Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Quality by Design (QbD) framework to enhance rapid-response RNA vaccine manufacturing against known and future viral pathogens. This QbD framework aims to support the development and consistent production of safe and efficacious RNA vaccines, integrating a novel qualitative methodology and a quantitative bioprocess model. The qualitative methodology identifies and assesses the direction, magnitude and shape of the impact of critical process parameters (CPPs) on critical quality attributes (CQAs). The mechanistic bioprocess model quantifies and maps the effect of four CPPs on the CQA of effective yield of RNA drug substance. Consequently, the first design space of an RNA vaccine synthesis bioreactor is obtained. The cost-yield optimization together with the probabilistic design space contribute towards automation of rapid-response, high-quality RNA vaccine production.

No abstract

While decomposition techniques in mathematical programming are usually designed for numerical efficiency, coordination problems within enterprise-wide optimization are often limited by organizational rather than numerical considerations. We propose a ‘data-driven’ coordination framework which manages to recover the same optimum as the equivalent centralized formulation while allowing coordinating agents to retain autonomy, privacy, and flexibility over their own objectives, constraints, and variables. This approach updates the coordinated, or shared, variables based on derivative-free optimization (DFO) using only coordinated variables to agent-level optimal subproblem evaluation ‘data’. We compare the performance of our framework using different DFO solvers (CUATRO, Py-BOBYQA, DIRECT-L, GPyOpt) against conventional distributed optimization (ADMM) on three case studies: collaborative learning, facility location, and multi-objective blending. We show that in low-dimensional and nonconvex subproblems, the exploration-exploitation trade-offs of DFO solvers can be leveraged to converge faster and to a better solution than in distributed optimization

No abstract

While decomposition techniques in mathematical programming are usually designed for numerical efficiency, coordination problems within enterprise-wide optimization are often limited by organizational rather than numerical considerations. We propose a "data-driven" coordination framework which manages to recover the same optimum as the equivalent centralized formulation while allowing coordinating agents to retain autonomy, privacy, and flexibility over their own objectives, constraints, and variables. This approach updates the coordinated, or shared, variables based on derivative-free optimization (DFO) using only coordinated variables to agent-level optimal subproblem evaluation "data." We compare the performance of our framework using different DFO solvers (CUATRO, Py-BOBYQA, DIRECT-L, GPyOpt) against conventional distributed optimization (ADMM) on three case studies: collaborative learning, facility location, and multiobjective blending. We show that in low-dimensional and nonconvex subproblems, the exploration-exploitation trade-offs of DFO solvers can be leveraged to converge faster and to a better solution than in distributed optimization.