Cambridge Healthtech Institute’s 4^th 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

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Monday, August 12

7:30 am Short Course Registration Open and Morning Coffee

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

REGULATORY EXPECTATIONS AND MANAGING HIGH RISK HCPs

12:30 pm Chairperson’s Opening Remarks

Yan-Hui Liu, PhD, Principal Scientist, Sterile Product and Analytical Development, Biologics Development, Merck & Co., Inc.

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 Regulating Host Cell Proteins

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 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?

2:10 Refreshment Break

2:30 Detection and Monitoring of High Risk HCPs

Georgeen Gaza-Bulseco, PhD, Senior Scientist III, Abbvie

3:00 Orthogonal Methods to Detect, Identify and Quantitate Problematic Host Cell Proteins

Nisha Palackal, PhD, Director, Protein Biochemistry, Regeneron Pharmaceutical, Inc.

HCPs constitute a major group of process-related impurities in a drug product. The risks associated with HCPs are primarily immunogenicity. This presentation will discuss the orthogonal methods to detect, identify and quantitate problematic Host Cell Proteins

3:30 Sponsored Presentation (Opportunity Available)

3:45 Session Break

3:55 Plenary Keynote Session View details

5:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

6:30 End of Day

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Tuesday, August 13

7:30 am Registration Open and Morning Coffee

DETECTING AND MONITORING HCPs

7:55 Chairperson’s Remarks

Fengqiang Wang, PhD, Associate Principal Scientist, Merck

8:00 Analytical Strategies for HCP

Heather Boux, PhD, Principal Scientist, Attribute Sciences, Process Development, Amgen

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 Sponsored Presentation (Opportunity Available)

9:45 Coffee Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

IMPROVING HCP DETECTION

10:30 Challenges of Implementing HCP Assays for Gene Therapy Programs

Emily Menesale, PhD, 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 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.

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 Characterization, Optimization and Application of an LC-MS based Workflow for HCP Identification and Control

Michael Schirm, PhD, Associate Director, R&D Proteomics, Proteomics, CAPRION BIOSCIENCES INC.

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 identification of individual/total HCP (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).

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing

MS STRATEGIES FOR DETECTING HCPs

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

3:00 Development of MS-based Analytical Assays to Support HCP Detection

Yan-Hui Liu, PhD, Principal Scientist, Sterile Product and Analytical Development, Biologics Development, Merck & Co., Inc.

3:30 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.

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

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

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.

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