Vaccines are the most successful public health initiative of the 20th century. They save millions of lives annually, add billions to the global economy and extended life expectancy by an average of 30 years. Even so, the UN estimates that globally 6 million children each year die before their 5th birthday. While vaccines do exist to prevent these deaths, it is limitations in manufacturing capacity, technology, costs and logistics that prevent us for reaching the most vulnerable. The UK is a world leader in vaccine research and has played a significant leadership role in several public health emergencies, most notably the Swine Flu pandemic in 2009 and the recent Ebola outbreak in West Africa. While major investment has been made into early vaccine discovery - this has not been matched in the manufacturing sciences or capacity. Consequently, leading UK scientists are forced to turn overseas to commercialise their products. Therefore, this investment into The Future Vaccine Manufacturing Hub will enable our vision to make the UK the global centre for vaccine discovery, development and manufacture. We will create a vaccine manufacturing hub that brings together a world-class multidisciplinary team with decades of cumulative experience in all aspects of vaccine design and manufacturing research. This Hub will bring academia, industry and policy makers together to propose radical change in vaccine development and manufacturing technologies, such that the outputs are suitable for Low and Middle Income Countries. The vaccine manufacturing challenges faced by the industry are to (i) decrease time to market, (ii) guarantee long lasting supply - especially of older, legacy vaccine, (iii) reduce the risk of failure in moving between different vaccine types, scales of manufacture and locations, (iv) mitigating costs and (v) responding to threats and future epidemics or pandemics. This work is further complicated as there is no generic vaccine type or manufacturing approach suitable for all diseases and scenarios. Therefore this manufacturing Hub will research generic tools and technologies that are widely applicable to a range of existing and future vaccines. The work will focus on two main research themes (A) Tools and Technologies to de-risk scale-up and enable rapid response, and (B) Economic and Operational Tools for uninterrupted, low cost supply of vaccines. The first research theme seeks to create devices that can predict if a vaccine can be scaled-up for commercial manufacture before committing resources for development. It will include funds to study highly efficient purification systems, to drive costs down and use genetic tools to increase vaccine titres. Work in novel thermo-stable formulations will minimise vaccine wastage and ensure that vaccines survive the distribution chain. The second research theme will aim to demystify the economics of vaccine development and distribution and allow the identification of critical cost bottlenecks to drive research priorities. It will also assess the impact of the advances made in the first research theme to ensure that the final cost of the vaccine is suitable for the developing world. The Hub will be a boon for the UK, as this research into generic tools and technologies will be applicable for medical products intended for the UK and ensure that prices remain accessible for the NHS. It will establish the UK as the international centre for end-to-end vaccine research and manufacture. Additionally, vaccines should be considered a national security priority, as diseases do not respect international boundaries, thus this work into capacity building and rapid response is a significant advantage. The impact of this Hub will be felt internationally, as the UK reaffirms its leadership in Global Health and works to ensure that the outputs of this Hub reach the most vulnerable, especially children.

Cell therapies, which use human cells to restore, maintain, or improve the functioning of human tissues or organs, hold enormous potential for the treatment of a wide range of diseases and conditions, including a variety of cancers. While cell therapies have the potential to improve healthcare for millions of patients worldwide, manufacturing remains a major hurdle for clinical translation. Today's cell therapies manufacturing processes, which include the use of patient's own cells or donor cells to manufacture the therapeutic product, involve manual, labour-intensive and open processes that require highly-skilled personnel. This in turn leads to high process variability, risk of contamination and high manufacturing costs, all of which are major obstacles for cell therapies to realise their full potential and bring about widespread access to the global patient population. New technologies are urgently needed to develop reliable and robust manufacturing processes that ensure quality and consistency of cell therapy products at an economically viable cost. This project will develop an on-demand sensor and monitoring technology that will enable, for the first time, real-time, non-disruptive measurement of key biochemicals in cell culture media. These unprecedented capabilities will be enabled by an innovative microfluidic sensing platform comprising smart, switchable electrode-tethered nanobodies. In contrast with conventional offline analysis, the acquisition of real-time process data will allow immediate response to process variations, thus providing a fine level of process control. This is essential for the consistent production of high-quality therapeutic cells in high yields, independently of the patient's or donor's cells. It will provide an exceptional opportunity to implement fully automated, robust cell therapy culture processes and bring down production costs, ultimately delivering cost-effective and impactful therapeutics to patients in need.

The Kings/Royal Free/UCL Gene Therapy Innovation Hub will manufacture clinical-grade gene therapies for the UK academic and clinical community. This will allow promising treatments for a wide range of rare and common diseases to be tested in patients. The results from these early clinical studies may then support larger-scale trials and ultimately new therapies for patients. Provision of suitable quality (GMP) gene therapy product is a key limiting factor for progress in this exciting field. Our Hub will address this directly through a major increase in UK capacity. This will cover the major types of gene therapy used, adeno-associated virus (AAV) and lentivirus, as well as gamma-retrovirus. In addition, we will invest in developing new approaches to increase the amount of gene therapy product that can be made at one time (in one batch). This will mean that each trial needs fewer batches, and that applications needing high doses (for example, administration systemically) become possible. It will also reduce costs of manufacture. We will also work to increase the UK's overall capabilities to manufacture gene therapies, through creation and provision of dedicated training courses, both online and in person, at a variety of levels, to suits varying needs of different groups. In addition to this, we will lend our expertise to other developing Gene Therapy Innovation Hubs, to help them to become operational as quickly as possible. King's, Royal Free and UCL offer unmatched expertise in the UK in gene therapy manufacturing, and we are ideally-placed to contribute to the UK's success in improving therapies for many poorly-treated diseases, and generating sustainable economic benefit for the country.

The lifETIME CDT will focus on the development of non-animal technologies (NATs) for use in drug development, toxicology and regenerative medicine. The industrial life sciences sector accounts for 22% of all business R&D spend and generates £64B turnover within the UK with growth expected at 10% pa over the next decade. Analysis from multiple sources [1,2] have highlighted the limitations imposed on the sector by skills shortages, particularly in the engineering and physical sciences area. Our success in attracting pay-in partners to invest in training of the skills to deliver next-generation drug development, toxicology and regenerative medicine (advanced therapeutic medicine product, ATMP) solutions in the form of NATs demonstrates UK need in this growth area. The CDT is timely as it is not just the science that needs to be developed, but the whole NAT ecosystem - science, manufacture, regulation, policy and communication. Thus, the CDT model of producing a connected community of skilled field leaders is required to facilitate UK economic growth in the sector. Our stakeholder partners and industry club have agreed to help us deliver the training needed to achieve our goals. Their willingness, again, demonstrates the need for our graduates in the sector. This CDT's training will address all aspects of priority area 7 - 'Engineering for the Bioeconomy'. Specifically, we will: (1) Deliver training that is developed in collaboration with and is relevant to industry. - We align to the needs of the sector by working with our industrial partners from the biomaterials, cell manufacture, contract research organisation and Pharma sectors. (2) Facilitate multidisciplinary engineering and physical sciences training to enable students to exploit the emerging opportunities. - We build in multidisciplinarity through our supervisor pool who have backgrounds ranging from bioengineering, cell engineering, on-chip technology, physics, electronic engineering, -omic technologies, life sciences, clinical sciences, regenerative medicine and manufacturing; the cohort community will share this multidisciplinarity. Each student will have a physical science, a biomedical science and a stakeholder supervisor, again reinforcing multidisciplinarity. (3) Address key challenges associated with medicines manufacturing. - We will address medicines manufacturing challenges through stakeholder involvement from Pharma and CROs active in drug screening including Astra Zeneca, Charles River Laboratories, Cyprotex, LGC, Nissan Chemical, Reprocell, Sygnature Discovery and Tianjin. (4) Embed creative approaches to product scale-up and process development. - We will embed these approaches through close working with partners including the Centre for Process Innovation, the Cell and Gene Therapy Catapult and industrial partners delivering NATs to the marketplace e.g. Cytochroma, InSphero and OxSyBio. (5) Ensure students develop an understanding of responsible research and innovation (RRI), data issues, health economics, regulatory issues, and user-engagement strategies. - To ensure students develop an understanding of RRI, data issues, economics, regulatory issues and user-engagement strategies we have developed our professional skills training with the Entrepreneur Business School to deliver economics and entrepreneurship, use of TERRAIN for RRI, links to NC3Rs, SNBTS and MHRA to help with regulation training and involvement of the stakeholder partners as a whole to help with user-engagement. The statistics produced by Pharma, UKRI and industry, along with our stakeholder willingness to engage with the CDT provides ample proof of need in the sector for highly skilled graduates. Our training has been tailored to deliver these graduates and build an inclusive, cohesive community with well-developed science, professional and RRI skills. [1] https://goo.gl/qNMTTD [2] https://goo.gl/J9u9eQ

We will establish a technology platform that changes the way we diagnose and treat patients. It involves detecting and producing nano-sized biological particles that act as communication machinery in nature. These particles are called exosomes and with significant investment in the engineering required to accurately capture and profile them, it will be possible to create a new class of diagnostics that can detect disease earlier than is currently possible, based on the release and detection of specific exosomes. It will also be possible to distinguish between different stages of disease, which will help to tailor the right treatment to an individual patient. The diagnostics platform will also form the basis for manufacturing analytics that will enable cell and gene therapies to be carefully monitoring during manufacture. Cell and gene therapies currently cost in the order of £100,000 to £1,000,000 per dose and is related to the fact that bioprocesses (the manufacturing approaches used to create them) are sub-optimal. A radical advance in manufacturing analytics will help to better monitor and control manufacturing, which will lead to improved product consistency and ultimately drive down cost of manufacturing, which will catalyse the routine adoption of cell and gene therapies in the NHS. Finally, by producing exosomes using industrial bioprocesses it will be possible to create new drugs based on exosomes, exploiting their communication machinery to target therapies to sites of disease. This will involve a combination of engineering exosomes to have increased potency, or loading them with powerful drugs and targeting them directly at the diseased tissue. Ultimately, this will radically advance personalised medicine across diagnostics, analytics and drug delivery. In 30 years' time this technology platform will be widely used in healthcare to diagnose and treat disease with high fidelity using bespoke formulations. In order to advance this vision, phase 1 feasibility studies will address engineering challenges in sensor development to detect exosomes at different orders of sensitivity. It will also address the consistent production of exosomes at pilot scale in order to advance the exosome therapeutic platform.