Cambridge Healthtech Institute’s Fourth Annual

Detection and Characterization of Particulates and Impurities

Rapid Tools for Risk Assessment, Prediction and Characterization of Impurities from Products, Excipients, Processes and Packaging

January 9-10, 2018


Particles and impurities can arise from the products and/or during any stage of bioprocessing or from the delivery devices and primary packaging. These impurities have the potential to impact stability, safety, efficacy of the biomolecules and biologic products. Therefore, early understanding, detection and characterization of the impurities are critical to ensure safety and efficacy of the drug product for its intended duration of use. The Fourth Annual Detection and Characterization of Particulates and Impurities conference provides a platform to explore novel tools and strategies to detect, characterize and carry out risk assessment of particles and impurities such as sub visible particles, host cell proteins, extractables and leachables, impurities from excipients and raw materials, glass and other particles etc.

We invite you to present a poster and attend to join with colleagues in this discussion of the key challenges and solutions for prediction, characterization, risk assessment of particles and impurities from products and processes.

Final Agenda


1:00 pm Registration

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing


2:00 Chairperson’s Opening Remarks

Maura Kibbey, Ph.D., Director, Global Biologics, U.S. Pharmacopeia


2:05 Anticipating Aggregation Propensity of Proteins at Early Formulation Development Stage: How to Support a Data-Based Approach for Immunogenicity Risk Assessment

Joël_RichardJoël Richard, Ph.D., Vice President, Peptides, CMC & Engineering, Ipsen

In the perspective of accelerating early stage protein formulation development, it has become key to anticipate and predict formulation, storage and processing conditions that will lead to aggregation. To anticipate aggregation propensity and avoid associated immunogenicity risks, it is proposed to focus on the very early steps of aggregation, often involving higher order structure (HOS) alterations and loss of colloidal stability, using a set of orthogonal characterization techniques.

2:45 USP Standards to Monitor and Characterize Impurities in Biologics

Maura_KibbeyMaura Kibbey, Ph.D., Director, Global Biologics, U.S. Pharmacopeia

The United States Pharmacopeial Convention (USP) is an independent scientific organization that protects public health through standards for medicines and their ingredients. As biological science contributes to more advanced therapies, standards continue to play a critical role in drug development and manufacturing. This talk will highlight new quality standards for demonstration of method performance, as well as measurement and characterization of impurities in peptides and biologics.

Cygnus_New 3:15 Best Practices and Strategies for Host Cell Protein ELISAs 

Eric_BishopEric Bishop, MBA, MSc, Vice President, Research & Development, Cygnus Technologies

Regulatory agencies around the world expect sponsors to have a good understanding of the HCP profile of their Drug Product. Knowing that low HCP results are due to HCP content and not due to an insensitive HCP ELISA is key. Talk will focus on current best practices and strategies to effectively demonstrate that an HCP ELISA is fit for purpose. (Selection of the best antibodies, assay design / qualification, and the integration of orthogonal methods.)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 Assessment of Immunogenic Risk Posed by Biologic Aggregation

Michael_SwansonMichael Swanson, Ph.D., Senior Scientist, Merck

Aggregated therapeutic antibodies have the potential to induce an immune response. Elucidation of the mechanism of responses to aggregated antibodies could mitigate the immunogenic risk. Utilizing cell-based in vitro models, we investigated the role of different innate immune receptors in responses to aggregated antibody. By comparing the ability of aggregated antibody and natural ligands to activate different receptors, we were able to begin to determine the relative risk posed by aggregates.

5:00 PANEL DISCUSSION: Strategies and Experience with Managing Regulatory Expectation for Particles and Impurities for Early and Late Stage Submissions


Maura Kibbey, Ph.D., Director, Global Biologics, U.S. Pharmacopeia


Michael Swanson, Ph.D., Senior Scientist, Merck

Eric Bishop, MBA, MSc, Vice President, Research & Development, Cygnus Technologies

Joël Richard, Ph.D., Vice President, Peptides, CMC & Engineering, Ipsen

5:30 Close of Day

5:30 - 5:45 Short Course Registration

5:45 - 8:45 Dinner Short Courses*

* Separate registration required


8:00 am Registration and Morning Coffee

Host Cell Protein and Process Impurities

8:30 Chairperson’s Remarks

Joël Richard, Ph.D., Vice President, Peptides, CMC & Engineering, Ipsen

8:35 Host Cell Proteins, What We Know, What We Don’t and How to Control [TALK CANCELLED]

Judy_ShimoniJudy Shimoni, Ph.D., Principal Scientist and Group Leader, Protein Analytical Chemistry, Genentech, Inc., a member of the Roche Group

The presentation is intended to share some current thinking and to use case studies to demonstrate the application of orthogonal methods complementing HCP testing and supporting process development and control strategy, and to illustrate the use of risk assessment for HCP identification and control with consideration of clinical information.

9:05 Quantitation of Affinity Ligand Leachate in Processing Samples – Why Commercial Kits Fail and What You Can Do About It

Xiaohui Lu, Ph.D., Senior Scientist, BioPharma Development, Biogen

  Caprion No Shadow 9:35 Identification and Quantification of HCPs in mAbs, Recombinant Proteins and Biosimilars by Mass Spectrometry

Michael_SchirmMichael Schirm, Ph.D., Associate Director, R&D Proteomics, 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).

10:05 Coffee Break in the Exhibit Hall with Poster Viewing


10:50 Understanding Mechanism of Interaction between E&L and Proteins to Minimize Risk on Product Safety and Quality Attributes

Kim_LiKim Li, Ph.D., DABT, MPH, Senior Manager, Environment, Health, Safety and Sustainability Product Stewardship Toxicology, Amgen

Plastic components are commonly used in the manufacture of drug-device combination products. The identification of the extractable and leachable (E&L) impurities from the device components form the basis for toxicology assessments. However, significant challenges remain with the quality evaluation of the therapeutic proteins. E&L impurities may interact with certain biological products, thus compromising the quality attributes (e.g. protein aggregates and structural modifications). This presentation will attempt to show how safety and quality evaluations can be bridged through the principles of Cramer classification in relation to adverse outcome pathway.

11:20 Identification of Micro Steel Particles Using Energy Dispersive X-ray Spectroscopy Coupled with Multivariate Statistics

Jonas_Hoeg_ThygesenJonas Hoeg Thygesen, Ph.D., Area Specialist, R&D - Microanalysis Centre, Novo Nordisk Pharmatech

Regulatory agencies call for identification and characterization of any intrinsic, inherent or extrinsic particles present in pharmaceuticals. USP <1787> outlines methods and strategies for particle identification and characterization. Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS) are two of the methods discussed in USP <1787>. This presentation will show how SEM and EDS in combination with multivariate statistics enable rapid identification of both visible and subvisible steel particles.

11:50 New NMR Methods for Fast and Efficient Analysis of Trace Leachables and Impurities in Biologics

Ken_SkidmoreKen Skidmore, Technical Development Scientist, Protein Analytical Chemistry, Genentech

Analyzing process pools and drug product for a broad spectrum of impurities is challenging. We will discuss three key NMR techniques we use for process development and regulatory filings: suppression of protein drug signals, while leaving impurity signals intact; quantitation by 2D NMR in complex matrices; and the use of CRAFT NMR, a powerful new technique which resolves the signals of trace impurities from those of protein and formulation components.

12:20 pm Enjoy Lunch on Your Own

Formulation, Raw Materials, Excipients and E&L Impurities (cont.)

2:00 Chairperson’s Remarks

Kim Li, Ph.D., DABT, MPH, Senior Manager, Environment, Health, Safety and Sustainability Product Stewardship Toxicology, Amgen

2:05 Challenges in Subvisible Particle Characterization

Miguel_SagguMiguel Saggu, Scientist, Late Stage Pharmaceutical Development, Genentech

This presentation will address challenges in subvisible particle analysis in biopharmaceutical formulations. It will discuss case studies to demonstrate how to address challenges in particle analysis using state-of-the-art particle analysis.

2:35 Protein-Excipient Interactions Evaluated via NMR Studies in Polysorbate-Based Multi-Dose Protein Formulations: Influence on Antimicrobial Efficacy and Potential Study Approach

Riccardo Torosantucci, Ph.D., Head of Laboratory Formulation Development, Pharmaceutical Development Biologics, Sanofi-Aventis Deutschland GmbH

Preservatives are excipients needed in biopharmaceutical multi-dose formulations to prevent microbial growth. However, they are known to interact with non-ionic surfactants like polysorbate and potentially with the active pharmaceutical ingredient (API). In the current study those interactions were successfully quantified via NMR and correlated to the stability and antimicrobial activity of the formulations. NMR represents therefore a powerful tool to support formulation development of multi-dose formulations.

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 SELECTED POSTER PRESENTATION: CFD Simulation and Verification for Local Pressure over Vials During Lyophilization at Laboratory Scale

Tatsuhiro Kodama, Ph.D. Visiting Scholar, Birck Nanotechnology Center, Purdue University

4:30 Characterization of Universal Stabilized Stem Flu Vaccine Candidates

Sashikanth_BanappagariSashikanth Banappagari, Ph.D., Scientist II, Formulation Development, Vaccine Production Program/VRC/NIAID/NIH

The Vaccine Research Center at the NIH has developed a series of pandemic flu vaccine candidate centered around self-assembling Ferritin-Hemagglutinin nanoparticle (HAF), intended to elicit responses across multiple influenza strains. This study describes a multi-valent biophysical characterization using CD, DSC, FTIR, Fluorescence and 2D UV. The data generated describes the basal physico-chemical properties, providing a basis for optimal formulation design and also to monitor vaccine quality during development and manufacturing.

5:00 Considerations for Assessment of Particles in Biologics Originating from Packaging and Standardization Initiatives

Diane_PaskietDiane Paskiet, MS, Director of Scientific Affairs, Scientific Affairs and Technical Services, West Pharmaceutical Services

It is critical to understand the types and sources of particulates in biologic products and how their presence may affect product quality and patient safety. The linkage between particles, biologic formulation and packaging development involves understanding contributions from all sources. This presentation will provide insight into measurements of particles originating from packaging components, comparison of data from various technologies and USP standardization initiatives.

5:30 - 6:45 Networking Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Detection and Characterization of Particulates and Impurities Conference


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