Rapid development and deployment of high‐volume vaccines for pandemic response

Abstract

Overcoming pandemics, such as the current Covid-19 outbreak, requires the manufacture of several billion doses of vaccines within months. This is an extremely challenging task given the constraints in small-scale manufacturing for clinical trials, clinical testing timelines involving multiple phases and largescale drug substance and drug product manufacturing. To tackle these challenges, regulatory processes are fast-tracked, and rapid-response manufacturing platform technologies are used. Here, we evaluate the current progress, challenges ahead and potential solutions for providing vaccines for pandemic response at an unprecedented scale and rate. Emerging rapid-response vaccine platform technologies, especially RNA platforms, offer a high productivity estimated at over 1 billion doses per year with a small manufacturing footprint and low capital cost facilities. The self-amplifying RNA (saRNA) drug product cost is estimated at below 1 USD/dose. These manufacturing processes and facilities can be decentralized to facilitate production, distribution, but also raw material supply. The RNA platform technology can be complemented by an a priori Quality by Design analysis aided by computational modeling in order to assure product quality and further speed up the regulatory approval processes when these platforms are used for epidemic or pandemic response in the future.

Manufacturing in the Time of COVID-19: An Assessment of Barriers and Enablers

“…The number of studies suggests that manufacturing is an essential pandemic management concern. This manufacturing concern includes mass production of WHO-identified personal protection equipment (PPE) and other medical equipment [8][9][10].…”

Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

“…The only component that needs to be changed in this process when switching to the production of a new vaccine is the DNA template based on which the RNA is synthesised using the T7 RNA Polymerase enzyme. The creation of a DNA template has been achieved within days after determining the genetic sequence of the SARS-CoV-2 virus [ 26 , 41 , 42 ]. The DNA template can be produced at large scale as plasmid DNA using well-established Escherichia coli ( E. coli ) fermentation-based processes [ 43 , 44 , 45 ] or by using enzymatic processes, such as the doggybone™ developed by Touchlight Genetics Ltd., U.K [ 46 , 47 , 48 ].…”

“…Information regarding mRNA and saRNA vaccine production processes and costs was obtained from the scientific literature [ 4 , 5 , 6 , 15 , 16 , 17 , 18 , 19 ], patent databases [ 20 , 21 , 22 , 23 , 24 ], from GMP grade material suppliers, such as TriLink BioTechnologies Inc., San Diego, CA, USA and Roche Diagnostics GmbH, Mannheim, Germany. In addition, details regarding the configuration of the production process was obtained by active involvement of the authors in RNA vaccine production process development activities [ 25 , 26 , 27 ] and by discussing with contract manufacturing experts from TriLink BioTechnologies Inc., San Diego, CA, USA and Centre for Process Innovation Ltd., Darlington, UK. Information regarding mRNA DS amount per dose was obtained from clinical trial databases [ 28 , 29 , 30 , 31 ] and the scientific literature [ 11 ].…”

“…The breakdown of operating cost and cost per dose components for LNP formulated DS production is shown in Figure S2. It is worth noting that the production cost per dose presented here is only a fraction of the selling price of the vaccine, which also accounts for the fill-to-finish and distribution costs, marketing expenses, a profit margin and the cost of the R&D, preclinical development and clinical trial related expenses [26]. It is worth noting that the production cost per dose presented here is only a fraction of the selling price of the vaccine, which also accounts for the fill-to-finish and distribution costs, marketing expenses, a profit margin and the cost of the R&D, preclinical development and clinical trial related expenses [26].…”

Advanced manufacturing and processing in the time of COVID‐19

“…[1] We are sure there are many of you who have worked long hours to innovate your manufacturing and processing systems to cope with the challenges of COVID-19 and we would welcome articles and commentaries on how advanced manufacturing can play a role in our collective response. In this issue of JAMP we share a commentary on the rapid manufacturing of vaccines as our contribution to understanding how our community might respond to COVID-19, [2] and we would like to encourage you to consider other ways in which our manufacturing systems will change in response to the pandemic. However, much as there is a need to address the short-term disruptions caused by a pandemic, and to understand how research can respond to create advanced manufacturing and processing systems with flexibility and resilience in the future, we also need to continue to push forward with efforts that provide new foundations for those features and we have curated articles that we hope fulfill that goal.…”