Advances in Characterization, Comparability & Analytical Similarity

Cutting-Edge Technologies, Novel Approaches, and Best Practices

October 1 - 2, 2020

The Advances in Characterization, Comparability, & Analytical Similarity conference explores the dynamic advances in analytics, from novel approaches such as machine learning and data analytics, to cutting-edge technologies such as MS, MAM, NMR for characterization, as well as best practices for CQAs, comparability and analytical similarity assessments, with the goal of determining a product's robustness, stability, safety, and consistency.

Thursday, October 1

8:00 am Registration and Morning Coffee

Cutting-Edge Technologies: MS, NMR, MAM

8:30 Chairperson's Opening Remarks
Krishna M.G. Mallela, PhD, Associate Professor, Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus
8:35 KEYNOTE PRESENTATION: Higher Order Structure Assessment of Biotherapeutics Using NMR
John P. Marino, PhD, Group Leader, Biomolecular Structure & Function Group, NIST

Development of high-resolution techniques for defining the higher order structure (HOS) of biotherapeutics has emerged as a priority in the pharmaceutical industry. This talk will describe applications of nuclear magnetic resonance (NMR) for HOS assessment, with a focus on mAb drugs. It will cover the extent to which NMR can detect and assign HOS differences and examples of chemometric methods for automated spectral analysis. 

9:05 KEYNOTE PRESENTATION: 2D NMR Methods for Analytical Characterization of Protein Drug Substances and Drug Products
Krishna M.G. Mallela, PhD, Associate Professor, Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus

Nuclear magnetic resonance (NMR) spectroscopy provides site-specific atomic-level information about protein drugs, and hence can detect any changes in local protein structure and dynamics that are often not detectable by global probes, such as circular dichroism and fluorescence. We will present recent case studies in which we used 2D NMR techniques to probe antibody-polysorbate interactions and the effect of chemical modifications on therapeutic proteins.

9:40 Sponsored Presentation (Opportunity Available)
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Bridging Product Quality Attributes and HOS of mAbs Using NMR**
Arun Alphonse Ignatius, PhD, Principal Scientist & Group Leader, Pharmaceutical R&D, Pfizer Inc.

Based on QbD principles, prior knowledge of the critical quality attributes and its potential impact on the safety and efficacy are strongly desired for mAb-based product development. Backbone and methyl group based 2D NMR fingerprinting provides for a robust technology to monitor HOS changes at an amino acid level during various stages of product development. Multiple attributes of mAbs can be monitored using a single NMR spectra acquired under non-denaturing solution conditions. In addition to the stress-induced impact on the global HOS, localized HOS changes spanning few residues that may be involved in functionally relevant protein-protein interactions can be monitored using NMR. A case study on the applications of NMR as a heightened characterization tool for bridging structure-function will be discussed.

11:20 Qualification of MAM for QC
Monica Sadek, Technical Development Research Associate, Protein Analytical Chemistry, Genentech, Inc.

Authors: Monica Sadek, Benjamin Moore, Zhiqi Hao, Chris Yu, Chengfeng Ren, Frank Macchi, Yan Chen, Milady Ninonuevo

Multi-Attribute Method (MAM) is a peptide–mapping based method that provides targeted monitoring of product quality attributes and non-targeted new peak detection. MAM has been implemented in the pharmaceutical industry for process development and is advancing into the Quality Control (QC) environment in alignment with Quality-by-Design principles. This talk describes the qualification of MAM as a potential platform method for QC at Genentech.

11:50 KEYNOTE PRESENTATION: Importance of Structure-Function Studies for Evaluation and Approval of Biosimilars and Other Protein Products
Emily B Shacter, PhD, Consultant, ThinkFDA LLC.
12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:50 Session Break

Machine Learning and Automation Approaches

1:40 Chairperson's Remarks
John P. Marino, PhD, Group Leader, Biomolecular Structure & Function Group, NIST
1:45 Laboratory Automation Supporting Process Development for Protein and Gene Therapy Modalities
Peter Bryngelson, PhD, Senior Scientist, Analytical Development, Biogen

Cell line and cell culture development require a great deal of data to make good decisions.  Manual analytical workflows are resource intensive and inefficient, our approach at Biogen is to provide lab and data workflows that are highly automated.  Here we will discuss two cases where automated analytical approaches support Protein and Gene Therapy modalities.

2:15 Bringing Data Science to Vaccine Development: First Principles
Elihu C. Ihms, PhD, Senior Scientist, Vaccine Production Program Lab, NIH NIAID

Data Science is now an inescapable buzzword in biotech, but what does it mean in the biotherapeutic development context, and how can its tools be adopted productively? This talk will describe the foundations of a robust data science platform applied to early stage development, how it can be integrated across functional units, and its potential benefits to developmental and operational efficiency.

2:45 Machine Learning Enables Accurate Prediction of Asparagine Deamidation Probability and Rate
Jared Delmar, PhD, Scientist I, Biopharmaceutical Development, AstraZeneca
3:15 The Future of Laboratory Automation: Elevating the Science via a Novel Pipetting Algorithm, 3D Printing Technology, and a Next-Generation Advanced Control Machine
Idris Mustafa, Lead Automation Scientist, BioMolecular Resources, Genentech, Inc.

The complexity of our assays are constantly evolving. As a result, our sample throughput has increased and scientific workflows have become more dynamic, requiring a sophisticated sample processing paradigm. The need to scale, rapidly facilitate our experiments and intuitively curate the required hardware components in this tech-driven environment is incontrovertible. Providing essential infrastructure to fuel these advances can be challenging, but an innovative/progressive approach has been identified.Three functional advances aim to manage the evolution of drug discovery in our organization: in-house advanced robotics programming, part design/architecturing and the liquid-handling robot of the future. Our patent-pending TipSort technology has exploited mathematical optimization for robot/process efficiency, 3D printing in the lab has dispersed a variety of containers/adapters, serving the automation, and the Vantage robot has expanded our technological capabilities.

3:45 Refreshment Break in the Exhibit Hall. Last Chance for Poster Viewing

Attributes Characterization and Comparison

4:15 Two-Dimensional Liquid Chromatography (2D-LC) for the Characterization of Biotherapeutics: Case Studies
Zhi Chen, PhD, Senior Research Investigator II, Bristol Myers Squibb Co.

Biotherapeutics are heterogeneous in nature and may contain numerous variants with differences in size, charge, hydrophobicity, etc., which may impact clinical efficacy, immunogenicity, and safety. Characterization of biotherapeutic variants is necessary to build structure-function correlation and establish a proper control strategy. Isolation and enrichment of variants by conventional chromatographic peak fractionation is labor-intensive and time-consuming. The instability of fractions during isolation and subsequent characterization may also be a concern. Hence, it is desirable to characterize biotherapeutics in an online and real-time manner and 2D-LC may be a viable tool for this purpose. In this presentation, a few case studies will be discussed including charge and size variant characterization of a monoclonal antibody (mAb) and aggregate characterization of combination products.

4:15 pm Statistical Comparison of Attributes of Pharmaceutical Products
Franz Innerbichler, Senior Fellow, Statistical Process & Technology Development, Novartis

Statistical comparison of quality attributes is important in many areas of pharmaceutical development, e.g. comparability, scale down model qualification, method transfer etc. Besides of well known equivalence test and similar Bayesian comparisons, new approaches will be presented, viewing the problem from a different, but basic angle: are minimum and maximum of both groups comparable? What about the results between minimum and maximum?

5:15 Close of Day and Dinner Short Course Registration
5:30 Dinner Short Courses
SC4: Gene Therapy Products: Phase-Appropriate Analytical Development Strategies

Friday, October 2

8:00 am Breakout Discussions with Continental Breakfast

Evaluation and Approval for Biosimilars and Protein Drug Products

9:15 Chairperson's Remarks
Renuka Sivendran, PhD, Director, Analytical Development, Five Prime Therapeutics, Inc.
9:20 QbD Quality Study for Evaluation of Analytical Similarity and Process Comparability of Biosimilar mAbs
Michael H. Xie, PhD, Vice President, Analytics; Head, Bioassay and Analytical Development, Shanghai Henlius Biotech, Inc.

QbD quality study and determination of CQAs of biosimilar mAbs were performed following a developed platform at Henlius, which was applied in analytical similarity and process comparability studies of biosimilar mAbs. The major results of analytical similarity and process comparability on the 1st China biosimilar mAb Hanlikang® (Henlius rituximab biosimilar HLX01 to MabThera®) and trastuzumab biosimilar HLX02 to Herceptin® will be presented and discussed.

9:50 Analysis of Glycosylation in Monoclonal Antibodies
Harleen Kaur, PhD, Senior Research Scientist I, Analytical Sciences, Aurobindo Pharma Ltd. (Aurobindo Biologics)

Monoclonal antibodies are a rapidly growing class of therapeutic molecules in biopharmaceuticals. Understanding the impact of glycosylation and close monitoring is critical for monoclonal antibodies development as a therapeutic molecule. This presentation will highlight the influence of different glycan variants on the drug’s behaviour inside the body and draw attention to commonly employed analytical techniques to determine and quantify glycan composition, structure, and glycosylation site.

10:20 Networking Coffee Break

CQA Assessment for Characterization and Comparability

10:50 Evaluating Process Changes on Gene Therapy Vectors Using Analytical Comparability & Characterization
Russell Goetze, PhD, Scientist I, bluebird bio

As autologous gene therapy programs reach late clinical and commercial stages, the vector manufacturing process must scale to meet increasing demand. Process changes needed for improved performance and scale-up require thorough evaluation of analytical comparability to ensure that vector continues to meet quality standards once changes are implemented. We will discuss an industry perspective on the strategy for assessing analytical comparability and review some examples.

11:20 Risk-Based Assessment of CQAs for Bispecific Molecules
Dana I. Filoti, PhD, Senior Scientist II, Research and Early Developability Group Leader, NBE Analytical R&D, AbbVie Bioresearch Center
11:50 Utilizing Traditional CQA Assessment for Comparability Studies of New/Novel Molecules
Renuka Sivendran, PhD, Director, Analytical Development, Five Prime Therapeutics, Inc.

The control strategy for biologic products requires identifying the CQAs that impact efficacy and safety of the product. Traditionally, CQA assessment for comparability required the knowledge of process history, control strategy and clinical experience. To successfully demonstrate comparability for new/novel modalities, the risk assessment should evaluate the type/extent of process change and its impact to CQAs that affect efficacy and safety of the product.

12:20 pm Close of Summit
**Presentations delivered via a live, interactive, video conferencing platform**
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