From early developability screening to assessing glycosylation and higher order structure, analytical techniques play an important role in identifying and characterizing the physico-chemical properties of the molecules, allowing scientists to better understand,
control and optimize their molecules’ properties.
At the 3rd Annual Advances in Characterization Methods & Approaches conference, we invite scientists to share fresh perspectives and novel approaches, particularly in the wake of novel and next-generation biotherapeutics.
Final Agenda
TUESDAY, MARCH 13, 2018
12:30 pm Registration
1:45 Chairperson’s Opening Remarks
Zahra Shahrokh, PhD, Chief Development Officer, STC Biologics, Inc.
1:50 Potency Assays for Biopharmaceuticals: Design, Validation and Beyond
Baolin Zhang, PhD, Senior Investigator, Review Team Leader, Office of Biotechnology Products, CDER, FDA
Potency tests are required throughout all stages of biopharmaceutical development programs, where they are performed as part of characterization, lot release, and stability testing. Assay acceptability depends on product type, mechanism of action, associated
risk, stage of development, and availability of other quality data. This presentation provides regulatory expectations on potency assays and discusses several case studies highlighting some of the relevant issues commonly seen in the regulatory submissions.
2:20 Informing the Criticality of Quality Attributes with Targeted Product Characterization: A Case Study
Jonathan van Dyck, Scientist, Analytical Sciences, Seattle Genetics
Defining and understanding the critical quality attributes (CQAs) of a therapeutic protein and their relevance to safety and efficacy is an important and necessary part of product characterization. ICH Q8(R2) defines CQAs as "A physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range or distribution to ensure the desired product quality". As products move through clinical development, CQAs should be identified and well understood, however this can be challenging given the structural and functional complexity of therapeutic proteins and the number of quality attributes that need to be evaluated. Initial CQA assessments can be informed by platform knowledge, literature, and risk ranking and filtering approaches. This knowledge can be supplemented with focused product specific experiments demonstrating the impact of a specific attribute on structure and function. Here we present a case study where oxidation and no-glycosylated heavy chain (NGHC) species were enriched via targeted degradation studies to understand impact to structure and function and inform the CQA risk assessment.
2:50 CQA Determination and Control Strategy Development for Besponsa
Jim (Jianming) Mo, PhD, Research Fellow, Analytical R&D, Pfizer, Inc.
3:20 Automated Data Processing and Analysis for Quality Monitoring of Biotherapeutics by Multi-Attribute Method (MAM)
Aude Tartiere, Scientific Account Manager, Expressionist, Genedata
MS-based methodologies offer the benefit of measuring many different quality attributes on a given biotherapeutic with a single test. The multi-attribute method (MAM) can potentially reduce development and manufacturing costs and at the same time
increase product quality. Here, we present an implementation of MAM using a single software platform for the data processing, analysis, and management of MS data.
3:50 Refreshment Break in the Exhibit Hall with Poster Viewing
4:30 Achievements, Disappointments and Lessons Learned from Characterization of Nanotechnology-Formulated Complex Drugs
Marina Dobrovolskaia, PhD, MBA, Senior Principal Scientist, Head of Immunology Section, NCL, Frederick National Laboratory for Cancer Research, NCI
There is an increasing evidence that nanotechnology can improve outcomes of vaccines and immunotherapies. However, translation of these formulations to clinic is accompanied with many challenges. This presentation will discuss achievements, disappointments
and lessons learned from characterization of nanotechnology-formulated complex drugs. Case studies focusing on various types of nanocarriers and APIs will be presented to demonstrate structure activity relationships, in vitro-
in vivo correlation, efficacy and toxicity.
5:00 Characterization of Dolaflexin-Based ADCs
David Lee, PhD, Director, Analytical Chemistry, Mersana Therapeutics
The use of Dolaflexin, a polymer-drug platform, enables the generation of ADCs with drug-to-antibody ratios between 12-15 while maintaining acceptable pharmacokinetics and drug-like properties. This talk will describe selected innovative analytical
approaches used to characterize these antibody-polymer-drug systems.
5:30 Analytical Challenges to Characterization of Self-Amplifying RNA Delivered by a Non-Viral Cationic Nanoemulsion
Mandy Xie, Senior Manager, Product Analytics, Analytical R&D, GSK
The self-amplifying mRNA (SAM) is a platform under early development in GSK vaccines to provide rapid response for pandemic situations. SAM contains a self-amplifying and a gene-of-interest portion, and is assembled via an in vitro transcription process. The novel design of the SAM construct substantially increases the potency with limited dosage requirement. However, the inherent large size of SAM also poses great analytical challenges. We will present the current state
of RNA analytical tools, challenges and potential solutions.
6:00 Welcome Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Day
WEDNESDAY, MARCH 14, 2018
8:00 am Morning Coffee
8:30 Chairperson’s Opening Remarks
David Lee, PhD, Director, Analytical Chemistry, Mersana Therapeutics
8:40 Analytical Strategies for Therapeutic Proteins
Aaron Beach, PhD, Scientist, Protein Analytics and Formulation, Integrated Biologics Profiling, Novartis
Institute of Biomedical Research
The Integrated Biologics Profiling group at Novartis uses custom analytical methods for developability assessments of wide ranging therapeutic protein modalities transitioning from research to development. A broad variety of diverse biologics
entities are evaluated by employing cutting edge analytical strategies such as automated LC method development using DoE, multiple cutting-edge liquid chromatography, and bottom-up and top-down LC-MS/MS.
9:10 In vitro Bioassays to Accelerate Immuno-Oncology Candidate Selection
Sofie Pattijn, CTO, ImmunXperts SA
This talk will cover the usage of in vitro assays to support immuno-oncology drug development. Early functional screening and unwanted immunogenicity assessment can accelerate drug development and lower attrition
rate. A series of assays using primary cells will be discussed and the limitations, challenges and opportunities will be highlighted.
9:40 Highly Glycosylated Therapeutic Proteins: Novel Methods for Sample Generation, Structural and Functional Characterization
Alexander Buettner, PhD, Scientist, Analytical Development and Quality Control,
Pharma Technical Development Europe, Roche Diagnostics GmbH
Glycoprotein function is strongly influenced by composition of glycan moieties. Glycan variety in combination with presence of multiple glycosylation sites can result in thousands of different proteoforms. We have been developing sample generation
techniques as well as structural and functional analysis methods to examine structure function relationships in this complex situation. The talk focuses on in vitro glycoengineering, chromatographic separation
of glycoforms and binding analysis (SPR).
10:10 Meet the Challenge of Discovering Unknowns: Functional Proteomics and Protein Modifications in Biotherapeutics
Zhaohui Sunny Zhou, PhD, Professor, Department of Chemistry and Chemical Biology, Faculty Fellow, Barnett
Institute of Chemical and Biological Analysis, Northeastern University
Scientific research, to a significant degree, is about discovering unknowns. However, without a priori knowledge of the enzyme-substrate pairs or the chemical nature and site of protein modification, it is extremely challenging to deploy proper
analytical methods and search algorithms. To this end, my laboratory (a.k.a. SunnyLand) has devised chemo-enzymatic approaches that complement both instrumental and traditional methods, as illustrated by the cases that will be presented at
the conference.
10:40 Coffee Break in the Exhibit Hall with Poster Viewing
11:20 Monoclonal Antibody Higher Order Structure Analysis Using High Throughput Protein Conformational Array
Yuanli Song, PhD, Scientist II, Late Stage Biologics Development, Bristol-Myers Squibb
Protein conformational array (PCA) is a novel method for determining higher order structure of mAbs. We applied PCA to analyze structural changes along bioprocessing steps. We deciphered mechanistic insights on structural information acquired
using PCA. We also correlated PCA results to protein stability results from other traditional methods such as size exclusion chromatography and protein thermal shift assay. PCA has potential applications in biologics discovery, and product
and process development.
11:50 Hydroxyl Radical Footprinting-Mass Spectrometry (HRF-MS): Expanding the Toolbox for Biotherapeutic Higher Order Structure Characterization
Aaron T. Wecksler, PhD, Technical Development Scientist, Protein Analytical Chemistry, Genentech
We are developing HRF-MS technology which utilizes a high power laser to photo-lyse hydrogen peroxide into hydroxyl radicals, initiating the sub-microsecond surface oxidation of solvent exposed amino acid residues. This technology is orthogonal
to HDX but has advantages that include: (1) ultra-fast labeling time scales, (2) irreversible protein modification and (3) information on the structural positioning of the protein side-chain residues. In this presentation, we show multiple
case studies demonstrating the utility of this emerging technology for the structural characterization of therapeutic mAbs.
12:20 pm Selected Poster Presentation: Structural and Physicochemical Characterization of Recombinant gE Protein of Varicella Zoster Virus
Ji-Youn Kim, MSc, Deputy General Manager, Analytical Method Development, GC Pharma
Varicella Zoster Virus (VZV) is a well-known and widespread viruses,
infection and propagation of which depend on envelope protein. This study
investigated the structural and physicochemical properties of a recombinant
form of gE protein, the envelope glycoprotein E of Varicella Zoster Virus, as its
characterization analysis. Physicochemical properties of the gE protein were
determined using size-exclusion chromatography, reversed-phase chromatography,
peptide mapping and SDS-PAGE. The gE protein preparation was shown to be of
high purity. We identified N-glycosites and O-glycosites. Various glycan
structures were found, such as N-glycans and O-Glycans with the wide
distribution of O-Glycans as analyzed by LC-MS. Particularly, we detected
considerable amounts of sialylated glycans, which were known to influence the
pI characteristic of proteins. These results may help to understand and reduce
risks associated with the desired product quality.
12:50 Luncheon Presentation: Deconstructing Complex Biologics Brick by Brick to Understand Their Personalities
Greg Adams, PhD, Senior Director, Global Analytical Strategy & Development, Analytical and Formulation Development, FUJIFILM Diosynth Biotechnologies
The emergence of more complex biotherapeutics has diminished the use of platformed analytics and increased the demand for more advanced analytics and individualized characterization steps for development of these products. How we evaluate
the “personality of a protein” along the process development trajectory is a critical component in developing robust processes and overcoming challenges associated with these new, unique and difficult molecules. This presentation
will highlight the application of advanced methods that provide insight into the multidimensional character of biotherapeutics. These methods are then directly adapted to routine manufacturing testing or characterization thereby ensuring
a consistent personality mapping strategy throughout the clinical development lifecycle.
1:20 Dessert Break in the Exhibit Hall with Poster Viewing
1:55 Chairperson’s Remarks
Sofie Pattijn, CTO, ImmunXperts SA
2:00 Integrating Protein Chemistry, Formulation and Biology for Effective Development of Biotherapeutics
Zahra Shahrokh, PhD, Chief Development Officer, STC Biologics, Inc.
2:30 Harnessing the Power of Automation to Support High-Throughput Analytics for Critical Characterization Platforms: MAM, Developability and Clone Selection
Stephen D’Eri, MSc, Scientist, Sanofi
Rapid technological growth in analytical instrumentation and data processing has enabled researchers to develop powerful new methods for use in the biopharmaceutical industry. Unfortunately, sample preparation methods have progressed at a
much slower rate, leading to a bottleneck in high throughput analytics. By incorporating automation into our sample preparation methods, we address the bottleneck issue while supporting harmonization of workflows across multiple sites.
3:00 Why Is Platform Approach to Formulation Development Obsolete? How to Leverage Advanced Analytical Technologies to Develop Better Formulations Faster While Reducing Resource Requirements?
Danny K. Chou, PharmD, PhD, President, Compassion BioSolution, LLC
One of the major dilemmas biopharmaceutical formulation scientists face today is whether to invest resources to develop formulations for molecules in the early stages of development or utilize a platform formulation. In this presentation,
we discuss an alternative approach that can effectively identify a good formulation design space that is tailored to a specific molecule without significant time and resource demand. The strategy utilizes multivariate study design
(response surface DoE) and high throughput analytical methods to develop biopharmaceutical products in accordance with the principles of QbD.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:10 Integrating Process, Analytics and Formulation to Optimize Development within the QbD Framework
Christina Vessely, PhD, Senior Consultant, CMC, Analytical and Formulation
Development, Biologics Consulting
The proper application of Quality by Design (QbD) can both reduce risk to patients and streamline the development path for any biologic. ICh Q8 was last updated in 2009 and includes a description of QbD principles and tools. Yet, as of
January 2018, many companies are still taking a tentative approach to full implementation of the principles. The purpose of this talk is to discuss the application of QbD beyond manufacturing process development and into the realm
of analytical and formulation development. The goal is to utilize information gained in all three disciplines to further optimize product development, leading to decrease development timelines and increased safety to patients across
the product development lifecycle,
4:40 Quantitative Analysis of Free Circulating Light Chains Using a Novel Time-Resolved Deconvolution Approach for Reliable Comparison of a Clinical Sample Cohort on the Tribrid Orbitrap Fusion Lumos
Yishai Levin, PhD, Head, de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science
Serum immunoglobulin free light chains (FLC) are secreted into circulation as a by-product of immunoglobulin production. Recent reports show that detection of high levels of FLC can be used to diagnose and monitor light chain amyloidosis
(AL), a rare and fatal disease. Evidence shows that these FLCs dimerize in patient sera. We present a quantitative analysis on a large clinical sample cohort from patients and controls using a time-resolved deconvolution approach for
unbiased and precise comparison that could eventually be used as a risk indicator of AL.
5:10 Close of Advances in Characterization Methods & Approaches/Short Course Registration
6:00 Dinner Short Courses*
SC3: Critical Quality Attributes and Testing Strategy for Biotherapeutics Development
*Separate registration applies.