| 00:00:00 | New technologies to improve the understanding of bioformulation stability |
| 00:02:33 | Aggregation of Therapeutic Proteins: Cause, Control, Adverse Immunogenicity and Roles of Nanoparticles |
| 00:03:04 | Acknowledgments |
| 00:03:11 | Outline |
| 00:03:40 | Causes of Protein Aggregation |
| 00:04:23 | Control of Aggregation in Solution: Maximize Conformational and Colloidal Stability |
| 00:06:01 | Effects of Conformational and Colloidal Stability on GCSF Aggregation |
| 00:08:13 | Particles going along for the ride |
| 00:09:06 | New Insights Into Causes of Aggregation from Quantifying Sub-visible Particles |
| 00:09:25 | Role of Nano- and Microparticles on IVIG Particle Formation during Agitation |
| 00:09:42 | Microparticle Concentrations after Initial Agitation and Subsequent Centrifugations |
| 00:10:01 | Nanoparticle Concentrations after Initial Agitation and Subsequent Centrifugation |
| 00:10:16 | Microparticles during agitation |
| 00:11:05 | Nanoparticle Concentrations during Agitation |
| 00:11:36 | Subvisible Particles are Critical Species on the Protein Aggregation Pathway |
| 00:12:01 | Why do subvisible protein particles so often look like the ones of the left? |
| 00:12:38 | Causes of Protein Particles: Interfaces |
| 00:13:17 | Gelation of a mAb at silicone oil-water interface |
| 00:13:59 | Experimental setup for gel rupture at the silicone oil-water interface |
| 00:14:14 | Gel rupture leads to loss of soluble protein |
| 00:14:42 | Presence of surfactants resulted in reduced aggregation |
| 00:14:54 | Presence of surfactants led to a decrease in the protein particle mass detected by RMM |
| 00:15:33 | Adverse Immunogenicity: When Miracle Drugs Fail |
| 00:16:41 | Immunogenicity: Particles as Adjuvants |
| 00:16:57 | Effects of route of administration on immunogenicity of rmGH |
| 00:17:18 | Particles in rmGH Samples: Only nanoparticles in ultracentrifuged sample |
| 00:18:03 | Ultracentrifuged rmGH (week 6): Nanoparticles cause Immunogenicity |
| 00:18:35 | Mishandling of Products by Pharmacies, Clinics and Patients |
| 00:18:54 | Stresses to Protein Therapeutics even during “Proper” Handling for IV Infusion |
| 00:19:29 | Mimicking the infusion setup… |
| 00:19:44 | IVIg in Saline – particle counts > 1µm |
| 00:20:15 | IVIg in Saline – total nanoparticle counts |
| 00:20:30 | IVIg-0.22um- filter FlowCam Images; Large particles downstream from filter |
| 00:20:48 | Removing tube downstream from filters reduces large subvisible particles formed |
| 00:21:28 | Polycarbonate Particles in IV Saline: G3 ID Raman Microspectroscopy |
| 00:22:12 | Conclusions |
| 00:22:54 | Advanced Technologies to Improve the Understanding of BioFormulation Stability |
| 00:23:54 | Content |
| 00:24:10 | Stability of Biotherapeutics |
| 00:24:11 | Industry Drivers |
| 00:24:41 | Stability Screening – Thermal Stability |
| 00:25:53 | Stability Screening – Thermal Stability |
| 00:26:26 | Understanding Protein Stability |
| 00:27:17 | Helix- Providing Further Understanding |
| 00:27:41 | Helix- Providing Further Understanding |
| 00:28:05 | Helix- Providing Further Understanding |
| 00:28:51 | Helix- Providing Further Understanding |
| 00:30:17 | Comparison of mAb with mmAb: Thermal Stability |
| 00:31:58 | Comparison of mAb with mmAb: Kinetics |
| 00:33:18 | Sub-visible Particles |
| 00:33:39 | Immunogenicity |
| 00:34:11 | NanoSight Technology |
| 00:35:04 | NanoSight – High Resolution SVP Characterisation |
| 00:35:36 | Characterizing Sub-visible Particles |
| 00:36:45 | Characterizing Sub-visible Particles |
| 00:37:41 | Archimedes: Distinguishing Protein and Silicone |
| 00:38:38 | Particle Identification |
| 00:38:51 | Particles in Protein Formulations |
| 00:39:19 | Characterizing/Identifying Contaminants |
| 00:39:42 | Characterizing/Identifying Contaminants |
| 00:40:21 | Characterizing/Identifying Contaminants |
| 00:40:38 | Characterizing/Identifying Contaminants |
| 00:41:07 | Sub-visible Particles |
| 00:41:25 | Sub-visible Particles |
| 00:41:50 | Closing Remarks |
| 00:42:40 | Thank you for your attentionAny questions? |
| 00:43:01 | Effects of Conformational and Colloidal Stability on GCSF Aggregation |
| 00:43:32 | Particles going along for the ride |
| 00:44:26 | Thank you for your attentionAny questions? |
| 00:56:57 | Contact Information |
Understanding the relationship between formulation stability and protein aggregation is a critical during bio therapeutic development. As a consequence, a number of new technologies, are now available which offer detailed insights into protein behaviour, allowing the evaluation of product stability and process impact. This course will discuss current understanding of Aggregation Pathways, Adverse Immunogenicity and Innovative Techniques to Assess the Quality and Stability of Biopharmaceutical Formulations.