March 4-8, 2019
Short Course: Tuesday, March 5, 6:30 – 9:00

Particles in Biotherapeutics: Characterization & Impact

Dean Ripple, Ph.D., Supervisory Physicist, Bioprocess Measurements Group, National Institute of Standards and Technology

Srivalli Telikepalli, Ph.D., Research Chemist, Biomolecular Measurement, National Institute of Standards and Technology

This short course will give an introduction to current issues surrounding particle formation & characterization in biotherapeutics. Regulatory expectations provide the context of why particle loads are characterized and controlled. The basics of why and how proteins can aggregate will be presented along with a discussion of other particle types. An overview of the recent technology to accurately characterize various classes of aggregates and particles will be discussed. Studies from the current literature will be used to highlight various key points throughout the course.

1. Introduction to Protein Aggregates & Other Particles

• Overview of particles in biotherapeutics: protein aggregates & other types
• Current regulatory expectations
• Rationale for characterization & control
• Recent experiences & case studies

2. Causes & Mechanisms behind Aggregation/Particle Formation

• Causes of protein aggregation
• Mechanisms behind formation of aggregates
• Sources of other types of particles
• Methods to minimize aggregation & particle formation
• Case studies

3. Technologies & Tools for Measuring & Characterizing Aggregates & Particles

• Visible particles (manual and automated inspection)
• Sub-visible particles (Microflow imaging, light obscuration, etc.)
• Sub-micrometer aggregates (Size exclusion SEC, AUC, FFF, etc.)
• Approaches to standardize particle counts
• Comparisons between technologies regarding limits of detection

4. Strategies for Particle Control & Characterization

5. Discussion with Q&A

Speaker Biographies

Dean Ripple, Ph.D., Supervisory Physicist, Bioprocess Measurements Group, National Institute of Standards and Technology

Dean received a Ph.D. from Cornell University in 1991 and began a post-doctorate position at the National Institute of Standards and Technology the same year. After a successful career at NIST supporting improved methods and standards in thermometry, in 2010 he became Leader of the Bioprocess Measurements Group. His research focuses on the development of new standards for protein particles. Dean has presented workshops on measurement issues to many industrial groups, ranging from petroleum producers to vaccination program coordinators. He is an active member of ASTM and USP committees, and he has received awards from the Department of Commerce, ASME, and ASTM.

Srivalli Telikepalli, Ph.D., Research Chemist, Biomolecular Measurement, National Institute of Standards and Technology

Srivalli Telikepalli received her B.A. in chemistry at Cornell University in 2008 and Ph.D. in Pharmaceutical Chemistry from the University of Kansas in 2014. Her thesis work was focused on understanding the formation of protein aggregates/particles as a function of different stresses and understanding the relationship between protein particle properties and their in-vitro immune responses. Upon completion of graduate school, she started working as a Research Chemist at the National Institute of Standards and Technology in the Biomolecular Measurements Division. Currently, her work focuses on developing protein-like particle standards, primarily subvisible and visible particle standards, as well as lending support to developing a monoclonal antibody reference material.