The development and distribution of a safe and effective vaccine is widely seen as the best resolution to the COVID-19 pandemic, and the most likely route back to normal life and economic conditions. There are estimated to be 300 vaccine candidates in development and dozens of clinical trials currently taking place, with some early front runners talking about vaccines becoming available in the next few months.
The UK government has already ordered 340 million doses of COVID-19 vaccines from several different manufacturers, with the hope that at least one will prove effective. If all of them prove successful, this would be enough to provide a single dose of vaccine to more than five times the UK population – however, this scenario is unlikely.
Typically, the time taken to develop a vaccine for widespread use is around ten years, but during this pandemic, researchers in academia and industry have been working effectively together and have condensed this process into a matter of months. This has, of course, necessitated a number of shortcuts – for example, millions of doses are being manufactured by pharmaceutical companies ‘at-risk’ – that is – without knowing the vaccine’s efficacy.
Currently, the most advanced vaccine candidates come from four different classes of biologics: adenoviral vector vaccines, mRNA vaccines, inactivated whole virus vaccines and protein adjuvant vaccines. All these candidates have their own particular manufacturing challenges.
Response to the challenge
The UK’s capability to manufacture vaccines received a significant boost with the recent announcement of a £100 million investment into a state-of-the-art Cell and Gene Therapy Catapult Manufacturing Innovation Centre. This is being established to accelerate the mass production of a successful vaccine. It is not due to open until December 2021 in Braintree, by which time it is forecast that COVID-19 vaccine candidates will be approved for use and, when operational, the Centre will produce millions of doses monthly. Once complete, the facility will produce enough vaccines to serve the entire UK.
The centre will complement the Vaccines Manufacturing and Innovation Centre (VMIC), a new, not-for-profit research company providing strategic vaccine development and manufacturing. It is supported by three founding members: University of Oxford, Imperial College and the London School of Hygiene and Tropical Medicine, and with in-kind industry funding from Janssen, MSD and Cytiva.
The government has invested an additional £38 million for the creation of a rapid deployment facility ‘Virtual VMIC’ which has been established to manufacture COVID-19 vaccine until the main facility comes online in 2021.
Technical issues with development
Rapid production of vaccines is challenging and requires all processes to be critically analysed. A review of the full set of processes is possibly outside the current scope of any one equipment supplier’s expertise.
Biologics-based therapies begin with the generation of a small number of modified cells possessing some form of therapeutic benefit, such as the ability to secrete antibodies. These are then ‘scaled-up’ to a higher number in microtiter plates or small flasks, and manual or automated cell picking methods are used to identify and extract the most viable cells. Once a healthy colony is established, the cells are expanded into sufficient volume to create a master cell bank (MCB) that may comprise of 10s of millions of cells.
This MCB may then be created by dispensing them into cryovials, either manually or via automation. These cryovials are tracked and stored at low temperatures, typically at or near the temperature of liquid nitrogen (–196°C).
A critical requirement is to manage workflows and ensure the master and working cell banks (WCB) can be stored and retrieved effectively and reliably.
Once the WCB is established, it is possible to manufacture small to medium batches to support testing, including early stage clinical trials.
If these are ‘suspension’ cells, the next step may be to defrost and pool the cryovials’ contents and scale-up to larger volumes, comprising maybe billions of cells using small scale bioreactors. If they are ‘adherent’ cells, the next step may be to defrost and pool the contents from the cell bank and scale-up to billions of cells using flask-based technologies such as the Cell Factory™, CellSTACK®, HYPERStack® and CELLdisc™ systems. Alternatively, in some applications it may be possible to grow the adherent cells on micro-carriers and expand within small scale bioreactors.
There are, however, significant problems with flask based systems because once they are filled, they can be heavy and very difficult to manipulate, and often rely on manual processes to fit and extract tubing, to attach and detach sensors and filters, and monitor how well the processes are progressing.
Robotic systems to enhance manufacture
Collaborative robotic technologies can help perform these processes, so that the benefits of operator interaction are maintained whilst also making use of automation to perform repetitive and heavy lifting tasks.
As the cost and complexity of robot automation drops, it is likely companies already using them will further extend their deployment.
“In the next five to 10 years we can expect a fundamental change in the kinds of tasks for which robots become technically and economically viable.”
The ability to rapidly measure and reliably process large amounts of data in real time during the manufacturing process, and to use this information to make sound process decisions with little or no human interference, is at the heart of true digital manufacturing. This started pre-COVID-19 and will continue to accelerate post COVID-19. Effective biologics manufacturing in the future will require seamlessly integrated, Cloud-based IT systems and will need to leverage robotics, the Internet of Things (IoT) and artificial intelligence (AI) systems. The next generation of biotech firms, always keen to disrupt the incumbent pharma industry, will need to embrace these aspects of innovation to avoid the issues of legacy technology and siloed data, lengthy product-development cycles, and risk aversion.
Once the vaccine has been manufactured, and suitable vials have been filled, the problem of distribution begins. Unprecedented steps will be required to ensure roll-out of the vaccine to the global population, but until then the best defence against Covid-19 remain social distancing, mask-wearing and handwashing. It is undoubtedly going to be a long journey.