Cambridge Healthtech Institute’s 5th Annual Detection and Characterization of Particulates and Impurities conference will bring together leading scientists from biopharmaceutical industry, academia and government to discuss hot topics, case studies, new technologies, and strategies to carry out risk assessment and mitigation for impurities arising from products, excipients, processes and packaging. Through new presentations, informative panel discussions, high-level poster presentations, and interactive discussions, top scientists will share new insights into detection, characterization and control of various impurities. Some of the hot topics for this year will be new and novel technologies contaminant detection, host cell proteins, lipases and enzymatic degradation, particles and aggregates, leachable, chemistry and manufacturing controls (CMC) strategy for regulatory filings.

Final Agenda

TUESDAY, JANUARY 15

1:00 pm Registration (Sapphire West Foyer)

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Risk of Immunogenicity Posed by Aggregates and Impurities
Aqua D

2:00 Chairperson’s Opening Remarks

Joël Richard, PhD, Head, Technical and Pharmaceutical Operations, MedinCell

KEYNOTE PRESENTATION

2:05 Aggregates and Particulates in Protein Formulation: Orthogonal Characterization Methods for a Data-Based Immunogenicity Risk Assessment

Joël Richard, PhD, Head, Technical and Pharmaceutical Operations, MedinCell

Aggregation remains a considerable challenge in the manufacturing, stability behavior and delivery of liquid protein formulations. Orthogonal biophysical techniques make it possible to characterize protein structure alteration and the subsequent mechanism of formation of sub visible aggregates and particulates, which are among the most striking issues suspected to trigger immunogenic reactions upon repeated subcutaneous administration. Clinical impact regarding potential safety issues will also be discussed, as identified by regulatory agencies.

PARTICLE CHARACTERIZATION AND ANALYTICAL METHODS DEVELOPMENT
Aqua D

2:45 NEW TALK: Next Frontier in Subvisible Particle Analysis: New Tools and Opportunities

Danny K. Chou, PharmD, PhD, President, Compassion BioSolution, LLC

 

In the past decade, we have witnessed the arrival of a large number of analytical technologies that are useful for characterizing sub-visible particles in protein therapeutics. Even with the diverse tools that are available today, there are still important gaps that have not been filled but yet have a significant role in our ability to fully analyze particles for either product characterization or formulation development purpose. The goal of this presentation is to highlight some of these gaps and share the opportunities that may be captured by new tools that are on the horizon.

 

3:15 Analysis of Various Process- Related Impurities by HPLC with Detection by ELSD, CAD or Fluorescence

Mario Dipaola, PhD, Senior Scientific Director, Biologics, Charles River Laboratory

During this presentation, several HPLC methods with varying detection methods will be discussed along with performance of these methods with respect to critical parameters such as LOD/LOQ/linearity range, etc. At least one case study will be presented, as well, to highlight some of the common challenges one is likely to face when developing a method for process residual testing.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Characterization of Subvisible Particles in Protein and Viral Vaccines
Aqua D

4:30 Characterization of Subvisible Particles in Protein and Viral Vaccines

Marina Kirkitadze, PhD, Deputy Director, Head of Biophysics and Conformation Unit, Analytical R&D Biochemistry, Sanofi Pasteur, Canada

The topic of this presentation is characterization of visible and subvisible particles in protein and viral vaccine formulations. Visible and subvisible particles were found to be inherent to the product, and were analyzed by several methods including MFI, DLS, and MS.

5:00 New Tools and Strategies for Characterization of Particles in Biologics

Tim Menzen, PhD, CTO, Coriolis Pharma Research GmbH

Particles in the nanometer and micrometer size range need to be characterized as part of drug product development, both as impurities (e.g. protein aggregates, polysorbate degradation) and as active (e.g. virus, cells). An overview on innovative methods for micrometer particles (backgrounded membrane imaging, imaging flow cytometry, etc.) and nanometer particles (resistive pulse sensing, novel flow imaging set-ups, etc.) will be given, including a critical comparison to existing methods.

5:30 Close of Day

5:30 - 5:45 Short Course Registration (Sapphire West Foyer)

5:45 - 8:45 Recommended Dinner Short Courses*

SC3: Protein Aggregation: Mechanism, Characterization and Consequences

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*Separate registration required

WEDNESDAY, JANUARY 16

7:45 am Registration and Morning Coffee (Sapphire West Foyer)

Detection, Characterization and Control of Process- and Product-Related Impurities
Aqua D

8:15 Chairperson’s Remarks

NEW Tim Menzen, PhD, CTO, Coriolis Pharma Research GmbH

8:20 USP Standards for Monitoring Impurities in Biotherapeutics

Diane McCarthy, PhD, Senior Scientific Liaison, 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. These impurities must be monitored and controlled to minimize safety concerns and ensure product quality. This presentation will provide an overview of approaches for monitoring impurities, including specific examples that leverage USP standards.

8:50 MS-Based HCP Identification and Quantitation for Drug Substance Analysis

Stéphane Parent, Senior Principal Scientist & Group Leader  , Caprion Biosciences Inc.

Biological drugs inevitably contain host cell protein (HCP) impurities. The identify and levels of HCPs may determine whether a biological drug is accepted or not by regulatory agencies. Mass spectrometry-based analysis are increasingly used for HCP identification and quantitation. In this study, MS-based platforms were developed for unbiased profiling of HCPs and for targeted HCP quantitation with an assay sensitivity in the 1 to 10 ppm range.

9:20 SELECTED POSTER PRESENTATION: Specifics of Sub-Visible Particulates Evaluation for Ultra High Concentration Monoclonal Antibody Formulations

Nidia Gonzalez Lopez, Development Associate III, Alexion Pharmaceuticals, Inc.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

10:35 Evaluation of Croda Super RefinedTM (SR) and TweenTM 20 High Purity (HP) PS20

Nidhi Doshi, MSc, Senior Research Associate, Late Stage Pharmaceutical Development, Genentech

Super RefinedTM Polysorbate 20 (SR PS20) and TweenTM 20 HP (HP PS20) by Croda differ primarily in refinement technology designed to provide better formulation stability in case of SR PS20. Side-by-side evaluation of the two grades revealed differences in surfactant degradation rates, particle formation risk as well as product quality impact. This talk will weigh the benefits and risks of using SR over HP PS20.

11:05 Comparison of Automated Methods for Quantitation of Host Cell Proteins

Jamie Rusconi, PhD, Staff Scientist, Bioanalytical Method Development, Regeneron Pharmaceuticals, Inc.

While ELISA assays generally offer the advantages of broad Host Cell Protein (HCP) recognition and sensitivity, they suffer from a limited linear dynamic range leading to the need for test article dilutions, multiple steps requiring analyst “hands on” time and limited opportunities for automation. Both the ELLA SimplePlex method and the ProteinSeq method were developed as alternatives to the traditional immunoassay format. In this presentation, we will explore our analysis and comparison of these two methods for quantitation of Host Cell Proteins.

11:35 NEW TALK: Polysorbate Stability

Christian Schöneich, PhD, Takeru Higuchi Distinguished Professor and Chair, Department of Pharmaceutical Chemistry, The University of Kansas

12:05 pm Session Break

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break

PLENARY KEYNOTE PANEL (Aqua Salon)

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PepTalk Perspectives: Point-Counterpoint Discussions

2:00 Plenary Keynote Introduction

Norman Packard, PhD, CEO, Daptics

2:10 Plenary Keynote Panel

Moderator:
Howard Levine, PhD, President and CEO, BioProcess Technology Consultants
Panelists:
George Badescu, PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG
Manon Cox, PhD, Co-Founder & CEO, NextWaveBio
Zhimei Du, PhD, Director, Bioprocess & Clinical Manufacturing, Merck
Paul Jorjorian, Vice President, BioProcess Sciences, Thermo Fisher Scientific
Marina Kirkitadze, PhD, Deputy Director, Head of Biophysics and Conformation Unit, Analytical R&D Biochemistry, Sanofi Pasteur, Canada
Stefan R. Schmidt, PhD, MBA, Head, Operations (COO), BioAtrium AG

 

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Excipients and Impurities in Pre-Filled Syringes and Freeze-Dried Formulations

Aqua D

4:00 Chairperson’s Remarks

Evgenyi Shalaev, PhD, Executive Director, Pharmaceutical Development, Allergan, Inc

4:05 Impact of Silicone Oil on Fatty Acid Solubility and Polysorbate Related Particle Formation

Raphael Fish, Engineer I, Process Development, Genentech

Silicone oil coatings on the interior of pre-filled syringes (PFS) may act as a sink for free fatty acids (FFAs) released upon hydrolytic degradation of polysorbates. FFAs were shown to partition from an aqueous to a silicone oil phase in a glass vial model. However, the partitioning effect was not large enough to translate to representative conditions. Silicone oil levels in representative PFS are not expected to reduce FFA particle risk.

4:35 NEW TALK: Heterogeneity Across the Lyophilization Batch

Robin Bogner, PhD, Professor, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut

 

 

5:05 Phase Behavior of an Alternative Surfactant, Poloxamer, during Freeze-Drying

Evgenyi Shalaev, PhD, Executive Director, Pharmaceutical Development, Allergan, Inc.

Poloxamers (e.g., P188) have been recently considered as alternative surfactants to polysorbates (tween20 and 80), as the latter are easily oxidized and can also undergo hydrolysis. In this study, complex phase behavior of aqueous solutions of a poloxamer is investigated using DSC, small-angle neutron scattering, and small- and wide-angle X-ray scattering.

5:35 SELECTED POSTER PRESENTATION: Effect of Freeze-Thaw Process Parameters on Stability of Lactate Dehydrogenase 

Bruna Minatovicz, PhD Candidate, Department of Pharmaceutical Sciences, University of Connecticut

Storage of biotherapeutics in a frozen state provides operational flexibility and extends the shelf life of protein solutions. This presentation will provide an overview of the impact of freeze-and-thaw process parameters on the stability of a model protein, lactate dehydrogenase, at a large scale. A phase-field theoretical model will further provide the mechanistic understanding of possible stresses arising during the freezing process and their ultimate effect on the protein stability.

6:05 - 7:00 Networking Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

7:00 Close of Detection and Characterization of Particulates and Impurities Conference