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Cambridge Healthtech Institute’s 11th Annual

Protein Aggregation and Emerging Analytical Tools
( 蛋白质聚集和新分析工具 )

Mechanism, Prediction, Immunogenicity, Developability, and Process Challenges

1月23日~24日

Part of the Formulation & Stability pipeline

The popular 11th Annual Protein Aggregation and Emerging Analytical Tools conference covers latest trends, challenges and solutions in understanding, characterization and mitigation of problems generated by protein aggregation in biopharmaceuticals. This conference will feature in-depth case studies, new and unpublished data and interactive discussions on immunogenicity of aggregates, mechanisms of aggregation, new tools for detection and quantitation of aggregates, and how the data is used in regulatory filings. It will also discuss mechanistic understanding of protein aggregation and present case studies on prevention of particle formation by engineering and formulation approaches, aggregation in ADCs, bispecifics, impact of aggregation on production, aggregates as a factor for immunogenicity, and approaches for improvement of biophysical properties of protein solutions.

We invite you to join with colleagues from around the world in this discussion of the key challenges and solutions in protein aggregation in biotherapeutics.

Final Agenda

1月21日(二)

5:45 - 8:45 Recommended Dinner Short Course*

 

SC5: Protein Aggregation: Mechanism, Characterization, and Consequences

Instructors:

Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire

Kevin Mattison, PhD, Principal Scientist, Malvern Pananalytical, Inc.

 

*Separate registration required 

1月23日(四)

7:45 am Registration and Morning Coffee

Understanding and Predicting Protein Aggregation

8:10 Organizer’s Welcome Remarks

Nandini Kashyap, Conference Director, Cambridge Healthtech Institute

8:15 Chairperson’s Opening Remarks

Peter Schurtenberger, PhD, Professor, Department of Chemistry, Lund University

 

KEYNOTE PRESENTATION

8:20 Understanding and Predicting Self-Association in High Concentration Antibody Solutions – A Colloid Approach

Peter Schurtenberger, PhD, Professor, Department of Chemistry, Lund University

We address the problem of enhanced self-association in high concentration antibody solutions and the concomitant high viscosities. In order to understand and predict the thermodynamic and flow properties of such formulations, we provide the first quantitative description of mAb self-association and viscosity as a function of concentration by combining experiments (static and dynamic scattering and microrheology), theory and computer simulations using a model based on analogies to patchy colloids.

9:00 Estimating Solution Nonideality from Measured Values

Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire

The concentration-dependent chemical potential of a species results from the sum of its repulsive and attractive interactions with neighboring species. The repulsive and attractive terms can be estimated using measured values of size, charge and association constants from a combination of one- and two-component solution measurements. The underlying concepts will be explained and the need for measured values will be highlighted.

9:30 Presentation to be Announced

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

In vivo Aggregation and Immunogenicity

11:00 Application of an in vitro Skin Model System to Assess Potential Risk of in vivo Aggregation and Immune Activation of Biotherapeutic Attributes

Josh Tokuda, PhD, Postdoctoral Fellow, Biological Relevance and Characterization, Amgen, Inc.

In this presentation, a new human in vitro skin model system will be presented that can be used to assess the potential of biotherapeutics to aggregate and cause immune activation in vivo.

11:30 PANEL DISCUSSION: Prediction and Control of in vivo Aggregation and Immunogenicity

Discussion Points:

  • Current Challenges
  • New Predictive Tools
  • Data Analysis and Management
  • Use of Artifical Intelligence in Better Prediction and Control

Moderator:

Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire

Panelists:

Peter Schurtenberger, PhD, Professor, Department of Chemistry, Lund University

Josh Tokuda, PhD, Postdoctoral Fellow, Biological Relevance and Characterization, Amgen, Inc.

John J. Correia, PhD, Professor, Department of Biochemistry, University of Mississippi Medical Center

Reza Esfandiary, Associate Director, Early Stage Formulation Sciences, BioPharmaceutical Development, AstraZeneca

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Session Break

12:40 Luncheon Presentation to be Announced

1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing

In silico Modeling, Tools, and Assay

2:15 Chairperson’s Remarks

Christoph Brandenbusch, PhD, Group Leader, Biochemical and Chemical Engineering, TU Dortmund

2:20 FDS-AUC Analysis of mAb Nonideality and Self-Association in Serum and Formulation Solutions

John J. Correia, PhD, Professor, Department of Biochemistry, University of Mississippi Medical Center

The Aviv Fluorescence Detection System (Aviv-FDS) has allowed the performance of sedimentation velocity experiments on therapeutic antibodies in highly concentrated environments, like serum and formulation buffers. Methods have been implemented in the software package SEDANAL for the analysis of nonideal, weakly associating AUC data acquired on therapeutic antibodies and proteins using absorbance or FDS optics. This involves determining both hydrodynamic nonideality Ks and thermodynamic nonideality BM1 plus association constants.

2:50 Mitigation of Reversible Self-Association and Viscosity of Monoclonal Antibodies via Structure-Guided Protein Engineering: Complementing Analytical and i n silico Tools

Reza Esfandiary, Associate Director, Early Stage Formulation Sciences, BioPharmaceutical Development, AstraZeneca

High protein concentrations can introduce additional development challenges due to issues such as reversible self-association or high viscosity. Protein engineering can provide a complementary mitigation approach to formulation optimization in improving high concentration developability properties. Here, case studies utilizing complementary analytical and in silico methods are presented where molecular hotspots in monoclonal antibodies, responsible for high concentration issues, are systematically identified and engineered to generate variants with improved developability profiles.

3:20 Networking Refreshment Break

3:45 Thermodynamics-Based Approach for Predicting Aggregation Propensity and Beneficial Solution Conditions in Antibody Formulations

Christoph Brandenbusch, PhD, Group Leader, Biochemical and Chemical Engineering, TU Dortmund

Protein aggregation is caused by the molecular interactions of all components in solution. We developed a thermodynamics-based approach to predict beneficial solution conditions taking the competition for water by a specific excipient, as well as the molecular interactions of the proteins in the presence of excipients into account. This allows predicting a first estimate on aggregation propensity induced by the respective excipients and thus enables a first choice of preferential excipients with a minimum of experimental effort.

4:15 Discerning the Synergistic Effect of Hydrodynamic Flow and Interfaces on Protein Aggregation

Paolo Arosio, PhD, Professor, Biochemical Engineering, Department of Chemistry and Applied Biosciences, ETH Zurich

Despite being an area of extensive investigation, the effect of hydrodynamic flow and shear on protein aggregation is still controversial. Here, we demonstrate the presence of a synergistic effect of interfaces and hydrodynamic flow in flow-induced protein aggregation. We propose that hydrodynamic flow and shear stress should be considered in close association with interfaces when discussing sources of protein aggregation.

4:45 Computer Simulations of Aggregation of Proteins and Peptides

Andrzej Kloczkowski, PhD, Professor, Pediatrics, Nationwide Children’s Hospital and The Ohio State University

Aggregation of proteins and peptides is an important biological phenomenon often related to protein misfolding and correlated with various diseases, such as Alzheimer’s or Parkinson’s; recently it has been shown that preeclampsia has similar molecular mechanism as Alzheimer’s. Computer simulations are excellent tools to study the molecular mechanism, structural features and dynamics of protein aggregation, and formation of amyloid filaments and fibrils. Results of our recent computational simulations studies focused on specific diseases such as Alzheimer’s, and preeclampsia will be revealed.

5:15 Close of Day

1月24日(五)

8:00 am Registration

8:00 BuzZ Sessions with Continental Breakfast

Protein therapeutics is a fast-growing global market. As the science improves, so does the complexity of the R&D organization. Ensuring product quality plus speed to market requires insights from stakeholders working across the stages of protein science R&D. Join experts representing this PepTalk pipeline, peers, and colleagues for an interactive roundtable discussion. Topics include highlights from the week’s presentations, new technologies and strategies, challenges, and future trends.

Click here for more details

Characterization, Developability Assessment, and Fill/Finish

9:00 Chairperson’s Remarks

Gerhard Winter, PhD, Professor, Chair, Pharmaceutical Technology and Biopharmaceutics, LMU Munchen

9:05 Qualifying a New Method for Submicron Particle Counting and Why It Matters

Gerhard Winter, PhD, Professor, Chair, Pharmaceutical Technology and Biopharmaceutics, LMU Munchen

We have tested and critically evaluated TRPS (Tunable Resistive Pulse Sensing) by using a rather affordable analytical equipment (IZON) and providing information on how to collect data, how to analyze and how to critically assess them. Comparisons with other techniques like RMM and NTA are made, and examples from very different primary packaging materials on what to expect from submicron particle counting and how to reduce particle burden are provided.

9:35 Challenges in Characterization and Developability Assessments of Multispecific Antibodies

Christian Lange, PhD, R&D Biologics Research, Assays and Analytics, Protein Therapeutics, Sanofi-Aventis Deutschland GmbH

The complexity of multispecific antibodies requires a comprehensive set of analytical techniques to guide lead discovery and optimization. An overview of these techniques will be presented with a focus on mispairing analysis and functional characterization of multispecific drug candidates. Furthermore, the integrated developability concept at Sanofi Biologics will be presented along with showcases highlighting potential challenges in characterization and developability of multispecifics.

10:05 Controlling Aggregation of a Range of Novel Biopharmaceutical Product Modalities

Jan Jezek, PhD, CSO, Arecor Ltd.

Whilst controlling aggregation of monoclonal antibodies has become a routine task through smart candidate screening and platform formulations, there are numerous novel modalities, such as multi-specific antibodies, ADCs, or gene therapy products, where aggregation remains a key problem. This talk will present case studies showing novel formulation approaches to reduce aggregation in these products and enable user-friendly formats.

10:35 Networking Coffee Break

11:00 Fill/Finish Strategies to Prevent and Overcome Aggregation Challenges

Marcel Tigges, PhD, Associate Director, The Janssen Pharmaceutical Companies of Johnson & Johnson

Fill & Finish processes for large molecule parenterals require a quality control toolbox that allows for efficient monitoring of stress factors potentially impacting drug product quality. New technologies and PAT (Process Analytical Technology) tools allow for real-time monitoring of protein concentration (FlowVPE) and low volume protein stability analysis (nanoDSF). Identification of critical process parameters (CPPs) and process steps that potentially cause protein aggregation guides the design of robust processes towards optimal mixing, filtration and filling conditions for highest drug product quality and stability standards.

11:30 Towards a Better Development of Robust High Concentration Protein Formulations

Vishal Toprani, PhD, Development Scientist-I, Pharmaceutical Development, Alexion Pharmaceuticals

The development of high concentration protein formulations presents a number of analytical, formulation, process and delivery challenges. This talk will focus on key aspects of successfully developing high concentration protein formulations by better understanding the physicochemical properties and degradation pathways of a molecule along with integrated efforts between various CMC groups.

12:00 pm Conference Wrap-Up

Jan Jezek, PhD, CSO, Arecor Ltd.

12:30 Close of Conference

* 活动内容有可能不事先告知作更动及调整。

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