Written Evidence Submitted by UCL-Oxford Vax-Hub

(EMD0039)

About the Vax-Hub

This response is submitted on behalf of the UCL-Oxford Future Vaccine Manufacturing Research Hub (Vax-Hub), established in 2018 with a grant from the UK Vaccine Network (UKVN) which was established as part of the Department of Health and Social Care (DHSC)’s Official Development Assistance (ODA) funding allocation. The Vax-Hub brings together academics, manufacturers, and policymakers with the aim of making the UK the global centre for integrated discovery through to bioprocess manufacture of next-generation vaccines. The Vax-Hub focuses on developing innovative tools and technologies to enhance future vaccine manufacturing whilst promoting long-term partnerships and upskilling.

The Vax-Hub is an example of the success of the DHSC's UKVN Project, which has provided a unique opportunity for the UK to contribute to the development of a portfolio of vaccines and vaccine technologies that can be used to respond to current and future epidemics in LMICs, with the potential to respond to global epidemics in other areas. An evaluation of the network found that the approach used was effective and that the UKVN project has been important for the UK’s rapid response to Covid-19.[1]

Question 1: How the Government is applying lessons from the Covid-19 pandemic, in areas such as:

-          Pandemic preparedness;

-          Testing capacity and approach;

-          Vaccine development and treatments;

-          Scientific advice in government; and

-          Accounting for the economic impact of pandemics

Vaccine development in the UK is key to scaling up vaccine production rapidly in a health emergency and to strengthen the UK’s ability to respond to future pandemics.[2] The UK had a leading role during the pandemic due to its strong vaccine development research base, which contributed to global efforts for the SARS-COV-2 vaccine.

Funding: It is important to recognise the years of research and sustained investment required along the whole vaccine supply chain to enable effective vaccine development and delivery, and to ensure UK pandemic preparedness. An example of good practice in the funding of research to improve preparedness for future global health crises is the DHSC’s funding for two “Future Vaccine Manufacturing Research Hubs”. One of the Hubs is a joint Hub between University College London and the University of Oxford, the Vax-Hub.[3] Researchers from the Hub have been instrumental in driving forward the UK’s vaccine discovery efforts in the Covid-19 crisis and in relation to other diseases with pandemic potential. Impact is felt both at the national and international level via knowledge transfer to the Hub’s partners in LMICs.  The Hubs were funded before the pandemic, and it was only because they were already funded that they were able to respond so quickly when the pandemic occurred. It is critical that funding and the necessary support is provided for this important work to continue.

Broad focus on technologies: The Vax-Hub’s focus on advancing novel research on a broader range of vaccine technologies has contributed to its success. For example, work undertaken within Vax-Hub on responsive technologies and accelerated quality control methods enabled rapid development and manufacture of the AstraZeneca vaccine against SARS-CoV-2 (licensed for emergency use in December 2020 via a not-for-profit partnership with AstraZeneca). Over 3 bn doses have now been given in over 180 countries.

The group was able to progress their vaccine to clinical trials at great speed (a matter of months instead of years), because they used a platform approach. A focus of the group has been on the development of vaccine platforms. Vaccine platforms use a ‘plug-and-play’ approach where generic components of vaccines are developed and tested in advance of disease outbreaks. When an outbreak occurs, the DNA of the pathogen is sequenced and an appropriate antigen is identified for inclusion in the ready-made vaccine delivery system, which allows for a rapid response to the new disease.[4] The platform approach allows extensive safety and efficacy testing to be carried out on the delivery system before the emergence of a new disease and the genetic information for the new disease is plugged-in at the time of an outbreak, drastically shortening development times.

It is essential to focus on different types of vaccine technology groups (including traditional, modern, and innovative platform groups).[5] [6] For instance, for some global health and non-viral threats, such as antimicrobial resistance (AMR), the only effective vaccines to date belong to the modern platforms group (glycoconjugates).[7] These vaccines are hard to develop, new technologies are at an early stage, and require scale-up. The Vax-Hub recognises the need for a broad focus on technologies, and focuses on innovative, modern, and traditional vaccine technologies. Building UK capabilities in different vaccine technology platforms offers acceleration, flexibility, and pandemic readiness for future disease outbreaks.

Building strong vaccine supply chains in the UK: It is necessary to create linkages across the whole supply chain for vaccine manufacturing, from research and development to clinical trials. Greater collaboration across the supply chain can contribute to overcoming some of the practical barriers related to the final fill-and-finish stages and the availability of raw materials and equipment in the UK.[8]

Investments in infrastructure and partnerships have been essential to promote, develop and grow the vaccine industry in the UK.[9] For example, the catapult model in the UK aims to foster collaboration across sectors and to provide businesses with access to expertise and facilities, such as the Cell and Gene Therapy Catapult Manufacturing Innovation Centre.[10]  The model used by AstraZeneca to expand manufacturing support of the Covid-19 vaccine candidate, AZD1222, also illustrates the value of partnerships between clinical biomanufacturing facilities and non-vaccine companies.[11] Not-for-profit initiatives, like the Vaccine Manufacturing and Innovation Centre (VMIC) that was sold to Catalent in 2022, are also needed in the UK. VMIC’s aim was to provide early-stage access to good manufacturing practice manufacture for new vaccines to bring them to clinical trials, as well as testbeds and training centres for new vaccine technologies. VMIC was founded in 2018, but significantly scaled up in response to Covid-19 to provide sufficient manufacturing capacity for the UK.[12] Lessons can be learned from VMIC to build similar centres at a smaller scale.

Building a skilled UK workforce: Investments in infrastructure and partnerships need to be complemented by training programmes that create a strong UK vaccine workforce. In the cell and gene therapy sectors, the UK skills demand forecast for 2026 is 10,000 bioprocessing jobs, indicating a growth of 151% from 2021.[13] Skills development is required along the whole vaccine development process from research and development, manufacturing, clinical development, regulation, and vaccine delivery.[14]

Skills development should focus on encouraging a range of talented individuals to enter the sector, through schools-based outreach programmes, industry partnerships and doctoral training. Links should also be created to complementary sectors, such as the cell and gene therapy sectors. For instance, the Advanced Therapies Skills Training Network funded by the (former) Department for Business, Energy and Industrial Development (BEIS) and Innovate UK is a national initiative that aimed to drive growth across the advanced therapies and vaccine manufacturing industry, by providing access to training facilities and an online platform to address the UK’s demand for skills.[15]

Regulatory flexibility: Regulatory flexibility was essential during the pandemic to ensure the continuity of scientific progress and to facilitate access to vaccines and treatments.[16] It is important that we create systems and frameworks that have sufficient levels of regulatory flexibility to respond to current and emerging needs. Concerted efforts are required across national and international regulatory systems. Global or regional frameworks and agreements can be conducive to accommodate this required flexibility.

The Medicines and Healthcare products Regulatory Agency (MHRA) collaborated with the DHSC and other healthcare partners and stakeholders to rapidly identify where flexibilities in the regulation of medicines and medical devices may be possible for Covid-19. For instance, they provided expedited scientific advice and rapid reviews of clinical trial applications to support manufacturers and encouraged off-site auditing to review data or documents where possible for products required to maintain continuity of supply.[17]

Question 2: The causes of zoonotic disease emergence and ‘spillover events’, the types of zoonotic disease most likely to emerge; and the potential global implications of a future zoonotic disease outbreak.

60% of known infectious diseases and up to 75% of new or emerging infectious diseases are zoonotic (an infection transmitted from animals to humans) in origin.[18] Although it is not possible to predict the precise timing of the next zoonotic disease outbreak, global trends of increased human-animal contact mean that spill-over events are becoming more frequent making the occurrence of future pandemics very likely.

There is an increased risk of spill-over events through drivers such as intensified agriculture and livestock production, antimicrobial resistance (AMR), climate change, and population mobility.[19] For instance, AMR has the potential to slowly grow to pandemic proportions, thereby setting back gains in human health significantly. Successful vaccines for AMR have been difficult and expensive to develop. Alternative technologies are at an early stage and the Vax-Hub has been working on the engineering input that is required to make them scalable.

Most of these spill-over events affect low- and middle-income countries. LMICs are therefore disproportionately affected by infectious diseases with pandemic potential. Health systems strengthening in LMICs is key to manage zoonotic disease threats before they become pandemics.

Question 3: The extent of UK preparedness for an emerging disease outbreak with pandemic potential, and how this could be enhanced, including an assessment of recent policy announcements such as the refresh of the UK Biological Security Strategy.

Question 4: The extent of co-ordination between Government departments and other bodies such as the UK Health Security Agency.

Coordination should happen before adverse events occur. This necessitates advance global and/or regional agreement on how to accommodate supply chain needs to enable plans to be triggered in the event of an emergency. Such global and/or regional agreement can aid decision-making, establish the required action and resources in a disease outbreak, speed up response times, increase efficiencies, and benefit national and global health outcomes.

Question 5: Whether the threat from animal and other diseases receives sufficient cross-government priority; and

Question 6: Additional policy initiatives and solutions needed in the UK and internationally to reduce the risk of the future spread of emerging diseases with pandemic potential.

Policy coherence: The Covid-19 pandemic has demonstrated the importance of creating alignment on key policy goals and objectives. Diverse stakeholders need to be brought into conversation with each other. Involving public health professionals and those working in vaccine development in decision-making, the Government can facilitate greater coherence between the policy and scientific community. For instance, the mRNA vaccine technology transfer hub (mRNA vaccine hub), announced by the WHO in 2021, aims to build capacity in LMICs to produce mRNA vaccines. The mRNA vaccine hub is located in South Africa and consists of a centre of excellence and training. It worked with the policy community and companies (including Afrigen Biologics, the South African Medical Research Council and Biovac) to create a global common good for the benefit of all by providing a range of different services along the entire vaccine value chain.[20]

Vaccine manufacturing networks: An important element of the UK’s efforts to reduce the risk of the future spread of emerging diseases with pandemic potential, is to strengthen vaccine manufacturing capabilities. A way to facilitate this is by participating in vaccine manufacturing networks, including those formed by the Africa CDC and their partnership for African Vaccine Manufacturing framework, that facilitates the sharing of knowledge, experiences, and technologies.

Skills development: Training and know-how are key to the promotion of innovation and upskilling, and the UK should identify and build on opportunities for its world leading life science community to participate in and help shape these efforts. Concerted efforts are necessary to train a new multi-disciplinary and permanent workforce that has knowledge that is scientific, technical, regulatory and product-specific for manufacturing, GMP, and quality control systems. It is important to develop a coherent and comprehensive training system that uses a combination of different training modules.

LMIC focus: LMIC health systems provide the front line against the majority of emerging pandemic threats, so health systems strengthening and enhancing vaccine manufacturing capability in LMICs are critical to global, and ultimately UK health security.

Covid-19 illustrated that uneven access to vaccines threatened the effectiveness of global efforts to control the pandemic. Vaccine manufacturing markets are concentrated in a few geographical regions, dominated by a small number of manufacturers, and focussed on a specific set of diseases.[21] To address inequity in vaccine access in a sustained way and to de-risk the supply chain by having a multitude of suppliers, vaccine manufacturing capacity must be built in LMICs.[22]

Technology transfer and capacity-building in LMICs can help address challenges related to costs and upfront capital requirements, access to technology and technology platforms, regulatory maturity, infrastructure capabilities, and vaccine manufacturing skills globally.[23]

By strengthening supply chains and building capabilities from the ground-up, LMICs can contribute to the whole vaccine value chain from research and development to manufacture. Future vaccine manufacturing can be enhanced globally through de-risked manufacture of new vaccine platforms, focussing on both established and novel platform technologies. For example, adaptable vaccine manufacturing facility design (such as ballroom facilities and modular facilities) that make use of single-use, disposable technologies allow for greater adaptability and reduces the risk of manufacturers locking themselves into a single process early on.[24] Support is also needed for research into vaccine formulation. Alternative vaccine administration routes (such as nasal sprays or patches instead of injections) could lead to greater shelf life and better temperature stability vaccines that are easier to administer in LMICs.[25]

(March 2023)