Mass Spec 2024

Session Chairs: Jason Rouse, Pfizer, Inc. and Christopher Yu, Genentech, a Member of the Roche Group

Session Description:

Mass spectrometry (MS) plays a pivotal role in the earliest stages of biotherapeutics development with respect to molecular design, developability and biotransformation. First, LC-MS characterization of multiple, early constructs in the ‘molecular design’ phase confirms that the intended molecule with the full-length sequence and expected posttranslational modifications was indeed expressed by the cell line and isolated by the purification process. For candidate molecules, ‘developability’ encompasses both predictive and experimental measures of physicochemical properties (including pharmacokinetics [PK]), which collectively enable selection of the optimal construct for more straightforward early- and late-stage product and process development, as well as clinical development (accounting for clinical indication, dosage, and administration route). As part of developability, stability studies combined with LC-MS/MS and biological activity measurements allow for early elucidation of structure-function relationships, in addition to the identification of potential sequence liabilities for subsequent engineering. Lastly, ‘biotransformation’, as monitored by LC-MS/MS, provides insight on how the molecular structure may change during in vivo circulation (after administration) to cause either a gain or loss of function (and/or altered circulating half-life). Biotransformation of therapeutic glycoproteins can involve protease fragmentation, glycosidase re-modelling, and increased deamidation, isomerization, oxidation, and glycation, in addition to removal of particular isoforms by certain receptors.

Session Speakers:

Intact Mass Characterization of Multi-Specific Therapeutic Antibodies

Kalie Mix, Sanofi

Antibody A In Vitro Biotransformation/Succinimide Characterization in Human Plasma by Immunoaffinity Purification (IA) – LC-MS and LC-MS/MS

Mei Han, Merck & Co., Inc.

Immunocapture Based LC/MS Investigation of Different Glycoform Clearance of a Biotherapeutic mAb in Human Serum 

Jayanta Kishor Chakrabarty, Boehringer Ingelheim

Session Chairs: : Rich Rogers, Umoja Biopharma and Chris Yu, Genentech, A Member of the Roche Group

Mass spectrometry (MS) has emerged as a powerful analytical tool in the field of cell and gene therapy. As these therapies continue to revolutionize medicine, understanding their complex processes and ensuring consistent product quality become critical objectives. In this session, we explore how MS-based analytical technologies are advancing our understanding and the manufacturing of cell and gene therapy drug products.

Session Speakers:

A Novel In-Vitro Expression LC/MS/MS Assay for mRNA Vaccine Characterization

Olga Friese, Pfizer, Inc.

Characterising Viral Vectors for Gene Therapy using Mass Spectrometry on Different Levels

Jonathan Bones, NIBRT

Enabling Biopharmaceutical Applications of Electrostatic Linear Ion Trap Charge Detection Mass Spectrometry (ELIT-CDMS)

Rebecca D’Esposito, Waters Corporation 

Session Chair: Frances Namuswe, CDER, FDA

Have a case study where mass spectrometry was used along with biophysical techniques or vice versa? Consider submitting your abstract to the joint CASSS MS and HOS session! For presentations at this session, the CASSS HOS and MS organizing committees are looking for examples of complimentary applications of various MS and HOS techniques to characterize complex systems and elucidate all types of structures. Bring your story of how HOS techniques and MS can solve challenging problems together!

Session Speakers: 

Radical Protein Footprinting in Stabilized Whole Blood

Joshua Sharp, University of Mississippi

Characterization and Mechanistic Insights into the Formation of a mAb Hetero-Clipped Dimer

Joseph Valente, Bristol-Myers Squibb Company 

Charge Detection Mass Spectrometry for Stoichometry and Assembly

Martin Jarrold, Indiana University 

Advancements in Subzero Temperature Chromatography for HDX-MS

Kyle Anderson, National Institute of Standards and Technology (NIST)

Diversity is not a color. It is who is represented in the workplace, research, and society. Examples include gender diversity, age diversity, ethnic diversity, physical ability and neurodiversity.

Equity: Fair treatment for all people resulting in equality. The unique circumstances of each person is considered, treatment is adjusted accordingly to ensure the end result is equal.

Inclusion: How the workforce experiences the workplace and to what degree organizations embrace all employees and enable them to make meaningful contributions. Inclusive cultures ensure that all voices are heard.

Session Speakers:

Penny Peterson, Tolmar, Inc.

Cynthia Ziwawo, Indiana University

Geoffrey Hutchinson, University of Washington

Olubukola Abiona, NIH-Oxford

Session Chairs: Ingo Lindner, Roche Diagnostics GmbH and Hillary Schuessler, Merck & Co., Inc. 

Session Speakers:

Advanced MS-based Technologies to Tackle Characterization Challenges of Complex Formats and New Modality Biotherapeutics

Feng Yang, Genentech, A Member of the Roche Group

High-throughput Screening Strategies to Characterize Protein Conjugation

Anumita Saha, Merck & Co., Inc.

Use of Multi-Attribute Methods for In-Process Monitoring and Quality Control of Complex Biologics

Anita Liu, Merck & Co., Inc.

Session Speaker:

Strategies for Expedited Characterization of Higher Order Structure: Microdroplet Reactions Coupled to Ion Mobility with Collision Induced Unfolding and Electron Capture Dissociation.

Thomas Walker, Agilent Technologies, Inc.

Session Chairs: Chris Chumsae, Bristol-Myers Squibb Company and Frances Namuswe, CDER, FDA

Session Speakers:

Glyco-Analysis of a Glycoengineered VHH-Radioligand Therapy Designed for Improved Biodistribution

David Bush, Novartis 

Characterization of ADCs in Serum and Formulation Buffer

Tun Liu, Johnson & Johnson

Development of Novel Chromatographic and Mass Spectrometric Techniques for Characterizations of BsAbs and ADCs

Fengfei Ma, Merck & Co., Inc.  

Session Chairs: Richard Rogers, Umoja Biopharma and Sarah Rogstad, CDER, FDA

Session Description:

The future of our field is heavily dependent on innovative science from new and upcoming researchers. The Next Generation Investigator (NGI) session will showcase the cutting edge work of three very talented early career scientists. We look forward to learning what these next generation investigators have been working on to advance applications mass spectrometry.

Session Speakes:

Proteoform Specific Microheterogeneity Assessment of Biopharmaceuticals Using a Modified Orbitrap Tribrid Mass Spectrometer

Corentin Beaumal, NIBRT, National Institute for Bioprocessing Research

Middle-down Approach Using Proton Transfer Charge Reduction Enables Unambiguous Drug-Payload Localization in Cys-linked Antibody Drug Conjugates

Linda Lieu, University of Oklahoma 

A Novel Mass Spectrometry-Based Footprinting Method for RNA Higher Order Structure

Natashia Yang, Washington University in St. Louis 

Session Chairs: Sarah Rogstad, CDER, FDA, and Frances Namuswe, CDER, FDA

Panelists:

Jinhui Zhang, CDER, FDA 

Trina Mouchahoir, NIST, 

Michael Strader, CBER, FDA 

Kevin Carrick, US Pharmacopeia

Session Chairs: Ingo Lindner, Roche Diagnostics GmbH and Da Ren, BioTherapeutics Solutions

Session Speakers: 

USP Standards and Tools to Establish System Readiness and Facilitate Implementation of the Multi-Attribute Method

Sheila Mugabe, US Pharmacopeia

Development of LCMS MAM Methods for Protein and Oligonucleotide Therapies

Serena Wu, Regeneron Pharmaceuticals, Inc. 

Towards the Global Approval of MAM Testing Strategy

Joseph Mulholland, Johnson & Johnson

Session Chairs: Chris Chumsae, Bristol-Myers Squibb Company and Andrew Mahan, Johnson & Johnson Innovative Medicine 

Session Speakers:

Application of Multi-Omics Analysis to Enhance Upstream Bioprocessing Understanding

Amr Ali, AbbVie

Deep Proteomic Profiling of the CHO Cells Reveals Correlates of Runaway Lactate 

Joshua Justice, Johnson & Johnson

Targeted Metabolomic Analysis of mAb producing CHO cells: Impact of Bioprocess Conditions on CHO Cell Metabolism and Lactate Runaway

Nandakumar Madayiputhiya, Bristol-Myers Squibb Company