Design and Conduct of Clinical Studies by Integration of Quality by Design (QbD) into Quality Management System (QMS) - A Pragmatic Approach

Quality is a prerequisite during entire drug development cycle. Clinical studies are required to prove effectiveness of experiment drug and to evaluate its safety profile in humans. To have a smooth design and conduct of clinical studies; Quality-by-Design (QbD) approach can be integrated with Quality Management System (QMS) to ensure the end-to-end quality optimization. Quality by Design is not widely used currently in clinical research.

Smooth Design of 3D Self-Supporting Topologies Using Additive Manufacturing Filter and SEMDOT

The smooth design of self-supporting topologies has attracted great attention in the design for additive manufacturing (DfAM) field as it cannot only enhance the manufacturability of optimized designs but can obtain light-weight designs that satisfy specific performance requirements. This paper integrates Langelaar’s AM filter into the Smooth-Edged Material Distribution for Optimizing Topology (SEMDOT) algorithm—a new element-based topology optimization method capable of forming smooth boundaries—to obtain print-ready designs without introducing post-processing methods for smoothing boundaries before fabrication and adding extra support structures during fabrication. The effects of different build orientations and critical overhang angles on self-supporting topologies are demonstrated by solving several compliance minimization (stiffness maximization) problems. In addition, a typical compliant mechanism design problem—the force inverter design—is solved to further demonstrate the effectiveness of the combination between SEMDOT and Langelaar’s AM filter.

Lanciau Bridge – First spatial tubular truss railway bridge

<p>The old Lanciau bridge, constructed in 1904, needed to be replaced by a new bridge which would allow for a continuous ballasted track.</p><p>The new bridge was designed with a view to maintaining the spirit of the old one by keeping a truss structure, while modernizing it both from the point of view of its shape (spatial triangular truss with variable height) and its sections (pipes). It took advantage of the presence of the concrete trough to connect this to the steel truss, in order to increase the rigidity of the bridge with the composite effect.</p><p>This bridge is one of the very first railway bridges made of tubular truss, which provides a pure and smooth design thanks to its compact and pure assembling nodes.</p><p>The new truss structure is really the key point of this bridge because of the tubular nodes which do not meet any standards. In particular, the fatigue resistance analysis of the 3D tubular nodes required the application of very specific documentation and results from PhD’s, as well as the use of volume finite element computations.</p><p>The new Lanciau bridge is now ready to service MOB panoramic trains, and to continue the tradition of Swiss alpine steel railway bridges.</p>

Flow Characteristics of an Optimized Axial Compressor Rotor Using Smooth Design Parameters

Blade designs have evolved from NACA series and free vortex assumptions to detailed meanline and forced vortex definitions. A design process is presented with numerous parametric options to explore a large design space. Smoothness in turbomachinery blade shapes is critical to an effective design. A cubic B-spline is used to control spanwise variations in the curvature definition of airfoil camber, thickness distribution, leading edge definition, inlet angles and outlet angles as parameters with a small number of control points. Varying parameters of individual blade sections requires more control variables that increases the parameter space and adds kinks in the 3D blade shape. Benefits of this smooth spanwise capability are demonstrated by linking the blade design tool with an aerodynamic optimization system. A single subsonic rotor (rotor 6 of a 10 stage axial compressor derived from the GE EEE design) has been considered as the baseline for the optimization process. Optimization is performed by varying curvature of the airfoil camberline as well as inlet and outlet angles in the spanwise direction. A single objective optimization was performed to optimize isentropic efficiency. An improvement in efficiency of 0.83% from 91.87% to 92.63% was obtained. The optimized blade geometry has a smooth transition from a traditional airfoil shape at the hub section to an S-shaped airfoil at the mid and tip sections. This unique blade shape was obtained because the airfoil camber curvature definition was allowed to vary smoothly spanwise. An S-shaped blade near the mid and tip section promotes flow to move radially downwards which allows for a reduction in entropy generation due to tip leakage flows. Entropy is used to quantify losses and improvement in efficiency.

Seismic Response of 20-Story-Tall Reinforced-Concrete Special Moment-Resisting Frames Designed with Current Code Provisions

This paper investigates the two-dimensional nonlinear seismic response of four 20-story reinforced-concrete special moment-resisting frames designed according to ASCE 7-10 and ACI 318-11 code provisions. Analytical models of the buildings are subjected to a set of ground motions scaled to the smooth design spectra for the design basis earthquake (DBE) and the maximum considered earthquake (MCE) for a site located in Los Angeles, California. Significant inelastic deformations of beams are observed at both hazard levels, but the deformations at the MCE level result in large inelastic tensile strains at the base of the columns. Current code provisions have been found to appreciably underestimate column axial forces and, depending on the procedure used, shear forces in columns as well. Beam growth effects were found to significantly contribute to the shear forces in the columns near the base. Methods for improving estimates of column axial and shear forces are presented.

A Maximum Confidence Enhancement Based Sequential Sampling Scheme for Simulation-Based Design

A maximum confidence enhancement (MCE)-based sequential sampling approach is developed for reliability-based design optimization (RBDO) using surrogate models. The developed approach employs the ordinary Kriging method for surrogate model development and defines a cumulative confidence level (CCL) measure to quantify the accuracy of reliability estimation when Monte Carlo simulation is used based on the developed surrogate model. To improve the computational efficiency, an MCE-based sequential sampling scheme is developed to successively select sample points for surrogate model updating based on the defined CCL measure, in which a sample point that produces the largest CCL improvement will be selected. To integrate the MCE-based sequential sampling approach with RBDO, a new sensitivity analysis approach is developed, enabling smooth design sensitivity information to be accurately estimated based upon the constructed surrogate model without incurring any extra computational costs, thus greatly enhancing the efficiency and robustness of the design process. Two case studies are used to demonstrate the efficacy of the developed approach.