Cambridge Healthtech Institute’s Second Annual
Detection, Characterization and Control of Impurities in Biologics
Hot Topics, Emerging Contaminants and Impurities, Case Studies and New Technologies
August 15-16, 2019
CHI's 2nd Annual Detection, Characterization and Control of Impurities in Biologics conference will bring together leading experts to discuss hot topics, emerging contaminants and impurities and new characterization tools for impurities that
may come from various sources and stages of product development. Through new presentations, informative panel discussions, high-level poster presentations, and interactive breakout discussions, top scientists will share new insights into characterization
and control of various impurities. Some of the hot topics for this year will be new and novel technologies for virus and pathogen detection, host cell proteins, lipases and enzymatic degradation, aggregations, leachable, chemistry and manufacturing
controls (CMC) strategy for regulatory filings.
Final Agenda
TUESDAY, AUGUST 13
Waterfront 1C
6:00-8:30 Recommended Pre-Conference Dinner Short Course* [Dinner will be served]
SC9: Impact of Impurities on Stability of Biologics - Detailed Agenda
Instructors:
Diane Paskiet, MS, Director of Scientific Affairs, West Pharmaceutical Services, Inc.
Katherine E. Bowers, PhD, Principal Scientist, Group Leader, Fujifilm Diosynth Biotechnologies
Impurities in protein therapeutics can originate from a variety of unexpected sources. As the protein molecule is taken through the upstream/downstream processes, final product manufacturing (fill/finish) and even during patient delivery, there is a myriad
of potential “hidden” impurities that can have an impact to the safety and efficacy of the bio-therapeutic. This course aims to answer the questions of what and where are the greatest risks for biologic impurities and how can we study
the impact of these impurities on the protein molecule. Our mission is to collectively discuss how to identify, evaluate and mitigate impurity risks from early development and throughout the product life cycle.
Thursday, August 15
11:30 am Registration Open
12:15 pm Enjoy Lunch on Your Own
1:15 Ice Cream Social in the Exhibit Hall with Last Chance for Poster Viewing
1:55 Chairperson’s Remarks
Diane McCarthy, PhD, Senior Scientific Liaison, Global Biologics, US Pharmacopeia
2:00 KEYNOTE PRESENTATION: USP Standards for Monitoring Product-Related and Process-Related Impurities in Biologics
Diane McCarthy, PhD, Senior Manager, Science and Standards Biologics Pipeline Development, Global Biologics, US Pharmacopeia
The complexity of biotherapeutic products and manufacturing processes can yield a variety of impurities, including process-related impurities, such as host cell protein, host cell DNA and particulates, and product-related impurities, such as precursors,
aggregates and degradation products. This presentation will provide an overview of approaches for monitoring impurities, including specific examples that leverage USP standards, as well as an update on new USP standards to support impurity testing.
2:45 Mitigating Uncertain Times: Challenges with Rapid Detection and Characterization of Biological and Chemical Threats and Accelerated Development of Pharmaceutical Countermeasures for Unanticipated Medical Needs
Douglas E.
Kiehl, MSc, Research Advisor, Bioproduct, Research & Development, Eli Lily and Company
Potentially catastrophic chemical and biological threats represent deliberate or unintentional actions placing civilian and military personnel at considerable risk. Rapid response requires novel approaches for detection and characterization of chemical
and pathogenic biological impurities and effective deployment of life-saving countermeasures with acceptable benefit/risk ratio. Challenges include the development of robust, portable technologies for rapid and reliable threat identification,
processes for development, manufacture, review/approval and deployment of countermeasures, and supply chain integrity.
3:15 Analytical Strategies for Characterizing Residuals in Autologous Chimeric Antigen Receptor (CAR) T-Cell Therapy
Hai Yue, PhD, Senior Scientist,
Analytical Development, Juno Therapeutics, A Celgene Company
The manufacturing of autologous CAR T-cell products starts with highly heterogeneous leukapheresis materials from patients and involves the use of various raw materials. This complex process may result in a formulation containing process- and product-related
residuals. A phase-appropriate, risk-based analytical development strategy for possible residual characterization will be presented.
3:45 Gene Therapies: Lessons Learned from Viral Clearance Studies
Akunna Iheanacho, PhD, Director of Research & Development, Texcell – North America
The manufacturing of Developing a robust viral clearance program requires a careful assessment of risk and a thorough understanding of the manufacturing process used to develop the biopharmaceutical product. In this presentation, case studies will
be used to highlight some strategies employed to evaluate viral clearance in a gene therapy setting.
4:00 Refreshment Break
4:15 Impurity Identification and Characterization – A Regulatory Approach
Katherine Galindo, Senior Manager Regulatory Affairs, TESARO, Inc.
As the industry expands beyond standard small molecule and monoclonal antibody products, regulatory agencies are taking different approached to their expectations around impurities. Novel products, such as RNA and gene therapy vectors do not fit
the mold of precedent set in the biologics field. In this presentation, we will review guidance and case studies around regulatory controls of impurities and how they vary for new technologies.
4:45 PANEL DISCUSSION: Guidelines, Risk Assessment and Management of Impurities in New and Complex Biologics
Moderator: Diane Paskiet, MS, Director, Scientific Affairs, Scientific Affairs and Technical Services, West Pharmaceutical Services
Panelists:
Diane McCarthy, PhD, Senior Scientific Liaison, Global Biologics, US Pharmacopeia
Akunna Iheanacho, PhD, Director, Research & Development, Texcell –North America
Hai Yue, PhD, Senior Scientist, Analytical Development, Juno Therapeutics, A Celgene Company
Katherine Galindo, Senior Manager Regulatory Affairs, TESARO, Inc.
Friday, August 16
7:30 am Registration Open
7:30 Small-Group Breakout Discussions with Continental Breakfast
This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish
collaborations or commiserate about persistent challenges.
8:30 Chairperson’s Remarks
David Cetlin, Founder & CEO, MockV Solutions LLC
8:35 Aseptic Processing Challenges for Biologics
Jen Juneau, Principal Scientist, Pharmaceutical Research and Development, Pfizer, Inc.
9:05 Second Generation Reference Materials for Adventitious Virus Detection by Metagenomics
Edward Mee, DPhil, Senior Scientist, Live Viral Vaccines, Virology, National Institute for Biological Standards and Control
Metagenomics offers great potential for improved adventitious virus screening; however, many practical challenges exist, including cost, complexity and the difficulty in defining limits of detection for unknown viruses. Well-characterized reference
materials containing representative virus genome, capsid and envelope structures will enable meaningful inter-laboratory comparisons, support method development and act as process run controls.
9:35 The Use of a Non-Infectious Minute Virus of Mice Surrogate to Predict Viral Clearance during Downstream Applications
Kevin Herbig, BS, Scientist, Biopharmaceutical Technology, GSK
Viral clearance studies are expensive and logistically challenging. A BSL-1 compatible, non-infectious Minute Virus of Mice surrogate was used to predict virus removal via nanofiltration and chromatography. The results from several studies are
presented here including High Throughput Screening, DOE and HIC data sets. Overall, the non-infectious particle was shown to accurately predict MVM clearance and can be used as an economic process development tool.
10:05 Networking Coffee Break
10:30 Improvements in Risk Management Through Better Characterization of Fetal Bovine Serum
Robert C Curry,
MBA, Director, International Serum Industry Association
A review of how the International Serum Industry Association (ISIA) is vastly reducing the risk of serum adulteration and contamination through its traceability program, animal origin, and age testing, and gamma irradiation of serum.
11:00 Host Cell Protein Characterization by LCMS
Guifeng
Jiang, PhD, Senior Manager, Analytical Science, Boehringer-Ingelheim, USA
Host cell protein (HCP) impurities need to be controlled and monitored for product safety, efficacy and quality. Although HCPs are typically measured by ELISA, these methods have significant limitations for HCP analysis. Orthogonal proteomic LCMS
methods have become hot topics due to the capability of identifying and quantifying individual HCP species. We will discuss our development of sensitive and quantitative analytical LCMS methods for HCP identification and quantitation.
11:30 Generating Data to Support the Understanding of Manufacturability of Monoclonal Antibodies
Michael Anyadiegwu, PhD, Senior Scientist, Downstream Processing, Centre for Process Innovation Ltd., National Biologics Manufacturing Centre
A short list of 50 monoclonal antibody sequences was selected based on experimental data from a long list of 200 monoclonal antibodies sequences. These 50 molecules covered a range of titres and quality attributes, were produced and purified
using standard CHO, USP and DSP platforms. This presentation reviews upstream, downstream, analytic and immunogenicity data linking the biochemical and quality properties of the antibody variants to sequence and structural liabilities.
12:00 pm Enjoy Lunch on Your Own
1:15 Session Break
1:25 Chairperson’s Remarks
Guifeng Jiang, PhD, Senior Manager, Analytical Science, Boehringer-Ingelheim, USA
1:30 Characterization of HCPs in the Downstream Processing
Rong Li , PhD, Associate
Director, Sanofi Genzyme
Various impurities are encountered during the downstream processing of the biologics. Host cell protein (HCPs) need to be monitored for product safety, efficacy, and quality. In this presentation, we will discuss the analytical characterization
and control of host cell protein (HCP) impurities.
2:00 Factors Influencing Polysorbate’s Sensitivity Against Enzymatic Hydrolysis and Oxidative Degradation
Wendelin Kranz, MSc, Scientist LC-MS, Coriolis Pharma Research GmbH
Polysorbate (PS) degradation is a hot topic for the pharmaceutical development of biologics. We compared the sensitivity of different grades of PS20 and PS80 against enzymatic hydrolysis and oxidative degradation. Systematic degradation
studies with multi-compendial PS20 and PS80, as well as all-laurate PS20 and all-oleate PS80 (compliant to Chinese Pharmacopoeia) will be presented, as well as a novel fast LC-CAD method to differentiate between hydrolytic and oxidative
PS degradation.
2:30 Molecular Interactions between Drug Product Formulation Excipients and Infusion Containers
Kashmira Dilrukshan, Associate Research Scientist, Drug Product Science Technology, Bristol-Myers Squibb
At the point of intravenous dosing, most biologics are typically diluted with diluents such as saline and dextrose in infusion containers. These are manufactured with a plasticized polymer. These additive polymers lend flexibility and
durability to the containers. The objective here was to measure and quantify the amount of plasticizers leaching from IV bags containing various infusion formulation compositions under several use-time conditions.
3:00 Understanding Polysorbate Degradation Due to Process Impurities: Rates and Mechanisms and Their Impact on Stability
Christopher O’Brien, PhD, Process Engineer III, Process Science, Sanofi
Different mechanisms and rates associated with polysorbate degradation pathways were evaluated. A mechanistic model was developed that links polysorbate degradation rate to process impurities. The understanding gained from the model was
used to support process improvements.
3:30 Close of Conference