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High-Concentration Protein Formulations conference - Day 2

High Concentration Protein Formulations 

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8:00 am Morning Coffee


Protein Aggregation Phenomena 

8:25 Chairperson’s Remarks

Jennifer Litowski, Senior Scientist, Drug Product Development, Amgen, Inc. - Biography 

8:30 Delivery of High-Concentration Protein Solutions Necessitates a Multi-Pronged Approach: From Molecule to Device Design

Vikas SharmaVikas Sharma, Ph.D., Sr. Scientist and Group Leader, Early Stage Pharmaceutical Development, Genentech - Biography 

This presentation will highlight the advances made to-date and attempts to demonstrate that the high concentration/high-dose challenge can be met by adopting a combination of diverse approaches such as (i) development of high-throughput screening tools to enable selection of candidates with desirable viscosity properties, (ii) protein engineering approaches to understand the molecular basis of high solution viscosity, and (iii) enhancement of current and development of new process technologies that enable the production and delivery of high-concentration/high-dose formulations.

9:00 Hydrophobic Interactions: A Key Player in Aggregation of Antibodies at High Concentrations

Ravi-ChariRavi Chari, Ph.D., Senior Scientist, Global Formulation Sciences Parenterals, Abbott - Biography
Co-developed with Vineet Kumar, Ph.D., Senior Research Scientist, Global Formulation Sciences Parenterals, Abbott

Development of high-concentration formulations of IgG-like bi-specific molecules (dual variable domain IgGs) showed that the molecular forces that govern their aggregation are different in nature and magnitude than those which control monoclonal antibody aggregation. Biophysical characterization and the result of stress studies on the aggregation and physical stability of dual variable domain IgGs versus that of mAbs is presented.

» 9:30 Featured Presentation: 

Predicting Protein Aggregation Kinetics in High Protein Concentration Solutions: Significance of Unfolding Thermodynamics

Atul Saluja, Ph.D., Senior Research Investigator, Drug Product Science and Technology, Bristol-Myers Squibb  

Co-developed with Venkatramana Rao, Ph.D., Associate Director, Drug Product Science and Technology, Bristol-Myers Squibb - Biography 

Prediction of protein aggregation rate under refrigerated conditions from short-term high-temperature studies is often critical during formulation development. In this work, using a multi-domain protein at moderate to high concentrations, we present data to highlight (i) the pitfalls of employing a simplistic Arrhenius model in rate predictions; and more importantly (ii) the significance of incorporating unfolding thermodynamics in aggregation rate prediction. Guanidinium HCL induced unfolding studies identified the rate-limiting step whereas non-isothermal kinetics indicated the domain/transition critical for the aggregation process. The challenges associated with an accurate prediction of shelf-life and the implications for biologics product development are discussed.

10:00 Coffee Break


Administration Challenges And Concerns Of High-Concentration Formulation 

10:30 Challenges in Development and Administration of High-Concentration Formulations for Monoclonal Antibodies

Meera-AgarkhedMeera Agarkhed, Formulation Scientist, Imclone Systems, Inc. - Biography 

Proteins are prone to aggregation when exposed to accelerated conditions, especially at high concentrations due to protein-protein interactions. Protein formulations are usually developed at low concentrations due to availability and cost constraints. However, a formulation optimized at low concentration may not provide the same stability at higher concentrations. A high concentration protein formulation may pose challenges during administration. A case study will be presented on issues encountered in development and administration of high concentration monoclonal antibody drug product.

Wyatt 11:00 Analyzing Protein-Protein and Protein-Excipient Interactions via Composition-Gradient Light Scattering (CG-MALS)Daniel SomeDaniel Some, Principal Scientist, Wyatt Technology CorporationOptimal formulation of biotherapeutics requires a good understanding of the intermolecular interactions that affect stability as well as equilibrium properties such as viscosity and reversible oligomerization. CG-MALS, implemented in Wyatt's Calypso system, is a key tool for achieving this goal. Calypso determines the essential biophysical parameters describing these interactions, at concentrations typical of protein-based drug formulations: A2 for non-specific repulsion or attraction, KD and stoichiometry for quasi-specific association.


11:30 Ultra-High Antibody Nanoparticle Dispersions Retain Activity and in vivo BioavailabilityJennifer-Maynard
Jennifer Maynard, Ph.D., Assistant Professor, Chemical Engineering, University of Texas at Austin - 
Biography We introduce a new form of proteins, nanometer-sized clusters, in which proteins are “self-crowded” to favor the compact folded state. The size of these equilibrium nanoclusters may be tuned reversibly by varying multiscale colloidal interactions with an extrinsic crowding agent and pH. Upon dilution, protein molecules released from the clusters are stable, as shown in vitro and in vivo in mice and exhibit full biological activity in the bloodstream. Antibody nanoclusters present a radical approach to protein formulation with the potential of patient self-administration of these biologics.

12:00 pm End of Conference

Arrive early to attend the sister conference focusing on Higher-Order Protein Structure (Mon. - Tues.)

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Download Conference & Course Catalog

CHI Catalog March 2018 - August 2018 Cover