Evaluating Clinical Safety and Analytical Impact of Subvisible Silicone Oil Particles in Biopharmaceutical Products.

Silicone oil is a commonly used lubricant in pre-filled syringes (PFSs) and can migrate over time into solution in the form of silicone oil particles (SiOPs). The presence of these SiOPs can result in elevated subvisible particle counts in PFS drug products compared to other drug presentations such as vials or cartridges. Their presence in products presents analytical challenges as they complicate quantitation and characterization of other types of subvisible particles in solution. Previous studies have suggested that they can potentially act as adjuvant resulting in potential safety risks for patients. In this paper we present several analytical case studies describing the impact of the presence of SiOPs in biotherapeutics on the analysis of the drug as well as clinical case studies examining the effect of SiOPs on patient safety. The analytical case studies demonstrate that orthogonal techniques, especially flow imaging, can help differentiate SiOPs from other types of particulate matter. The clinical case studies showed no difference in the observed patient safety profile across multiple drugs, patient populations, and routes of administration, indicating that the presence of SiOPs does not impact patient safety.

Vismodegib (ERIVEDGE) pregnancy prevention programme: assessment of risk awareness.

INTRODUCTION: Vismodegib (Erivedge; Roche), a Hedgehog pathway inhibitor (HPI), is indicated for the treatment of symptomatic metastatic basal cell carcinoma (BCC) and locally advanced BCC inappropriate for surgery or radiotherapy. Due to the known risk of HPI teratogenicity, the Erivedge Pregnancy Prevention Program (PPP) was introduced at approval (2013) as part of the EU Risk Management Plan. METHODS: Structured, quantitative Web-based surveys were conducted in 2015 (Wave 1), 2016 (Wave 2), and 2017/2018 (Wave 3) among prescribing oncologists and dermato-oncologists in Austria, France, Germany, Hungary, and the United Kingdom to assess the effectiveness of the Erivedge PPP. RESULTS: Overall, 95%, 87%, and 91% of respondents in Waves 3 (N = 181), 2 (N = 214), and 1 (N = 207), respectively, were vismodegib prescribers. The surveys consistently showed a high awareness about the risk of teratogenicity associated with vismodegib (98%, Wave 3; 95%, Wave 2) and that a high proportion of prescribing physicians took appropriate precautions to minimize this risk (95%, Wave 3; 92%, Wave 2; 88%, Wave 1). Physicians were also highly aware of the Erivedge PPP (70%, Wave 3; 67%, Wave 2; 71%, Wave 1). CONCLUSION: Survey data suggest that the risk of teratogenicity with vismodegib has been effectively communicated to the prescribing community.