Day 1 | Day 2
Download Biotherapeutics Analytical Summit Brochure or Download This Track Brochure
Monday, March 19
About this conference:
This event covers advanced characterization technologies for a range of complex therapeutic proteins to provide a fuller understanding of the product, to ensure safety and efficacy, and to facilitate smooth and efficient interaction with the regulatory authorities. It focuses on assay methodology and validation, identification of hot spots for liability, post-translational modifications, impurities, critical quality attributes, formulation and stability. There will be a strong emphasis on case studies and practical application.
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12:00 pm Registration
2:00 pm Chairperson’s Opening Remarks
John T. Stults, Director, Protein Analytical Chemistry, Genentech, Inc.
2:05 Application of Hydrogen/Deuterium Exchange with Mass Spec. Detection (H/DX-MS) to Assess the Spatial and Temporal Structural Comparability of Protein Biopharmaceuticals during Their Development
Steven A. Berkowitz, Ph.D., Principal Investigator, Analytical Development, Biogen Idec, Inc. - Biography
Developments in instrumental hardware and computer software now enable H/DX-MS to be employed in the biopharmaceutical industry in a practical and routine way. As a result, biopharmaceutical comparability studies aimed at monitoring the higher-order structure and the associated structural dynamics of these important drug molecules can be greatly improved.
2:35 Mass Spectrometry for Directing Discovery and Early Stage Product Development
Johnson Varghese, Ph.D., Associate Director, Analytical Biochemistry, MedImmune, Inc. - Biography
Mass spectrometry is used extensively during recombinant protein product development to verify the structure of the protein molecule and associated variants. The unique capabilities offered by this technique are able to identify the structure of the potential drug candidate during the discovery phase, elucidate various structural features, and help to identify attributes that may be important for biological activity. Applications from areas such as proteomics, glycomics, and higher-order structure characterization will be used to illustrate the utility of mass spectrometry during discovery and early-stage product development. Strategies for understanding the impact of changes on biological function elucidated by mass spectrometry will also be discussed.
3:05 Application of MALDI TOF/TOF CID Tandem Mass Spectrometry for the Rapid Identification of Unknown Disulfide-Bonded Peptides in Protein Digestions
Jennifer F. Nemeth, Principal Research Scientist, Biologics Mass Spectrometry & Allied Technologies, Centocor R&D, Inc., a division of J&J PRD - Biography
The analysis of a protein’s disulfide bond network provides insight into a protein’s fold and function. Here we present a quick, efficient method for the identification of unknown disulfide bonded peptides using MALDI TOF/TOF MS in combination with high-energy collision-induced dissociation of native digestions without the need for further chemical or analytical analysis.
3:35 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 Buried and Unpaired Cysteines in Antibodies: A Broken Intra-Chain Disulfide Bond
Yung-Hsiang Kao, Ph.D., Principal Scientist, Protein Analytical Chemistry, Genentech, Inc. - Biography
Several recombinant mAbs were found to contain an unusually high amount of variants missing a specific intra-chain disulfide bond (i.e. the cysteines remained in the reduced form) in the variable heavy or light chain domain. The characterization, impact and causes of these unpaired cysteines will be discussed in this presentation.
Featured Presentation
4:30 Glycosylation of IgG-Fab (VH/VL) of Therapeutic IgG Antibodies: Impact on Antigen Binding, Pharmacokinetics etc.
 Roy(ston) Jefferis, Ph.D., C.Chem., FRSC, MRCP, FRCPath, D.Sc., Professor Emeritus, Immunity & Infection, University of Birmingham - Biography
Human IgG may bear complex diantennary oligosaccharides in both the Fc and Fab that differ in galactosylation and sialylation levels. The therapeutic antibody Erbitux, produced in NS0 cells, bears, in addition, galactose in alpha 1,3 linkage to galactose residues that may provoke IgE responses and anaphylactic reactions in patients.
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5:00 Characterization Case Study: Early Quality Assessment of Candidates
Shara M. Dellatore, Ph.D., Lead, Preclinical & Clinical Characterization, Bioprocess Development, Merck and Co, Inc. - Biography
A case study is presented to highlight the importance of up-front characterization of lead candidates to ensure developability success. Two complimentarity determining region (CDR) sequences against the same target were identified for development. Both CDR sequences contained residues that were predicted by molecular modeling to be exposed and susceptible to degradation. The constructs were evaluated by a toolkit of characterization assays to inform lead candidate selection.
5:30 Breakout Discussions
Table 1: Benefits and Challenges of Advances in Analytical Technology for Characterizing the Higher-Order Structure of Biopharmaceuticals
Moderator: Steven A. Berkowitz, Ph.D., Principal Investigator, Analytical Development, Biogen Idec, Inc. - Biography
• Advances offered by new technologies and their applicability in biopharmaceutical research and process development
• Challenges experienced with implementing new methodologies, e.g. cost, trained personnel, LOQ
• Implications of these advancements in analytical technologies in regulatory filings
Table 2: Evaluation of Post-Translational Modification Hot Spots and Liability Sites
Moderator: Yung-Hsiang Kao, Ph.D., Principal Scientist, Protein Analytical Chemistry, Genentech, Inc. - Biography
• How PTMs can impact on the function of the product
• How criticality depends on where the PTMs occur
• Presentation of PTMs to the FDA
Table 3: Glycosylation as a Strategy to Improve Antibody-Based Therapeutics
Moderator: Roy(ston) Jefferis, Ph.D., C.Chem., FRSC, MRCP, FRCPath, D.Sc., Professor Emeritus, Immunity & Infection, University of Birmingham - Biography
• Impact of glycosylation on the mechanism of action
• Means of manipulating glycosylation
• Risk assessment approach regarding glycosylation
Table 4: Challenges of Structure and Sequence Analysis
Moderator: John T. Stults, Director, Protein Analytical Chemistry, Genentech, Inc.
- Identifying and avoiding pitfalls arising from sequence variants over the course of product development
- Differences that can be tolerated / what matters and what doesn’t
- Consequences of sequence variants from a regulatory perspective
Table 5: Sanity Check on Host Cell Protein Assays
 Moderator: Nadine Ritter, Ph.D., Senior CMC Consultant, Biologics Consulting Group, Inc.
• When and how can I use a commercial HCP assay?
• What if some HCPs are not picked up by HCP reagents?
• How do I bridge old data to new data for HCPs?
Table 6: Qualification Requirements for a Characterization Study
 Moderator: Randall Burton, Ph.D., Senior Scientist, Process Sciences, Abbott Bioresearch Centre, Inc. - Biography
• Data sets required for characterization and comparability
• Justifying different results from studies at different times
• Working with the regulatory authorities
Table 7: Managing Successful Analytical Technology Transfer
 Moderator: Stacey Traviglia, Senior Scientist, Analytical Technology, Biogen Idec, Inc.
• Successes and failures with CROs and CMOs
• Experiences with equipment and ensuring everything is in place
• Appropriate experimental designs to demonstrate successful transfer
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6:30 End of Day One of Analytical Characterization
Day 1 | Day 2
Download Biotherapeutics Analytical Summit Brochure or Download This Track Brochure