Zoltán Kis is a leading researcher in biopharmaceutical manufacturing and supply currently addressing the issues surround the supply of a vaccine for COVID-19.

Dr Zoltán Kis, who achieved his PhD in Bioengineering, is now a research associate in the Future Vaccine Manufacturing Research (FVMR) Hub at Imperial College London alongside leading academics Professor Nilay Shah and Dr Cleo Kontoravdi. The FVMR Hub aims to develop manufacturing technologies capable of producing vaccines against known and unknown pathogens, quickly, at high volumes, high-quality, and at a low cost. Global Engineering Futures spoke with Zoltán who shared his insight into the vaccine manufacturing challenges, especially those that exist for developing countries.

Working in the FVMR Hub has made Zoltán distinctly aware of the imminent threat of a pandemic. There have been multiple global risk assessments carried out by organisations such as the World Health Organisation (WHO), the World Bank, and the Organisation for Economic Co-operation and Development (OECD) who identified a pandemic as a major threat to humanity. However, not enough investment, development and preparation had been achieved for the COVID-19 pandemic.

“We, as humanity, should have done more before the COVID-19 pandemic. We should have taken the threat more seriously as outlined by the many global risk assessments. On a positive note, with the COVID-19 pandemic, the development of rapid-response vaccine production technologies has been accelerated. If there is to be a similar situation, we would be better prepared to respond and combat an outbreak.”

The FMVR Hub, led by Professor Robin Shattock, had previously been developing vaccines before the COVID-19 pandemic. However, as the vaccine development process is so time consuming they had not reached an ideal stage of preparedness for the COVID-19 pandemic. Scientists and engineers are currently attempting to develop a vaccine in 12 to 18 months, which is extremely fast compared to conventional vaccine development timelines which can take around 10 years. According to Zoltán, a promising solution that is being developed and tested for pandemic-response is the RNA and viral vector platform. RNA is a natural molecule we all have in our body that is constantly being produced and used to express proteins. However, you can also use RNA to produce vaccine antigens in the cells of the human body using natural cellular processes.

“The RNA vaccine platform is a very powerful technology because you can make any antigen sequence with the same production process. These RNA sequences can then translate to any vaccine antigen when inserted into the cells of the human body. Therefore, candidate vaccines can be produced for virtually any known and currently unknown disease using the same production process. If RNA vaccines had already been used as treatments for previous diseases, producing a COVID-19 vaccine could have had been substantially faster”

In the case of self-amplifying RNA vaccines, the production is very scalable and the production cost could be very low. Due to its self-amplification, the RNA amount per dose would be lower, leading to a lower cost per dose, and a higher number of doses can be produced using the same production process per unit volume and unit time. The production cost per dose depends on the production scale, the scheduling, and the RNA amount per dose, which is currently being determined in Imperial College London clinical trials.

Zoltán states one of the biggest concerns facing the production of a vaccine concerns developing countries. Organisations such as the Gates Foundation, UNICEF, Coalition for Epidemic Preparedness Innovations (CEPI), and WHO are aiding this matter and looking to find ways to distribute the vaccines to developing countries affordably. It is crucial that the vaccine is accessible to all, including developing countries where the affordability is a critical factor. The main cost drivers of the RNA active ingredient production are the raw materials. At global scale production of several billion doses per year, the cost of the RNA active ingredient in the vaccine can be below $0.05 per dose. The cost of the final vaccine drug product, which is the formulated vaccine in vials or other containers, at this global scale could be below $1 per dose depending mostly on the type of container, with lower costs per dose to be achieved in case of multi-dose vials.

Zoltán Kis has presented his research on vaccine supply chains at leading conferences including those by the American Institute of Chemical Engineers.

The challenges for developing countries also comes when considering the supply chain. The main problem is the thermostability of the vaccine and the temperature that will be needed for the transport and storage. Most vaccinations are stable at 2°C to 8°C. The worst-case scenario, in the case of COVID-19, is for the vaccine to be stored and transported at –80°C. Picture that in rural areas of a developing country where there are often no roads or electricity combined with very hot weather conditions.

Zoltán explains how the biopharmaceutical industry is taking great risks to ensure health of the global population. For example, Pfizer and AstraZeneca announced that they will be investing disproportionate amounts of money into vaccine development for the COVID-19 pandemic. According to Zoltán, many of the drug manufacturing companies are making these investments almost at a non-profit basis to ensure global health. However, these companies take large risks all the time when it comes to drug development. Zoltán discloses how conventionally, 93% of vaccines fail on average. Only 7% of vaccines succeed from research & development to a licensed product. To be approved, the vaccine must also pass pre-clinical, Phase I, Phase II, and Phase III trials. During Phase II clinical trials an average of 66% of vaccine candidates fail.

At times, the biopharmaceutical industry will start or plan production of a vaccine without knowing whether or not the vaccine works and/or without proper licensing to put it on the market. Industry may manufacture a vaccine, stockpile the vaccine and hope the trials go well, when in reality, most trials fail. The alternative is to only start manufacturing after the trials have finished which could delay the distribution and administration of vaccines. This additional time is harmful to the population when we see with each passing day the number of deaths rising and a failing economy. Overall, the risk of manufacturing a vaccine which might not be used is overshadowed significantly by the possible gains.

The notion of gains brings up an interesting topic on what has been prioritised during the pandemic: human health versus the economy. Zoltán was asked if he thinks that people underestimated the virus by prioritising the economy. He answers that balance is key. We need to balance the economy versus health care and the overall health of the population. To him, this is tricky, and he states that the right balance would always be to sacrifice the economy more to ensure survival and good health of the population. Overall, Zoltán believes that there have been both positive and negative impacts on sustainability as a result of the pandemic. The pandemic has slowed down the economy, meaning less flights, travel and transportation, less oil and fossil fuels burned, less energy and materials used globally. However, the economy has been impacted significantly. Businesses have closed temporarily or permanently; many businesses have gone bankrupt. Socially, he believes that the pandemic has made people more isolated, which has the possibility of leading to mental health issues. On the other hand, because you are more isolated, you develop an appreciation for human interaction.

Zoltán leaves us with two key things we should adapt as a society for a sustainable future. First, be more understanding and kinder to each other. Secondly to consider a fully diverse range of perspectives in all key decision making. Finally, think long-term of what humanity should achieve instead of being short-sighted. Environmental, healthcare, and economic sustainability challenges are what humanity needs to solve in the coming decades - engineering will play a major role in developing solutions for these.

Zoltán Kis on why delivering COVID-19 vaccines to developing countries is so challenging.

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