An Intra-Company Analysis of Inherent Particles in Biologicals Shapes the Protein Particle Mitigation Strategy Across Development Stages

Not the Usual Suspects: Alternative Surfactants for Biopharmaceuticals

“…Similarly, most of the investigations have been performed on mAbs since they represent the most relevant therapeutic protein class to date. However, the surface behavior of mAbs together with surfactants is not necessarily representative of other protein classes, as observed in this work by the different behavior of the partially disordered TP (P1) and corroborated by a multi-year analysis of particulate matter in Novartis …”

“…However, the surface behavior of mAbs together with surfactants is not necessarily representative of other protein classes, as observed in this work by the different behavior of the partially disordered TP (P1) and corroborated by a multi-year analysis of particulate matter in Novartis. 44 While this study demonstrates the short-and long-term robust stabilizing effect and resistance to degradation of the lead candidates VEDG-2.2 and VEDS in a variety of protein modalities and formulations, several questions remain unanswered and will be addressed by our group in a complementary twin publication, namely, elucidating the mode of action, exploring the structure−function relationship, and characterizing the safety profile. All the results in this study point to an interphase displacement mechanism, but a more thorough mode of action description is required (for example, probing any possible protein−surfactant interactions in model systems).…”

“…While these studies thoroughly investigate many aspects of surfactants development, they were only performed on mAbs and thus fail to provide universal functional and mechanistic understandings applicable to other therapeutically relevant protein classes, such as fusion proteins, single chain fragments, or partially disordered proteins (among others). mAbs possess a high level of stability, which often translates to a significant reduction in particle generation compared to non-mAbs, as observed in the recent analysis of 10 years of particles issues at Novartis . Non-mAbs must therefore be included in the analysis of any potential novel surfactants to both prove their efficacy and be able to extract mechanistic understanding potentially applicable to the multiple new protein modalities that are foreseen to arise in drug development.…”

“…mAbs possess a high level of stability, which often translates to a significant reduction in particle generation compared to non-mAbs, as observed in the recent analysis of 10 years of particles issues at Novartis. 44 Non-mAbs must therefore be included in the analysis of any potential novel surfactants to both prove their efficacy and be able to extract mechanistic understanding potentially applicable to the multiple new protein modalities that are foreseen to arise in drug development.…”

Real-Time Assessment of the Size Changes of Individual Sub-Visible Protein Particles under Buffer Variations: A Microfluidic Study

“…However, the production of biopharmaceuticals presents several challenges, including issues related to protein aggregation into large protein particles that can adversely affect product quality, efficacy, and patient safety. A recent analysis of particle-related issues at Novartis highlighted the prevalence of large, visible protein particles [ 3 ], particularly in large-scale manufacturing. In addition, novel biologics formats (non-mAbs) are more prone to particle formation, highlighting the importance of a better understanding and control of biologics aggregation [ 4 ].…”