Nanomedicine is seen as a potential central player in the delivery of personalized medicine. Biocompatibility issues of nanoparticles have largely been resolved over the past decade. Despite their tremendous progress, less than 1% of applied nanosystems can hit their intended target location, such as a solid tumor, and this remains an obstacle to their full ability and potential with a high translational value. Therefore, achieving immune-tolerable, blood-compatible, and biofriendly nanoparticles remains an unmet need. The translational success of nanoformulations from bench to bedside involves a thorough assessment of their design, compatibility beyond cytotoxicity such as immune toxicity, blood compatibility, and immune-mediated destruction/rejection/clearance profile. Here, we report a one-pot process-engineered synthesis of ultrasmall gold nanoparticles (uGNPs) suitable for better body and renal clearance delivery of their payloads. We have obtained uGNP sizes of as low as 3 nm and have engineered the synthesis to allow them to be accurately sized (almost nanometer by nanometer). The synthesized uGNPs are biocompatible and can easily be functionalized to carry drugs, peptides, antibodies, and other therapeutic molecules. We have performed in vitro cell viability assays, immunotoxicity assays, inflammatory cytokine analysis, a complement activation study, and blood coagulation studies with the uGNPs to confirm their safety. These can help to set up a long-term safety-benefit framework of experimentation to reveal whether any designed nanoparticles are immune-tolerable and can be used as payload carriers for next-generation vaccines, chemotherapeutic drugs, and theranostic agents with better body clearance ability and deep tissue penetration.

This chapter addresses the challenges of evaluating the business case for continuous manufacturing of pharmaceuticals, looking beyond traditional technical assessments made at the unit operations or individual production facility level. It provides an overview of key concepts, approaches and tools for the early assessment of supply network configuration opportunities enabled by continuous production processing interventions. Multiple levels of analysis are considered with the aid of examples based on major UK research programmes on continuous production process technologies. Particular emphasis is placed on the potential for achieving enhanced product flexibility (in terms of volume and variety) and depending on scale, the optimum number and location of manufacturing operations to support speed to market and system-level cost benefits. In the case of multiple manufacturing operations using continuous production process technologies, where production facility replication through digital twins is becoming a key enabler, the chapter sets out a supply network design and analysis approach that evaluates the commercial and operational viability of alternative manufacturing supply network scenarios.

No abstract

The COVID-19 pandemic exposed vulnerabilities in upstream pharmaceutical supply chains (PSC). One is that the global supply of active pharmaceutical ingredients (APIs) is overly dependent on few locations and large-scale batch manufacturing. Regulators hope to enable more dependable location decisions and improved processing quality with the adoption of advanced technologies such as process intensification through continuous manufacturing (CM). Conceptual work suggests that the benefits of shifting from batch to CM accrue end-to-end across the PSC. Yet detailed quantitative information about CM is limited at an early stage of evaluation, and too specialised to inform managerial decisions about PSC reconfiguration. Supply chain and engineering criteria are rarely combined in the early-stage evaluation of alternative CM technologies. Extant CM research typically overlooks implications for supply chain managers. To address the current gap, this article evaluates, at an early stage of adoption, alternative CM reactor technologies for the synthesis of APIs in selected therapeutic areas. With evidence from secondary data, relevant technologies and criteria are identified, and their relative importance is evaluated in a semi-quantitative fashion following analytical hierarchy process (AHP) principles, ensuring that findings are intelligible to both engineers and managers. The proposed empirical work enriches previous conceptual frameworks predicated on volume-variety considerations. Specifically, findings suggest that, all things considered, microreactor technologies outperform alternatives. However, PSC managerial considerations introduce nuances in specific therapeutic areas, for example, antivirals where a tension between complex chemistry and the need for flexibility in unit operations may favour batch manufacturing. For analgesics the need to exploit the existing manufacturing base whilst addressing inventory reduction favours technologies that incorporate elements of batch and CM. The proposed analysis is in line with real-world decisions that global medicines manufacturers are increasingly facing, as governments seek to develop local health countermeasures to the COVID-19 pandemic in the absence of detailed information.Parminder Kaur Aulakh was with the University of Cambridge at the time this research was carried out.

No abstract