This case study is the first to address the risk, at the device-to-vial interface, of a spike pushing a stopper into a vial. It was performed after healthcare workers at cancer care hospitals complained about the risk of possible exposure to hazardous injectable drugs during the transfer if the spike pushed the stopper into the vial. This case study took a three-step approach to understand the device-to-vial interface, and the factors that determine stopper push-in force threshold and spike puncture force, respectively. The results show that the stopper push-in force threshold varies with the spike size, stopper properties, and stopper design; while the spike puncture force is determined by spike design, spike surface lubricity, stopper properties, and stopper design. The case study suggests that, to mitigate the risk of stopper push-in, the spike puncture force needs to be significantly lower than the stopper push-in force threshold, measured with a flat tip test probe having the same outside diameter as typically used spikes. In addition, although some factors which impact stopper push-in force threshold also impact spike puncture force in the same trend, such as stopper material, other factors which impact stopper push-in force threshold do not impact spike puncture force, and vice versa. For example, the spike length and cross section area contribute to stopper push-in force threshold but do not have significant impact on puncture force. It would be misleading to just compare the absolute values of spike puncture forces but neglect the dimensional factors. From the stopper and spike compatibility perspective, the case study provides a methodology to quantify the risk of stopper being pushed into the vial by the spike, and suggests a process to prevent the stopper push-in from occurring. The study also shows that the human factor is another important element in the stopper push-in issue. It emphasizes the need for a joint effort for risk mitigation across the board among stopper manufacturers, spike manufacturers, pharmaceutical manufacturers, device manufacturers, and hospitals (pharmacies & healthcare workers). Device and drug developers need to properly select and test stoppers and containers with intended spikes. Healthcare workers need to use compatible stoppers and spikes, and need to use them correctly.

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This study is conducted on a real live highway to investigate the driver’s performance in estimating the speed and distance of vehicles behind the target lane during lane changes. Data on the participants’ estimated and actual data on the rear car were collected in the experiment. Ridge regression is used to analyze the effects of both the driver’s features, as well as the relative and absolute motion characteristics between the target vehicle and the subject vehicle, on the driver’s estimation outcomes. Finally, a mixed algorithm of extreme gradient boosting (XGBoost) and deep neural network (DNN) was proposed in this paper for establishing driver’s speed estimation and distance prediction models. Compared with other machine learning models, the XGBoost-DNN prediction model performs more accurate prediction performance in both classification scenarios. It is worth mentioning that the XGBoost-DNN mixed model exhibits a prediction accuracy approximately two percentage points higher than that of the XGBoost model. In the two-classification scenarios, the accuracy estimations of XGBoost-DNN speed and distance prediction models are 91.03% and 92.46%, respectively. In the three-classification scenarios, the accuracy estimations of XGBoost-DNN speed and distance prediction models are 87.18% and 87.59%, respectively. This study can provide a theoretical basis for the development of warning rules for lane-change warning systems as well as insights for understanding lane-change decision failures.

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Sufficient rubber stopper sealing performance throughout the entire sealed product life cycle is essential for maintaining container closure integrity in the parenteral packaging industry. However, prior publications have lacked systematic considerations for the time-dependent influence on sealing performance that results from the viscoelastic characteristics of the rubber stoppers. In this paper, we report results of an effort to study these effects by applying both compression stress relaxation testing and residual seal force testing for time-dependent experimental data collection. These experiments were followed by modeling fit calculations based on the Maxwell-Wiechert theory modified with the Kohlrausch-Williams-Watts stretched exponential function, resulting in a nonlinear, time-dependent sealing force model. By employing both testing evaluations and modeling calculations, an in-depth understanding of the time-dependent effects on rubber stopper sealing force was developed. Both testing and modeling data show good consistency, demonstrating that the sealing force decays exponentially over time and eventually levels off because of the viscoelastic nature of the rubber stoppers. The nonlinearity of stress relaxation derives from the viscoelastic characteristics of the rubber stoppers coupled with the large stopper compression deformation into restrained geometry conditions. The modeling fit with capability to handle actual testing data can be employed as a tool to calculate the compression stress relaxation and residual seal force throughout the entire sealed product life cycle. In addition to being time-dependent, stress relaxation is also experimentally shown to be temperature-dependent. The present work provides a new, integrated methodology framework and some fresh insights to the parenteral packaging industry for practically and proactively considering, designing, setting up, controlling, and managing stopper sealing performance throughout the entire sealed product life cycle. Historical publications in the parenteral packaging industry have lacked systematic considerations for the time-dependent influence on the sealing performance that results from effects of viscoelastic characteristic of the rubber stoppers. This study applied compression stress relaxation testing and residual seal force testing for time-dependent experimental data collection. These experiments were followed by modeling fit calculations based on the Maxwell-Wiechert theory modified with the Kohlrausch-Williams-Watts stretched exponential function, resulting in a nonlinear, time-dependent sealing force model. Experimental and modeling data show good consistency, demonstrating that sealing force decays exponentially over time and eventually levels off. The nonlinearity of stress relaxation derives from the viscoelastic characteristics of the rubber stoppers coupled with the large stopper compression deformation into restrained geometry conditions. In addition to being time-dependent stress relaxation, it is also experimentally shown to...