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Cambridge Healthtech Institute’s 2nd Annual
Detection and Characterization of Particulates and Impurities
Rapid Tools and Strategies for Risk Assessment, Prediction and Characterization of Particles and Impurities from Products, Excipients and Processes
January 19-20, 2016

Particles and impurities can come from the products, any stage of bioprocessing or the packaging containers. The presence of particulates and impurities in the drug product can 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 2nd 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.

We invite you to present a poster and join 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 Conference Registration


2:00 Chairperson’s Opening Remarks

Shawn Cao, Ph.D., Principal Scientist, Process and Product Development, Amgen, Inc.


2:05 Characterization of Biotherapeutics and Detection of Impurities

Fouad_AtoufFouad Atouf, Ph.D., Director, Biologics and Biotechnology, United States Pharmacopeia

USP is developing a broad range of standards addressing biological medicines for the USP-NF that encompass monographs, general chapters and associated reference standards. Special focal points of the current revision cycle include the development of standards for peptide and protein products. This presentation will focus on the role of compendial standards in the control and measurement of process-related and products-related impurities in biotherapeutics.

2:45 Measurement Biases & Calibration of Flow Imaging Instruments

Dean_RippleDean Ripple, Ph.D., Leader, Bioprocess Measurements Group, National Institute of Science and Technology

Flow imaging is a powerful tool for analysis of particles in the size range from 1 μm to 100 μm. This talk will discuss sources of measurement error that affect reported particle size or count, including fundamental limits on optical resolution and the effects of high protein monomer or excipient concentration. Calibration methods to correct for these errors are proposed, and the utility of these methods is assessed.


3:15 Refreshment Break in the Exhibit Hall with Poster Awards

4:00 Subvisible Particle Analysis: How to Get the Most Bang for Your Buck

Danny_ChouDanny Chou, Ph.D., former Senior Research Scientist, Biologics Development, Gilead Sciences; President and Founder, Compassion BioSolution

Subvisible particles (SVP) analysis is a hot topic in the biopharmaceutical development and manufacturing due to their impact on quality and safety. With the imminent arrival of USP <1787> there will be significant expansion of recommended techniques. Given the reality of having limited resources to address the subvisible particle “challenge,” the focus of this presentation is on how one can get the most value (lowest cost/benefit ratio) from the array of technologies available to advance drug development.

4:30 Visible and Subvisible Particles in BCG Immunotherapeutic Product

Marina_KirkitadzeMarina Kirkitadze, Ph.D., MBA, Deputy Director, Analytical R&D Biochemistry, Sanofi Pasteur

Bacille Calmette-Guerin, BCG, is a live attenuated bovine tubercle bacillus used for treatment of non-muscle invasive bladder cancer. In this study, an Electrical Sensing Zone (ESZ) method was developed to measure the particle count and the size of BCG immunotherapeutic (BCG IT) vaccine using a Coulter Counter Multisizer 4® instrument. The developed method was used to assess manufacturing process consistency using 10 production scale lots of BCG IT product.

5:00 Q&A with Session Speakers


8:00 am Conference Registration and Morning Coffee


8:30 Chairperson’s Remarks

Marina Kirkitadze, Ph.D., MBA, Deputy Director, Analytical R&D Biochemistry, Sanofi Pasteur

8:35 Particle Identification by Multi-Technique Methods

Jonas_Hoeg-ThygesenJonas Hoeg Thygesen, Ph.D., Research Scientist, R&D - Microanalysis Centre, Novo Nordisk Pharmatech

The USP <1787> gives guidance on how subvisible particles may be analyzed. This presentation will outline how several of the analytical techniques in USP <1787> (including SEM/EDS, FTIR and Raman spectroscopy) may be used during particle analysis and identification. The presentation will include discussions on the advantages of the different techniques, and illustrate how the combination of techniques may complement each other to ensure a robust and precise analytical answer.

9:05 Analysis of Subvisible Particles in Protein Therapeutics: Methods and Applications

Shawn Cao, Ph.D., Principal Scientist, Process and Product Development, Amgen, Inc.

The subvisible particles that might be present in protein therapeutics have been identified by the regulatory agencies as a potential safety issue. Analytical methods are needed for the monitoring and control of these subvisible particles, and to study the mechanism of particle formation. The methods available to subvisible particle analysis, their strengths and weaknesses, and some case studies showing how these techniques can be applied to address particle characterization during the product lifecycle will be discussed in this presentation.

Millipore Sigma9:35 Characterization of Protein Aggregates and Subvisible Particles using Imaging Flow Cytometry

Christine Probst, MSc, Application Scientist, Biology Research and Development, Amnis- A Part of EMD Millipore

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


10:50 Critical Considerations for Surfactant Stability in Biopharmaceutical Formulations-When Degraded By Enzyme

Pervina Kei, Senior Research Associate, Early Stage Pharmaceutical Development, Genentech Inc.

Recently polysorbate instability has drawn intense scrutiny. Polysorbate degradation was observed in protein products, and evidences support enzymatic degradation. Polysorbate is made of multiple components, which are susceptible to enzymatic degradation in a unique fashion. The polysorbate degradation pattern varies when exposed to enzymes from different sources; thus, can be used as a fingerprint analysis in identifying the enzymes that co-purify with drug substance.


11:20 Understanding Particle Formation: Solubility of Free Fatty Acids as Polysorbate 20 Degradation Byproducts in Therapeutic Monoclonal Antibody Formulations

Nidhi_DoshiNidhi Doshi, Associate Scientist, Late Stage Pharmaceutical Development, Genentech, Inc.

The purpose of this work was to determine the aqueous solubilities at 2-8°C of the major free fatty acids (FFAs) formed by Polysorbate 20 (PS20) degradation and identify possible ways to predict, delay or mitigate subsequent particle formation in monoclonal antibody (mAb) formulations. For the first time, a 3D correlation between FFA solubility, PS20 concentration and pH has been reported providing a rationale approach for the formulator to balance these with regards to potential particle formation.

11:50 Recent Advances In Monitoring The Kinetics Of Protein Aggregation And The Onset And Evolution Of Particulates Using Simultaneous Multiple Sample Light Scattering (SMSLS)

Wayne_ReedWayne F. Reed, Ph.D., Murchison Mallory Chair Professor of Physics and Founding Director, PolyRMC, Tulane University

Continuous monitoring of light scattering intensity from protein formulations allows stability to be assessed and, when aggregation occurs, a quantitative measure of the kinetics. Results presented will show kinetics under a variety of stressors, including temperature, controlled stirring and exposure to different air/liquid and solid/liquid interfaces. Furthermore, the method has been extended to monitoring the onset and evolution of particulate formation via large scattering spikes produced by particles that reach a certain size.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own


2:00 Chairperson’s Remarks

Vishal C. Nashine, Ph.D., Senior Research Investigator II, Drug Product Science & Technology, Bristol-Myers Squibb

2:05 Identification and Characterization of Impurities in Diagnostic Proteins

Jeffery_FishpaughJeffrey Fishpaugh, Ph.D., Senior Principal Research Scientist, Diagnostic Analytical Chemistry R&D, Abbott Laboratories

The analysis of pharmaceutical biologics has been well discussed; in contrast, biologics utilized in diagnostic assays have not been as well covered. Diagnostic biologics are reviewed by government regulatory bodies with similar requirements as pharmaceutical biologics, especially biologics used in commercial blood screening assays. We have recently completed an analysis of 40+ biologics to determine impurities present, variability of impurities and their potential impact on our assays.

2:35 Root Cause Analysis of Reversible Aggregates that Impact Opalescence of a Monoclonal Antibody Formulation

Radhakrishna_MarojuRadhakrishna K. Maroju, Ph.D., Scientist, CMC Management, Drug Product Development, Teva Biopharmaceuticals USA

High concentrated monoclonal antibody (mAb) formulations are generally associated with opalescence, which is known as a thermodynamic event rather than kinetic. However, reversible aggregates that usually cause opalescence can be formed by kinetic reactions. The present case study describes rare occurrence of increased opalescence over time of a mAb clinical inventory, focusing on possible root cause of the reversible aggregates to essentially correlate the observed opalescence with identified chemical degradation products.

3:05 Assessment of Protein Sensitivity to Residual Hydrogen Peroxide when Filled in Isolator

John_WangY. John Wang, Ph.D., Principal Scientist, Late Stage Pharmaceutical Development, Genentech, Inc.

Protein product filled in isolator is vulnerable to the residual hydrogen peroxide. Reaction mechanism and kinetics between hydrogen peroxide and the Fc methionine in mAb products will be presented. Also formulation excipients that may influence the reaction rates will be discussed. With this understanding, one can estimate the duration of the study needed in order to qualify filling operation in isolator, or if such study is needed.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 Probing Protein-Surface Interactions and Their Role in Particulate Formation: A Case Study

Vishal_NashineVishal C. Nashine, Ph.D., Senior Research Investigator II, Drug Product Science & Technology, Bristol-Myers Squibb


5:00 Separation of Protein from Non-Proteinaceous Particles in Biopharmaceutical Formulations with MVAS by Microflow Imaging MFI

Zahir Akhunzada, Ph.D., Research Scientist, ABD, Bristol-Myers Squibb

Subvisible Particles (SVPs) are major challenge in development of therapeutic protein formulations. Distinction between proteinaceous and non-proteinaceous SVPs is vital in monitoring the formulation stability. The current compendial method based on light obscuration (LO) has limitations. This presentation reveals a method that successfully characterizes and distinguishes, both potentially proteinaceous and non-proteinaceous SVPs in protein formulations by using Microflow Imaging (MFI) in conjunction with the MVAS (MFI View Analysis Suite) software.

6:30-7:30 Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Conference