“…The manufacturing of new vaccines is typically a lengthy (6 to 36 months), challenging and expensive process, as no standard process is available [11] , [12] . To deliver effective, precise, and consistent vaccines it is imperative to use good manufacturing practice (GMP) compliant equipment, facilities, and procedures.…”
Vaccines are one of the most important tools in public health and play an important role in infectious diseases control. Owing to its precision, safe profile and flexible manufacturing, mRNA vaccines are reaching the stoplight as a new alternative to conventional vaccines. In fact, mRNA vaccines were the technology of choice for many companies to combat the Covid-19 pandemic, and it was the first technology to be approved in both United States and in Europe Union as a prophylactic treatment. Additionally, mRNA vaccines are being studied in the clinic to treat a number of diseases including cancer, HIV, influenza and even genetic disorders.
The increased demand for mRNA vaccines requires a technology platform and cost-effective manufacturing process with a well-defined product characterisation. Large scale production of mRNA vaccines consists in a 1 or 2-step
in vitro
reaction followed by a purification platform with multiple steps that can include Dnase digestion, precipitation, chromatography or tangential flow filtration. In this review we describe the current state-of-art of mRNA vaccines, focusing on the challenges and bottlenecks of manufacturing that need to be addressed to turn this new vaccination technology into an effective, fast and cost-effective response to emerging health crises.
“…The manufacturing of new vaccines is typically a lengthy (6 to 36 months), challenging and expensive process, as no standard process is available [11] , [12] . To deliver effective, precise, and consistent vaccines it is imperative to use good manufacturing practice (GMP) compliant equipment, facilities, and procedures.…”
Vaccines are one of the most important tools in public health and play an important role in infectious diseases control. Owing to its precision, safe profile and flexible manufacturing, mRNA vaccines are reaching the stoplight as a new alternative to conventional vaccines. In fact, mRNA vaccines were the technology of choice for many companies to combat the Covid-19 pandemic, and it was the first technology to be approved in both United States and in Europe Union as a prophylactic treatment. Additionally, mRNA vaccines are being studied in the clinic to treat a number of diseases including cancer, HIV, influenza and even genetic disorders.
The increased demand for mRNA vaccines requires a technology platform and cost-effective manufacturing process with a well-defined product characterisation. Large scale production of mRNA vaccines consists in a 1 or 2-step
in vitro
reaction followed by a purification platform with multiple steps that can include Dnase digestion, precipitation, chromatography or tangential flow filtration. In this review we describe the current state-of-art of mRNA vaccines, focusing on the challenges and bottlenecks of manufacturing that need to be addressed to turn this new vaccination technology into an effective, fast and cost-effective response to emerging health crises.
“…Since the first cases of COVID-19 were reported in December 2019 [ 2 ], numerous researchers have taken great efforts to control this disease. Development of prophylactic vaccines against SARS-CoV-2 is a proven strategy to prevent and to terminate the unprecedented pandemic [ 3 ]. Currently, different types of vaccines have been developed or under development against SARS-CoV-2 [ 4 ].…”
“… Scaled-Down Manufacture and Supply Chain Close to Points of Care Although revenues from vaccine sales are higher in developed countries, greater volume of sales occur in low- and middle-income countries. Nevertheless, vaccine manufacturers in developing countries already supply over half of the vaccines in their immunisation programmes [ 50 , 51 ], so this initiative is far from needing to be started from scratch. Given the large number of doses that are possible from small volumes of product, final production could happen in a variety of locations if they comply with regulations: adapted university laboratories; laboratories at university teaching hospitals; and small company facilities at science parks and medical campuses.…”
Section: Distributed Manufacturing a More-sustainable Vaccine Modelmentioning
confidence: 99%
“…Although revenues from vaccine sales are higher in developed countries, greater volume of sales occur in low- and middle-income countries. Nevertheless, vaccine manufacturers in developing countries already supply over half of the vaccines in their immunisation programmes [ 50 , 51 ], so this initiative is far from needing to be started from scratch.…”
Section: Distributed Manufacturing a More-sustainable Vaccine Modelmentioning
The vaccines industry has not changed appreciably in decades regarding technology, and has struggled to remain viable, with large companies withdrawing from production. Meanwhile, there has been no let-up in outbreaks of viral disease, at a time when the biopharmaceuticals industry is discussing downsizing. The distributed manufacturing model aligns well with this, and the advent of synthetic biology promises much in terms of vaccine design. Biofoundries separate design from manufacturing, a hallmark of modern engineering. Once designed in a biofoundry, digital code can be transferred to a small-scale manufacturing facility close to the point of care, rather than physically transferring cold-chain-dependent vaccine. Thus, biofoundries and distributed manufacturing have the potential to open up a new era of biomanufacturing, one based on digital biology and information systems. This seems a better model for tackling future outbreaks and pandemics.
The Vaccine Production Model Needs to ChangeThe COVID-19 crisis has cast the vaccines industry into scrutiny [1]; an industry that has been silently beleaguered for decades (https://www.who.int/immunization/programmes_systems/ procurement/mi4a/platform/module2/2019_Global_Vaccine_Market_Report.pdf?ua=1). A United States National Academy of Sciences study from 2003 [2] concluded that the amount that the nation spent on vaccines 'appears to be insignificant compared with that spent on other medical and social interventions that may have lesser social benefits.' Large company numbers that supply vaccines have steadily reduced [3]: some 80% of vaccines arise from five multinationals (https://www.who.int/immunization/programmes_systems/procurement/market/ global_supply/en/). At the heart of the problem is a tension between relatively poor financial returns to the vaccine industry and the high costs in production and R&D [4].Compared to small molecule pharmaceuticals, centralised vaccine production facilities are capital intensive [5]. Fixed costs are high [6], especially for new vaccines. For example, the need for eggs for production is at least 70 years old, is expensive and time-consuming, but difficult to replace [7]. In past high-income countries have paid a higher price until the fixed costs are amortised. Then lower-income countries have adopted vaccines as the price has dropped after paying the fixed costs. However, there is now tremendous pressure for a COVID-19 vaccine to be available for all who need it, effectively everyone.
Distributed Manufacturing, a More-Sustainable Vaccine ModelThe long distribution chains of centralised vaccine production are patchy, resulting in incomplete geographical coverage [8] (Box 1). Even if there is no overall shortage, there may be where they are needed most. Centralisation of labour and production has been the norm in many industries, but in 2015 the World Economic Forum (WEF, see Glossary) put distributed manufacturing in its top ten emerging technologies for the year (https://www.weforum.org/agenda/2015/03/top-
HighlightsBiofoun...
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