Increasing capacity utilization and lowering manufacturing costs are critical for pharmaceutical companies to improve their competitiveness in a challenging environment. Development of next generation cell lines, improved media formulations, application of mature technologies and innovative operational strategies have been deployed to improve yields and capacity utilization. This article describes a large-scale perfusion strategy for the N-1 seed train bioreactor that was successfully applied to achieve higher inoculation cell densities in the production culture. The N-1 perfusion at 3,000-L scale, utilizing a inclined settler, achieved cell densities of up to 158 × 10(5) cell mL(-1) at perfusion rates of 2950 L day(-1) and a retention efficiency of >85%. This approach increased inoculation cell densities and decreased cultivation times by ~20% in a CHO-based, fed-batch antibody manufacturing process while providing comparable culture performance, productivity, and product quality. The strategy therefore yielded significant increase in capacity utilization and concomitant cost improvement in a large scale cGMP facility. Details of the strategy, the cell retention device, and the cell culture performance are described in this article.

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Recently, "design for manufacturability" (DFM) has become a veritable buzzword in the semiconductor manufacturing community. DFM activities cover a broad spectrum ranging from the improvement of the electrical and structural robustness against process variations to the reduction of layout parts critical for statistically distributed defects or sensitive to systematic process weaknesses. In our work we focus only on those aspects of DFM concerned with the structural integrity of patterns on the wafer. We show that a purely geometrical analysis of product layouts offers a powerful tool to strengthen the link between design and manufacturing. It allows, for instance, a visualisation of the extent to which intra-and inter-layer design rules determine the geometry configurations dominating the layout and the identification of patterns occurring only rarely. Furthermore, in combination with the geometry-resolved information about the accuracy of "optical proximity correction" (OPC) models and "critical dimension" (CD) control, such an analysis provides valuable input for systematic improvements on both, the product layout and manufacturing process side. In this sense it supports the progress towards making real designs still manufacturable at the limits of process tool capabilities.

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