Convolutional Neural Networks Enable Highly Accurate and Automated Subvisible Particulate Classification of Biopharmaceuticals.

Quantification of subvisible particles, which are generally defined as those ranging in size from 2 to 100 µm, is important as critical characteristics for biopharmaceutical formulation development. Micro Flow Imaging (MFI) provides quantifiable morphological parameters to study both the size and type of subvisible particles, including proteinaceous particles as well as non-proteinaceous features incl. silicone oil droplets, air bubble droplets, etc., thus enabling quantitative and categorical particle attribute reporting for quality control. However, limitations in routine MFI image analysis can hinder accurate subvisible particle classification. In this work, we custom-built a subvisible particle-aware Convolutional Neural Network, SVNet, which has a very small computational footprint, and achieves comparable performance to prior state-of-art image classification models. SVNet significantly improves upon current standard operating procedures for subvisible particulate assessments as confirmed by thorough real-world validation studies.