Cambridge Healthtech Institute’s 4th Annual
Host Cell Proteins
Detection, Analysis and Control
August 12-13, 2019
Controlling process-related impurities such as host cell proteins (HCPs) is a critical part of bioprocessing. Analytical methods are available but coverage and specificity is limited. Moreover, the emergence of new techniques, such as mass spectrometry
has further compounded these limitations with regulators now pressing companies for more HCP data.
CHI’s Host Cell Proteins conference brings together industry leaders to discuss critical HCP topics such as: risk assessment and control strategies, HCP characterization, assay coverage, critical reagents and platforming, plus questions relating
to biosimilars, in-process testing and the latest data supporting the link between HCPs and immunogenicity.
Final Agenda
Monday, August 12
7:30 am Short Course Registration Open and Morning Coffee
Waterfront 2
8:30-11:00 Recommended Short Course*
SC3: Quality Considerations for Gene Therapy Viral Vectors
Instructor:
Christopher Bravery, PhD, Consulting Regulatory Scientist, Consulting on Advanced Biologicals Ltd.
Gene therapy viral vectors are complex biological medicinal products which pose a number of challenges with respect to quality and overall adventitious agent safety. Firstly, they are large complex viral particles which must be designed to be replication
incompetent. Secondly, as the product is a suspension of viral particles, application of traditional viral reduction and elimination steps is not possible, so control of materials and the process become more important. This course outlines the testing
expected to address these fundamental features and ensure a safe product of suitable quality is released.
11:00 Main Conference Registration Open
12:30 pm Chairperson’s Opening Remarks
Fengqiang Wang, PhD, Associate Principal Scientist, Merck.
12:40 KEYNOTE PRESENTATION: USP Standards to Support Host Cell Protein Analysis
Diane McCarthy,
PhD, Senior Manager, Science and Standards Biologics Pipeline Development, USP
Residual host cell proteins (HCPs) in biotherapeutic products can pose a risk to patients and to the quality of the product and therefore must be monitored and controlled. This presentation will provide an overview of approaches for monitoring HCPs, with
an emphasis on the use of orthogonal methods, and an update on development of new physical standards to support identification and quantitation of high risk and high abundance HCPs.
1:10 Regulatory News and Views on HCP Control
Erika Friedl, PhD,
Quality Expert, Hematology and Transfusion Medicine, Paul-Ehrlich-Institute
Host cell proteins are considered critical quality attributes which have the potential to negatively impact the quality and safety profile of a pharmaceutical product. The removal and the tight control of these impurities is required and outlined in several
guidelines. Case studies will be selected to highlight the regulatory decisions taken. New approaches regarding HCP assay and reagent developments in view of the existing regulatory framework will be discussed.
1:40 HCP Panel Session: Regulations and Standards
Diane McCarthy,
PhD, Senior Manager, Science and Standards Biologics Pipeline Development, USP
Erika Friedl, PhD,
Quality Expert, Hematology and Transfusion Medicine, Paul-Ehrlich-Institute
2:10 Refreshment Break
2:30 Managing High Risk HCPs
Fengqiang Wang,
PhD, Associate Principal Scientist, Merck
Host cell proteins (HCPs) are process-related impurities that may co-purify with biopharmaceutical drug product. Within this class of impurities there are some that are more problematic. These problematic HCPs can be considered high-risk and can include
those that are immunogenic, difficult to purify and/or degrade both product molecules and excipients. Why should the biopharmaceutical industry worry about these high-risk host cell proteins? What approach could be taken to deal with these high-risk
HCPs?
3:00 BIOPHORUM Development Group - A A Multi-Company Collaboration; Views on "High Risk" HCPs
Nisha Palackal,
PhD, Director, Protein Biochemistry, Regeneron Pharmaceutical, Inc.
Host cell proteins (HCPs) are process-related impurities that may co-purify with biopharmaceutical drug product. Within this class of impurities there are some that are more problematic. These problematic HCPs can be considered high-risk and can include
those that are immunogenic, difficult to purify and/or degrade both product molecules and excipients. Why should the biopharmaceutical industry worry about these high-risk host cell proteins? What approach could be taken to deal with these high-risk
HCPs? To answer these questions the BioPhorum Development Group (BPDG) HCP Point Share initiated a collaboration among its 24-company team with the goal of industry alignment around high-risk HCPs. A sub team was formed, in which the members performed
literature searches and discussed the information available around this topic. The BPDG HCP Point Share team members were surveyed, which led to team discussions and insight into a list of problematic frequently seen HCPs. These HCPs can be classified
based on available information into different risk categories that could be beneficial to the biopharmaceutical industry.
3:30 Q&A
3:45 Session Break
3:55 Plenary Keynote Session View details
5:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing
6:30 End of Day
Tuesday, August 13
7:30 am Registration Open and Morning Coffee
7:55 Chairperson’s Remarks
Fengqiang Wang, PhD, Associate Principal Scientist, Merck
8:00 HCP Assay Development and Optimization for the Quality Control Laboratory
Jeff Schneiderheinze, PhD, Director, Bioanalytical Method Development, Regeneron
Assessment of host cell protein levels is critical to understanding process consistency as well as ensuring patient safety. Over the years, methodologies have developed to enable and deepen characterization and understanding of host cell proteins
in process pools and drug substances. Quality control testing remains a critical component of the control strategy. This presentation will focus on advances and issues pertaining to HCP analysis in the quality control laboratory.
8:30 Monitoring Host Cell Proteins: From an ELISA Assay to a Comprehensive HCP Program.
Yiwei Zhao, PhD, Senior Scientist, Analytical Development: Biologics, Takeda Pharmaceuticals
An on-going Host Cell Protein (HCP) characterization program in Takeda is introduced in the presentation. In addition to traditional ELISA HCP assay, multiple HCP risk assessment tools are presented and discussed. A commercial monoclonal antibody
is used for assay method development and result demonstration. Risk assessment tools include LC/MS/MS HCP identifications followed by in silico immunogenicity assessment as well as multiplex cytokine release assay.
A process workflow is also introduced.
9:00 HCP Immunoassays and
Integration of Orthogonal Methods for Determination of HCP Impurities in
Downstream Samples
Eric Bishop, Vice
President of R&D Research and Development, Cygnus Technologies
Well-developed and broadly-reactive HCP ELISA are typically used during the purification process to ensure removal of HCP and to demonstrate process consistency and final drug substance purity. Regulatory guidelines require use of orthogonal methods
to ensure the HCP ELISA is fit for purpose. AAE and MS have emerged as tools for identifying HCPs that persist through downstream purification processes. When used in conjunction with well-developed ELISA, these methods provide a more complete
HCP impurities analysis.
9:30 ELISA HCP Coverage by
Immunocapture and LC-MS
Ejvind Mortz, Chief
Operating Officer, Alphalyse
Alphalyse has developed an improved HCP coverage analysis based on ELISA antibody immunocapture followed by LC-MS protein identification. The analysis aid ELISA development; A) for selecting antibodies with the broadest coverage, B) for selecting
ELISA antibodies detecting HCPs in the drug substance, and C) for fit-for-purpose validation of the ELISA.
9:45 Coffee Break in the Exhibit Hall with Poster Viewing
10:30 Challenges of Implementing HCP Assays for Gene Therapy Programs
Emily Menesale,
Senior Associate Scientist, Analytical Development, Biogen
Gene therapy has become a promising new therapeutic in the drug development field. With the development of gene therapy products also comes new challenges in the field of HCP assay development. Such challenges include logistics around safety precautions,
small sample volumes, and working with non-traditional cell lines. Here, we explore these challenges and assess potential solutions to the typical immunoassay including new technologies and more thorough reagent characterization.
11:00 Identification and Impact of Individual Host-Cell Proteins in CHO-Based Biomanufacturing
Abraham M. Lenhoff, Allan P. Colburn Professor, Department of Chemical and Biomolecular Engineering, University of Delaware
Although CHO host-cell proteins are usually tracked primarily by overall amounts, via ELISA, in bioprocessing, even small quantities of individual, deleterious HCPs can be problematic in drug product. Determining how effectively individual HCPs are
removed in different process steps is gradually being revealed by the increasing use of proteomic methods. This presentation will discuss recent findings gleaned from a variety of process steps.
11:30 Quantitative Analysis of Host Cell Proteins by LC-MS/MS
Ying Zhang, PhD, Principal
Scientist, Analytical Research & Development, Pfizer
In recent years, biotherapeutics development laboratories have established LC-MS/MS as an orthogonal approach to ELISA, providing qualitative and quantitative information on individual HCPs. To assess the accuracy and precision of quantitation in
the LC-MS/MS method, we investigated our LC-MS/MS method alongside published sample preparation protocols for both fully purified and in-process samples to better understand the advantages and disadvantages toward enhancing the reliable detection
and quantitation of residual HCPs.
12:00 pm Improved 1D MS-based HCP Platform with Single-digit ppm Sensitivity, Enhanced HCP Coverage and Shorter Turnaround Time
Gwenaël Pottiez, Principal Scientist, Proteomics, CAPRION BIOSCIENCES
Basic (1D) LC-MS/MS workflows can provide sensitivity in the 10ppm range, whereas 2D-LC-MS/MS workflows allow to obtain single-digit ppm sensitivity. However, fractionation prior to LC-MS/MS analysis is a time-consuming process. An optimized 1D HCP
workflow was developed with higher throughput. Optimization of sample processing resulted in shorter processing time. Optimization of the chromatography and implementation of new MS technology (timsTOF Pro), enabled a 4-fold increase in assay
sensitivity with enhanced HCP coverage and data quality.
12:30 Enjoy Lunch on Your Own
1:15 Cake Break in the Exhibit Hall with Poster Viewing
1:55 Chairperson’s Remarks
Ying Zhang, PhD, Principal Scientist, Analytical Research & Development, Pfizer
2:00 Verification Strategies for HCP Identification and Quantification Data Obtained by LCMS
Veronika Reisinger, PhD, Lab Head Physico-Chemical Characterization, Technical Research & Development, Novartis-Global Drug Development
Host cell protein analysis by mass spectrometry represents a powerful complementary method to ELISA testing. In general, mass spectrometry techniques are well established for analysis of proteins but the reliable identification and quantification
of low abundant species remains challenging. Here we present different approaches used for verification of qualitative and quantitative results in host cell protein analysis by mass spectrometry.
2:30 Improvements in LC-MS/MS HCP Detection Workflows: More Sensitivity, Better Quantification, and Faster Data Processing
Don Walker, PhD, Pharma Technical Development, Genentech
LC-MS/MS is a powerful tool for host cell protein (HCP) analysis of biotherapeutics, but limitations remain in terms of sensitivity, throughput, quantification, and data processing. In this presentation we evaluate methods for improving HCP detection
sensitivity and assess throughput and robustness. Then we discuss methods and approaches to quantify HCP’s, which provides critical information to support process optimization and safety assessment.
3:00 NEW: HCP Analysis by SWATH LC-MS for Process Development of Biologics
Ejvind Mortz, Chief Operating Officer, Alphalyse
The presented LC-MS method is developed on 60+ projects on mAbs, gene therapy products, vaccines and therapeutic proteins with the aim to: Detect and quantify HCPs of concern for product stabilty and patient safety, Aid and document HCP Clearance
of process, Compare GMP batch consistency at individual HCP level.
3:30 Panel Session: Best Practices for HCP Analysis using Mass Spectrometry
Moderators: Ying Zhang, PhD, Principal Scientist, Analytical Research & Development, Pfizer
Veronika Reisinger, PhD, Lab Head Physico- Chemical Characterization, Technical Research & Development, Novartis-Global Drug Development
Don Walker, PhD, Pharma Technical Development, Genentech
Ejvind Mortz, Chief Operating Officer, Alphalyse
4:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:15 - 4:30 Stretch Break
4:45 Breakout Discussions
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.
5:45 End of Conference
Waterfront 1C
6:00-8:30 Recommended Dinner Short Course*
SC9: Impact of Impurities on Stability of Biologics
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.