase productivity. Challenges associated with these approaches include monitoring PQAs in large datasets, setting specifications, and transferring methods from development to QC. Herein, we will demonstrate how these challenges can be addressed with a compliance-ready platform solution.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break


1:25 Chairperson’s Remarks

Parag Kolhe, PhD, Group Leader and Associate Research Fellow, Pfizer

1:30 A Systematic Approach to Establish Drug Product Control Strategy during Process Characterization

Parag_KolheParag Kolhe, PhD, Group Leader and Associate Research Fellow, Pfizer

The International Conference on Harmonization (ICH) Q8 (R2), Q9, Q10 and Q11 guidelines provide complementary guidance on pharmaceutical development, quality risk management, and quality systems, respectively, to ensure product quality using a scientific and risk-based approach. Process and product understanding are building blocks of control strategy to ensure consistent product quality. A case study will be presented which outlines the systematic approach that was taken for development of a vaccine.

2:00 Continuous, Online Antibody Quality Monitoring Using a Nanofluidic Device for Continuous Biomanufacturing

Taehong_KwonTaehong Kwon, Graduate Research Assistant, Electrical Engineering and Computer Science, MIT

Continuous biomanufacturing is a growing trend in biopharmaceutical industry. Monitoring the critical quality attributes of biologics is essential at all stages of manufacturing process. We recently developed a nanofluidic system for continuous-flow multivariate protein analysis for real-time critical quality assessments. In this talk, we introduce our latest work on the integration of perfusion culture using a membraneless microfluidic cell retention device with nanofluidic system enabling real-time product quality assessments.

2:30 Upstream Process Control Strategy: Beyond Keeping Consistency with the Past

Juhong_LiuJuhong Liu, PhD, Independent CMC Consultant

Advances in analytics and understanding of clinically relevant product quality attributes indicate current control strategy may no longer be sufficient to identify drifts before products reach patients. Recent events demonstrated unintentional or seemingly innocent changes to upstream processes can impact these attributes. Updates to existing process and product controls to rapidly discover product quality drifts not covered in the initial approval may be necessary.

3:00 A Systematic Approach to Establish Upstream Control Strategy During Process Characterization

Daniel_TongDaniel Tong, PhD, Research Scientist, Gilead Sciences

This case study describes a systematic approach from risk assessment to the establishment of upstream control strategy for process characterization of a mAb production process characterization. Upstream process characterization studies were planned with DOE tool and executed in qualified SDM bioreactors. CPPs and KPPs were identified using both statistical analysis and practical significance analysis. NORs and PARs were defined for each CPP and KPP based on Monte Carlo simulation.

3:30 Close of Conference


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