Modular and on-Demand Pharmaceutical Manufacturing

Drug shortages cost hospital systems an estimated $500M annually [1]. Despite this tremendous market, the lack of a regulatory framework capable of rapidly approving drug products makes this market largely inaccessible. This “regulatory framework” refers to the set of requirements established by the FDA to ensure that any drug product meets rigorous standards for process validation, impurity profiling, analytical characterization, and reproducible manufacturing documentation. Without detailed chemical process data, including reaction kinetics, mechanistic pathways, impurity origins, and validated separation methods, regulatory reviewers cannot assess product quality, reproducibility, or safety. Conversely, without a regulatory framework to guide these studies, generating the necessary process data is delayed or deprioritized. This paradox has prevented timely responses to many drug shortages. By systematically optimizing reaction pathways, catalysts, reaction conditions, and separation strategies in a continuous-flow process, we can develop a sustainable, scalable, and cost-effective synthesis of Bupivacaine Hydrochloride. By varying reaction parameters such as temperature, concentration, pressure, or catalyst identity in a factorial design of experiments, it is possible to determine kinetic parameters such as the rate constant, Arrhenius pre-exponential factor, and reaction order for the four synthesis reactions. These parameters will then be fit to a series of rate law regressions, which will then be compared using confidence intervals and AIC/BIC scores, which balance model accuracy against complexity. With a final model, batch reaction yields can be estimated from any array of initial parameters, which will be validated against standard trials. Transitioning to a continuous scheme, the validated kinetic model will guide the specification of reactor type, set-point intervals, and operating conditions via transport and thermodynamic equations for the novel Bupivacaine Hydrochloride synthetic pathway.