(T1430-09-55) Development of Analytical Tools for Investigating Drug-Device Interactions: A Case Study on mAb Stability and Silicone Coating Integrity

Purpose: Understanding drug-device interactions is crucial to ensuring the stability and efficacy of biopharmaceutical combination products, and therefore patient safety. While the use of pre-filled syringes (PFS) offers many advantages that have led to their widespread adoption, it also introduces risks that must be evaluated during development. A classical approach to addressing these risks involves conducting stability studies with drugs in PFS to identify potential failure modes related to drug degradation or device performance. However, such studies are often costly and time-consuming. To mitigate this, we developed analytical tools to screen these interactions earlier and anticipate failure modes, thereby guiding the selection of an appropriate PFS product for a specific drug. Monoclonal antibody (mAb) formulations are widely used in the pharmaceutical industry, and their storage in PFS exposes them to multiple interfaces that can lead to their structural alterations, aggregation, and eventually degradation. Surfactants are commonly included in formulations to reduce drug adsorption and mitigate these risks ^[1,2]. However, their presence entails other risks related to silicone coating stability and potential generation of silicone sub-visible particles which can further interact with mAbs in solution. We present a case study investigating Trastuzumab-device interactions, encompassing adsorption behavior on glass and silicone model surfaces, the propensity of mAbs to interact with silicone, and the release of silicone oil particles into solution.

Methods: The adsorption of Trastuzumab was investigated in situ using Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) to assess how surfactants influence the drug’s interaction with glass and siliconized glass model surfaces. Additionally, interfacial tension (IFT) measurements were employed to evaluate how various surfactants affect the drug’s affinity for silicone oil. To further explore the risk of silicone oil release into solution, a novel method using siliconized multi-well plates has been developed to quantify silicone migration (patent EP 24306587.7) using fluorescence. The concordance between early-stage screening outcomes and in-syringe assay results further supports the predictive value of the developed tools.

Results: QCM-D analysis allows to observe that PS80 effectively prevents monoclonal antibody (mAb) adsorption. However, this protective effect is limited to siliconized surfaces and is not observed on bare glass, highlighting the importance of surface treatment in formulation studies ^[3,4]. Interfacial tension (IFT) measurements further revealed a stronger affinity of PS80 for silicone oil compared to other surfactants, such as P188 and PS20, suggesting a preferential interaction that may impact the silicone coating stability (Figure 1). Additionally, experiments using a multi-well plate system demonstrated that PS80 induces more significant silicone oil migration into solution than P188 and does so with faster kinetics than PS20 ^[3,4]. The screening of silicone desorption using this well-plate setup yielded results consistent with in-syringe assays, demonstrating the potential of our pre-screening approach for the early detection of silicone-related instabilities.

Conclusion: These findings highlight the complementary strengths of QCM-D, IFT, and the multi-well plate system (patent EP 24306587.7) as powerful pre-screening tools for early-stage investigations of drug-device compatibility. Together, they provide a detailed understanding of drug-surface interactions, enabling the rapid identification of potential stability risks such as adsorption, drug degradation, and silicone oil migration. Integrating these investigations into the combination product development workflow enables more informed decision-making at early stages, thereby accelerating the path toward of robust and stable biologic products.

References: [1] Lefebvre, G., et al. (2021/07/01). "Adsorption rate constants of therapeutic proteins and surfactants for material surfaces." Colloids and Surfaces B: Biointerfaces 203.
[2] Lefebvre, G., et al. (2021-12-13). "Surfactant Protection Efficacy at Surfaces Varies with the Nature of Hydrophobic Materials." Pharmaceutical Research 2021 38:12 38(12).
[3] Rodriguez, M. (2023). Interactions entre médicaments biologiques et matériaux à usage médical: étude à l’interface de la couche d’huile de silicone et de la formulation dans les seringues préremplies.
[4] Rodriguez, M., et al. (submitted 2025) “Fluorescence quantification of silicone oil release upon contact with liquid therapeutical formulations.”

Interfacial tension of Trastuzumab and surfactants with PDMS silicone oil. The placebo refers to the Trastuzumab formulation buffer without any added surfactant. Interfacial tensions of Trastuzumab, PS80, P188, and their combinations were measured using this same placebo buffer.