Kanstruplevin9438

addition to pulmonary vascular parameters.

The coexistence of two complex physiologies such as Fontan and pregnancy is still not fully understood. We aim to add a unique and essential knowledge to help our colleagues in the management of Fontan patients that undergo pregnancy as well as the fetus and the placenta perfusion.

We analyse the coexistence of Fontan and pregnancy physiology on a complex case of a woman with hypoplastic left heart syndrome palliated with a univentricular repair who became pregnant, delivered very prematurely and had atypical placental findings.

Histopathological analysis of the placenta could help us to refine the understanding of Fontan physiology adaptation during pregnancy, predict women and fetal outcomes as well as to plan a better pre-pregnancy status. However, further evidence is needed in order to reach a more solid and unified conclusion.

Histopathological analysis of the placenta could help us to refine the understanding of Fontan physiology adaptation during pregnancy, predict women and fetal outcomes as well as to plan a better pre-pregnancy status. However, further evidence is needed in order to reach a more solid and unified conclusion.There is no abstract for this piece.Single-use systems find increasing application downstream of final filters in the production of antibody, vaccine, gene, and cell therapy drug products. For such critical applications, particulate matter attached to the interior (product-contacting) surfaces of the single-use system could potentially be released and contaminate the drug product. Risk reduction requires methods that reliably detect particulate matter on the inside of single-use systems. Here we describe the results from the development and validation of a manual visual inspection method for the detection of particulate matter inside transparent single-use systems. Test kits consisted of single-use systems (2 D bags, tubing lines, and bag/tubing assemblies) internally seeded with test particles (black, clear, or fiber) ranging from 100 to 2000 µm in size. A designed experiment determined the optimal light intensity, inspection time, and time between inspector breaks required to maximize the probability of detection (POD) for particles. POD > 70% for black and clear particles started at particle sizes exceeding 400 to 1000 µm depending on the single-use system type and size, but the POD for 2000 µm fibers was marginal to poor. Thus, for single-use systems, the particle size to achieve POD > 70% shifted to significantly larger sizes than the 150-250 µm particle size typically detectable in drug products. Overall, the POD decreased as the bag size or tubing line length increased. An attribute gage repeatability and reproducibility study using three inspectors validated the inspection method for reliable detection of black and clear particles ≥ 1000 µm in size over the entire size range of single-use assemblies and tubing lines examined. Fibers of length 1000 and 2000 µm were not reliably detected. Oxaliplatin The results highlighted the challenges in reliably detecting particulate matter in a visual inspection of the interior surfaces of single-use systems.How to decide whether a statistically significant trend is of practical relevance? In the context of stability data of pharmaceuticals, this publication provides a way forward to use different measures of (method) variability to compare to the observed changes over time. A panel of analytical experts assessed whether statistically significant trends were of practical relevance or not. For different types of assessing variability, recommendations for decision criteria were derived that best matched these assessments, i.e., finding a suited balance between not detecting a relevant trend and between flagging a trend wrongly as relevant. For this purpose, more than 60 data sets from Biosimilar projects of Sandoz/Novartis were leveraged. Hence, this article provides a scientific way to assess whether a statistically significant trend is of practical relevance or not, and a case study is presented and discussed.A statistically robust set of rules is proposed for trending excursions in environmental monitoring data. These rules were designed to minimize false alarms when the process is in control, but signal quickly when the process goes out of control. An adverse trend is an early warning that the system is drifting from normal operating conditions. Prompt action may prevent further deterioration and avoid costly out-of-specification events. Adverse trends are defined as an alert level excursion rate of >2.5% and an action level excursion rate of >0.15%. These definitions were derived from setting action levels at the 99.85th percentile and alert levels at the 97.5th percentile. These percentiles were chosen because they are functional equivalents of control limits and warning limits used in statistical process control charting, which are set at three and two standard deviations above the mean, respectively. In addition, the U.S. Pharmacopeial recommended microbial recovery rates should also be implemented as trend metrics for microbial environmental monitoring of aseptic processing facilities. Occasional isolated alert level excursions may occur even if the process remains in a state of control. However, repeated alert level excursions occurring at a rate >2.5% indicate the process is changing and the system is drifting from normal operating conditions. An adverse trend of alert level excursions should be investigated for root cause. It is critical to determine if an alert level excursion, at its onset, indicates an adverse trend. A total of 24 rules at various sample sizes were tested for their ability to detect an adverse trend at the onset of an excursion using data obtained over a period of 1 year. The rationale for choosing these rules is described.The solubility of the drug is a significant aspect to be considered during manufacturing of pharmaceutical products. Poor aqueous solubility of drugs imparts depleted bioavailability. In this regard, several techniques are available for enhancing drug solubility or dissolution. However, only few of them are scalable and industrially applicable. Hot-melt extrusion (HME) is one such technique that has been widely used in the industry. It is a single-step, continuous manufacturing, and scalable method that has proved successful in improving the solubility of poorly soluble drugs. This review highlights the numerous pharmaceutical applications of HME, such as formulations of sterile implants, taste masking of unpleasant drugs, cocrystallization, salt formation, sustained and controlled release formulations, etc. It also describes various hydrophilic and hydrophobic carriers utilized in HME. This review also briefly discusses the recent advances in HME and gives an update on the currently available marketed products.