Big data analytics streamlining therapeutic drug development from micro-scale through to industrial-scale (cell culture)

The aim of this EngD is to generate a data-driven decisional tool to speed up the delivery of novel therapeutics from cell line development to full-scale manufacturing. The project will focus on streamlining the data management, visualisation and analytics of all available on-line, off-line and product quality data generated by cell culture operations recorded across multiple facilities and scales. The project will develop advanced machine learning algorithms and apply them to novel applications related to industrially-relevant cell culture datasets. The application of these algorithms will enable exploratory analysis to test hypotheses, identify patterns and correlations and uncover trends unlocking novel insights that will directly translate into the faster delivery of novel therapeutic proteins. The project will initially focus on cell line development to evaluate the key performance drivers defining robust and stable cell lines that perform as expected as they scale-up from micro-scale (AMBR (15 ml) to lab-scale (3-7 L) and ultimately to commercial manufacturing (15,000 L). The project also aims to quantify the variability and assess the performance of each cell line during scale-up to better forecast any potential failures or expected process issues at the larger scales.

The project aims to provide an opportunity to investigate different big data and machine learning algorithms through the use of software's such as Python and R to analyse data of high dimensions. Other skills to be gained also focus on mammalian cell culture and laboratory automation as well as proficiency in data science and mechanistic modelling.

The CDT has a proven track record of delivering impact from its research and training activities and this will continue in the new Centre. The main types of impact relate to: (i) provision of highly skilled EngD and sPhD graduates; (ii) generation of intellectual property (IP) in support of collaborating companies or for spin-out company creation; (iii) knowledge exchange to the wider bioprocess-using industries; (iv) benefits to patients in terms of new and more cost effective medicines, and (v) benefits to the wider society via involvement in public engagement activities and impacts on policy.

With regard to training, provision of future bioindustry leaders is the primary output of the CDT and some 96% of previous EngD graduates have progressed to relevant bioindustry careers. These highly skilled individuals help catalyse private sector innovation and biomanufacturing activity. This is of enormous importance to capitalise on emerging markets, such as Advanced Therapy Medicinal Products (ATMPs), and to create new jobs and a skilled labour force to underpin economic growth. The CDT will deliver new, flexible on-line training modules on complex biological products manufacture that will be made available to the wider bioprocessing community. It will also provide researchers with opportunities for international company placements and cross-cohort training between UCL and SSPC via a new annual Summer School and Conference.

In terms of IP generation, each industry-collaborative EngD project will have direct impact on the industry sponsor in terms of new technology generation and improvements to existing processes or procedures. Where substantial IP is generated in EngD or sPhD programmes, this has the potential to lead to spin-out company creation and job creation with wider economic benefit. CDT research has already led to creation of a number of successful spin-out companies and licensing agreements. Once arising IP is protected the existing UCL and NIBRT post-experience training programmes provide opportunities for wider industrial dissemination and impact of CDT research and training materials.

CDT projects will address production of new ATMPs or improvements to the manufacture of the next generation of complex biological products that will directly benefit healthcare providers and patients. Examples arising from previous EngD projects have included engineered enzymes for greener pharmaceutical synthesis, novel bioprocess operations to reduce biopharmaceutical manufacturing costs and the translation of early stem cell therapies into clinical trials. In each case the individual researchers have been important champions of knowledge exchange to their collaborating companies.

Finally, in terms of wider public engagement and society, the CDT has achieved substantial impact via involvement of staff and researchers in activities with schools (e.g. STEMnet), presentations at science fairs (Big Bang, Cheltenham), delivery of high profile public lectures (Wellcome Trust, Royal Institution) as well as TV and radio presentations. The next generation of CDT researchers will receive new training on the principles of Responsible Innovation (RI) that will be embedded in their research and help inform their public engagement activities and impact on policy.