Protein Stability & Aggregation banner

The Protein Stability & Aggregation conference at PEGS Europe highlights new approaches in tackling protein aggregation by assessing protein self-association, non-specificity and folding/unfolding mechanisms, Additionally, the conference will discuss analytics for stability assessment and prediction, as well as explore the impacts on stability due to polysorbate challenges, viscosity measurements, and formulation.

Sunday, 13 November

Recommended Short Courses*14:00

SC1: Developability of Bispecific Antibodies 
*Separate registration required. See short courses page for details.

Wednesday, 16 November

Registration and Morning Coffee (Garden Room)07:30




Chairperson's Opening Remarks

Karoline B. Bechtold-Peters, PhD, Senior Strategy & Technology Leader, Pharmaceuticals & Biopharma Process, Novartis Pharma AG


Assessing the Isothermal Aggregation of Partially Unfolded Antibodies during Candidate Selection and Formulation Development

Hristo Svilenov, PhD, Associate Professor, Ghent University, Belgium

In this presentation, I will explain the importance of studying the aggregation of partially unfolded antibodies during candidate selection and formulation development. Furthermore, I will present and discuss orthogonal analytical approaches to study this phenomenon.


A Structure-Based Approach to Tackle Protein Aggregation in Parkinson's Disease

Salvador Ventura, PhD, Professor & Chair, Biochemistry & Molecular Biology, University Autonoma De Barcelona

a-Synuclein aggregation is a key driver of neurodegeneration in Parkinson’s disease. Here, we have exploited the structural properties of toxic oligomers and amyloid fibrils to identify a family of peptides that bind to these a-synuclein species with low nanomolar affinity, without interfering with the monomeric functional protein. This activity is translated into a remarkable anti-aggregation potency and the ability to abrogate oligomer-induced cell damage. With a structure-function relationship in hand, we identified human candidates expressed in the brain with exceptional binding, anti-aggregation, and detoxifying properties. These chemical entities represent a new therapeutic paradigm and are promising tools to assist diagnosis.

09:30 Measuring Change in Secondary Structure and Oligomeric State for a mAb in Stress and In-Process Testing with MMS and SEC

Daniel Myatt, PhD, Senior Scientist, Analytical Group, Centre for Process Innovation

Microfluidic Modulation Spectroscopy (MMS) is a new type of Mid-Infrared (MIR) spectroscopy with better sensitivity than traditional MIR and the ability to automate the measurement of samples over a large concentration range. In this talk, we examine the use of MMS to determine the secondary structure of stressed and in-process mAb samples and link these changes to aggregation of the target mAb as seen by size-exclusion chromatography (SEC).

09:45 Some Like it Hot – Thermal Ramp and Isothermal Stability Testing on Uncle

Joanna Winkler, PhD, Marketing Application Scientist, Unchained Labs

When developing a biologic, thermal ramps are fast and loaded with information (Tm and Tagg), but the full stability story needs results from long-term isothermal tests. Uncle – the all-in-one stability platform – now packs 5 isothermal apps to take the hassle out of long-term testing, so you can tackle it in early-stage screening. We’ll show data for proteins in several formulations and check out rapid viscosity data delivered from Honeybun.

Coffee Break in the Exhibit Hall with Poster Viewing (Verdi and Vivaldi 1&2)10:00



Development of New Methods for Characterization of Antibody Self-Association and Non-Specificity

Nikolai Lorenzen, PhD, Principal Scientist, Biophysics and Injectable Formulation, Novo Nordisk AS

The propensity of antibodies for non-specific interactions and self-association are some of the most important developability parameters. I will present highlights from ongoing collaborations with research groups at ETH Zürich and University of Cambridge, on the development of new methodologies that can help us to reliably measure and obtain a better understanding of these phenomena. The methodologies include custom-made microfluidics and A4F and they provide important data that complement existing methods.


3D-DLS: Benchmarking an Optical Microrheological Viscometer for Biologics Development

Joy Puthawala, Principal Research Associate, Sanofi

A key hurdle when developing high concentration biotherapeutics is the manifestation of high viscosity at therapeutic concentrations, which is problematic for both product manufacturing and final administration. Current standard methods, such as capillary rheometry, can be of limited use due to their sample consumption requirements. This presentation explores 3-Dimensional Dynamic Light Scattering optical microrheology as an attractive alternative to current development paradigms while considering its potential applications and practical limitations.


Biophysical and Functional Characterisation of IgG1 Antibodies with Engineered Hexamerization Propensity

Simone De Haij, PhD, Director Functional Characterization & Bioassays, Genmab BV

Mutations stimulating hexamerization can potentiate complement activation and clustering of cell surface receptors. Fc-Fc interactions are enhanced selectively at the cell surface and not in solution (controlled oligomerization). Case studies will be discussed with special emphasis on development of assays demonstrating hexamerization potential, functional and biophysical behavior during long-term stability, and impact of formulation.

12:15 Single Use Fluoropolymer Systems for Biomanufacturing: From Bench to Clinic

Julien Muzard, Field Applications Engineer, Life Sciences - EMEA, Entegris

Disposable technologies are now widely accepted as gold standard in the industry covering every single steps of the biomanufacture process. This presentation examines the benefits of fluoropolymer film that cope with a wide scope of applications (e.g. cell banking, cell & gene therapy, vaccinology, purified proteins at various scales. This presentation will be illustrated with recent case studies on carefully selected molecular entities (e.g. lactalbumin) and submicron particles of biopharmaceutical interest.

12:30 Fast, Simple and Convenient Solution to Monitor the Protein Functionality During Your Stability Studies

Ruizhi Wang, PhD, CEO & Founder, HexagonFab

We will showcase the protein binding assay to assess the functionality of your protein in as little as 25 min to aid your stability studies. Current protein analysis instruments predominantly use optical technology and thus require sophisticated and bulky equipment that leads to high running costs and maintenance schedules. HexagonFab’s first product, Bolt, runs automated protein binding assays with minimal hands-on time, by dipping electrical sensors in your samples of interest.


Session Break12:45

Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:50

Dessert Break in the Exhibit Hall & Last Chance for Poster Viewing (Verdi and Vivaldi 1&2)13:50

Breakout Discussions14:45

Breakout Discussions are informal, moderated, small-group 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 while sitting with delegates around a table. For virtual attendees, the format will be in an online networking platform. 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. 


Assessment of Self or Non-Specific Interactions of Therapeutic Proteins and ADCs (IN-PERSON ONLY)

Bernhard Valldorf, PhD, Principal Scientist & Lab Head, Formulation Development, EMD Serono

  • In silico molecular descriptors – how well can we predict aggregation behavior of mAbs or fusion proteins? Where are the limitations? 
  • What is your favorite method/tool to characterize self-association and why?
  • How do conjugation sites and methods influence self or non-specific interactions? How can we assess developability of ADCs?  
  • What kind of short-term dataset is required to predict long-term stability? 
  • High-concentrated formulations – how can we prevent aggregation with new excipients or technical solutions?​​

Polysorbate Challenges in Biotherapeutic Formulations (IN-PERSON ONLY)

Camille Dagallier, PhD, Senior Formulation Scientist, Biologics Drug Product Development & Manufacturing, Sanofi R&D

  • Root causes for polysorbate degradation
  • Mitigation strategies against polysorbate degradation
  • Alternative approaches and surfactants



Chairperson's Remarks

Salvador Ventura, PhD, Professor & Chair, Biochemistry & Molecular Biology, University Autonoma De Barcelona


Long-Term Stability Predictions of Therapeutic Proteins in Solution from Short-Term Stability Data

Matjaz Boncina, PhD, Associate Director, Biologics Drug Product, Technical Research and Development, Global Drug Development, Novartis

Stability data are key aspects of drug development and although being relatively simple on one hand they are very time-consuming on the other hand. Achieving robust and reliable long-term stability predictions from accelerated stability studies would be a holy grail of biologics development. In this presentation, I will demonstrate accurate long-term stability predictions of multiple quality attributes for some proteins from short-term accelerated stability studies by using simple kinetic models.


Impact of Conjugation Site Selection & Method on the Stability and PK of ADCs

Christian A. Schroeter, PhD, Associate Director, ADCs & Targeted NBE Therapeutics, Merck KGaA

Appropriate selection of conjugation sites and conjugation technologies is now widely accepted as crucial for the success of antibody-drug conjugates (ADCs). Herein, we present ADCs conjugated by different conjugation methods to different conjugation positions being systematically characterized by multiple in vitro assays as well as in vivo pharmacokinetic (PK) analyses in transgenic Tg276 mice.

16:30 The Use of Osmolality in Assessing Protein Stability and Aggregation

Kendal Studd, Scientific Support Specialist, Application Sciences, Advanced Instruments LLC

Understanding the causes of protein instability and aggregation is critical in the biomanufacturing space. One method that is showing renewed interest in biomanufacturing, is osmolality. This well-established technique for measuring the concentration of a solute, has been shown to be impactful in a number of applications; AAV manufacturing, mAb production and downstream UF/DF processes. Today’s seminar will provide insights on the use and benefit of osmolality in protein stabilization and aggregation.



Highly Concentrated SubQ Formulations and Tackling Protein Aggregation

Karoline B. Bechtold-Peters, PhD, Senior Strategy & Technology Leader, Pharmaceuticals & Biopharma Process, Novartis Pharma AG

Subcutaneous administration of therapeutic proteins has gained increasing importance and allows many benefits for patients. However, since application volumes are limited compared to IV, much higher protein concentrations must be achieved, which promote protein-protein interactions and possibly protein aggregation. Recent developments target excipients that prevent this or completely different technical solutions, namely concentrated suspensions instead of solutions. SubQ application should be in mind already in the design phase of drugs.


The Polysorbate Challenges in Biotherapeutic Formulations – Digging into the Mechanism of Metal-Catalyzed Oxidation of PS80 & mAb to Develop Mitigations

Camille Dagallier, PhD, Senior Formulation Scientist, Biologics Drug Product Development & Manufacturing, Sanofi R&D

Polysorbates commonly used as surfactants in biotherapeutic formulations are known to be prone to degradation, mainly by oxidation or enzymatic hydrolysis. Results of a study that examined the oxidation of polysorbate 80 (PS80) and of a monoclonal antibody (mAb) are presented. In particular, the impact of different conditions and factors was evaluated, focusing on different formulation components and on the presence of iron contaminants.

  • Root causes for polysorbate oxidation
  • Mitigation stratégies against polysorbate oxidation
  • Alternative approaches and surfactants

Understanding Protein-Protein Interaction in Protein Coformulation Drug Product

Jing Song, Associate Principal Scientist, Analytical Enabling Capabilities, AR&D, MSD

Development of co-formulated protein products is one of the enhanced formulation strategies to obtain a better product aiming to overcome resistance, eliminate co-administration errors, reduce cost in clinics and provide patients with convenience. Potential protein-protein interactions in the co-formulated products, however, cause potential risks in product stability, biological activities, lead to pharmacokinetic interactions, and impact clinical safety. To ensure the safety and efficacy of the co-formulated products, a risk assessment and phase-appropriate approach for protein-protein interaction characterization are recommended, especially on their impact on the critical quality attributes of the protein components during co-formulated protein product development. 

Close of Summit18:30