Characterize subvisible protein particles in formulations

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00:00:00 Characterization of Subvisible Particles in Therapeutic Protein Formulations: Challenges from Silicone Oil and Nanobubbles
00:03:18 Archimedes
00:04:58 Resonant Mass Measurement (RMM)
00:05:38 Resonant Mass Measurement (RMM)
00:06:18 Resonant Mass Measurement (RMM)
00:06:53 What do we measure and how do we get size?
00:08:14 RMM Resolution
00:08:50 Sub-Visible Particle Identification
00:09:51 Micro and nano sensors and their detection ranges
00:11:00 Upper detection limits – geometry sets the limits
00:11:50 Recommended Practices – Sensor Cleaning
00:14:16 Recommended Practices – Sensor Cleaning
00:15:18 Characterization of Subvisible Particles in Therapeutic Protein Formulations: Challenges from Silicone Oil and Nanobubbles
00:15:23 Outline
00:15:54 Loss of Efficacy: When Miracle Drugs Fail
00:16:22 Factors affecting immunogenicity of therapeutic drugs
00:17:20 Foreign Particles from Container/Closure/Filters/Pumps/Tubing/Bags
00:17:43 Foreign Particles
00:18:44 Particles as Adjuvants: Interferon-b Products
00:19:19 Neutralizing Antibody (NAb): Summary of Clinical Data for IFN-b Products
00:19:41 Dosage Form/Formulation of Ifn-β Products Tested
00:20:05 Aggregate Levels by SEC and Analytical Ultracentrifugation
00:20:23 Particle Counts by Microflow Imaging (>1µm)
00:20:59 Particle Counts by Microflow Imaging (>1µm): Protein and/or Silicone Oil Microdroplets?
00:21:30 With Archimedes, silicone oil droplets distinguished from protein particles
00:22:43 Conclusions from IFN- β Analyses
00:23:24 Causes of Protein Particles: Interfaces
00:24:39 Experimental setup for rupture of protein gel at the silicone oil-water interface
00:25:14 Gel rupture results in particle formation as detected by MFI
00:25:59 With Archimedes, total masses of protein particles and silicone oil droplets determined directly
00:27:39 Presence of surfactants decreases protein particle formation during interface rupture
00:28:35 Nanobubbles in reconstituted freeze-dried formulations
00:30:51 Typical visible bubbles observed 30 minutes after reconstitution of IVIG formulations
00:31:17 High particle counts in some reconstituted samples: Not affected by degassing or optical filtering
00:33:32 With Archimedes both protein particles and air bubbles could be quantified
00:35:01 Nanobubbles persist even 11 days after reconstitution
00:36:42 Conclusions
00:39:15 2015 Colorado Protein Stability Conference
00:39:49 Contact Information
00:58:34 Find out more about Archimedes

Guest presenter - Prof. Dr. John Carpenter, University of Colorado

Counting and sizing of subvisible particles in therapeutic protein formulations are critically important activities for product development and quality assurance. Such characterization can be challenging for products in prefilled syringes in which silicone oil droplets can be at high concentration and interfere with analysis of protein particles. Similarly, we have recently found that nanobubbles that form upon reconstitution of lyophilized protein formulations can dominate in particle analyses. Fortunately, these challenges can be overcome by using the resonance mass measurement technique available with the Archimedes system.

In this presentation, Prof. Carpenter presents case studies which demonstrate the value of this approach for products in prefilled syringes and in model studies of silicone oil effects on protein aggregation. New data documenting the presence and stability of nanobubbles in reconstituted lyophilized formulations will also be highlighted.