Current advances in biopharmaceutical informatics: guidelines, impact and challenges in the computational developability assessment of antibody therapeutics.

Therapeutic monoclonal antibodies and their derivatives are key components of clinical pipelines in the global biopharmaceutical industry. The availability of large datasets of antibody sequences, structures, and biophysical properties is increasingly enabling the development of predictive models and computational tools for the "developability assessment" of antibody drug candidates. Here, we provide an overview of the antibody informatics tools applicable to the prediction of developability issues such as stability, aggregation, immunogenicity, and chemical degradation. We further evaluate the opportunities and challenges of using biopharmaceutical informatics for drug discovery and optimization. Finally, we discuss the potential of developability guidelines based on in silico metrics that can be used for the assessment of antibody stability and manufacturability.

Delayed bolus-tracking trigger at CT correlates with cardiac dysfunction and suboptimal portovenous contrast phase.

OBJECTIVE: To assess whether delayed trigger during bolus-tracking for CT correlates with reduced heart function and suboptimal portovenous contrast phase. METHODS AND MATERIALS: Patients who underwent portovenous abdominal CT using bolus-tracking and echocardiography within 2 weeks were included and excluded if there was a non-standard contrast injection. The bolus trigger time (BTT) at 100 Hounsfield units in the abdominal aorta, patient age, congestive heart failure (CHF) history, and ejection fraction were recorded. Two radiologists scored the liver contrast phase (1-5, 5 being an optimal portovenous phase). When applicable, the BTT and contrast score of the most recent comparison examination with equivalent technical parameters were also recorded. Simple linear regression (univariate) was used to test for associations with trigger time. RESULTS: 114 patients with a mean age of 61 ± 15 years fulfilled criteria. The mean trigger time was 18 ± 6 s (range: 6-38 s) and the mean ejection fraction was 52 ± 12% (range: 19-69%). A longer bolus trigger had a significant correlation with reduced ejection fraction (P = 0.0018), lower hepatic contrast score (P < 0.0001), history of CHF (P = 0.0212), and older age (P = 0.0223). Contrast score differences between the study exam and available prior exams revealed score differences of 0 (n = 73), 1 (n = 15) and 2 (n = 5); these were associated, respectively, with a mean bolus trigger time difference between exams of 2 s (range, 0-6 s), 6 s (range, 1-15 s), and 11 s (range, 5-13). The P-value comparing bolus trigger time and contrast score differences was less than 0.0001. A lower ejection fraction also significantly correlated with suboptimal PV contrast phase (P < 0.0001). CONCLUSION: Delayed time to trigger during bolus-tracking for CT can indicate cardiac dysfunction and may not adequately adjust to provide an optimal portovenous contrast phase.