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High-Concentration Protein Formulations conference - Day 1

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High Concentration Protein Formulations 

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TUESDAY, AUGUST 21


6:00 - 9:00 pm Recommended Short Course* 

SC4 Sub-Visible Particle Analysis in High-Concentration Protein Formulations  


*Separate registration required 


WEDNESDAY, AUGUST 22


At higher concentrations, proteins or antibodies exhibit characteristic problems including aggregation, precipitation, gelation, and increased viscosity. Development of these high protein concentration formulations results in several manufacturing, stability, analytical, and delivery challenges. Thus, development of formulations for protein drugs requiring high dosing and subcutaneous (SC) delivery requires specific strategies.

8:00 am Registration and Morning Coffee

 

Lyophilization And Reconstitution Of Highly Concentrated Protein Formulations 

8:25 Chairperson’s Opening Remarks

Jennifer Maynard, Ph.D., Assistant Professor, Chemical Engineering, University of Texas at AustinBiography 

» Special Keynote Co-Presentation: 

Fundamentals of Reconstitution Times with Highly Concentrated Monoclonal Antibody Systems

8:30 Part 1: Freeze-Drying of Highly Concentrated Protein Formulations: Formulation, Process Considerations and Reconstitution Issues

Serguei-TchessalovSerguei Tchessalov, Ph.D., Associate Research Fellow, Pharmaceutical Sciences, BioTx R&D, Pfizer - Biography 

An increase in protein concentration allows a significant decrease in drying time without notable effect on product quality (moisture, stability and cake appearance). While dryer overload could become a limiting factor, process optimization paired with lyophilizer characterization should minimize this problem. However, reconstitution time of lyophilized material significantly increases with concentration. Effect of formulation, process conditions, reconstitution media and container closure configuration will be reviewed in this presentation.

9:00 Part 2: Underlying Factors that Contribute to Long Reconstitution Times of Highly Concentrated Protein Pharmaceuticals

Robin-BognerRobin Bogner, Ph.D., Associate Professor of Pharmaceutics, School of Pharmacy, University of Connecticut - Biography 

A systematic study of the effects of protein concentration and formulation components revealed that wetting is a major factor in long reconstitution times of a model protein. Formulation can be adjusted to reduce the reconstitution time. The processing conditions, particularly primary drying temperature, can alter the solid state of some formulation components causing a change in the reconstitution time.

» 9:30 Featured Presentation 

Development of Lyophilized High-Concentration Formulations

Michael-PikalMichael Pikal, Ph.D., Pfizer Distinguished Endowed Chair in Pharmaceutical Technology & Professor of Pharmaceutics, University of Connecticut - Biography 

Formulation development for high concentration actives usually means monoclonal antibodies, where the formulation would consist of the protein, a disaccharide stabilizer, such as sucrose, and perhaps small amounts of buffer and a small molecular weight polyol, to enhance stabilization. Although storage stability increases with increasing amount of stabilizer, a high concentration of protein and the practical processing limits imposed by high solids content means the level of stabilizers need to be limited. Such relationships between formulation and process will be emphasized. 

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

 

High-Concentration Liquid Formulation 

10:45 Formulation of Highly Concentrated PEGylated Proteins

Ahmed-BesheerAhmed Besheer, Ph.D., Research Fellow, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilians University - Biography 

Except monoclonal antibodies, the majority of marketed and investigational biopharmaceuticals are small, and thus rapidly eliminated through the kidneys. Currently, PEGylation is the gold-standard for half-life extension. However, a new challenge is the need to administer high doses of proteins subcutaneously for chronic use, raising questions about safety, stability and feasibility. We synthesized and characterized mono-PEGylated anakinra, and evaluated the stability and viscosity of highly concentrated formulations of PEGylated anakinra. The consequences of viscosity and stability for the application of highly concentrated PEGylated protein solutions are discussed.
 

11:15 High-Throughput High-Concentration Liquid Formulation Developability Assessment Platform for Protein Candidate Screening

Yu-TangYu Tang, Ph.D., Investigator, Integrated Biologics Profiling, Novartis - Biography 

Discovery of stable protein therapeutics with good drug-like properties requires an assessment of developability parameters to minimize risk of late stage development failures. However, low material availability and a short timeline necessitates a high-throughput formulation assessment to help discovery select the best candidates for late stage development. This high-throughput formulation developability assessment platform is composed of: 1) high protein concentration formulation process; 2) biophysical and physicochemical analysis; 3) data evaluation. In this talk, case studies will demonstrate the workflow, analytical package, and data readout, as well as the technical challenges.

11:45 Featured Poster Presentation
A Fast and Simple Method for Determining Protein-Protein Interactions (PPI) at High and Low Protein Concentration using DLS

Martin Skov Neergaard, Ph.D Student, Section for Biologics, School of Pharmaceutical Sciences, University of Copenhagen
 

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:55 Chairperson’s Remarks

Robin Bogner, Ph.D., Associate Professor of Pharmaceutics, School of Pharmacy, University of Connecticut - Biography 

2:00 Enhanced Viscosity Screening with Improved Resolution and Throughput

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

High viscosities pose a significant challenge in the development of highly concentrated protein formulations. Decisions are typically based on experiments targeting a single combination of protein and excipient, but these measurements are highly sensitive to small variations in concentration. Testing a wide concentration range greatly improved data quality, but required a combination of automated sample preparation and high-throughput measurements to be practically achievable. We applied this approach to a screening experiment which successfully identified excipients with lower viscosity and propose an explanation for these differences.

2:45 The Influence of Charge Distribution on Self-Association and Viscosity Behavior of High Concentration Antibody Solutions

Sandeep YadavSandeep Yadav, Ph.D., Scientist, Late Stage Pharmaceutical Development, Genentech, Inc. - Biography 

The work emphasizes role of electrostatic surface potential distribution on self-association and viscosity behavior of mAbs which represent two of the most critical consequences of developing a high concentration formulation. Two IgG1’s with 92% sequence similarity but widely different self-association and viscosity behavior were studied for charge residue differences in the primary sequence and subsequently the contribution of these sequence specific motifs to intermolecular interaction, structure factor, hydrodynamic interactions and consequently self-associating behavior have been investigated by making site specific mutations to modulate surface charge distribution. 

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

 

PROTEIN-PROTEIN INTERACTIONS IN HIGHLY CONCENTRATED PROTEIN FORMULATIONS 

4:15 Detection and Quantitation of Protein-Protein Interactions in Highly Concentrated Solution

Allen-MintonAllen Minton, Ph.D., Senior Investigator, Physical Biochemistry, NIH - Biography 

The presence and magnitude of both attractive and repulsive protein-protein interactions in highly concentrated solution may be determined by measurement of the concentration dependence of static light scattering, sedimentation equilibrium, and viscosity. We will summarize recent experimental results and their interpretation.

4:45 Use of Self-Interaction Chromatography and Osmotic Pressure Measurements to Study Protein-Protein Interactions in Highly Concentrated Antibody Solutions

Andrew-ZydneyAndrew Zydney, Ph.D., Department Head and Walter L. Robb Family Endowed Chair, Department of Chemical Engineering, The Pennsylvania State University; Editor-in-Chief, Journal of Membrane Science - Biography
Elaheh Binabaji, Department of Chemical Engineering, The Pennsylvania State University - Biography 

Protein-protein interactions can have a critical impact on the behavior of the highly concentrated antibody solutions required in current formulations. Self-interaction chromatography and osmotic pressure measurements have been used to evaluate the magnitude of these interactions for a model monoclonal antibody. Data were obtained over a wide range of solution pH and ionic strength and in the presence of different buffer excipients. These results have important implications for the design of effective ultrafiltration systems for antibody concentration and formulation.

5:15 Networking Reception, Last Chance for Exhibit and Poster Viewing

6:45 End of Day



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