Advances in Biopharmaceutical Analysis

Supplement to

october 2015

Advances in

Biopharmaceutical Analysis

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Advances in

Biopharmaceutical Analysis

6

Introduction

Pat Sandra and Koen Sandra

An introduction from the guest editors of this special supplement.

8

Modern Column Technologies for the Analytical Characterization

of Biopharmaceuticals in Various Liquid Chromatographic Modes

Szabolcs Fekete, Jean-Luc Veuthey, and Davy Guillarme

The recent trends in column technology for reversed-phase LC, SEC,

IEX, and HIC for analysis of biopharmaceuticals at the protein level is

critically discussed.

16 Monoclonal Antibodies and Biosimilars -- A Selection of Analytical Tools for Characterization and Comparability Assessment Koen Sandra, Isabel Vandenheede, Emmie Dumont, and Pat Sandra With the top-selling mAbs evolving out of patent there has been a growing interest in the development of biosimilars. In demonstrating comparability to the originator product, biosimilar developers are confronted with an enormous analytical challenge. This article presents a selection of state-of-the-art analytical tools for mAb characterisation and comparability assessment.

24 Harnessing the Benefits of Mass Spectrometry for In-depth Antibody Drug Conjugates Analytical Characterization Alain Beck and Sarah Cianf?rani Recent progress in high-resolution mass spectrometry (HRMS) and liquid chromatography?mass spectrometry (LC?MS) methods for the structural characterization of brentuximab vedotin and trastuzumab emtansine are presented.

31 Higher Order Mass Spectrometry Techniques Applied to Biopharmaceuticals Christian G. Huber An outline of the basic principles of MS techniques used to investigate higher order structural features of biopharmaceuticals, as well as some insights into applications relevant to the pharmaceutical industry.

38 Advances in Liquid Chromatography?Tandem Mass Spectrometry (LC?MS?MS)-Based Quantitation of Biopharmaceuticals in Biological Samples Nico C. van de Merbel The technical requirements for a successful LC?MS?MS method for the quantitation of biopharmaceuticals are presented and the advantages and disadvantages compared to ligand-binding assays are evaluated.

45 Analyzing Host Cell Proteins Using Off-Line Two-Dimensional Liquid Chromatography?Mass Spectrometry Koen Sandra, Alexia Ortiz, and Pat Sandra The use of off-line 2D-LC?MS for the characterization of HCPs and their monitoring during downstream processing.

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Editorial Advisory Board

Kevin Altria GlaxoSmithKline, Harlow, Essex, UK Daniel W. Armstrong University of Texas, Arlington, Texas, USA Michael P. Balogh Waters Corp., Milford, Massachusetts, USA Brian A. Bidlingmeyer Agilent Technologies, Wilmington, Delaware, USA G?nther K. Bonn Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Austria Peter Carr Department of Chemistry, University of Minnesota, Minneapolis, Minnesota, USA Jean-Pierre Chervet Antec Leyden, Zoeterwoude, The Netherlands Jan H. Christensen Department of Plant and Environmental Sciences, University of Copenhagen,

Copenhagen, Denmark Danilo Corradini Istituto di Cromatografia del CNR, Rome, Italy Hernan J. Cortes H.J. Cortes Consulting, Midland, Michigan, USA Gert Desmet Transport Modelling and Analytical Separation Science, Vrije Universiteit, Brussels, Belgium John W. Dolan LC Resources, Walnut Creek, California, USA Roy Eksteen Sigma-Aldrich/Supelco, Bellefonte, Pennsylvania, USA Anthony F. Fell Pharmaceutical Chemistry, University of Bradford, Bradford, UK

Attila Felinger Professor of Chemistry, Department of Analytical and Environmental Chemistry,

University of P?cs, P?cs, Hungary Francesco Gasparrini Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Universit? "La Sapienza", Rome, Italy

Joseph L. Glajch Momenta Pharmaceuticals, Cambridge, Massachusetts, USA

Jun Haginaka School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan Javier Hern?ndez-Borges Department of Analytical Chemistry, Nutrition and Food Science University of Laguna, Canary Islands, Spain John V. Hinshaw Serveron Corp., Hillsboro, Oregon, USA Tuulia Hy?tyl?inen VVT Technical Research of Finland, Finland Hans-Gerd Janssen Van't Hoff Institute for the Molecular Sciences, Amsterdam, The Netherlands

Kiyokatsu Jinno School of Materials Sciences, Toyohasi University of Technology, Japan Huba Kal?sz Semmelweis University of Medicine, Budapest, Hungary Hian Kee Lee National University of Singapore, Singapore Wolfgang Lindner Institute of Analytical Chemistry, University of Vienna, Austria Henk Lingeman Faculteit der Scheikunde, Free University, Amsterdam, The Netherlands Tom Lynch BP Technology Centre, Pangbourne, UK Ronald E. Majors Agilent Technologies, Wilmington, Delaware, USA Phillip Marriot Monash University, School of Chemistry, Victoria, Australia

David McCalley Department of Applied Sciences, University of West of England, Bristol, UK Robert D. McDowall McDowall Consulting, Bromley, Kent, UK Mary Ellen McNally DuPont Crop Protection,Newark, Delaware, USA Imre Moln?r Molnar Research Institute, Berlin, Germany Luigi Mondello Dipartimento Farmaco-chimico, Facolt? di Farmacia, Universit? di Messina, Messina, Italy Peter Myers Department of Chemistry, University of Liverpool, Liverpool, UK

Janusz Pawliszyn Department of Chemistry, University of Waterloo, Ontario, Canada Colin Poole Wayne State University, Detroit, Michigan, USA Fred E. Regnier Department of Biochemistry, Purdue University, West Lafayette, Indiana, USA Harald Ritchie Trajan Scientific and Medical, Milton Keynes, UK Koen Sandra Research Institute for Chromatography, Kortrijk, Belgium Pat Sandra Research Institute for Chromatography, Kortrijk, Belgium Peter Schoenmakers Department of Chemical Engineering, Universiteit van Amsterdam, Amsterdam, The Netherlands Robert Shellie Australian Centre for Research on Separation Science (ACROSS), University of Tasmania, Hobart, Australia Yvan Vander Heyden Vrije Universiteit Brussel, Brussels, Belgium

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Advances in Biopharmaceutical Analysis ? October 2015

PHARMACEUTICAL n HEALTH SCIENCES n FOOD n ENVIRONMENTAL n CHEMICAL MATERIALS

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