Cambridge Healthtech Institute’s 5th Annual
Comparability & Analytical Similarity
Practical Considerations and Best Practices
March 7-8, 2019 * The Westin Alexandria * Alexandria, VA
The 5th Annual Comparability and Analytical Similarity conference looks at the changing paradigms of analytical similarity, discusses practical considerations and strategies for evaluating analytical comparability and similarity,
and showcases methods for higher order structure, and conformational analysis.
WEDNESDAY, MARCH 6, 2019
5:40 pm Networking Reception in the Exhibit Hall with Poster Viewing
THURSDAY, MARCH 7, 2019
8:00 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Methal Albarghouthi, PhD, Associate Director, MedImmune
8:40 FEATURED PRESENTATION: Analytical Similarity: A Changing Paradigm
John P. Gabrielson, PhD, Vice President, Analytical Sciences and Site Head, Elion Labs, a division of KBI Biopharma, Inc.
This presentation will address key factors for development of a comprehensive analytical characterization strategy intended to satisfy regulatory requirements for approval of biosimilars. Unfortunately, the current biosimilar development paradigm
suffers from the high costs of reference product sourcing, lack of reference product availability, lack of statistical independence of reference product lots, and significant under-utilization of data. Ultimately, these challenges increase the likelihood
of developing a Quality Target Product Profile that does not adequately represent the features of the reference product and an analytical similarity plan that is insufficient in demonstrating that the two products are highly similar. By employing
a carefully designed analytical characterization strategy that leverages an information re-distribution model, many of these challenges may be overcome, leading to rapid and cost-effective development and licensure of high-quality biosimilar drugs.
9:10 Current Expectations for Method Qualification and Lab Data Integrity in Similarity vs Comparability Studies
Nadine M. Ritter, PhD, President & Analytical Advisor, Global Biotech Experts
This presentation will provide an overview of how the quality practices for biosimilarity data compare to characterization and comparability data. It will compare method qualification to method validation, including the type of deliverables each should
produce and how they might be reviewed by regulatory agencies. Finally, it will highlight elements of data integrity practices that should be implemented for non-GMP analytical labs (internal, contract or academic) that conduct tests for characterization,
comparability and/or biosimilarity studies.
9:40 NEW: Developments in Biophysical Analysis of Proteins using Microfluidic Modulation Spectroscopy (MMS)
John Linnan, North American Sales Manager, RedShiftBio
Biotherapeutics require better measurement techniques for protein structure analysis. IR has been applied to characterizing secondary structure. However, measurement is challenging due to lack of sensitivity and automation. Manual cell handling for
background subtraction introduces more noise, limiting it’s application. MMS addresses these shortcomings, as demonstrated by (a) Absorbance measurements of mAb from 1.0mg/ml-150mg/ml (b) Protein spiking experiments show MMS 30x better than
FTIR and (c) Thermal and chemical denaturing of proteins.
10:10 Coffee Break in the Exhibit Hall with Last Chance for Poster Viewing
10:50 Analytical Similarity Assessment: Determination of Therapeutic Protein Concentration for Subcutaneous Injection – A Case Study
Zen, PhD, Senior Director, Biologics CMC, Manufacturing, AnaptysBio Inc.
In this presentation I will review analytical methods of protein concentration determination for monitoring protein concentration during upstream process, downstream process, and final fill of manufacturing bio-therapeutic drug substances and drug
products. A new case study will be presented to compare several spectroscopic methods on in-process samples and final finish products for high concentration therapeutic proteins.
11:20 Strategies to Achieve High Analytical Similarity and Product Differentiation for Biosimilar Product
PhD, Vice President, Product Development, Coherus
Establishing the bio-chemical similarity and product differentiation is very critical for developing and commercializing biosimilar product. A successful CMC strategy can significantly reduce development and commercialization risk and help to acquire
HA approval. In this presentation, we will discuss the general strategies to establish product similarity and differentiation. A novel drug product technology will also be discussed for better product differentiation.
11:50 Poster Highlight:
Use of Head-to-Head Degradation Rate Studies for Analytical Comparability Assessments
Yonghui Wang, PhD, Senior Scientist, Janssen Pharmaceuticals
Evaluation of stability data is an essential element of analytical comparability assessments. In this case study, a head-to-head, 8-week degradation rates study was performed to compare the pre- and post-change drug products for a monoclonal antibody.
Based on the results, the post-change drug product showed similar degradation pathways, trends, and rates compared to the pre-change drug product. Differences observed for some attributes were related to product design changes. This study demonstrated
that head-to-head degradation rates studies can be utilized in analytical comparability assessments and can provide valuable insights to the potential impact of product/process changes on stability.
12:10 Enjoy Lunch on Your Own
12:50 Session Break
1:40 Chairperson’s Remarks
Wasfi Al-Azzam, PhD, GSK Fellow, Investigator - Biopharm Analytical Sciences, Biopharm Product Development & Supply, Pharmaceuticals R&D, GSK
1:45 Risk-Based Comparability Strategy for Development of Therapeutic Proteins
Methal Albarghouthi, PhD, Director, Analytical Sciences, MedImmune
Manufacturing process changes during the course of development for therapeutic proteins should be evaluated for the potential impact to safety and efficacy. A risk-based comparability strategy for pre- and post-change material can be designed based
on the extent of the manufacturing process changes, knowledge of product quality attributes, and phase of clinical development. Considerations for managing variation in quality attributes and establishing acceptance criteria will be discussed.
2:15 Phase Appropriate Approach to Analytical Comparability for Innovator Biotherapeutics – How Much Is Enough?
Sonia Taktak, PhD, Principal Scientist, Analytical R&D, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc.
As drug candidates move through development, manufacturing process improvements and formulation changes can impact product quality attributes. The goal of a comparability exercise is to ensure that these changes have no adverse impact on the quality,
safety and efficacy of the drug. In this presentation, we will review key components of a successful analytical comparability strategy based on product-specific considerations, phase of development (early, late) and nature of the change(s).
2:45 Use of AMIDE I and AMIDE II Infrared Bands for Secondary Structure Determination and Comparability of Protein Therapeutic Higher Order Structure
Wasfi Al-Azzam, PhD, GSK Fellow, Investigator - Biopharm Analytical Sciences, Biopharm Product Development & Supply, Pharmaceuticals R&D, GSK
Higher Order Structures (HOS) characterization and comparability packages are critical in the development of novel and biosimilar therapeutics candidates. Analysis of the second derivative of amide I region of Fourier transform infrared (FTIR)
spectra is a common technique to determine secondary structure composition of proteins. This method has not been systematically assessed. We evaluated this method for quantitative characterization and comparability of four model proteins.
In addition, we evaluated the analysis of amide II FTIR spectra as an alternative to using amide I region to analyze protein secondary structure. We used various algorithms for the quantitative comparison herein such as spectral correlation
coefficient (SCC), area of overlap (AO), a QC function found in OMNIC software, and a new algorithm termed modified AO, are described herein for comparing amide I FTIR spectra.
3:15 Networking Coffee Break
3:45 Biologics Characterization and Comparability
Yemin Xu, PhD, Manager, CMC Regulatory Affairs, Regeneron Pharmaceuticals
Biologics development is rapidly growing in the pharmaceutical market. Biologics development and marketing application require thorough physicochemical and biological characterization. Across development stages, analytical comparability exercises
are commonly required when changes are implemented into the manufacturing process. Analytical comparability plays a crucial role to demonstrate that pre- and post-change products are comparable and have no adverse impact on safety, identity,
purity, or efficacy of the product.
4:15 Role of Analytics in the Control Strategy of Dolaflexin
Yuanyuan Li, PhD, Senior Scientist, Analytical Chemistry, Mersana Therapeutics
Mersana uses its unique Dolaflexin® platform which allows conjugation of 10 to 15 molecules of Auristatin F-hydroxypropylamide to the antibody via a biocompatible, biodegradable polymer linker. Dolaflexin is a semi-synthetic polymer composed
of a hydrophilic polyacetal backbone functionalized with sidechain substituents for payload and maleimide linker attachment. The talk will introduce the role of analytical analysis as in-process controls for the manufacturing and characterization
4:45 FEATURED PRESENTATION: Artifacts in the Analysis of Protein Pharmaceuticals
Zhaohui Sunny Zhou, PhD, Faculty Fellow, Barnett Institute of Chemical and Biological Analysis, Department of Chemistry & Chemical Biology, Northeastern University
Analysis is critical in the assurance of quality and compatibility of protein pharmaceuticals, such as biosimilars. However, given the complexity of biotherapeutics and the analytical processes, analytical artifacts abound, e.g., during
sample preparation, separation, mass spectrometry and data analysis. Moreover, many artifacts are often overlooked, particularly when the process and results are reproducible. In this presentation, common and crucial artifacts will
be reviewed, their mechanisms discussed and potential solutions proposed.
5:15 End of Day/Short Course Registration
6:00 - 8:30 Dinner Short Courses*
FRIDAY, MARCH 8, 2019
8:00 am Morning Coffee
8:30 Chairperson’s Remarks
John P. Gabrielson, PhD, Vice President, Analytical Sciences and Site Head, Elion Labs
8:40 Qualitative and Quantitative Measurements of Protein Topography by Hydroxyl Radical Protein Footprinting
Joshua S. Sharp, PhD, Assistant Professor, Pharmacology, Biomolecular Sciences, University of Mississippi
Hydroxyl radical protein footprinting (HRPF) is a method for higher order structure analysis that is recently growing in popularity due to its flexibility and ability to both qualitatively and quantitatively measure protein surfaces,
often at single amino acid spatial resolution. Here I will describe the fundamentals and important concepts behind HRPF, introduce examples of applications, and demonstrate its ability to quantitatively measure amino acid solvent
exposed surface area.
9:10 The Precision of Hydrogen-Deuterium Mass Spectrometry Measurements of Fab Fragments and mAb Glycoforms
Jeff Hudgens, PhD, Research Chemist, IBBR Fellow, Institute for Bioscience and Biotechnology Research, Biomolecular Measurement Division, NIST
For hydrogen-deuterium exchange mass spectrometry (HDX-MS) to emerge as a tool for quality control or for establishing dynamic similarity between a biosimilar and an innovator therapeutic, an understanding of HDX-MS reproducibility
is needed. We present the results of an interlaboratory comparison project that analyzed 78,900 HDX-MS measurements for the Fab fragment of NISTmAb reference material. We also report on HDX-MS measurements that can distinguish
glycoforms of an IgG1.
9:40 Characterizing Potential Structural Changes of Bioanalytical Assay Reagents
Jihong Yang, PhD, Principal Scientist, Bioanalytical Sciences, Genentech
Bioanalytical assay reagents are extensively utilized in ligand binding assays (LBAs) during drug discovery and development, as well as in post-marketing monitoring strategies. Many reagents are protein based and it is critical to
preserve the structural integrity of a reagent to ensure its consistent function. Emerging technologies offer complementary information to help elucidate potential structural changes upon reagent production and storage. Case studies
will be given throughout the talk to highlight the values of these technologies in the process of reagent production and characterization.
10:10 BREAKOUT DISCUSSION SESSION with Refreshments
Join your peers and colleagues in facilitated, small-group discussions to exchange ideas, share best practices, discuss challenges and make new contacts.
Repeatability and Reproducibility in Higher Order Structure Analysis
Moderator: Joshua S Sharp, PhD, Asst Professor, Pharmacology, Biomolecular Sciences, University of Mississippi
- What level of repeatability and reproducibility in higher order structure analysis is necessary (or meaningful)?
- How should repeatability/reproducibility requirements change at different levels of product development (discovery vs. development vs. biosimilar equivalency testing)?
- What level of repeatability/reproducibility in higher order structure analysis is feasible with current technology?
- What are the current bottlenecks in achieving the desired level of repeatability/reproducibility in higher order structure analysis?
The Study of Biologics Structure and Immunogenicity Correlation with Novel Technologies
Moderator: Xing Wang, PhD, President, Array Bridge, Inc.
- What are the technologies available to study correlation between biologics structure and immunogenicity?
- What are the pros and cons for each of the technologies?
- What kind of assays are available?
- What are the pros and cons for those assays?
Analytical Characterization for Innovator and Biosimilar Products - How Much is Enough?
Moderator: Sonia Taktak, PhD, Principal Scientist, Analytical R&D, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc.
- How should one design a comparability study in early/late stage development vs. commercial?
- Should there be a comparability plan with pre-determined acceptance criteria?
- What stability/stress studies need to be included in comparability studies?
- Should one use statistics for assessing comparability/evaluating rates or routes of degradation?
11:10 PCA Technology for Novel and Biosimilar mAb HOS Comparability and Immunogenicity Analysis
Xing Wang, PhD, President, Array Bridge, Inc.
Biologics Higher Order Structure (HOS) is important to its safety and efficacy but difficult to define. A novel technology called Protein Conformational Array (PCA) is developed to analyze mAb HOS. This presentation will present case
studies using the PCA for novel as well as biosimilar mAb comparability analysis. Case studies will also be provided on the study of the correlation between mAb’s HOS and its potential in immunogenicity including cytokine
release and complement activation in the human whole blood system.
11:40 Assessment of mAb Higher Order Structure Using Harmonized 2D-NMR Methods
Robert Brinson, PhD, Research Chemist, Biomolecular Structure and Function Group, Institute for Bioscience and Biotechnology, NIST
Nuclear magnetic resonance spectroscopy is becoming increasingly utilized to characterize the critical quality attribute of higher order structure. However, harmonization of the 2D-NMR method is essential for widespread implementation
of this emerging technology for mAbs. To address this need, a global interlaboratory study was conducted with 26 laboratories equally from industry, government and academia. Chemometric analyses using multivariate statistics allowed
benchmarking of the precision and robustness of NMR fingerprints for the evaluation of mAb HOS.
12:10 End of Conference