Analytical Characterisation of Biotherapeutics banner

The Analytical Characterisation of Biotherapeutics presents a forum for scientists to share their experiences in supporting the R&D to CMC for novel formats and complex modalities, by looking at advanced techniques and solutions, such as multi-attribute methods, microfluidics and analytical ultracentrifugation, to help bring these novel biotherapeutics to clinic and to market.

Sunday, 13 November

Recommended Short Course*14:00

SC4: Potency Assays and Comparability for Cell & Gene Therapies
*Separate registration required. See short courses page for details.

Tuesday, 15 November

Registration and Morning Coffee (Garden Room)07:30




Chairperson's Opening Remarks

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


Harmonised MAM Platform across Sanofi CMC Development Sites for Process Support and Characterization

MAM allows a CQA-driven CMC development according to QbD approach, providing a better process and product knowledge, decreasing comparability risk, and enabling easy site-to-site transfer. MAM allows to follow efficiently the biologics process development in a fast and cost-effective way. We will present our MAM platform including automated sample preparation, LC-MS, data treatment automation, the inter-sites comparability, examples for batch analysis, cell culture, and purification development.


A Rapid and Routine-Friendly Multi-Attribute Method (MAM) for the Monitoring of Critical Quality Attributes in Biotherapeutic Monoclonal Antibodies

Monitoring the critical quality attributes (CQAs) of therapeutic proteins to ensure their quality, safety, and efficacy is essential. Bottom-up LC-MS is a versatile methodology that could be added to the routine QC toolbox for monitoring degradative events of therapeutic antibodies. However, due to the time-consuming sample preparation and complex data interpretation its applicability for routine product quality monitoring is likely to be limited. Here, we present a rapid and QC-friendly multi-attribute method that can accomplish identity testing, N-glycan mapping, sequence variant analysis, and the monitoring of a variety of PTMs.


Challenges and Solutions in MAM-Based Workflows – Recent Case Studies from a Biopharmaceutical Development Lab

Multi-attribute method (MAM) using mass spectrometric detection and quantitation of biopharmaceutical quality attributes, at the amino acid level, is used extensively in biopharmaceutical development and increasingly for cGMP testing. At Symphogen challenges are regularly observed with conventional trypsin-based MAM workflows, due to poor LC MS performance of critical tryptic peptides of some products. Case studies highlighting challenges using conventional MAM, and solutions using alternative approaches, will be presented.

10:00 All-in-One Solution to Measure Molecular Interactions? The Bruker SPR Pro Series

Sven Malik, Senior Application Specialist, Applications, Bruker Daltonics SPR

Here we describe the possibilities of the Pro series instruments from Bruker that empowers the scientists with many tools or ways to perform their work. The systems use a valve-less microfluidic system enabling fast transitions from sample to buffer, state-of-the-art sensitivity and robustness to allow for the analysis of all types of samples, from ions to crude samples. High flexibility in assay development is ensured by individual sensor spot addressing options.

10:15 Automating Biopanning in Phage Display and Determining Immunogenic Affinity in Whole Blood with FO-SPR.

Filip Delport, PhD, CTO, Systems Research & Development, FOx BIOSYSTEMS

SPR turned inside out with an optical fiber dip sensor enables binding characterization in crude samples and on large particles. Large particle sensing, including isolation, is presented in semi-automated biopanning on phage-display, and provides immediate readout in panning cycles and in kinetic characterization. Highlighted by a study on COVID samples FO-SPR allows kinetic affinity measurement in whole blood samples, potentially applied to clinical severity of disease or response to therapies.


Session Break and Transition into Plenary Keynote10:30




Plenary Keynote Introduction


Evolution of Antibody Technologies

It is nearly fifty years since the discovery of monoclonal antibodies, the first drug approval coming soon after in 1986. From this early success, approval rates took time to ramp up and significant efforts were focused on building a range of technologies to deal with the technical challenges of antibody-drug discovery. This talk will discuss how antibody technologies have evolved and consider where future innovation may lie.

Coffee Break in the Exhibit Hall with Poster Viewing (Verdi and Vivaldi 1&2)11:30


Chairperson's Remarks

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


Building Analytical Platform to Enable Efficient Drug Development

Platform analytical approaches lead to higher efficiency during drug development which has been evident with the development of mAbs in the past two decades. Recently, the advent of other therapeutic modalities, such as gene therapy and antisense oligonucleotide-based products, has brought on a desire to apply the same strategy in standardizing their analytical approach. The emerging analytical platforms and their application will be discussed for these modalities.

12:45 Faster Titer and Impurity Analysis with Automated Immunoassays

Jose L. Moreno, PhD, Field Application Specialist, Engineering, Gyros Protein Technologies AB

 Immunoassay platforms are utilized for bioanalysis in biotherapeutic development, and the critical need to generate high quality data, support efficient method development and release tests for both CMC and final product manufacturing remains. The Gyrolab technology, automating immunoassays like ELISA, has been identified to be a reliable and robust platform for high-throughput titer and impurity analysis, contributing to an increased productivity and reduced hands-on time.

Session Break13:15

13:20 Integrating The Carterra LSA High-Throughput SPR Array in to UCB’s Antibody Discovery Platform

Oliver Zaccheo, PhD, Senior Group Leader, SPR and Biophysical Assays, UCB

Surface Plasmon Resonance (SPR) provides a key screen to identify and characterise high-affinity, species cross-reactive antibodies generated by UCB’s Core antibody discovery platform. We have performed a head-to-head comparison of the Biacore 4000 and Carterra’s LSA (high-throughput SPR array) and shown that the LSA is well-suited to the challenge of generating high-quality, high-throughput antibody binding data from individual b-cells. We have now incorporated the LSA to our routine workflows to guide molecule selection based on kinetic binding data and epitope binning. 

13:50 Binding Kinetics with WAVEsystem for Innovative Drug Development

David Moreno Delgado, PhD, Group Leader, Early Drug Discovery, Galapagos

Binding kinetics are important parameters enabling and extending the understanding of small molecule and target interactions. In Galapagos, we have used RAPID mode in WAVEsystem to determine kinetic constants but also to investigate different modes of action. Come and discover the story of how we used WaveRAPID and its impact in our drug discovery programs.

Session Break14:20



Chairperson's Remarks

Bernice Yeung, PhD, Head of Analytical Development, Chemistry, Biogen


Applications of a Real-Time, Optical Technique for Quantifying Proteins Directly within Mixtures

We have developed a novel, label-free optical technique for quantifying proteins directly within mixtures in real-time. Applied to chromatographic separations, the elution profiles of two biophysically-similar proteins can be tracked independently even when there is overlap in their elution profiles. We are also developing ligand-binding assays based on our virus laser technology. In this talk, I will explore applications of the technologies including the characterisation of bispecific antibodies.


Combining Mammalian Libraries and Microfluidics for Versatile Antibody Hit Discovery and Optimization

POC studies applying mammalian libraries for both antibody optimization (screening for manufacturability and selectivity), as well as microfluidics-assisted high-throughput cellular binding or functional screening, exemplify the versatility and powerful options when combining these two emerging technologies.

15:35 Automated Assessment of Multiple Attributes of Monoclonal Antibodies Using Multidimensional LC-MS

Jelle De Vos, Senior Scientist, RIC biologics, RIC group

Unraveling the structural complexity of monoclonal antibodies demands for a range of complementary analytical tools. Using multidimensional LC (mD-LC), several of these methodologies can be combined in one automated platform allowing simultaneous assessment of different structural characteristics. In this presentation various mD-LC-MS protein analyzers will be discussed and their application to real life samples will be demonstrated.

Refreshment Break in the Hall with Poster Viewing (Verdi and Vivaldi 1&2)16:05


Microfluidic Characterisation of Extracellular Vesicles

We present a microfluidic device capable of simultaneously characterizing multiple properties of extracellular vesicles (EVs) such as size, concentration, composition, presence of specific subpopulations, and purity. The method requires a limited amount of material and minimal sample handling.


Botulinum Toxin Structural Dynamics Using Hydrogen/Deuterium Exchange Mass Spectrometry

Botulinum toxins are inherently dynamic and are therefore highly suited to hydrogen/deuterium exchange mass spectrometry (HDX-MS) studies. The work presented describes the HDX-MS workflow for Botulinum toxin and investigates structural changes that occur upon binding to the toxin receptor SV2c. By furthering our understanding of botulinum toxin structure and mechanism of action we can further optimise this class of molecules as biopharmaceutical products.


AAV Characterization by Multi-Wavelength Analytical Ultracentrifugation

Multi-wavelength analytical ultracentrifugation offers two highlyprecise and orthogonal characterization methods in one experiment to identify the ratio of any loadingstate of AAV virions, ranging between empty capsids to overfilled capsids. Furthermore, our method is able to detect contaminants such as protein aggregates and free nucleic acids. The method can be performed in sedimentation velocity mode, providing ultimate resolution, extended molar massdynamic range, and highly accurate molar ratios for protein and DNA. The method is performed in a physiological buffer. The second method employs analytical buoyant density equilibrium (ABDE) sedimentation, which offers higher throughput and sensitivity, and much lower sample requirements. For both methods, multi-wavelength decomposition of the hydrodynamic dimension additionally provides an orthogonal characterization dimension, further improving the resolution of this approach. In this talk I will present examples, and discuss the experimental approaches used to characterize viralvectors and their nucleic acid cargo load by multi-wavelength analytical ultracentrifugation.


The Biophysical Characterisation of a SARS-CoV-2 Self-Amplifying mRNA Vaccine

The current COVID-19 pandemic has accelerated the development of mRNA vaccine technology. The production of these large mRNA vaccine molecules has required concomitant development of novel analytical characterisation techniques. In this talk, I describe the use of several biophysical techniques, including DLS, CD, and SEC-SAXS to determine size, shape, and structure of an RNA vaccine molecule.

Close of Analytical Characterisation of Biotherapeutics Conference19:00