Rapid Prototyping at Zero Gravity for In-Flight Repairs and Fabrication on Space Station Freedom

The ability to perform in-flight rapid prototyping would be of great benefit to NASA in two ways. First, repair parts could be fabricated from CAD designs beamed up from earth based laboratories which might allow a failed experiment to proceed. The mission specialists themselves, under the creative influence of space flight, might design a new part or tool and fabricate it on board in a matter of hours. Second, with metal casting and ceramic sintering facilities on board, rapid prototyping would allow manufacturing in space. This paper presents some test criteria for evaluating two of the rapid prototyping techniques, stereolithography and fused deposition, in microgravity conditions. Effects of the variation of head speed and strip width for the fused deposition process on the resulting mechanical properties are presented. The mechanical strength of the polyamide test bars increased with both increasing head speed and strip width. Increasing head speed would be desirable in microgravity applications.Mechanical Engineerin

Delivering a toolbox of flexible platforms for clinical and commercial bioprocessing production: ‘Defining the business drivers for development and implementation’

Despite the growing success, the biopharmaceutical industry continues to face competitive challenges from multiple sources. The cost pressures include evolving reimbursement, global competition and loss of drug exclusivity. As a result, there is a significant drive to boost the overall productivity of bio therapeutic programs by shortening development timelines and lowering both development and production costs, while maintaining product quality. Low cost production solutions must be aggressively pursued due to the large number of drug candidates in development, and their relatively high dosing requirements. The industry is facing an expanding range of modalities such as bispecifics and nanobodies, that provide a more heterogeneous product pipeline and a wider range of product demand (kg/yr). In addition supply chains need to be more responsive to the patient needs in a more personalized approach. These industry challenges need flexible solutions that can provide agility and lower cost. The presentation will discuss the business case, development and implementation of such a toolbox of low cost flexible platform solutions to meet a range of scenarios faced in clinical development, that also provide a line of sight to commercial. Examples will include the simple single use fed batch process for low demand processes versus advanced integrated/continuous automated processing for higher demands. The implementation strategy through the clinical phases to commercial will be discussed for commodity mAb production using a fully automated continuous process with product attribute control and real time release. This provides a supply responsive approach to rapid changes in demand to provide a ‘supply on demand’ process. This production synchronization should provide a responsive approach to changing drug demand, shorten clinical and commercial timelines and minimize inventory costs. These cost reduction initiatives, in combination with regional manufacturing, should help to expand patient accessibility to biologics and vaccines

Beyond the City Limits: Regional Equity As an Emerging Issue

Our thesis is that this linkage depends upon definition and achievement of regional equity fairness in the distribution of, and opportunities for access to, developed urban land

Manufacturing processes

The following issues are covered: process development frequently lags behind material development, high fabrication costs, flex joints (bellows) - a continuing program, SRM fabrication-induced defects, and in-space assembly will require simplified design

U(1) Fields from Qubits: an Approach via D-theory Algebra

A new quantum link microstructure was proposed for the lattice quantum chromodynamics (QCD) Hamiltonian, replacing the Wilson gauge links with a bilinear of fermionic qubits, later generalized to D-theory. This formalism provides a general framework for building lattice field theory algorithms for quantum computing. We focus mostly on the simplest case of a quantum rotor for a single compact $U(1)$ field. We also make some progress for non-Abelian setups, making it clear that the ideas developed in the $U(1)$ case extend to other groups. These in turn are building blocks for $1 + 0$-dimensional ($1 + 0$-D) matrix models, $1 + 1$-D sigma models and non-Abelian gauge theories in $2+1$ and $3+1$ dimensions. By introducing multiple flavors for the $U(1)$ field, where the flavor symmetry is gauged, we can efficiently approach the infinite-dimensional Hilbert space of the quantum $O(2)$ rotor with increasing flavors. The emphasis of the method is on preserving the symplectic algebra exchanging fermionic qubits by sigma matrices (or hard bosons) and developing a formal strategy capable of generalization to $SU(3)$ field for lattice QCD and other non-Abelian $1 + 1$-D sigma models or $3 +3$-D gauge theories. For $U(1)$, we discuss briefly the qubit algorithms for the study of the discrete $1+1$-D Sine-Gordon equation.Comment: 19 pages, 10 figure

Protein Refinery Operations Lab (PRO Lab): A sandbox for continuous protein production & advanced process control

Significant strides towards implementation of continuous bioprocessing are being made at an ever increasing rate. Advances in technology for traditional unit operations such as cell-retention devices in perfusion cell culture, continuous multi-column chromatography (CMCC) and single-pass tangential flow filtration have led to demonstrations of both semi-continuous and fully-continuous protein production processes operating at periodic steady states at the pilot-scale. Previous proof of concept work at Merck & Co., Inc. has shown an automated (DeltaV) and single-use monoclonal antibody (mAb) purification scheme through Protein A CMCC and pH viral inactivation with minimal human interaction for 30 days fed from a perfusion bioreactor1. This automation scheme has since been expanded to encompass an integrated mAb upstream and platform downstream process, resulting in an entirely automated ‘protein refinery’ sandbox. In this presentation a vision for a continuous bioprocessing facility of the future will be presented wherein the integration of Process Analytical Technologies (PAT), Multivariate Data Analysis, (MVDA), and feedback control strategies will lead to more streamlined plant operations and high product quality consistency. A discussion of how the control strategies put into place in PRO Lab lays the groundwork for this vision and how PRO Lab will be used to pilot PAT, MVDA, and feedback control as they become mature enough for integration into the continuous platform will be provided. These tools, working together, and validated in the sandbox environment, will ultimately enable real-time-release of drug substance. PRO Lab will also enable better holistic process understanding by enabling perturbation analysis and propagation throughout the production line. Process and product quality consistency data through a period of \u3e30days will be presented from PRO Lab as an initial step towards toward the ultimate vision of an automated well-controlled, well characterized protein refinery