RESUMO
While bioanalytical outsourcing is widely adopted in the pharmaceutical industry, AbbVie is one of the few large biopharmaceutical companies having an internal bioanalytical unit to support nearly all its drug metabolism and pharmacokinetic studies. This article highlights our experience and perspective in building an integrated and centralized laboratory to provide early discovery and preclinical-stage bioanalytical support with high operational efficiency, cost-effectiveness and data integrity. The advantages of in-house nonregulated bioanalytical support include better control of data quality, faster turnaround times, real-time knowledge sharing and troubleshooting, and lower near- and long-term costs. The success of an in-house model depends upon a comprehensively optimized and streamlined workflow, fueled by continuous improvements and implementation of innovative technologies.
Assuntos
Laboratórios , Serviços Terceirizados , Automação , Tecnologia , Indústria FarmacêuticaRESUMO
BACKGROUND: BK polymavirus (BKPyV), a member of the family Polyomaviridae, is associated with increased morbidity and mortality in allogeneic stem cell transplant recipients. METHODS: In our previous retrospective study of 2477 stem cell transplant patients, BKPyV replication independently predicted chronic kidney disease and poor survival. In this study, using the same cohort, we derived and validated a risk grading system to identify patients at risk of BKPyV replication after transplantation in a user-friendly modality. We used 3 baseline variables (conditioning regimen, HLA match status, and underlying cancer diagnosis) that significantly predicted BKPyV replication in our initial study in a subdistribution hazard model with death as a competing risk. We also developed a nomogram of the hazard model as a visual aid. The AUC of the ROC of the risk-score-only model was 0.65. We further stratified the patients on the basis of risk score into low-, moderate-, and high-risk groups. RESULTS: The total risk score was significantly associated with BKPyV replication (P < .0001). At 30 days after transplantation, the low-risk (score ≤ 0) patients had a 9% chance of developing symptomatic BKPyV replication, while the high-risk (score ≥ 8) of the population had 56% of developing BKPyV replication. We validated the risk score using a separate cohort of 1478 patients. The AUC of the ROC of the risk-score-only model was 0.59. Both the total risk score and 3-level risk variable were significantly associated with BKPyV replication in this cohort (P < .0001). CONCLUSIONS: This grading system for the risk of symptomatic BKPyV replication may help in early monitoring and intervention to prevent BKPyV-associated morbidity, mortality, and kidney function decline.
