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As new product formats progress through development and into the regulatory process, the role of analytical characterization is taking on new meaning. Regulatory agencies are themselves learning about these new formats, and to support filings, industry companies are being asked to provide ever more complex data across a wide range of analytical methods. The use of platformed analytical programs, developed as a cost and time saver by the industry, is now diminishing as novel molecules and product formats demand more individualized characterization steps. In addition, instrumentation suppliers are striving to support this new era with unique product features, software and feature combinations. The PEGS Characterization of Biotherapeutics meeting will explore these changes in the progression of analytical development, and offer a case study forum for those working in the field to share ideas, experiences and solutions that support the development of exciting new biotherapeutics.

Day 1 | Day 2 | Download Brochure | Register 


Recommended Pre-Conference Short Course* 

SC7: Immunogenicity Risk Assessment and Regulatory Strategies 

*Separate registration required.


MONDAY, MAY 4

7:00 am Registration and Morning Coffee

plenary keynote session

8:30 Chairperson’s Opening Plenary Remarks

8:40 Building an Antibody Discovery Company in a Crowded Field – the Adimab Story

Tillman Gerngross, Ph.D., CEO, Co-Founder, Adimab

The presentation will cover the evolution of Adimab from its founding in 2007 to becoming one of the few privately held profitable biotech companies in the last decade. Industry trends and specific strategic decisions along the way will be discussed and used to illustrate the importance of integrating finance and scientific information to build successful capital efficient biotech companies.

9:25 Cancer Stem Cells and Mechanisms of Malignant Progression

Robert A. Weinberg, Ph.D., Founding Member, Whitehead Institute for Biomedical Research; Professor, Biology, Massachusetts Institute of Technology

The cell-biological program termed the epithelial-mesenchymal transition (EMT) plays a role in conferring aggressive traits on carcinoma cells. In addition, it generates cancer stem cells (CSCs) that have the ability, following dissemination, to serve as founders of new metastatic colonies. The relationship between these CSCs and the SCs residing in normal tissues, and the participation of the CSCs in metastatic dissemination will be described.

10:10 Coffee Break

10:45 Chairperson’s Remarks

Alain Beck, Ph.D., Senior Director, Antibody and ADC Physico-Chemistry, Center of Immunology, Pierre Fabre; Associate Editor, mAbs


10:50 KEYNOTE PRESENTATION

The Analytics of Macromolecular Comparability

Unpublished DataC. Russell Middaugh, Ph.D., Distinguished Professor of Pharmaceutical Chemistry, University of Kansas

The development of biosimilars (follow-on biologics) has led to the necessity for rigorous methods to compare target macromolecules. In this presentation I will discuss the availability and utility of such methods and mathematical approaches that can be used to combine and analyze multiple methods for the purpose of establishing the structural identity of macromolecular systems.


Characterization for Bioconjugates 

11:20 Native and Subunit Analysis of Antibody-Drug Conjugates

Unpublished DataAlain Beck, Ph.D., Senior Director, Antibody and ADC Physico-Chemistry, Center of Immunology, Pierre Fabre; Associate Editor, mAbs

Most of the current ADCs in clinical trials are controlled, but heterogeneous, mixtures of isomers and isoforms. Drug loading and distribution, amount of naked antibody and average drug to antibody ratio (DAR) are Critical Quality Attributes for ADCs. At the top level, the advantages of cutting-edge mass spectrometry (MS) techniques such as native MS and Ion-Mobility MS will be compared to Hydrophobic Interaction Chromatography (HIC). In addition, optimization of middle up and bottom up strategies will be presented allowing structural assessment of positional isomers.

11:50 High Throughput Multimode Stability Measurements
Facilitate Formulation and Characterisation of Biologics

Daniel Lund, Ph.D., Product Manager, Avacta Analytical

The stability and characterisation of biologics are crucial steps in the development of modern medicines. Screening for and optimising conditions used by biologics can increase long-term stability, manufacturability and prolong shelf life. Bringing these measurements into the pre-formulation stage can de-risk development and aid in the selection of the optimum candidate. However, achieving this has been challenging for many years due to the lack of high-throughput, low sample consumption analytical tools. The Optim instruments from Avacta Analytical overcome these inadequacies and allow researchers to develop stable proteins in optimal formulations which can be more easily manufactured and stored for longer.

12:20 pm Luncheon Presentation I to be Announced

12:50 Luncheon Presentation II (Sponsorship Opportunity Available)

1:20 Session Break

1:50 Chairperson’s Remarks

Alain Beck, Ph.D., Senior Director, Antibody and ADC Physico-Chemistry, Center of Immunology, Pierre Fabre; Associate Editor, mAbs

1:55 FTiH Support of an ADC: Stability, Assay Development, and Clinical Experiences

Unpublished DataJohn Kellie, Ph.D., Investigator, Bioanalytical Sciences and Toxicokinetics, GlaxoSmithKline

Characterization of circulating ADC species (conjugated antibody, total antibody, and payload) is critical to understanding the safety and efficacy of ADC therapeutics. Current methodology requires development and validation of immunoassays and liquid chromatography-mass spectrometry assays. This presentation will share experiences from assay validation through first time in human bioanalytical study support along with an update and outlook for state-of-the-art technologies set to drive ADC method development in the future.

2:25 Comparative Clinical Pharmacokinetics of Antibody-Drug Conjugates in First-in-Human Phase 1 Studies

Case StudyCelene Amara, Ph.D., Senior Pharmacokineticist, Sanofi

Comparison of the clinical pharmacokinetics (PK) for ADCs now in development is challenging because of the large number of targets, ADC constructs, dosing regimens, and patient populations. This presentation presents an evaluation of ADC clinical PK properties, dosing regimens, determination of doses ranges and associated maximum tolerated doses. The effect of structural characteristics and target types (hematological vs. solid tumors) on PK will also be discussed.

2:55 Bioanalytical Strategy for Development and Validation of Ligand Binding Assays for ADCs

Unpublished Data and Case StudySeema Kumar, Ph.D., Principal Scientist, Pfizer, Inc.

The dynamic and heterogeneous mixture of ADCs containing various drug-to-antibody ratios (DAR) species and different conjugation sites may have different binding affinities for the capture and detection reagents typically used in ligand binding assays (LBA). These differences in binding affinity may translate into a variation in the ability of the LBA to accurately detect various DAR species. The case studies presented will evaluate various bioanalytical strategies employed for the development and validation of DAR independent LBAs for ADC bioanalysis.

3:25 Characterization of Fusion Proteins

Case StudyWilma Lau, Ph.D., Senior Scientist, Large Molecule Research, Roche Pharma Research & Early Development, Roche Innovation Center Penzberg

The engineering of multi-domain proteins such as Fab-Cytokine or Fab-Toxin fusion proteins promises the advancement of superior biotherapeutics. Their development requires design and characterization strategies tailored to the properties and the critical quality attributes of the combined domains. Here, we present examples for early design testing using Hapten and Sortase coupling technologies, for adaption of developability concepts for fusion proteins and for equitable evaluation of fusion protein characteristics.

3:55 Refreshment Break in the Exhibit Hall with Poster Viewing

4:35 Problem-Solving Breakout Discussions

5:35 Welcome Reception in the Exhibit Hall with Poster Viewing

6:50 End of Day


Day 1 | Day 2 | Download Brochure | Register 

TUESDAY, MAY 5

8:00 am Morning Coffee


Analyzing the in vivo Behavior of Biotherapeutics 

8:25 Chairperson’s Remarks

Yelena Lyubarskaya, Ph.D., Senior Principal Scientist, Biogen Idec

8:30 Application of in vitro Models to Understand and Optimize Pharmacokinetic Properties of Biologic-Based Molecules

Unpublished Data and Case StudyTim Carlson, Scientific Director, Pharmacokinetics & Drug Metabolism, Amgen, Inc.

Proteins and peptides are attractive drug candidates due to their biological activity, but they often have suboptimal pharmacokinetic properties. These molecules are prone to high clearance and low bioavailability, limiting their duration of action and systemic exposure. We are developing and applying in vitro approaches to predict the in vivo stability of peptides and proteins. The goal is to characterize pharmacokinetic liabilities and ultimately to design molecules with more optimal properties.

9:00 In vitro Biological Characterization of IFN-β-1a Major Glycoforms

Case StudyHorst Bierau, Ph.D., Scientific Advisor and Relation Manager, Merck Serono S.p.A.

Interferon β-1a glycoforms were subjected to physico-chemical and biological characterization by means of mass spectrometry, sialic acid content, thermal denaturation and various in vitro bioassays. The in vitro bioassay responses revealed a correlation mainly with the glycan antennarity. It is therefore suggested that all glycoforms are having biological activity and play a role in modulating the overall IFN-β biological activity with higher-antennarity glycoforms being able to better sustain IFN-β-1a bioactivity over time.


ANALYTICAL STUDIES IN SUPPORT OF PROCESS
DEVELOPMENT AND PRODUCT QUALITY
 

9:30 Characterization and Control of Product Variants Applying QbD Principles

Case StudyJochen Felix Kepert, Ph.D., Senior Manager, Pharma Technical Development Europe, Roche Diagnostics GmbH

The application of quality by design principles on characterizing and controlling product variants for a recently approved therapeutic monoclonal antibody is illustrated. During development several product variants and process related impurities were characterized and categorized into critical and non-critical quality attributes (CQAs) applying a risk ranking and filtering tool. The identified CQAs were further monitored in process development studies and an attribute testing strategy was developed encountering process capability and CQA impact.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 Protein Characterization for APC: Monitoring Product Quality Attributes for Process Development and Manufacturing

Case StudyYelena Lyubarskaya, Ph.D., Senior Principal Scientist, Biogen Idec

Advanced process control can provide flexibility and efficiency in biopharmaceutical manufacturing. Understanding of the effect of manufacturing process variables on product quality attributes is required in support of APC development. The use of mass spectrometry for monitoring glycan distribution of a glycoprotein during cell culture process will be demonstrated. The measurements are performed to obtain early readout of product quality to enhance process understanding and explore potential process analytical tools.

11:20 Novel Method for Assessing Host Cell Protein Assays

Susan Flor, Senior Research Associate, Analytical Operations, Genentech

Immunoassays are typically used to monitor residual host cell protein (HCP) clearance from biopharmaceuticals. Antibodies to a complex mixture of total HCPs are generated for this purpose. Health authorities often request a quantitative assessment of HCP coverage with the antibody used in the immunoassay. 2D gels and Westerns have inherent limitations that prevent accurate quantification of coverage. We explore a new method for HCP reagent coverage characterization.

11:50 High-Throughput Analytics in Support of Process Development and Identification of Critical Quality Attributes

Unpublished DataHui Cai, Ph.D., Research Investigator, Process Development Analytics, Bristol Myers Squibb

The Quality by Design (QbD) initiative aims to thoroughly understand the product and the manufacturing process for better product quality and faster product development. One of the first steps in the QbD approach consists in identification of the critical quality attributes (CQA). At BMS, we use automation for both process development and process analytics. Here we present data that show the use of automation in the facilitation of CQA establishment.

12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing


Characterization of Bispecific Antibodies
and Novel Biologics
 

2:00 Chairperson’s Remarks

Timothy Fenn, Ph.D., Principal Scientist, Boehringer Ingelheim

2:05 Analytical Development for Bispecific Antibodies

Unpublished DataMatthew Bunce, Ph.D., Principal Research Scientist, Janssen

2:35 Pharmacology of Blood–Brain Barrier-Permeable Bispecific Antibodies

John Kelly, Ph.D., Team Lead, Proteomics, National Research Council, Canada

3:05 Sponsored Presentation (Opportunity Available)

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:25 Development and Characterization of Novel Antibody Formats

Unpublished DataMelissa Geddie, Ph.D., Principal Scientist, Merrimack Pharmaceuticals

Multispecific antibodies and antibody-like molecules broaden the therapeutic application of IgGs, but can be challenging to engineer and manufacture. Using a network biology approach to identify key design parameters, we have engineered novel formats for specific biological targeting. We then use rapid design cycles followed by high-throughput characterization of these formats to select for potential therapeutic candidates with robust pharmaceutical properties.

4:55 FDA/Sponsor Interaction on the Development of a Control Strategy for the Albumin Domain of an Albumin-fusion Protein

Jason Bock, Ph.D., Vice President, Global CMC Biologics, Teva Biopharmaceuticals USA

Fully recombinant Albumin fusion proteins are an established platform for extending the serum half-life of therapeutic proteins. While control strategies for the therapeutically active domain are common, including a cell-based potency assay, the control of the albumin portion of the product needed to be developed. This talk will present a case study where a comprehensive control strategy was designed with FDA input based on a fundamental structure/function assessment of the criticality of Quality Attributes.

5:25 End of Conference

5:30 Registration for Dinner Short Courses



Recommended Dinner Short Course* 

SC11: Overcoming the Challenges of Immunogenicity Assessment 

*Separate registration required


Day 1 | Day 2 | Download Brochure | Register