The impact of unspecific viral adsorption on pharmaceutical container surfaces in vaccine process development

Unspecific adsorption of viral particles to container materials represents an under-recognized source of product loss in vaccine and viral gene-therapy manufacturing. While protein adsorption is well described, dedicated investigations of viral particle adsorption remain limited. Understanding virus-surface interactions and selecting appropriate container materials is essential, as adsorption can cause substantial product losses, particularly during process steps involving purified viruses. These losses are further amplified by the low viral protein concentrations typically used in vaccine development, combined with high surface-to-volume ratios in small-scale operations, potentially compromising analytical accuracy, mass balance assessments, and subsequent decision-making. We evaluated viral particle adsorption across commonly used pharmaceutical containers, including PETG bottles and single-use bags, using multiple model viruses. All container types exhibited measurable nonspecific adsorption, enabling differentiation between low- and high-binding materials. Scanning electron microscopy and contact angle measurements identified distinct surface appearances and material-dependent differences in viral binding, with surface energy dominated by non-polar, hydrophobic interactions. These surface properties could be modulated through excipient addition. Excipient screening identified effective mitigation strategies, with surfactants such as Pluronic F-68 and proteins such as albumin nearly eliminating viral adsorption. These findings highlight the need to consider adsorption effects early in vaccine development and underscore the value of selecting low-binding materials and suitable excipients to safeguard process performance and product recovery. • Pharmaceutical containers like PETG bottles and single-use bags are a significant source of viral particle loss. • Small-scale operations are particularly prone to adsorption due to high surface-to-volume ratios. • Viral binding is driven mainly by non-polar, hydrophobic interactions. • Excipients such as surfactants (e.g., Pluronic F-68) and proteins (e.g., albumin) mitigate this adsorption. • Modulating surface properties and blocking binding sites reduce virus binding.