As new product formats progress through development and into the regulatory process, the role of analytical characterization is taking on new meaning. Very new modalities present challenges to both analytical scientists and regulatory agencies alike,
and this steep learning curve requires a near-constant cycle of adaptation and innovation. The agencies are requiring sponsors to provide ever more complex data across a wide range of analytical methods, and instrumentation suppliers are striving
to support this new era with unique product features, software and feature combinations. The PEGS “Characterization of Biotherapeutics” conference explores the progression of analytical development for an exciting range
of emerging modalities and offer a case study forum for those working in the field to share ideas, experiences and solutions that support the preclinical and clinical development of new biotherapeutics.
Final Agenda
MONDAY, APRIL 8
7:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Opening Remarks
William C. Motel, PhD, Director, Regulatory Affairs, IQVIA Global Regulatory Affairs
8:40 Identifying Early Production Truncated Drug Candidates by Top-Down Mass Spectrometry
Zhe Zhang, PhD, Senior Scientist,
Novartis Institutes for BioMedical Research
Mass spectrometry has shown to be a powerful tool to characterize different therapeutic protein formats. With intact MS and peptide mapping, identification and site-specific characterization can be achieved. Top-down mass spectrometry, however, can provide
added value, for example avoiding digestion and artifact generation, sequence coverage on special regions, etc. Two case studies from different projects found truncation problem in early production stage. MS, especially Top-down MS, was able to provide
sequencing information with high efficiency, quick turnover and independency.
9:10 Characterization of Novel and Complex Antibody Formats
Markus Haberger,
PhD, Senior Scientist, Roche, Germany
The number of novel biotherapeutic antibody-based formats in drug development is continuously increasing. Characterization of these formats is challenging. Since established physiochemical and mass spectrometric methods show limited capabilities for characterization
of product related impurities, new analytical strategies have to be developed. Here, we present a native MS based analytical approach which successfully assisted in the elucidation of size and charge variants of complex antibody formats such as bispecific
antibodies or antibody fusion proteins.
9:40 Expanding Role of Mass Spectrometry in Development of Biotherapeutics
Dhaval Nanavati, PhD, Senior Scientist, AbbVie
The versatility of mass spectrometer has made it the prevailing analytical platform for understanding the distribution, target interaction, off target interaction of biotherapeutics. The role of mass spectrometry in dissecting post translational modified
variants of a putative target is also critical in identification of unique targets and development of novel bio therapeutics. In this work, we show specific examples of enhanced foot print of mass spectrometry in early stages of development of biotherapeutics.
10:10 Networking Coffee Break (Harbor & Mezzanine Level)
10:50 The Regulatory Path for Breakthrough Designations and Orphan Drugs
William C. Motel, PhD, Director, Regulatory Affairs, IQVIA Global Regulatory Affairs
The U.S. Food and Drug Administration (FDA) offers several special designations to aid in progression of a drug’s approval. The orphan drug designation specifically targets products that treats a rare disease or condition affecting fewer than
200,000 Americans, while the breakthrough therapy designation applies to a drug that is aimed at treating a serious or life-threatening disease or that may demonstrate substantial improvement over existing therapies.
11:20 CMC Analytical Strategies Designed for Regulatory Dialog Intended for Early Phase IND Filings
Vaneet K. Sharma, PhD, Manager, Analytical Development, Vaccine Development & Manufacturing, International AIDS Vaccine Initiative (IAVI)
This presentation will outline phase appropriate CMC analytical strategies intended for successful regulatory submissions, especially for exploratory and phase 1 programs. A case study will be presented to demonstrate the application of the regulatory
accepted phase appropriate analytical characterization to support HIV vaccine development.
11:50 KEYNOTE PRESENTATION: Planning the Extent and Timing of Analytical Studies: What is the Risk to Benefit Impact in Relation to Drug Development Stage?
Jennifer F. Nemeth, PhD, SCPM, Director, Biophysics, Structural Characterization, Biologics Discovery Sciences, Janssen Research & Development
New biologic drug development is costly, and where money is spent impacts a company’s pipeline. Upfront spend can allow for quicker Go/NoGo decisions or while limited development allows for a faster path to PoC. This talk will focus on the benefits/risks
of applying analytical assays before vs after New Molecular Entity Declaration, and which assay were found to be the most impactful for selection to justify the spend and time.
12:20 pm ProteinMentor Developability Assessment: Case Studies for Therapeutic Proteins
Belinda Pastrana, PhD, CEO, Protein Dynamic Solutions
Two case studies will be presented on developability analysis of therapeutic proteins. An array-based biophysical platform was used for deamination assessment, stability and higher order structure determination. Drug substance and drug products were
evaluated and the data generated can be used for computational modeling for logic-driven protein design.
12:35 Cryo-EM Unveils Antibody-Mediated Neutralization Mechanism of Enteroviruses
Xiaodong
Yan, PhD, Executive Director, Biortus Biosciences Co., Ltd.
Cryo-electron microscopy (cryo-EM) becomes a very powerful tool for epitope-mapping. We hereby present near-atomic cryo-EM structures of three Enteroviruses (CVA6, CVA10 and D-68) and their immune complexes. The ensemble of structures reveals molecular
mechanisms of antibody-mediated neutralization and will facilitate the development of effective vaccines and therapeutics against Enterovirus infections.
12:50 Luncheon Presentation I: Boost Your Protein Quantification with Same-Time Quality Measurements
Lisa Adamiak, PhD, Product Manager, Marketing, Unchained Labs
There are many reasons to 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 thawed or stressed samples. With Stunner,
you can now perform painless quality checks by determining the concentration, hydrodynamic size, and polydispersity at the same time with just 2 µL of sample, enabling you to move on to the next steps in your workflow with confidence.
1:20 Luncheon Presentation II: MS-Based Characterization of Biotherapeutics and HCPs in Production Bioprocesses Using a Single Software Platform
Xiaojuan Li, PhD, Associate Principal Scientist, Protein Mass Spectrometry Department, Merck & Co., Inc
This presentation describes application of automated MS data processing workflows for intact mass analysis, released N-glycan analysis, and peptide mapping that provide efficient, in-depth characterization of biotherapeutic products. In addition,
we present a workflow that automatically detects and quantifies host cell proteins in bioprocess monitoring while reducing the number of false positive identifications.
1:50 Session Break
2:20 Problem-Solving Breakout Discussions - Click here for details (Commonwealth
Hall)
3:20 Networking Refreshment Break (Harbor & Mezzanine Level)
4:00 Chairperson’s Remarks
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
PLENARY KEYNOTE SPEAKER
4:10 Vision for How Immunotherapy Will Shape Future of Cancer Care
Leena Gandhi, MD, PhD, Vice President, Immuno-Oncology Medical Development, Lilly Oncology
Immunotherapy is considered by many as a pillar of cancer care today, but in many ways we have only scratched the surface. Our knowledge and understanding of the complexities of immunotherapy and its mechanisms continue to evolve. The future of
cancer care will be defined by our ability to systematically identify and implement opportunities for combination therapy to improve and standardize patient response.
YOUNG SCIENTIST KEYNOTE
4:55 The Lassa Virus Glycoprotein: Stopping a Moving Target
Kathryn Hastie, PhD, Staff Scientist, Immunology and Microbiology, The Scripps Research Institute
Lassa virus causes ~5000 deaths from viral hemorrhagic fever every year in West Africa. The trimeric surface glycoprotein, termed GPC, is critical for infection, is the target for neutralizing antibodies, and a major component of vaccines. Structural
analysis of Lassa GPC bound to antibodies from human survivors reveals a major Achilles heel for the virus and provides the needed template for development of immunotherapeutics and improved vaccines.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:15 End of Day
TUESDAY, APRIL 9
8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:25 Chairperson’s Remarks
Qin Zou, PhD, Group Leader, Analytical Research and Development, Pfizer Inc.
8:30 Regulatory Expectations for Gene Therapy CMC Information
Michelle Joubert, Scientist, Analytical Development, Sanofi
An increasing number of gene therapy products are entering clinical development, and several approvals are anticipated in the near future. As a consequence of this intense activity, regulatory guidance has evolved to become more specific for
these advanced therapies. This was highlighted by the recent publication by the FDA of several draft guidance documents for cell and gene therapies. We will discuss current thinking for gene therapy CMC packages and expectations for an
IND filing. We will also share experiences and feedback we have encountered.
9:00 Application of Analytical Ultracentrifugation: from Protein Therapeutics to Gene Therapy
Qin Zou, PhD, Group Leader, Analytical Research and Development, Pfizer Inc.
This presentation will intend to provide an overview on using analytical ultracentrifugation in biotherapeutic development. Specific case studies will be provided to highlight these applications to various modalities. A stage-tailored strategy
in using the technology during drug development is discussed.
9:30 Leveraging High-Dimensional ‘-omics’ Technologies for Comprehensive Profiling of CAR T Cells to Resolve Drug Product Complexity
Eric S. Alonzo,
PhD, Scientist, Process and Analytical Development, bluebird bio
Clinical-grade CAR T cell drug products contain a heterogenous mixture of phenotypically and functionally distinct cells. Such heterogeneity necessitates innovative and comprehensive strategies to characterize CAR T cell therapy investigational
drug products. A case study will be presented to demonstrate how high dimensional ‘-omics’ is used in CAR T manufacturing and beyond to resolve drug product complexity and identify potentially key clinical correlates.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
10:50 Analytical Challenges During CAR-T Process Development
Ken Prentice, Associate Director, Manufacturing Technologies, Shape Therapeutics
11:20 Challenges Associated with Manufacturing and Release of Autologous Cell Therapy Products
Kuldip Sra,
PhD, Senior Director, CRISPR Therapeutics
An autologous cell therapy product to treat B cell malignancies was approved in the USA in 2017 and in the EU in September 2018. Since cell therapy products manufacturing takes 6-7 days and to deliver the final product to sick patient
within 2-3 wks of leukophoresis, rapid and robust analytical methods must be adapted to release final products in less than one week.
11:50 Lentiviral Vector Engineering and Characterization of Vector Potency for Cell Therapy
Marc-André Robert, PhD, Scientist, Technology Development, BioMarin Pharmaceuticals
Lentiviral vectors (LV) are currently investigated for cell therapy because they can integrate into the cell genome and provide sustainable gene expression. Thus, they can be used to replace a defective gene by providing a functional version
of it. The model presented here is hematopoietic stem cells used to treat blood disorders. The presentation will focus on improving and characterizing the potency of LV, a critical quality attribute of LV.
12:20 pm Luncheon Presentation I: In-depth Evaluation of Maurice CE-SDS System for Method Development and QC Environment
Pegah Abadian, PhD, Scientist II, Biologics Development (Analytical Method Development), Bristol Myers Squibb
CE-SDS method is employed in biologics DS/DP control. The SCIEX PA800+ is the current standard instrument and provides repeatable results. However, next-generation CE‑SDS instruments such as ProteinSimple Maurice can increase throughput
and decrease cost‑per‑injection, among other benefits. This project provides an in-depth comparison of the Maurice with the PA800+ using BMS biologics assets in regard to 1) Onboard Stability, 2) Reported Purity, 3) Method Robustness,
and 4) Flexibility of applying Custom Gels to QC Space.
12:50 Luncheon Presentation II: Enabling Routine and Reproducible Biotherapeutic Analysis when Data Integrity Matters
Henry Shion, Principal
Scientist, Waters Corporation
Driven by increasing industry demand for a robust accurate mass MS system for routine biotherapeutic analysis within the process, development and quality organizations, a new small footprint bench-top LC-MS system
was purposefully designed and developed to offer simplified operational modes, and optimized automation with accurate and reproducible mass measurements for proteins, peptides and released glycans. In this work, we show specific examples
of deploying this compliance-ready bench-top system in late stage development of biotherapeutics.
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
2:00 Chairperson’s Remarks
Zhimei Du, PhD, Director, Bioprocess, Merck & Company, Inc.
2:05 Domain Characterization of Protein Therapeutics In Vivo by Multiplexed NanoLC-HRMS Approaches
Jessy Fan, PhD, Scientist, Amgen
Next generation protein therapeutics are designed to enable enhanced pharmacology, greater selectivity, and altered drug disposition for an overall improved therapeutic profile. Engineering efforts entail addition of nonconventional domains
that require robust characterization of molecular instabilities. Online multiplexed Peptide Immuno-affinity Enrichment (PIE) LC-MS workflow enables simultaneous assessment of molecular integrities through detection of individual domains
of the therapeutic proteins. Case studies presented herein demonstrate different properties of therapeutic proteins in vivo.
2:35 The Roadmap of Bispecific Recombinant Protein Drug Development
Zhimei Du, PhD, Director, Bioprocess, Merck & Company, Inc.
Bispecific recombinant proteins are emerging fields in biological drug development. These new modalities have significantly expanded the functions of conventional mAbs as biotherapeutics. There are many protein scaffolds in bispecifics
field. Besides targeting two antigens simultaneously, different molecule designs have very different features and challenges in bioactivity, pharmacokinetics, and manufacturability. We will discuss challenge details and solutions in
various CMC development areas that directly impact product yield and product qualities.
3:05 A Platform Approach to Manage Developability and Manufacturability Risks of Biologics Molecules
Amanda Fitzgerald, PhD, Senior Scientific Consultant, Biologics, Genedata
We present a workflow system that enables systematic developability and manufacturability assessments, using both in silico and high throughput analytical confirmatory methods, over the entire biologics
R&D process from initial discovery all the way to final candidate selection. We show use cases for mAbs and other complex multi/bispecific formats and discuss building predictive developability models utilizing this system. We
also present the underlying molecule and task management needed for analytical organizations to accomplish this.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:25 Characterization of Antibody Drug Conjugates
Liqiang (Lisa)
Zhou, Senior Scientist, Protein Analytics, AbbVie
Antibody-drug conjugates (ADCs) are becoming an increasingly important class of biotherapeutics. Different levels of heterogeneity contributed by mAbs and the conjugated drugs lead to complexity in ADC characterization. In-depth understanding
of the physicochemical properties of ADCs is essential to drug development and process control. A wide variety of analytical methods have been used in the characterization of an interchain cysteine-conjugated ADC, with particular focus
on the charge variants and size variants.
4:55 Impurity characterization, Control Strategy and Specification Justification in Small Molecules (Payload and Linker)
Jane Zhao, PhD, Principal Scientist, Immunogen
DM4 and Sulfo-SPDB are payload and linker in the ADC manufacturing process of mirvetuximab soravtansine drug substance. Impurities in these two small molecule intermediates are well characterized and specified with acceptance criteria
that are based on manufacturing capability, downstream clearance and clinical exposure. Impurity fate mapping and trending in each step of the synthetic route and during process development and PAR studies enable better control of
impurities and hence improve product quality.
5:25 End of Characterization of Biotherapeutics
5:30 Registration for Dinner Short Courses (Commonwealth Hall)