The Bioprocessing Summit
2013 Archived Content

August 19-20, 2013

Cambridge Healthtech Institute’s Second Annual
Higher-Order Protein Structure: Characterization and Prediction


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Monday, August 19


Designing Quality in Biopharmaceuticals: Structural and Formulation Considerations (Shared Session) 

1:00 pm Chairperson’s Opening Remarks

Sujit K. Basu, Ph.D., Senior Director, Drug Product Development, Shire Human Genetic Therapies


1:10 KEYNOTE presentation:

Current Trends and Challenges in Biologics Development

Palani PalaniappanPalani Palaniappan, Ph.D., Vice President and Head, Biologics CMC, CMC Center, Millennium: The Takeda Oncology Company - Biography 

Biologics development continues to evolve into newer territories. New modalities such as antibody drug conjugates, fusion proteins, fragments and others are growing in trend. New modalities bring new challenges and opportunities in ways CMC development is carried out including in areas of process, formulation and analytical development. Some recent experiences will be discussed. 

1:45 FEATURED PRESENTATION:

Assessing Higher-Order Structure and Comparability of Protein Therapeutics – a Regulator’s Perspective

Evi StrubleEvi B. Struble, Ph.D., Pharmacologist, Center for Biologics Evaluation and Research, US Food and Drug Administration - Biography 

In this talk, a discussion of factors that influence the structure of protein therapeutics during the production process as well as pertinent regulatory guidance to ensure quality and demonstrate comparability following manufacturing changes will be presented.

 

2:15 Probing Higher-Order Structure in Protein Pharmaceuticals Using Infrared and Raman Vibrational Optical Activity

Laurence NafieLaurence A. Nafie, Ph.D., Distinguished Professor Emeritus, Department of Chemistry, Syracuse University - Biography 

Vibrational optical activity (VOA), comprised of infrared vibrational circular dichroism (VCD) and Raman optical activity (ROA) have shown enhanced sensitivity to higher order structure (HOS) in proteins. Examples of the sensitivity of VOA to both protein secondary structure and HOS in proteins will be provided as a sensitive new tool for evaluating structural differences between original biopharmaceutical products and their biosimilars.

2:45 Refreshment Break

3:15 Characterizing the Higher-Order Structure (HOS) of Protein Drugs in the Biopharmaceuticals Industry

Steven BerkowitzSteven Berkowitz, Ph.D., Principal Scientist, Analytical Development, Biogen Idec - Biography 

This talk will initially focus its attention on the present capabilities and limitations of the most commonly used biophysical tools employed in the biopharmaceutical industry to characterize the HOS of protein drugs. Attention will then turn to those less commonly used biophysical tools that offer improved capabilities to better satisfy the needs of industry.

3:45 Hydrophobic and Electrostatic Interactions Impact the Drug-Like Properties of a Protein Solution

Ravi ChariRavi Chari, Ph.D., Senior Scientist, Pharmaceutics, AbbVie Bioresearch Center - Biography 

In this study we investigated the unusual behavior of a protein formulation during solubility/stability studies. Both surface mutations and changes in formulation conditions were investigated to improve the drug-like properties, and thus the behavior, of the protein in solution. The underlying mechanism governing this behavior seemed due to hydrophobic interactions. Computer modeling was performed to further elucidate the mechanism.

4:15 Small-Group Breakout Discussions

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.

Topic 1:  Integrating Information from Different Methods to Quantify Protein Aggregation

Moderator: Nicolas Fawzi, Ph.D., Assistant Professor, Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University

• Which tools match which questions when characterizing protein aggregation?
• How can complementary tools be used to validate observations?
• How can the integrated aggregation profiles be best used to improve protein yields, stability, homogeneity, etc?

Topic 2:  Appropriate Biophysical (Higher Order Structure) CMC Package for Protein Drug Regulatory Filings

Moderator: Steven Berkowitz, Ph.D., Principal Scientist, Analytical Development, Biogen Idec

• What does a good biophysical CMC package look like?
• What does the impact of doing an internal vs. external comparability study have on the biophysical components of a CMC BLA filing?
• How can we employ informative advanced biophysical characterization tools that are very expensive (especially for smaller biopharmaceutical companies), require highly specialized personnel to run and interpret the data they generate and are not used that frequently or/and have low sample throughput?
• What are your thoughts about employing informative advance biophysical characterization tools that are only made by one instrument vendor?
• What is the role of industry/government/academia in developing better biophysical CMC package and how can we do a better job in developing them?

Topic 3: Principles of Protein Folding and Stability

Moderator: Philip N. Bryan, Ph.D., Institute for Bioscience and Biotechnology Research and Department of Bioengineering, University of Maryland

• Designing stable, soluble proteins
• Analytic methods relating to determining protein conformation and stability
• Relationships between stability and protein conformation change

Topic 4: Predicting Stability and Aggregation

Moderator: Daniel Some, Ph.D., Principal Scientist and Director of Marketing, Wyatt Technology

• Which tools have been applied to predictions of stability and aggregation, both computational and experimental?
• How do the predictions or rankings of each method correlate to experimentally determined stability and aggregation?
• Can individual techniques provide reliable insight into specific forms of instability (e.g. accelerated thermal, freeze-thaw, and agitation)? Specific types of aggregates?
• Can multiple techniques be combined through well-determined recipes to predict overall stability and aggregation?
• How important is it to measure under true formulation conditions?
• Can these conclusions be generalized to smaller or larger classes or molecules such as: specific platforms; monoclonal antibodies; protein therapeutics?
 

5:15 Discussion Report-Outs

5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:00 Close of Day



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