The multi-attribute method (MAM) is gaining popularity in the analysis of biopharmaceuticals as it has the potential to replace traditional methods and address gaps in control systems. Roche/Genentech is currently implementing MAM for quality control, and the presentation will provide valuable insights, address challenges, and offer solutions related to IT system and instrumentation preparation, method development, suitability assessment, and validation.

Polarized Excitation-Emission Matrix (pEEM) spectroscopy provides a more detailed and informative, non-destructive measurement of proteins in solution. pEEM is a 4D (?_ex, ?_em, I_F, r) measurement where polarization provides information about particle content, protein size, and mobility. Parallel and perpendicular polarized EEMs can provide more sensitive monitoring of particle content or protein structure changes respectively. Here we discuss some case studies such as protein conjugation (e.g. ADCs, PEGylation), liposome-protein interaction analysis, and mAb quality testing. The key advantages of pEEM is that it measures intrinsic protein emission, avoids the use of labels, and is fast and easy to implement. 

A key objective for the analytical control strategy in biopharmaceutical development is to map product variants with altered safety and efficacy profiles. Here, learnings from the implementation of automated LC peak fractionation combined with chemical and biological characterisation workflows will be illustrated through case studies. Robustness, flexibility, and the ability to combine any LC separation technique with any characterisation workflow, including intact mass analysis and peptide mapping, will be discussed.

Abbvie celebrates the 10th years anniversary of our high-throughput formulation development approach this year by expanding our capabilities and getting ready for the next decade. This presentation will provide a comprehensive overview of the advantages and difficulties in utilizing such an approach and how it is intertwined with some of the current trends in using AI.

Antibody-drug conjugates (ADCs) are inherently complex molecules which can be generated using a diverse range of payloads, linkers, and antibodies. Furthermore, established conjugation methodologies often result in heterogeneity with a distribution of species being observed. Analytical platform methods must therefore be flexible to accommodate a variety of molecules. Here, we consider ADC-specific critical quality attributes, analytical methods we employ for their determination, and our characterisation strategy in ADC discovery.

Recently, classical but also novel biophysical technologies have evolved to enable characterisation of covalent, complex protein-protein, or even cell-protein interactions. New modalities' expansion within the last years have strongly complexified hit characterisation and validation. The detection of some interactions has technical challenges, high residence time, protein-protein interaction, and conformational changes. Here, we will present some case studies containing technological proposals to solve these kinds of phenomena.

During this presentation, I will share our latest work on antibodies with ultra-long complementarity-determining regions (ulCDRs). We applied an array of orthogonal analytical techniques to explain a remarkable structural and stability conservation in antibodies that share the same framework but have very different ulCDRs and antigen specificity. The presentation is aimed at an audience interested in advanced analytical characterisation of antibodies and new therapeutic antibody modalities.

LINC-Ig, which has an extra disulfide bond between two CH1 domains of each heavy chain, is a unique molecule designed by Chugai. LINC format is functionally important to decrease toxicity and formed in a manufacturing process on purpose, therefore the analytical method is required as a QC test. An enzymatic activity specific for LINC format was discovered in the development of the analytical method.

Analytics represents a fundamental pillar in the development of biosimilars and innovative biologics. Although they are both biopharmaceuticals, the analytical strategies differ in terms of purpose, scope, analytical methods, and timelines. With extensive experience in developing both types of biologics, Novartis has recently shifted its focus entirely toward innovative medicine. This presentation highlights the critical distinctions between biosimilars and innovative biologics, emphasising scientific and organisational aspects of analytical development.