Cambridge Healthtech Institute’s 2nd Annual
Host Cell Proteins
Detecting, Analyzing and Removing Host Cell Proteins
Part of CHI's Ninth Annual The
Bioprocessing Summit
August 21-22, 2017 | Westin Copley Place | Boston, MA
A critical part of bioprocessing is the control of process-related impurities such as host cell proteins (HCPs), which co-purify with the drug substance and can cause adverse effects such as immunogenicity. Analytical methods are available but coverage
and specificity is limited. Moreover, the emergence of new expression systems, new products and new techniques such as mass spectrometry has further compounded these limitations with regulators now pressing companies for more HCP data.
CHI’s 2nd Annual 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 21
8:00 am Short Course Registration Open
9:00 – 11:30 Recommended
Morning Short Courses*
SC2: Comparability Strategies for Cell and Gene Therapies
* Separate registration required
11:30 Main Conference Registration Open
1:00 pm Chairperson’s Opening Remarks
Carl Co, Ph.D., Senior Scientist, Biogen
1:10 A Holistic Phase Appropriate Strategy for HCP-Limits and HCP Characterization
Markus Haindl, Ph.D., Director, Development Analytics, Roche
Increased usage of new technologies like Mass Spectrometry opens up entirely new strategic possibilities to test and characterize HCP – not only in purified Drug Substance to ensure patient safety but also for in-process samples to characterize
downstream process performance. A smart and phase-appropriate combination of traditional assay formats with new technologies becomes key to support an IMP product during its development lifecycle until launch.
1:45 Host Cell Protein Control Strategy Reassessment for a CHO-Derived Protein Therapeutic
John M. Rolf, Ph.D., Director, Corporate Product Quality, Amgen
Immunoassay tests are standard to establish HCP impurity specifications and monitor protein therapeutic lot-to-lot consistency. However, multi-analyte Immunoassay tests may over- or under-quantify. In this case study, Mass Spectroscopy (MS) identified
and quantified individual HCPs from protein product drug substance, comparing results to the Immunoassay. The case study demonstrates how MS testing (and supplemental characterization data) was used to redefine the HCP control strategy – without
impacting product or patient safety.
2:15 Specific Immune Response to PLBL2, a Host Cell Impurity in Clinical Material
Melissa L. Cheu, Principal Scientific Researcher, BioAnalytical Sciences, Genentech, Inc.
A product-related impurity was identified in material used in a clinical study. To assess the potential of patients developing an immune response to the impurity and the impact on immunogenicity of the therapeutic, two bridging ELISAs were developed and
validated. Samples from subjects were evaluated in both assays. This presentation will discuss the results of the immunogenicity assessment to the impurity and observed immunogenicity rate of the antibody therapeutic.
2:45 Refreshment Break
3:15 Impacts of Advanced HCP Characterization on Cell Culture and Purification Process Development and Optimization
Chongfeng Xu, PhD., Scientist II Protein Analytical Development, Biogen
3:45 Sponsored Presentation (Opportunity Available)
4:00 Obtaining EU-Wide (CHMP) Scientific Advice for HCP Issues
Ruth Paul, Independent Consultant
I will share my experiences of working with the pharma industry to obtain EU-wide scientific advice on issues relating to HCP levels in biotech products. I will discuss the issues raised, the strategic advice that EMA/CHMP gave (in general terms) and
highlight some of the potential pitfalls of the process from the company’s perspective.
4:30 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. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.
Regulatory Requirements for HCPs
Ruth Paul, Independent Consultant
- HCP regulatory expectations throughout development
- Common pitfalls made by companies
- European vs. US expectations
Best Practices for Host Cell Protein Analysis using Mass Spectrometry
Ying Zhang, Senior Scientist, Analytical Research & Development, Pfizer
- Choice of Instrumentation
- System Suitability and Performance Validation
- Best Practice for Quantitation
- Next Gen HCP Analysis
5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Conference
Tuesday, August 22
7:30 am Registration Open and Morning Coffee
7:55 Chairperson’s Remarks
Fengqiang Wang, Ph.D., Associate Principal Scientist, Merck Research Laboratories, Merck & Co. Inc
8:00 Reducing Host Cell Protein Burden by Molecular Design and Selection
Yiqing Feng, Ph.D., Research Fellow, BioTechnology Discovery Research, Eli Lilly and Company
Removing host cell proteins has become a critical aspect of biopharmaceutical process development. It will be advantageous to design and select therapeutic candidates that have reduced tendency for HCP association to make the removal easier during the
purification process. We have explored the molecular attributes of monoclonal antibodies that contribute to HCP association which will be discussed in this presentation.
8:30 Recent Case Studies of Identification and Quantification of Host Cell Proteins by Mass Spectrometry
Veronika Reisinger, Ph.D., Lab Head, Physico-Chemical Characterization, Novartis Technical
LCMS/MS can be used as a complimentary method to ELISA for detection and monitoring of residual host cell proteins (HCP). A platform approach was established for CHO and E. coli-derived products to identify and relatively
quantify HCPs. In the presented case studies, comparability exercises for two FDA-approved biosimilars are discussed.
9:00 Increased Throughput and Accuracy in Host Cell Protein Quantitation Using Spectral Library Searches
Michelle Busch, Scientist, Bioanalytics Characterization, Sanofi
A high throughput method was developed to identify and quantify residual host cell proteins (HCPs) throughout purification. A spectral library was created from manually verified peptides to increase the speed of data analysis and reduce error and
false positive matches. The library search could then be utilized for subsequent experiments, allowing knowledge of the product and its HCPs to accumulate and not have to be discovered repeatedly.
9:30 Vendor Neutral Host Cell Protein Detection and Reporting for LCMSMS Data
St John Skilton, Ph.D., Senior Director, Global Sales and Marketing, Protein Metrics Inc.
Mass spectrometry has been successfully used to accurately identify and quantify Host Cell Proteins in biotherapeutics for more than a decade – but largely by specialists. Here we present vendor-neutral mechanisms that report the data automatically in formats more easily understood by process development scientists.
9:45 Coffee Break in the Exhibit Hall with Poster Viewing
10:30 Quantitative Investigation of Host Cell Protein Impurities: Bridging the Gap between ELISA and Orthogonal LC-MS/MS Analysis
Ying Zhang, Senior Scientist, Analytical Research & Development, Pfizer
LC-MS/MS has emerged as an orthogonal approach to ELISA for analyzing HCPs, providing both qualitative and quantitative information on individual HCPs. Sample prep, method parameters, and different mass spectrometers were investigated. We found that
the quantitative readouts between HCP-specific ELISAs and LC-MS/MS were quite comparable, permitting “real-time” targeted-HCP monitoring during process development and comprehensive HCP analysis for final purified drug substance.
11:00 HCP Identification and Absolute Quantification with a Multifaceted Mass Spectrometry Platform
Laura McIntosh, Ph.D., Vice President Translational Research, Scientific Management, CAPRION
BIOSCIENCES INC
Gel-free, label-free mass spectrometry (MS) enables identification and quantitation of total and individual HCP in biotherapeutic products, and represents an orthogonal method to ELISA. Examples will be presented showing use of semi-quantitative
HCP discovery (LC-MS/MS) and absolute quantitation of HCP (LC-MRM/MS), as applied to monitoring of process changes/improvements, scale-up, batch uniformity, clearance, and comparison of Biosimilars vs Innovators. Caprion’s HCP platform
features customizable organism/process-specific databases, highly controlled analytical processes and reproducible robust detection (to ~1ppm).
11:30 Navigating through the Challenges Encountered in Development of New HCP Reagents
Elise Levi, Associate Scientist III, Analytical Development, Biogen
Generation of HCPs reagents takes up to a year and must therefore be methodically planned in order to meet process development and testing support deadlines. Unforeseen challenges may arise during the development of these reagents and require
strategic decision making to meet project demands and support. In this talk, we present several case studies which highlight how we experimentally navigated through these challenges to make critical and timely decisions.
12:00 pm Development
of a Specific E. coli HCP ELISA based on Antibody Fragments
Karsten Daehn, Senior Scientist, Immunoassay Development, BioGenes GmbH
Biopharmaceuticals need to be free of contaminating HCPs prior to approval. For HCP determination of drug substances in early phases or during the DSP development commercial HCP-ELISAs are commonly used. In challenging cases special properties
of the drug substance limit the use of full-length antibodies in ELISA, thus commercial HCP-ELISAs are not applicable during DSP development. BioGenes successfully overcame this issue by developing a specific E. coli HCP ELISA based on fragments of rabbit antibodies.
12:30 Luncheon Presentation: New Strategies for Quality Control of Host Cell Protein Impurities.
Olaf Stamm, Senior Specialist, Biological Testing Solutions, Charles River
In this presentation we will show case studies from more than twenty year’s experience in the field of HCP assay development. We will highlight critical parameter and quality attributes along the entire assay development process
1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing
1:55 Chairperson’s Remarks
Fengqiang Wang, Ph.D., Associate Principal Scientist, Merck Research Laboratories, Merck & Co. Inc
2:00 Case Study: Qualifying an ELISA for HCP Quantification and Its Ability to Inform Purification Process Decisions
Samantha Kecman, Senior Analytical Development Associate, Pharmaceutical Sciences, Genocea
ELISA is the most common method for HCP quantification. This presentation will cover aspects of anti-HCP ELISA assay development and qualification in the context of clinical-phase biopharmaceutical development. Discussion will include the generation
and evaluation of anti-HCP antibodies against SF9 antigens using different animal systems and how quantification of HCPs from in-process samples can inform and influence purification process choices.
2:30 Applications of Magnetic Bead Technology for Use in HCP Analysis
Jeffrey Schneiderheinze, Ph.D., Associate Director, Biochemistry
Method Development, Regeneron Pharmaceuticals, Inc.
While ELISA assays generally offer the advantages of broad HCP recognition and sensitivity they also suffer from a limited linear dynamic range. In this presentation, we will explore the application of using magnetic bead technology as an
alternate approach to ELISA for HCP analysis.
3:00 Late Phase Process Development and Process Impurities Clearance – The Application and Optimization of HCP and Lipase Assays
Satish K. Sharma, Ph.D., Scientist II, Process Development Analytics, Bristol-Myers Squibb
In a bioprocess development environment, HCP removal is essential in order to have a robust and safe commercial process. In a dynamic PD environment continuous process and method optimization is critical. Constant monitoring and risk assessment
at early stage can minimize failure at late process development stage. Case studies and mitigation approaches that show correlation between HCP profile and specifically lipases will be discussed.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Case Study: Clearance of an Immunogenic Host Cell Protein Impurity in a CHO-Derived Biotherapeutic Leading to a Standard Purification Approach
Ben Tran, Purification Development, Genentech, Inc.
This case study highlights a specific CHO host-cell protein, Phospholipase B-like 2 (PLBL2). PLBL2 was isolated and identified from a clinical product during investigation of atypical “non-linear” sample dilution behavior in
a multi-product CHOP ELISA. High-throughput screening and multivariate studies identified two modes of purification that effectively and robustly reduced PLBL2 levels. These screening tools have since been used to understand PLBL2
clearance and troubleshoot other co-purifying HCPs.
4:45 Panel Discussion: HCP Moving Forward
Moderator: Fengqiang Wang, Ph.D., Associate Principal Scientist, Merck Research Laboratories, Merck & Co. Inc
5:15 Close of Conference
6:00 – 8:30 Recommended Dinner Short Course*
SC5: Potency Assay Development for Cell and Gene Therapy Products
* Separate registration required