Day 1 | Day 2 | Download Brochure
Part One | Part Two | Short Courses
In Part Two, FDA representatives and experts present regulatory expectations in the US and Europe for change implementation and for biosimilars regarding the product and the process. Part Two also presents analytical controls focusing on quality targets, and analytical tools and strategy. Case studies cover all stages of development from early development to commercial stage and include clinical comparability with PKPD, biophysical and biochemical assessments, functional tests and immunogenicity for a range of biotherapeutics including biosimilars.
Wednesday, March 13
8:00 am Registration and Morning Coffee
8:30 Chairperson's Opening Remarks
Vibha Jawa, Ph.D., Principal Scientist, Clinical Immunology, Medical Sciences, Amgen, Inc.
» FEATURED PRESENTATION
8:35 Analytical Controls : How to Know What We Don't Know
Alain Bernard, Ph.D., Vice President, Biopharma Process Sciences (BPS), UCB SA - Biography
With continued technological advances and improved understanding of biological product quality attributes, we are coming closer to our long pursued control of the biotech processes and the product by an array of analytical controls. Nevertheless, it is clear that there are still frequenet situations where we do not know the impact of minor deviations and where products and processes that we thought were well characterized turned out not to be so. Biopharmaceuticals remain complex entities, heterogeneous by nature and we should not underestimate this complexity. We will illustrate a few studies where this complexity has been addressed in order to maintain product integrity and benefit to the patients.
9:05 Defining Product Quality Targets during Development
Yung-Hsiang Kao, Ph.D., Principal Scientist and Senior Group Leader, Protein Analytical Chemistry, Genentech, Inc. - Biography
During biopharmaceutical development, there are strong drivers to optimize the manufacturing process while meeting an aggressive timeline. In order to provide safe and effective medicines to patients, and to maximize the chances of a successful development program, it is also essential to focus on delivering the desired product quality throughout the development life cycle. This presentation will discuss strategies for setting product quality targets for a biopharmaceutical product during development.
9:35 Reprocessing of Recombinant Derived Biotechnology Products
Joseph Kutza, Ph.D., Director, Regulatory Affairs CMC, MedImmune, Inc. - Biography
This presentation will focus on points to consider from a regulatory perspective on how to develop a testing plan to support an unexpected and unapproved reprocessing step. Approved products and those still in development will be discussed.
10:05 Automating Comprehensive Site-Specific Glycosylation Analysis of a Recombinant Glycoprotein Using a Differential Feature-Finding Software Workflow
Monica Lane, M.Sc., Staff Scientist II, Biological Mass Spectrometry & Biomarker Research, Genzyme, A Sanofi Company
Glycosylation is a critical quality attribute of a glycoprotein drug candidate. Due to high structural heterogeneity, qualitative and quantitative analysis of glycosylation has been challenging even though such analysis is essential to ensure a consistent manufacturing process. Here we establish an automatic data processing workflow using Genedata Expressionist for Mass Spectrometry for isotopic peak integration, parallel processing and peak identification. The new method shows significant improvement in throughput, reproducibility, and can be implemented for routine analysis.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Lessons Learned from Biologics Comparability Studies: From Pre-IND to Post-Phase III Change Management of Originator and Onto Biosimilar Development
Zahra Shahrokh, Ph.D., Chief Development Officer, STC Biologics
The inevitability of change during product development is best managed by defining an upfront and integrated approach to change implementation, taking into consideration the complex interplay of factors such as nuances of the disease indication, industry or in-house knowledge base, nature of change and phase of development, available analytical and in vivo tools for product characterization, regulatory history and expectations, and capabilities and resources for execution. This talk summarizes the strategic, technical, and practical experiences and lessons learned from two decades of positioning and executing comparability studies at various stages of development, with application to biosimilar development.
» FEATURED PRESENTATION
11:30 Clinical Comparability
Meena Subramanyam, Ph.D., Vice President, Translational Medicine, Biogen Idec, Inc. - Biography
Modification and enhancement of the manufacturing process is an inevitable part of the drug development continuum. The challenge frequently is to understand the relative impact of the changes not only on the biological activity of the product, but also on the pharmacokinetic (PK) behavior and the pharmacologic effects (PD) of the "modified" product. A typical comparability plan includes extensive biophysical and biochemical comparability assessments along with bioactivity assessments. In the absence of a fundamental understanding of structure activity relationship, most comparability protocols also include in vivo evaluations of pharmacokinetics and pharmacodynamics to understand the impact. This talk will illustrate the utilization of a combination of in vitro and in vivo assessments to assess comparability of therapeutic proteins through case studies.
12:00 pm Risk Assessment Approach for Evaluating Aggregate Mediated Immunogenicity Risk of Human Biotherapeutics
Vibha Jawa, Ph.D., Principal Scientist, Clinical Immunology, Medical Sciences, Amgen, Inc. - Biography
Aggregation of fully human biotherapeutics has the potential to induce an immunogenic response. The attributes that can increase the risk of innate and adaptive immune response include the aggregate type, sequence derived immunogenicity risk, immune status of donor, and a certain size and high number of particles. An 8 innate cytokine profile was observed when human PBMC were challenged ex vivo with aggregates. We propose the use of such assays for comparability of immunogenicity risk of biosimilars to their innovator equivalent.
12:30 Luncheon Presentation (Opportunity available, please contact Jon Stroup, jstroup@healthtech.com)
2:00 Chairperson's Opening Remarks
Alain Bernard, Ph.D., Vice President, Biopharma Process Sciences , UCB SA
2:05 Risk-Based Comparability Strategies for Biologics from Early Development to Commercial Stage: General Considerations and Case-Studies
Veronique Bailly, Ph.D., Principal Scientist, Analytical Development, Biogen Idec, Inc. - Biography
Demonstration of comparability is critical for biopharmaceutical product development and throughout the entire product life cycle. Biogen Idec has established an in-house strategy to define the intended analytical comparability after process change and prior to manufacturing campaign. The approach includes an assessment of risk on the product to define the appropriate testing protocol, and statistical analysis of prior batch data and/or assay performance to set the comparability criteria. General considerations on comparability strategies will be presented as well as some case studies for products from early development stage to commercial stage.
2:35 Introducing New Methodologies for Comparability Studies
Stacey Traviglia, Ph.D., Associate Director, Analytical Technology, Biogen Idec, Inc.
Improving analytical methods during the lifecycle of a program is not an exception, it’s the rule. The challenges that exist when introducing a new methodology are amplified when it coincides with manufacturing changes. Method comparability, cross-over studies, and a strategy for comparability will be presented as case study.
3:05 Raman Spectroscopy Combined with DLS Correlates Protein Structure to Aggregation Events
Neil Lewis, Ph.D., CTO, Head, Bioscience Development Initiative, Malvern Instruments
The integration of Raman spectroscopy with Dynamic Light Scattering enables the sequential determination of chemical, structural and physical properties of protein biotherapeutics. The complementary nature of these results provides the opportunity to directly compare Higher Order Protein Structure with aggregation events.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 – 5:00 Breakout Discussions
Table 1: Comparability Using More Advanced Characterization Methodologies than the Original Application
Moderator: Veronique Bailly, Ph.D., Principal Scientist, Analytical Development, Biogen Idec, Inc.
Table 2: Factors and Mechanisms behind Aggregate Induced Immunogenicity Risk
Moderator: Vibha Jawa, Ph.D., Principal Scientist, Clinical Immunology, Medical Sciences, Amgen, Inc.
Table 3: Critical Quality Attributes and Critical Process Parameters
Moderator: Yung-Hsiang Kao, Ph.D., Principal Scientist and Senior Group Leader, Protein Analytical Chemistry, Genentech, Inc.
Table 4: Analytical Studies Required to Support Process Change such as Scale-Up, Change of Manufacturing Site, Formulation Change etc.
Moderator: Alain Bernard, Ph.D., Vice President, Biopharma Process Sciences (BPS), UCB SA
Detailed Agenda
5:00 End of Day One of Comparability for Change Implementation and for Biosimilars
Day 1 | Day 2 | Download Brochure
Part One | Part Two | Short Courses