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34 Pharmaceutical Technology ® Trends in Manufacturing eBook May 2023 PharmTech.com INTERPHEX RouNduP deploy the vaccine itself. He pointed out that somewhere around 3.5 billion doses of the various mRNA vaccines have been injected to ward off COVID-19. He also em- phasized that the administration of these doses rep- resented an outstanding success in many regards, but particularly in parallel development as well as in man- ufacturing scale-out and scale-up. Fouad Atouf, senior vice-president, Global Biologics, US Pharmacopeia, gave a presentation that combined many facets of the mRNA landscape, including busi- ness and biological elements, but mostly he cantered on a nearly mature set of monographs and protocols for measuring critical quality attributes and other quality measurements. In particular, he mentioned the work John Cipollo and others at the US Pharmaco- peia, whose Quality Assessment Toolkits for COVID-19 vaccines include resources supporting virus-like par- ticle, DNA, and attenuated virus vaccines and rounds out the applicable vaccine platforms for COVID-19. Organ on a Chip On April 26, a Keynote session included a world-class lineup representing some veteran companies and one new arrival in the field of organ on a chip technology. Speaking recently about this technology, Donald Ing- ber, founding director, Wyss Institute for Biologically Inspired Engineering at Harvard University, said he believes organ chip technology is at the tipping point when it comes to drug discover y and personalized medicine. Referencing a recent paper, Ingber stated, "Perhaps even more important for their acceptance by regulatory agencies and the pharma world, this study included an economic analysis that estimated drug developers would save about $3 billion per year if this one animal model were replaced by [o]rgan [c] hip technology, given the huge costs of drugs failing once they get into clinical trials" (2). Yaakov Nahmias, founder and chief scientific officer of Tissue Dynamics, an emerging organoid company, estimates (in a dramatic claim) that the company could cut drug development costs by 40–80%, and, time re- quired, by 30–50% overall. The company's approach is to ab initio embed sensors into the organoid while its being grown, which allows artificial intelligence-driven computation to directly interrogate biology every step along the development process. "This allows the robot to start screening drugs against different models of disease. It can perform, by itself, safety assessments in the microtissues and identify the drug that works best and causes the least damage to human organs, and it does this extremely fast. We can do it in 19,000 tissue samples at once. It is the equivalent of [testing on] 5000 patients," said Nahmias (3). Process management After using a process analytical technology (PAT)-au- tomated tangential flow filtration (TFF) system that is controlled by real-time concentration measurement for ultrafiltration and diafiltration (UF/DF) processes, it was found to be an innovative solution for companies looking to automate their TFF process and increase pro- cess control, according to a poster study from Derek Car- roll and Teva Smith from Repligen, which was presented at INTERPHEX 2023 (4). Using rea l-time concentration management is intended to ensure consistent targeted concentra- tion results, insensitive to the t y pes of variation commonly seen in mass balance-only systems. Further, automated process control is demonstrated for various final concentration endpoints, which suggests a better solution for the UF/DF process with key advantages over existing methods, according to Carroll and Smith. Carroll and Smith used the Repligen real-time pro- cess management system (RPM) automation, which is driven by an in-line variable pathlength UV/Vis device, the CTech FlowVPX system. This system's search algo- rithm assigns a collection start value of 1 absorbalance and measures 5 to 10 decreasing pathlengths to gener- ate a slope value, according to the poster. Carroll and Smith then introduced the KrosFlo KR2i RPM System, which utilizes Open Platform Commu- nication-United Architecture (OPC-UA) to provide seamless PAT-driven process control with two-way communication bet ween each device wit hin t he system. The RPM system using innovative PAT and OPC-UA reduces user input, greater process control, and reliable process output. The objective of the study was to integrate an au- tomated TFF process based on real-time concentra- tion, and the study included testing the efficacy of the systems automation via repeatably and post-run mixing outcomes. To achieve this, the FlowVPX vari- able pathlength spectrophotometer and KrosFlo KR2i TFF system conducted a total of 15 UF/DF processes. The UF/DF runs were conducted using bovine serum albumin (BSA) in replicates of three with starting concentrations 5, 7.5, and 10 mg/mL. The final target concentrations for the processes were 50, 125, and 200 Phil Challis spoke with PharmTech about challenges in mRNA. Phil Challis, vice-president of product development at eTheRNA, discusses four of the major challenges in working with mRNA therapeutics. Some topics he touches on include; what makes a good RNA construct; making RNA more tolerable; storage and distribution of lipid nanoparticles; and more.