The phenomenon of protein aggregation has perplexed many scientists. All mechanisms of aggregation are not conclusively known, while sources of aggregation continue to surface. Regulatory authorities put great emphasis on the identification and characterisation
of these aggregates, particles and impurities due to their implications on product safety, efficacy and immunogenicity risks; thus, companies are constantly on the lookout for better and more robust ways to detect and mitigate these aggregates.
PEGS Europe’s 5th Annual Protein Aggregates & Particles brings the latest understanding on mechanisms and sources of aggregation, strategies to mitigate aggregation during engineering and process development,
as well as technologies and approaches to characterise and control these impurities.
Final Agenda
Day 1 | Day 2 | Download Brochure | Interactive Speaker Biographies
THURSDAY 15 NOVEMBER
13:00 Registration (Foyer C)
13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
14:00 Chairperson’s Opening Remarks
14:05 Regulatory Considerations for Impurity Characterization and Control for Biological Products
Audrey Jia, PhD, Principal Consultant,
CMC, DataRevive LLC and exFDA Senior CMC Reviewer
Impurity characterization and impact to the product quality is important for both novel biologic and biosimilar development. To what extent the impurity needs to be characterized and analyzed to satisfy the regulatory need will be discussed.
14:35 Factors Influencing Biotherapeutic mAb Aggregation
Linda Yi, PhD, Senior Scientist, Analytical
Development, Biogen
Aggregation has been identified as one of the major degradation pathways that may affect safety, quality and efficacy of therapeutic mAbs. Aggregate present in mAb products can be complex, varying by size, type and origin, with underlying mechanisms not
always being well-understood. This presentation will provide an overview of the factors that may influence biotherapeutic mAb aggregation. A case study will follow on impact of a chemical modification catalyzed by metals on aggregation of mAbs.
15:05 Get Peace of Mind with Quick and Reliable Protein Quality Checks
Dina Finan, PhD, Marketing Manager, Analytics Marketing, Unchained Labs
There are many good reasons to quickly assess the quality of protein samples prior to downstream analysis, such as comparing batches of purified material, changing formulation conditions, or checking the integrity of frozen samples after thawing.
Physical or chemical stress, like agitation or oxidation, can also lead to protein aggregation. We will discuss methods for doing painless quality checks, enabling you to save time and ensure the homogeneity of your samples.
15:35 Networking Refreshment Break (Foyer D)
16:00 KEYNOTE PRESENTATION: Protein Gelation at Interfaces: Implications for Aggregation and Particle Formation
Theodore W. Randolph, PhD, Kenneth and Genevieve Gillespie
Professor, Department of Chemical and Biological Engineering, University of Colorado
16:30 Weak, Promiscuous IgG Self- and Hetero-Association: Implications for Aggregation and Viscosity
Thomas
Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire
The interactions between seven fluorescently labelled tracer IgG mAbs differing in V and C regions were detected and characterized by analytical ultracentrifugation. All interactions were found to be attractive, variable in strength, affected by both
the variable and constant regions, but indiscriminate with respect to IgG subclass. Furthermore, weak attractive interactions were observed for all the mAbs with freshly purified human poly-IgG. The universality of the weak interactions suggests
that they may contribute to effector function cooperativity in the normal immune response, and could be important contributors to viscosity.
17:00 End of Day
Day 1 | Day 2 | Download Brochure
17:00 Dinner Short Course Registration* (Foyer C)
17:30 – 20:30 Dinner Short Courses
Recommended Short Course*
SC7: Protein Aggregation: Mechanism, Characterization and Consequences - View Detailed Agenda
Thomas
Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire
Protein aggregation is recognized by regulatory agencies and the biopharmaceutical industry as a key quality attribute of biotherapeutic products. Various aggregates hold the potential for adversely impacting production and patients in a variety
of ways. This in-depth workshop reviews the origins and consequences of aggregation in biotherapeutics, and then examines strategies for predicting and quantifying aggregation in biopharmaceuticals. It benefits scientists engaged in development,
production, analytical characterization and approval of biotherapeutics and who require a good working knowledge of protein aggregation.
*Separate registration required.
FRIDAY 16 NOVEMBER
08:00 Registration (Foyer C) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Joël Richard, PhD, Head , Technical and Pharmaceutical operations, MedinCell
08:35 Detecting and Separating Sub-Visible Protein Aggregates from Other Particulates
Alain Pluen, PhD, FHEA, Lecturer, Director, BSc Pharma Science, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester
09:05 A New Alternative to Conventional Aggregate Quantitation and Sizing
Oliver Bannach, PhD,
CEO, Attyloid GmbH
According to a recent FDA guideline, subvisible aggregates ranging from 0.1-1 µm are of special concern regarding immunogenicity of biologicals. The FDA further emphasizes the need for quantitative methods covering this size range. sFIDA
fills this gap by quantitating aggregates from 10 nm to 50 µm. sFIDA is a novel platform technology for quantitation and sizing of protein aggregates. The technology combines the selectivity of immunological assays with the sensitivity
of high-resolution fluorescence microscopy.
09:35 Scale-Down Models for Freezing/Thawing Process to Control Aggregation
Karoline Bechtold-Peters, PhD, Senior Strategy and Technology Leader, Biologics Technical Development & Manufacturing, Novartis Pharma AG
10:05 Networking Coffee Break (Foyer D)
10:35 Development Strategy of Fibril-Prone Peptide Therapeutics: Aggregation Kinetics, Predictive Methods, and Detection Methods
Jingtao Zhang, PhD, Principal
Scientist, Pharmaceutical Sciences, Merck & Co.
Peptide aggregation such as fibrillation presents significant challenges for DS and DP development of peptide therapeutics. Different development criteria and control strategy is required for fibril development in contrast to protein aggregation.
Approaches to close gaps in these areas will be shared in the presentation, which includes the investigation on the aggregation kinetics of a fibril-prone peptide, the projection of physical stability shelf-life, and the development of highly
sensitive characterization methods for fibrils.
11:05 Capreomycin Inhibits the Initiation of Amyloid Fibrillation and Suppresses Amyloid Induced Cell Toxicity
Rizwan Khan, PhD, Professor,
Interdisciplinary Biotechnology Unit, Aligarh Muslim University
Protein aggregation and amyloid fibrillation are responsible for several serious pathological conditions (like type II diabetes, Alzheimer’s and Parkinson’s diseases, etc.) and protein drugs ineffectiveness. Therefore, a molecule that
can inhibit the amyloid fibrillation and potentially clear amyloid fibrils is of great therapeutic value. In this manuscript, we investigated the antiamyloidogenic, fibril disaggregating, as well as cell protective effect of an anti-tuberculosis
drug, Capreomycin (CN).
11:35 New Tools to Anticipate and Prevent Protein Aggregation Undergoing Freeze-Thaw
Miguel Rodrigues, Professor, Co-Founder, SmartFreez
11:50 Sponsored Presentation (Opportunity Available)
12:05 Problem-Solving Breakout Discussions with a Light Snack (Foyer
E&F)
Freezing, Thawing and Storage of API Solutions of Therapeutic Proteins – A Practical Exchange
Moderator: Karoline Bechtold-Peters, PhD, Senior Strategy and Technology Leader, Biologics Technical Development & Manufacturing, Novartis Pharma AG
- What are adequate long-term storage conditions, minus 20°C, minus 30°C, minus 40°C, minus 80°C?
- How can we achieve controlled freezing and thawing in various containers? Are some better/worse? Does it matter?
- Do newer formats of proteins constitute further challenges?
- Container closure integrity under frozen condition?
Protein Aggregation Mechanisms for mAbs, ADCs and Multivalent Antibodies
Moderator: Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire
- Interaction energetics control aggregation
- Both protein and solvent contribute to the energetics
- What you can do to control aggregation
- Excipients and interaction impact on interactions energetics
13:00 Chairperson’s Remarks
Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire
13:05 Using Chemical Denaturants to Improve Predictions of Biopharmaceutical Aggregation during Storage
Robin Curtis, PhD, Senior
Lecturer, Chemical Engineering and Analytical Science, University of Manchester
Here we show how to account for the high concentration of denaturants in the data analysis, which if unaccounted for, could lead to data misinterpretation. We then correlate light scattering measurements of five monoclonal antibodies at high denaturant
concentration with their shelf stability. The results indicate there is a window of denaturant concentration over which the self association behaviour provides an indicator for the aggregation propensity upon storage.
13:35 Prediction of Aggregation Propensity at Early Development Stage Using Orthogonal Characterization Methods
Joël Richard, PhD,
Head, Technical and Pharmaceutical Operations, MedinCell
In the perspective of accelerating early stage protein formulation development, it has become key to anticipate and predict formulation, storage and processing conditions that will lead to aggregation. To anticipate aggregation propensity, evaluate
aggregation rate under critical conditions and mitigate associated immunogenicity risks, it is proposed to focus on the very early steps of aggregation, often involving higher order structure (HOS) alterations and loss of colloidal stability,
using a set of orthogonal characterization techniques.
14:05 Using Physics-Based Simulations to Understand the Determinants of Viscosity in Concentrated Antibody Solutions
Saeed Izadi, PhD, Scientist, Early Stage Pharmaceutical Development, Genentech, Inc.
We have developed a physics-based multi-scale coarse-grained approach to explore how high viscosity can emerge from weak self-interactions. Key developments that enabled this approach are discussed, including our novel strategies to preserve electrostatic
fields and hydrophobicity features. Our method improves on currently available approaches, evidenced by its accuracy when compared against experimental data, along with providing unexpected insights into the problem that enable consideration
of mitigation strategies before material is available for testing.
14:35 Stability of Protein Disulfides: Sensitive Targets for Oxidation and Light-Induced Degradation
Christian
Schoneich, PhD, Professor, Pharmaceutical Chemistry, University of Kansas
Protein disulfides are important for the structural integrity of proteins. Nevertheless, they are sensitive targets for multiple pathways of protein degradation, where specific degradation products have been detected in immunogenic protein samples.
Hence, a thorough characterization of disulfide degradation pathways of biotherapeutics presents an important task. Recently, we detected about 60 different degradation products resulting from the light-induced degradation of a small protein,
human growth hormone, and significantly more products may be expected from the degradation of monoclonal antibodies.
15:05 14:35 Quantification and Degradation Monitoring of PS80
in One Single Analysis Using QDa Mass Detector
Pierre Guibal, PhD, Deputy
Head, Analytical Development, BioAnalytics, Sanofi
Different methods already exist for PS80 monitoring, but to our knowledge, no method is able to quantify intact PS80 and monitor its potential degradation – oxidation or hydrolysis – in one single analysis. We present here a new chromatographic
method based on ion source versatility of QDa, a single quadrupole mass detector. Using specific single ion recording signals, this is the first method allowing quantification of intact PS80 and covering all known degradation in one single
analysis.
15:35 15:05 Protein-Excipient Interactions Evaluated via NMR Studies in Polysorbate-Based Multi-Dose Protein Formulations: Influence on Antimicrobial
Efficacy and Potential Study Approach
Riccardo Torosantucci, PhD, Lab Head, Formulation Development, Pharmaceutical Development Biologics, Sanofi-Aventis Deutschland GmbH
Preservatives are excipients needed in biopharmaceutical multi-dose formulations to prevent microbial growth; however, they are known to interact with non-ionic surfactants like polysorbate and potentially with the active pharmaceutical ingredient
(API). In the current study those interactions were successfully quantified via NMR and correlated to the antimicrobial activity of the formulations. NMR represents therefore a powerful tool to support formulation development of multi-dose
formulations.
16:05 15:35 End of Summit
Day 1 | Day 2 | Download Brochure