3PC-020 Comparison of robotic and manual reconstitution: stability assessment of protein drugs in hospital compounding

<h3>Background and Importance</h3> Reconstitution of protein drugs (PDs) in hospitals is typically done manually by trained staff. Despite strict protocols, human error and post-reconstitution stressors can affect PD stability, leading to immunogenicity, reduced efficacy, or adverse reactions.^{1 2} Robotic reconstitution systems offer benefits, such as standardising procedures and improving occupational health through ergonomic advantages. These systems reduce reliance on manual preparation, which may lead to more consistent product quality. <h3>Aim and Objectives</h3> The study aims to compare the stability of four model PDs reconstituted using different robotic programmes. Traditional and advanced analytical techniques were used to evaluate whether robotic reconstitution programmes preserve PD quality and stability. <h3>Material and Methods</h3> Four protein drugs, including nanobodies and bispecific antibodies, were reconstituted using a Kiro Grifols chemotherapy robot. Five different methods were compared: four robotic programmes (Slow 3, Slow 10, Fast, Wave) and one manual process. Analytical tools included Dynamic Light Scattering (DLS), Flow Imaging Microscopy (FIM), Size-Exclusion Chromatography (SEC), and visual inspection. Additionally, smart labels (CPI, UK) monitored environmental factors (e.g., vibration, shock), and Principal Component Analysis (PCA) was applied to identify correlations between protein stability and reconstitution conditions. <h3>Results</h3> Protein A showed significant air bubbles and particles (&gt;25 µm), especially with the robotic Wave programme, while Protein B exhibited minimal foaming. Proteins C and D demonstrated varying particle counts across all reconstitution methods, with protein morphology influenced by factors like vial dimensions. The PCA revealed that mechanical factors such as vibration did not significantly impact stability, suggesting that robotic methods are on par with manual processes. <h3>Conclusion and Relevance</h3> Robotic reconstitution systems provide equivalent stability compared to manual methods for the studied drugs, offering advantages in reducing human error and standardising preparation processes. While particle formation was observed, it was not directly tied to the robotic method used. Further optimisation of robotic reconstitution programmes may enhance PD stability and hospital compounding practices. <h3>References and/or Acknowledgements</h3> Cappelletto E, <i>et al. J.Pharm.Sci</i>. 2024 May;S0022354924001953. Martínez CS, <i>et al. J. Pharm. Sci</i> 2023 Nov;<b>112</b>(11):2799–810. <h3>Funding statement</h3> This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement N° 101007939 (RealHOPE). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. <h3>Conflict of Interest</h3> No conflict of interest