Cambridge Healthtech Instituteの第4回年次会議

Analytics and Characterisation
(アナリティクスと特性評価)

新しいバイオ医薬品のモダリティとプロセス制御の向上に対する新興技術

2023年3月14 - 15日、CET(中部欧州標準時)

新しい製品フォーマットの開発が進み、規制プロセスに入るにつれ、アナリティクスの特性評価の役割は新しい意味を持ちつつあります。非常に新しいモダリティは、アナリティクスの科学者と規制当局の両方に同様の課題をもたらします。この急激な学習曲線には、適応とイノベーションのほぼ一定のサイクルが必要です。第4回「アナリティクスと特性評価」年次会議では、新規のバイオ医薬品を評価するための新しい技術ソリューションと、最適化された上流工程・下流工程のバイオプロセスにおけるプロセスアナリティクスの役割の増大に対応するための対話が検討されます。

3月14日(火)

Registration and Morning Coffee07:00

EXPANDING THE USABILITY AND APPLICATIONS OF MS
MSの有用性と用途の拡大

08:25

Chairperson's Remarks

Yunlong Zhao, PhD, Staff Scientist, Analytical Chemistry, Regeneron Pharmaceuticals, USA

08:30

LC/MS for Host Cell Protein Monitoring and Characterization

Thomas Waerner, PhD, Senior Principal Scientist & Laboratory Director, Analytical Development & Quality Control, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany

Host cell proteins (HCPs) are process-related impurities that must be adequately cleared from recombinant biopharmaceuticals during the downstream process to ensure product quality, purity, and patient safety. It is well known that some HCPs with very little abundance have a strong impact on product quality. Understanding how HCPs escape the purification process and the detection of those HCPs is a prerequisite for developing a suitable HCP depletion process. Here, we assess our research on methods for detection of low abundant HCPs by MS/MS and compare 3 different methods (Hexapeptide-, partial digest, and immunoaffinity-chromatography) to enrich HCP levels in samples.

09:00

A New Affinity CE-MS Approach to Assess Antibody-Fc Receptor Interaction

Christoph Gstoettner, PhD, Postdoctoral Researcher, Center for Proteomics and Metabolomics, Leiden University Medical Center, Netherlands

Monoclonal antibodies consist of a mixture of different proteoforms (e.g. glycoforms) with potentially different functionalities. mAbs activate the immune response via binding to Fc receptors. Therefore, it is important to study their binding to individual mAb proteoforms. Common approaches, such as SPR, provide an overall affinity response for all mAb proteoforms. In this presentation, we want to show an innovative approach based on sheathless CE-MS to study relative affinities of different mAb proteoforms in mixtures towards the FcRn and FcyRIIa receptors. Overall our approach has the capability to boost the study of interactions in a proteoform-resolved manner.

09:30 Advanced Orthogonal Methods to Fully Characterize Process HCPs

Eric Bishop, Vice President of Research and Development, Research and Development, Cygnus Technologies

In recent years we have learned that Host Cell Proteins (HCP) can cause problems with respect to patient safety, Drug Substance (DS) stability, and DS efficacy.  As such, it is more important than ever to fully understand the HCPs in your process.  This talk will focus on using advanced methods of immunoaffinity chromatography and mass spectrometry to fully characterize the Host Cell Protein ELISA as well as the individual HCPs in in-process and DS samples.

Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing10:00

10:45

Developing Protein Interaction Analysis by Chemical Crosslinking and Mass Spectrometry into a Diagnostic Tool

Franz Herzog, PhD, Professor and Head, Mass Spectrometry, Bioanalytics, FH Krems University of Applied Sciences, Germany

Chemical crosslinks identified by mass spectrometry have been widely applied to study the architectures of protein complexes and networks even in organelles and whole cells. The quantification of crosslinks will provide information on the mechanism of protein complexes like binding affinities and interfaces. Capturing changes in protein interactions in samples like biopsies will aid understanding the molecular basis of diseases at the system level and the classification of disease types.

11:15

Automated Iterative LC-MS/MS (HCP-AIMS) for Therapeutic Protein Development

Yu Huang, PhD, Staff Scientist, Analytical Chemistry, Regeneron Pharmaceuticals, Inc., USA

To meet challenges in host cell protein (HCP) analysis during drug development, especially downstream process development, which entails fast turnaround time and robustness while identifying high level of HCPs and their clearance trend for further purification development, we have developed HCP-automated iterative MS (HCP-AIMS): It is a simple, automated, and robust HCP workflow with deep and unbiased identification and relative quantification capability. This HCP-AIMS approach only requires easy direct digestion of the samples without enrichment or pre-treatment. With the fully automated precursor ion exclusion in MS/MS mode, low-abundance HCP peptides could be selected for MS/MS analysis in iterative replicates.

11:45 KEYNOTE PRESENTATION:

Addressing Challenges in Sample Preparation and Chromatographic Performance of MS-Based MAM Workflows

Dan Bach Kristensen, PhD, Principal Scientist, Symphogen, Denmark

Peptide mapping by LC-MS, and the related Multi-Attribute Method (MAM), are powerful and well-established tools for mapping and quantitation of quality attributes at the amino acid level in biopharmaceutical development. Here, alternative MAM workflows based on automatic hands-off digestion are presented, which significantly 1) reduced the number of missed cleavages compared to established workflows, and 2) radically reduce chromatographic peak tailing and carry-over of hydrophobic peptides.

12:15 Getting to Know Your Protein; a CDMO's Perspective

Daniel Pettit, Director of Analytical Development, Process Development Operations, FUJIFILM Diosynth Biotechnologies

Daniel will discuss analytical challenges associated with the analysis and characterisation of biologics, both in terms of the broad diversity of molecular entities and the complexity of manufacturing processes.  Daniel will discuss the orthogonal approach towards ‘getting to know your protein’ and will highlight current challenges now and in the future with the emergence of next generation therapeutics, high throughput process development and continuous manufacturing.

Networking Lunch (Sponsor Opportunity Available)12:45

EMERGING METHODS AND INSTRUMENTS
新興の手法と機器

13:45

Chairperson’s Remarks

Franz Herzog, PhD, Professor and Head, Mass Spectrometry, Bioanalytics, FH Krems University of Applied Sciences, Germany

13:50

Preclinical in vitro Studies on Parameters Governing Immune Complex Formation

Paul Wassmann, PhD, Senior Principal Scientist, NIBR Biologics Center, Novartis, Switzerland

With the introduction of combined modalities like bispecifics, ADCs, and fusion proteins the complexity of biotherapeutics has experienced a significant increase over the last decades. Herewith associated, the risk of adverse events in patients becomes a critical safety aspect. Understanding the mechanisms, which underlie immunogenicity of biotherapeutics, is a key component for earlier identification, monitoring, and counteracting of such liabilities. Our study provides an in-depth analysis of cross-related factors that govern the formation of ADA-driven immune complexes. Besides, a critical evaluation of analytical methodology will be provided.

14:20

Knowing More from Less: A Microfluidic Analytical Toolbox for the Monitoring of Bioprocesses

Ines Fernandes Pinto, PhD, Postdoctoral Researcher, KTH, Sweden

The development of miniaturized systems with automation of analytical methods represents an attractive approach to achieve a better understanding of cell culture processes. In this context, we developed a novel microfluidics-based modular system to be coupled to a mAb-producing mammalian cell bioreactor aiming at performing (1) multiplexed immunodetection of relevant proteins, (2) evaluation of glycosylation profile of the target mAb, and (3) analysis of amino acids using microchip capillary electrophoresis.

14:50 Talk Title to be Announced

Speaker to be Announced

Refreshment Break in the Exhibit Hall with Poster Viewing15:20

15:40

Identifying Product-Related Impurities with TRIFLE

John Hales, PhD, Biochemical Engineering, University College London, United Kingdom

Time-resolved intrinsic-fluorescence-lifetime extraction (TRIFLE) is an emerging analytical technology for quantifying product and impurities in real-time. TRIFLE can be used to identify and quantify biophysically-similar proteins even when there is overlap in their chromatographic elution profiles. I will discuss examples of TRIFLE being used to identify product and product-related impurities for different modalities, including mAbs and viral vectors, and I will introduce our work on another analytical technology: virus lasers.

16:10

LC-MS and LC-IM-MS Software for Analysis of Glycopeptides and Released Glycans in Bioprocessing

Ian Walsh, PhD, Senior Staff Scientist, Bioprocessing Technology Institute (A*STAR), Singapore

A significant burden in biomanufacturing is the characterization of glycans and glycopeptides on biopharmaceuticals. To address the need for customized software to handle multi-attribute data arising from combinations of liquid chromatography, ion mobility, and mass spectrometry (LC-IM-MS), two semi-automated software programs for released glycan and glycopeptide characterization and quantitation are described. Both programs can identify glycans/glycopeptides more accurately and quicker compared to other methods.

16:40

Glycine Additive Facilitates Site-Specific Glycosylation Profiling of Biopharmaceuticals by Ion-Pairing Hydrophilic Interaction Chromatography Mass Spectrometry

Yunlong Zhao, PhD, Staff Scientist, Analytical Chemistry, Regeneron Pharmaceuticals, USA

Glycine as a signal-boosting additive solves the dilemma between excellent peak separation and sufficient MS sensitivity for glycopeptide analysis using regular-flow ion-paring HILIC-MS. Here we present showcases where this platform was applied to support early and late stages of biopharmaceutical development, including quick glycosylation profiling of monoclonal antibody and fusion proteins, discovery of atypical glycosylation sites of low occupancy in monoclonal antibody, and targeted-based subclass-specific IgGs N-glycosylation profiling in serum.  

Interactive Discussions17:10

Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. For in-person events, the facilitator will lead from the front of the room while attendees remain seated. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussion page on the conference website for a complete listing of topics and descriptions.


Presentation to be Announced17:10

Welcome Reception in the Exhibit Hall with Poster Viewing17:40

Close of Day18:45

3月15日(水)

Registration and Morning Coffee08:00

ANALYTICAL SUPPORT FOR PRODUCT QUALITY MONITORING AND CONTROL
製品品質の監視・管理向けアナリティクス支援

08:25

Chairperson’s Remarks

Christine Carapito, PhD, Co-Head of the BioOrganic Mass Spectrometry Laboratory, CNRS Research Director, University of Strasbourg, France

08:30

MAM (Multi-Attribute Methods) in Process Characterization and Control

Dietmar Reusch, PhD, Director, Development Analytics, Roche, Germany

Multi-attribute monitoring (MAM) by LC-MS has gained increased interest by Biopharma companies to replace multiple traditional assays in the control system. In this presentation, we will provide Roche/Genentechs perspective on the practical considerations and strategies on MAM use in quality control and replacement of traditional assays, including target attribute selection, new peak detection for stability studies, and bridging strategies to justify traditional assays replacement with MAM.

09:00

FEATURED PRESENTATION: Advanced Sample Preparation, LC-MS/MS and Data Processing Workflows for Host Cell Protein Impurities Quantification

Christine Carapito, PhD, Co-Head of the BioOrganic Mass Spectrometry Laboratory, CNRS Research Director, University of Strasbourg, France

The quantification of individual host cell proteins (HCP) is a major analytical challenge that bottom-up proteomics workflows start tackling. The implementation of new standards for robust and accurate quantification of HCP will be presented. The potentialities of Data Independent Acquisition coupled with ion mobility separation will be assessed on various latest-generation instrumental platforms. Finally, benefits of using innovative artificial intelligence algorithms for data processing will be highlighted.

09:30

The Role of CQAs for Product Quality Control from Manufacturing to Shelf Life

Dirk Haubert, PhD, Analytical Project Lead, Biologics, Novartis Pharma AG, Switzerland

Product quality is controlled at all stages of the manufacturing process, at release, and on stability to define the shelf life. Criticality assessment of each product quality attribute provides the basis for defining the required level of control. By combining available knowledge of the molecule’s degradation behavior with understanding how the individual steps of the manufacturing process impact critical quality attributes, a smart control strategy can be developed allowing for manufacturing flexibility without compromising quality and safety of the product.  

10:00 Talk Title to be Announced

Speaker to be Announced

Coffee Break in the Exhibit Hall with Poster Viewing10:30

PLENARY SESSION: EMERGING MODALITIES, PLATFORMS, AND TECHNOLOGIES - FROM mRNA TO PROTEINS
基調講演:新興のモダリティ、プラットフォーム、技術 - mRNAからタンパク質へ

11:15

Chairperson's Opening Remarks

Margit Holzer, PhD, Owner, Ulysse Consult

11:20 PLENARY PRESENTATION:

Overcoming CMC and Supply Chain Challenges for mRNA Technologies

Gregory Troiano, Chief Manufacturing Officer, mRNA Center of Excellence, sanofi

Thanks to the rapid development of mRNA vaccines for COVID-19, the industry now has the momentum and resources to overcome many of the early CMC challenges and realize its enormous potential. This presentation will discuss the strategies in place to overcome CMC and supply chain challenges for mRNA technologies already and future innovations primed to take it to the next level.

11:50 PLENARY PRESENTATION:

Affinity Proteins for Biotechnological and Medical Purposes

Sophia Hober, PhD, Professor, School of Biotechnology, KTH Royal Institute of Technology

Affinity proteins are crucial for life, for building structures, performing reactions, and for signaling purposes. In life sciences and medicine, affinity proteins are used to generate knowledge, but also for diagnostic and therapeutic purposes. This talk will cover how antibodies and small affinity molecules can be used to map the human proteome, develop diagnostic tools for in vivo visualization as well as efficiently purify therapeutics based on antibodies.

Transition to Sessions12:20

Sponsored Presentation (Sponsor Opportunity Available)12:30

Networking Lunch (Sponsor Opportunity Available)13:00

Close of Analytics and Characterisation14:00

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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Prelim Agenda Now Available

3月14 - 15日

CELL CULTURE AND BIOPRODUCTION

ADVANCES IN RECOVERY & PURIFICATION

GENE THERAPY CMC AND ANALYTICS

CELL THERAPY MANUFACTURING

ANALYTICS AND CHARACTERIZATION

3月14 - 15日

CELL LINE DEVELOPMENT

INTENSIFIED & CONTINUOUS PROCESSING

GENE THERAPY MANUFACTURING

CELL THERAPY CMC AND ANALYTICS

FORMULATION AND STABILITY