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HOS 2019: Roundtable Session Information
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The Roundtable session will be a truly interactive workshop to connect and discuss real issues with your peers. These sessions were designed to be informal (but structured) discussions on topics which are of interest to participants. Participation will be on a first come, first serve basis. Each topic will include a facilitator, whose role is to help assist the discussion and ensure a lively exchange, and a scribe, whose role is to make general, anonymous notes about the discussion. Notes will be posted on this page two weeks after the conference. See below for a list of this year's topics.

Table 1: Common Practices and Workflows in Protein HOS Characterization
Facilitator: 
Joshua Sharp, University of Mississippi
Scribe: Vito Fodera, University of Copenhagen

Scope: Protein higher order structure (HOS) is a complex and crucial problem in the discovery and development pipelines of biotherapeutic companies. An impressive and constantly expanding suite of tools for the characterization of HOS enables the gathering of an impressive array of information, but no tool is suitable for answering every HOS question in every protein system. This roundtable will focus on discussing the suite of modern tools for protein HOS characterization at a general level of utility, figures of merit and limitations. Participants will discuss their common workflows for initial HOS characterization of protein targets. Considerations in selecting particular methods of HOS characterization and common modes of failure they experience in popular HOS analysis methods will be discussed. Finally, we will discuss unmet needs in HOS analysis, and potential areas for innovation that remain. 
View Abstract and Notes


Table 2: Characterization of Protein Aggregates
Facilitator: 
Christian Fischer, Bruker BioSpin
Scribe: P
aul Dalby, University College London

Scope: Aggregation is frequently a concern during the manufacture, processing, formulation, storage, and transport of protein based therapeutics.  There are a number of existing techniques and experimental approaches that can characterise aggregates and in turn, multiple ways of improving the degree of mechanistic understanding of the factors that drive aggregation.  This discussion will focus on the most important areas where aggregation is of primary concern - since this drives the technical context of the characterisation methods (eg. concentrations, purity/presence of excipients, physical conditions).  Is it more important to characterise and control at the point of manufacture, or during subsequent formulation and storage?  Does the presence of excipients make the job of characterisation harder, and if so which excipients and how can their effect(s) be overcome?  The discussion will then focus upon existing as well as nascent characterisation methods that may be applied to this measurement.  What are the most important limitations of currently available tools (eg. based on sedimentation, chromatography or spectroscopy)? How are these tools improving in response to known difficulties (eg. improvements in sensitivity, reduction in the volume of material required for the tests, improving the fidelity of the tests, increased throughput of measurement?  What else?). Also, what are the most promising “new” characterisation methods that are becoming available?  What factors are driving their development, and what do we predict their performance will be? What research and development challenges should be addressed first and why? The workshop focus will be on characterisation methods in the context of the stage where the questions arise but important “peripheral” subjects will also be included, for example how is the primary data from the method interpreted, how is the data stored and analysed as well as how is the link made between the characterisation method and the fundamental science?
View Abstract and Notes


Table 3: Determining Lifecycle Appropriate Implementation of HOS Technologies
Facilitator: 
John Schiel, National Institute of Standards and Technology (NIST)
Scribe: Robert Brinson, National Institute of Standards and Technology (NIST)

Scope: Development and eventual implementation of novel analytical technologies requires rigorous evaluation of performance metrics to demonstrate suitability for an intended purpose.  Analytical technologies may be implemented at various stages throughout a product lifecycle including process development, characterization, quality control, comparability, and biosimilarity.  This roundtable will include a discussion on recent innovation and technology that is or has the potential to improve the industry ability to select and accelerate the well-characterized products with appropriate lifecycle implementation.  We will also discuss mechanisms (publication, interlaboratory studies, pre-competitive reference materials, and consortia) for establishing a technique and translation to appropriate implementation.
View Abstract and Notes    


Table 4: HOS Analysis for Biotherapeutic Modalities such as Adeno-associated Virus Therapies, Bi-specific Monoclonal Antibodies, Nanobodies, Fusion Proteins, and Vaccines
Facilitator:
Aaron Wecksler, Genentech, a Member of the Roche Group
Scribe: 
Yves Aubin, Health Canada

Scope: The advent of biosimilars has fostered the development of new technologies for the characterization of the higher order structure of protein drugs such as cytokines, hormones and monoclonal antibodies.  As new entities, such as AAV, bi-specific mAbs, and others, enter the therapeutic space (development, manufacturing, and market), these bring new and unique challenges in the field of HOS characterization. This roundtable session will provide attendees the opportunity to discuss the new challenges brought by these new modalities, how current technologies can addressed them, and what new methods or approaches could help filling gaps.  Below, a set of questions may serve to stimulate a casual and collegial discussion, during which participants can share their insights and propose answers to these and other pressing questions related to this topic.  
View Abstract and Notes


Table 5: Biological Consequences of HOS
Facilitator:
Wasfi Al-Azzam, GlaxoSmithKline
Scribe: 
Ron Orlando, GenNext Technologies, Inc.

Scope: There good amount of data published regards protein therapeutics require a native-like structure in order to minimize interference with the immune system and avoid adverse effects in addition to possible loss of efficacy. Therefore, the Food and Drug Administration (FDA) has recently suggested that the biopharmaceutical industry should invest more effort into the HOS characterization of biological products as early as possible in their development stage. In this round table discussion, we would like to have discussion to share information, data, previous experiences around the assessment of higher order structure (HOS), which involves the analysis of secondary structure, tertiary structure, and particles of proteins and their impacts on safety and activity of protein therapeutics.   
View Abstract and Notes


Table 6: HOS Characterisation as a Tool in Method and Process Development
Facilitator: 
John Hickey, University of Kansas
Scribe: Natalie Ciaccio, BioMarin Pharmaceutical Inc.

Scope: HOS characterization can be used to obtain a deeper and more comprehensive understanding of analytical methods and processes used in biologic drug development.  For example, size exclusion chromatography multi-angle light scattering (SEC-MALS) may be used to determine the size or oligomeric state of aggregates that would be routinely quantified using SEC or analytical ultracentrifugation (AUC) may be used as an orthogonal approach to confirm SEC results.  Furthermore, HOS is also commonly used to inform decisions and optimization of manufacturing and formulation processes.  For example, additional characterization of protein structure and stability in different solution conditions may influence process and product design.  In this session, we will discuss how HOS characterization may inform method development and optimization as well as process development for biologic therapeutics.      
View Abstract and Notes


Table 7: Considerations for Alternate Delivery Routes - Challenges and Opportunities
Facilitator:
Pradyot Nandi, Bristol-Myers Squibb
Scribe: 
Katherine Bowers, FUJIFILM Diosynth Biotechnologies U.S.A., Inc.

Scope: The most practical method of delivering proteins still fundamentally remain as either intravenous (clinical setting) or subcutaneous (self-administration) due to complex challenges associated with delivery of a macromolecule by non-invasive methods. In this roundtable, the discussion will be focused around non-standard delivery methods (oral, pulmonary, etc.) and factors that need to be considered when designing molecules with non-IV product profiles. First, an overview of this area will be discussed; this will be followed by an analysis on the major gaps in this field and perspectives around requirement, recent progress, potential as well as challenges associated with delivering a protein therapeutic via alternative routes.  
View Abstract and Discussion Questions (notes not available)


Table 8: HOS in Candidate Selection & Optimization
Facilitator: 
Darren Bates, Amgen Inc.
Scribe: Alexander Bepperling, Novartis Pharmaceuticals Corporation

Scope: The purpose of this round table is to discuss how Higher Order Structure is used in candidate selection. We will discuss how big a role HOS plays in candidate assessment, what HOS may or may not indicate about the developability of a molecule, and ways in which newer technologies are used in the assessment of HOS.     
View Abstract and Notes


Table 9: HOS in Relation to Comparability Studies
Facilitator: 
Marc Neglia, Applied Photophysics
Scribe: 
Galahad Deperalta, Genentech, a Member of the Roche Group

Scope: Process changes in manufacturing of a drug product are required to respond to regulatory demands, increase scale, improve product quality and stability, comparability studies must ensure the absence of adverse effects by those changes on the quality, safety or efficacy of the bio-pharmaceutical product. Though established as an essential part of comparability studies, Higher Order Structure comparisons of protein therapeutics and biologics cause ongoing challenges throughout product development.    This roundtable will aim at identifying, collecting and prioritizing the challenges accompanying HOS comparisons in comparability studies. We will focus on technical limitations, heterogeneity of approaches and impact of regulatory requirements.    Strategies to meet these challenges will be addressed to explore how both experimental procedures and data analysis might be harmonized across the industry, how orthogonal techniques can be selected and used effectively to allow for correlations, how to fulfill general and individual requirements with limited resources, and how best practice of HOS comparisons can be established.    
View Abstract and Notes

Table 10: Regulatory Expectations and Filing Strategy 
Facilitator: 
Dean Clodfelter, Beckman Coulter, Inc.
Scribe: William Weiss, Eli Lilly and Company

Scope:The possible impact of the biophysical attributes of a biomolecule on the efficacy, time action, and immunogenicity have been widely reported. As a result, the ability to measure and understand changes in higher order structure has taken increasing role in regulatory submissions and filling strategies. This has placed challenging demands on the analytical strategies and methods used to measure these attributes.   This roundtable will focus specifically on the regulatory strategies and methods used to control these biophysical attributes. These strategies include those used to support biosimilars, phase I IND submissions, and later phase submissions. It can cover the characterization across a large molecular weight range from insulin related molecules to viral vectors. It covers the role of formulation and process development on higher order structure. It also covers the requirements for the instruments and methods used for biophysical characterization in regulatory submissions.   
View Abstract and Notes


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