The 4th Annual Comparability and Biosimilarity conference continues to build upon the past years’ discussion on regulatory requirements and guidelines on comparability and biosimilarity assessments; analytical strategies and techniques to evaluate
batch-to-batch comparability during process, site or manufacturing changes; equivalence testing of biosimilars with innovator products plus the use of mathematical modeling and statistical data to establish analytical biosimilarity; as well as strategies
toward ICH harmonization in comparability and biosimilarity.
We invite scientists who are leading the analytical development in comparability or biosimilarity assessment to share case studies, proven strategies and best practices.
Final Agenda
THURSDAY, MARCH 15, 2018
7:30 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
John Marino, PhD, Leader, Biomolecular Structure & Function Group, National Institute of Standards and Technology
8:40 Application and Data Evaluation of HDX-MS Results in the Analytical Comparability Studies of Complex Non-mAb Biotherapeutics
Bernice Yeung, PhD, Global Head of Characterization, Analytical Development, Shire
High data content is obtained in HDX-MS analysis, especially for highly glycosylated and other complex biotherapeutics. The approach and benefit of using similarity scores will be demonstrated which are used to establish appropriate acceptance criteria
in an analytical comparability study. The resulting comparability acceptance criteria are quantitative and objective, and alleviate the issues of relying on qualitative comparison of butterfly plots or other arbitrary cut-off limits.
9:15 Data Integrity and Lab Quality Practices for Non-GMP and GMP CMC Studies
Nadine Ritter, PhD, President and Senior Analytical
Advisor, Global Biotech Experts, LLC
Numerous CMC process and product development studies are necessary for the development, approval and commercial support of biotech/biosimilar products. This talk will highlight the key non-GMP vs. GMP data sets generated during the product lifecycle,
present the data integrity elements currently expected for GMP laboratories, and illustrate a set of best practices for non-GMP R&D labs to consider as a means of assuring the reliability and integrity of the data they generate.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing
10:20 Biosimilarity Index: A Systematic, Reliable and Objective Statistical Development That Calculates the Percentage of Similarity Between A Biosimilar Candidate and its Reference Product, from Qualitative and Quantitative Results, in the Analytical Characterization
Jorge Joel Cruz Bejerano, MSc, Director, Biosimilars, Laboratorios de Especialidades Inmunologicas S.A. de C.V.
The data analysis - in the analytical characterization of a biosimilar drug - is currently limited to the ANOVA test, with software such as Exel, R, SPSS, SAS and Minitab, among others. However, none of them was designed to evaluate biosimlarity, generating results with little use or subjective interpretation - especially for the qualitative tests. We developed an algorithm that integrates 3 statistical tests that is able to compare a biosimilar candidate to its reference medicine, based on experimental results obtained in the analytical characterization. The results of the qualitative and quantitative tests are used with already processed values, along with the results obtained as analytical responses in each test to obtain the Biosimilarity Index (BSI). The BSI software performs the analysis with the dispersion test ANOVA, and with central tendency tests (TOST mean relation). These results are converted into probability values using the binomial distribution and the Bayes factor.
10:20 Strategies for Comparability Assessments of Early Phase Gene Therapy Products
Eric Pastor, Principal Scientist, Analytical Development, Sanofi
10:50 Risk-Based Comparability for Complex Molecules during Expedited Development: Leveraging Enhanced Technology and Regulatory Mechanisms
John Armando, MSc, Senior Associate II, Regulatory Affairs CMC, Biogen
There are many challenges faced during expedited biopharmaceutical development. Advancements in technology, program needs, and product knowledge inevitably result in the need for comparability assessments. The use of enhanced technologies and risk-based
approaches can build robustness in one’s comparability assessments and improve both product and process knowledge. As comparability assessments become increasingly important for evaluating changes during expedited development or in planning
for post-approval changes, risk-based approaches and increased agency and industry collaboration are essential enablers for success.
11:20 Selected Poster Presentation: Determination of Higher Order Structure Comparability for a Highly Glycosylated Protein by Advanced HDX-MS Approaches
Shiaw-Lin (Billy) Wu, PhD, CSO, BioAnalytix, Inc.
A high resolution HDX-MS method was developed to effectively correlate HOS to several key glycan and PTM attributes in Idursulfase, a highly glycosylated protein therapeutic. The advanced HDX-MS method and data analysis approaches further enabled
statistically quantitative comparability assessments of the drug's HOS across multiple production lot and stressed samples.
11:40 Enjoy Lunch on Your Own
12:30 Dessert Break in the Exhibit Hall with Last Chance for Poster Viewing
1:15 Chairperson’s Remarks
Joseph L. Glajch, PhD, Director, Analytical Development, Momenta Pharmaceuticals
1:20 Risk-Based Approaches to Demonstrate Comparability during Clinical Development
Matt Kalo, PhD, Associate Director, Protein Analytical Chemistry, Genentech
During clinical development, it is expected and perhaps even beneficial that product quality will be altered by manufacturing changes. Process modifications before commencement of pivotal clinical studies have reduced development and regulatory risks
than modifications during or after pivotal clinical trial initiation. The assessed impacts of changes are based on the potential for detectable patient-impacting differences. Unlike post-approval changes, a clinical development team’s favorable
assessment will be confirmed by clinical studies that are closely monitored.
1:50 Approaches to Comparability following a CMC Change
Vedangi Sample, PhD, Scientist, CMC Regulatory Sciences, Regeneron Pharmaceuticals
2:20 Multivariate Analysis of 2D NMR for Assessment of Biopharmaceutical Structure
John Marino, PhD, Leader, Biomolecular Structure & Function Group, National Institute of Standards
and Technology
The application of two-dimensional nuclear magnetic resonance (2D-NMR) methods for the acquisition of 1H-13C spectral ‘fingerprints’ for the standard monoclonal antibody (NISTmAb) and glycan remodeled NISTmAb at natural isotopic abundance
will be described. Using this sample set, principle component analysis (PCA) applied directly to the spectral data matrices will be shown to discriminate highly similar species, with low limits of detection, which could not be distinguished by
visual inspection or simple intensity based statistical approaches.
2:50 Roundtable Breakout Session with Refreshment Break
Current Practice and Expectation on Demonstrating Higher Order Structures
Moderator: Bernice Yeung, PhD, Global Head of Characterization, Analytical Development, Shire Pharmaceuticals
- What are the most useful and informative techniques for HOS determination during process development?
- What are the most useful and informative techniques for HOS determination for demonstrating product understanding (e.g., structure-function studies)?
- What techniques are less useful and why are we still using them?
- What is the recent experience for the above in regulatory submissions?
Forced Degradation Studies: Trends & Challenges
Moderator: Christine Chan, PhD, Principal Scientist /Technical Lead, Global Manufacturing Sciences & Technology, Sanofi
- Study conditions and choice of assays
- Managing resources and data: phase-appropriate considerations
- FD studies in comparability assessment: how many lots, profile and rate comparisons
- Relevance to process excursions, accelerated stability, real-time stability
Usage and Application of in vitro Assays during Drug Development
Moderator: Sofie Pattijn, CTO, ImmunXperts
- Challenges and opportunities
- Standardization
- How to translate results
3:50 Developing Third Wave Biosimilars
Florian Wolschin, PhD, Director, Protein Analytics, Formycon
Third wave biosimilars are versions of biologic reference product drugs that come off patent after 2020. The talk will center on some of the opportunities and challenges that come with the development of such products.
4:20 Selected Poster Presentation: Biosimilarity Index: A Systematic, Reliable and Objective Statistical Development That Calculates the Percentage of Similarity Between A Biosimilar Candidate and its Reference Product, from Qualitative and Quantitative Results, in the Analytical Characterization
Jorge Joel Cruz Bejerano, MSc, Director, Biosimilars, Laboratorios de Especialidades Inmunologicas S.A. de C.V.
The data analysis - in the analytical characterization of a biosimilar drug - is currently limited to the ANOVA test, with software such as Exel, R, SPSS, SAS and Minitab, among others. However, none of them was designed to evaluate biosimlarity, generating results with little use or subjective interpretation - especially for the qualitative tests. We developed an algorithm that integrates 3 statistical tests that is able to compare a biosimilar candidate to its reference medicine, based on experimental results obtained in the analytical characterization. The results of the qualitative and quantitative tests are used with already processed values, along with the results obtained as analytical responses in each test to obtain the Biosimilarity Index (BSI). The BSI software performs the analysis with the dispersion test ANOVA, and with central tendency tests (TOST mean relation). These results are converted into probability values using the binomial distribution and the Bayes factor.
4:40 Close of Day
FRIDAY, MARCH 16, 2018
8:00 am Morning Coffee
8:30 Chairperson’s Opening Remarks
Bernice Yeung, PhD, Global Head of Characterization, Analytical Development, Shire
8:40 Fingerprint-Like Similarity: Making the Connection between Product Characteristics and Clinical Outcomes
Joseph L. Glajch, PhD, Director, Analytical Development, Momenta Pharmaceuticals
Starting with a detailed understanding of the product, clinical indications and safety profile of the reference product and/or other similar products, attributes (physicochemical and functional) that are either known or likely to impact clinical
outcomes can be determined. The assessment of fingerprint-like similarity can then be based on both (1) the full physicochemical and functional comparison of the product to the reference product and (2) the detailed analysis using sensitive
assays, that allow for linkage between key product attributes and clinical outcomes.
9:10 Challenges for Demonstrating Biosimilarity and Data Quality for Sponsors of Biosimilars for the US Market
Stephan O. Krause, PhD, Director, QA Technology, Clinical/Commercial Operations, MedImmune/AstraZeneca
9:40 The Use of Structural Biology to Demonstrate Finger-Print Like Similarity
Edward R. Zartler, PhD, Senior Group Leader, Biophysics, Analytical R&D, Pfizer
10:10 Networking Coffee Break
10:40 Assessment of Critical Quality Attributes vs. Demonstration of Bio-Similarity
Renata Varga, PhD, Manager R&D, Analytical Sciences and Operations, Teva Pharmaceuticals
Critical quality attribute assessment is a crucial step in antibody development either if it’s innovative or biosimilar. But when we are developing a biosimilar product, we tend to mix up CQA assessment with biosimilarity; however, these
two should be clearly distinguished, but still kept in relation. The presentation will focus on special aspects of CQA assessment for biosimilar mAbs.
11:10 Statistical Considerations for Analytical Biosimilarity Assessments
Shu-Yi Su, PhD, Scientist, Physical Chemistry Characterization, Technical Development Biosimilars,
Novartis
The analytical similarity assessment of critical quality attributes (CQAs) is an important step to demonstrate the biosimilarity of a proposed biosimilar to the reference product. This talk will present recent work aimed at exploring statistical
approaches for assessing analytical biosimilarity.
11:40 Challenges in Assessing the Structural Component of Biosimilarity
Steve Berkowitz, PhD, Independent Consultant
A key component in assessing the biosimilarity of a biosimilar to its reference product is the adequate demonstration of its structural similarity to the structure of the reference product. The process for achieving this involves extensive
analytical physicochemical testing. In this talk, the underlining challenges in making these measurements will be reviewed. In so doing, particular emphasis will be focused on the biophysical part of this process.
12:10 pm Close of Conference