The rise of personalised and highly complex drug product profiles necessitates significant advancements in pharmaceutical manufacturing and distribution. Efforts to develop more agile, responsive, and reproducible manufacturing processes are being combined with the application of digital tools for seamless communication between process units, plants, and distribution nodes. In this paper, we discuss how novel therapeutics of high-specificity and sensitive nature are reshaping well-established paradigms in the pharmaceutical industry. We present an overview of recent research directions in pharmaceutical manufacturing and supply chain design and operations. We discuss topical challenges and opportunities related to small molecules and biologics, dividing the latter into patient- and non-specific. Lastly, we present the role of process systems engineering in generating decision-making tools to assist manufacturing and distribution strategies in the pharmaceutical sector and ultimately embrace the benefits of digitalised operations.

Hydrogel microparticles (HMPs) find numerous practical applications, ranging from drug delivery to tissue engineering. Designing HMPs from the molecular to macroscopic scales is required to exploit their full potential as functional materials. Here, we explore the gelation of sodium carboxymethyl cellulose (NaCMC), a model anionic polyelectrolyte, with Fe3+ cations in water. Gelation front kinetics are first established using 1D microfluidic experiments, and effective diffusive coefficients are found to increase with Fe3+ concentration and decrease with NaCMC concentrations. We use Fourier Transform Infrared Spectroscopy (FTIR) to elucidate the Fe3+-NaCMC gelation mechanism and small angle neutron scattering (SANS) to spatio-temporally resolve the solution-to-network structure during front propagation. We find that the polyelectrolyte chain cross-section remains largely unperturbed by gelation and identify three hierarchical structural features at larger length scales. Equipped with the understanding of gelation mechanism and kinetics, using microfluidics, we illustrate the fabrication of range of HMP particles with prescribed morphologies.

No abstract

Viral vectors are advanced therapy products used as genetic information carriers in vaccine and cell therapy development and manufacturing. Despite the first product receiving market authorization in 2012, viral vector manufacturing has still not reached the level of maturity of biologics and is still highly susceptible to process uncertainties, such as viral titers and chromatography yields. This was exacerbated by the COVID-19 pandemic when viral vector manufacturers were challenged to respond to the global demand in a timely manner. A key reason for this was the lack of a systematic framework and approach to support capacity planning under uncertainty. To address this, we present a methodology for: (i) identification of process cost and volume bottlenecks, (ii) quantification of process uncertainties and their impact on target key performance indicators, and (iii) quantitative analysis of scale-dependent uncertainties. We use global sensitivity analysis as the backbone to evaluate three industrially relevant vector platforms: adeno-associated, lentiviral, and adenoviral vectors. For the first time, we quantify how operating parameters can affect process performance and, critically, the trade-offs among them.Results indicate a strong, direct proportional correlation between volumetric scales and propagation of uncertainties, while we identify viral titer as the most critical scale-up bottleneck across the three platforms. The framework can de-risk investment decisions, primarily related to scale-up and provides a basis for proactive decision-making in manufacturing and distribution of advanced therapeutics.

No abstract