New Industrial Systems: Optimising Me Manufacturing Systems

The Optimising Me Manufacturing System [OMMS] project is developing a healthcare microfactory that provides on-the-body manufacturing of therapeutics. The concept arose during the EPSRCs New Industrial Systems workshop held in May 2017, bringing together researchers from a diverse range of disciplines to work together to create transformative impact on our manufacturing industries. The initial proof-of-concept focuses on the development of a manufacturing system for T-cell immunotherapies, located on the body and delivered on demand in response to the patient's needs. The long-term vision the creation of modular microfactories, built using a range of underlying common technologies, enabling future on-body manufacturing of a range of different therapeutics.

OMMS goes beyond the current state of the art and re-defines healthcare manufacturing. It offers a step change in current manufacturing trajectories, enabling responsive delivery of bespoke therapeutics as part of a distributed manufacturing system. T-cell delivery was chosen chosen specifically because of its demonstrable therapeutic capability. In September 2017, they will become the first gene therapy to have been approved by the US FDA. From the clinical data presented thus far it appears these genetically modified T-cells present a CURE for some of the most aggressive forms of cancer (Acute Lymphoblastic Leukaemia, Chronic Lymphoblastic Leukaemia). The current manufacture of T-cells is undertaken in a laboratory and can take up to 21 days, depending on the quality of the patient's starting cellular material. The long, complex and expensive process poses the risk of contamination and further complications due to patient variations. The development of a continuous manufacturing capability will address some of these shortcomings and would allow the continuous manufacture and delivery of the therapy to the patient. Moving therapeutic manufacturing away from the current one-size-fits-all approach could enable advances which deliver patient-specific therapies of sufficient precision and quality for personalised medicine.

By creating a proof-of-concept platform within a very short timeline, OMMS will demonstrate distributed therapeutic manufacture on/at-patient, with clear scope for extension towards other pharmaceutical manufacturing targets e.g. diabetes monitoring and control. The project takes steps towards de-risking the development of key technologies in on-body integration, manufacturing process and biometrology (measurement of the product throughout the microfactory to ensure that strict quality and regulatory requirements are met). The development of technologies that are transferable to a number of future healthcare manufacturing systems will pave the way for the broader uptake of the microfactory platform concept.

The project has three main over-arching objectives:
1. Proof-of-concept for a new microfactory platform for therapeutic manufacturing, moving pharmaceutical manufacturing from a non-responsive, centralized process towards a bespoke, distributed manufacturing process.
2. Direct engagement with industrialists, academics and policy makers towards this new vision of therapeutic and healthcare manufacturing in the U.K.
3. Delivery of a prototype of the microfactory platform, based on T-cell immunotherapy, incorporating 4 main elements into the factory on-body:
a. Specific cell isolation directly from the patient's blood.
b. Processing of these raw materials towards a deliverable therapeutic.
c. Complete integration of biometrology, to ensure quality control, from isolation through the microfactory process.
d. Fully integrated feedback between the location, biometrology and manufacturing process phases of the microfactory, responding dynamically to demand and quality parameters.

It is expected that the OMMS project will result in multiple levels of impact for a range of different beneficiaries from academic in the short term, through to industrial, clinical, regulatory, patient groups and the general public in the long term.

Once the vision of a personalised microfactory is realised, the primary beneficiary will be patients who will benefit from increasing levels of targeted therapeutic precision and improved clinical outcomes. In particular, the exemplar selected for the OMMS project is one that is both timely and clinically-relevant given the successful clinical trial data and the potential to develop an effective therapy against aggressive forms of cancer (acute lymphoblastic leukaemia and chronic lymphoblastic leukaemia). Moreover, this project aims to redefine the manufacture of therapeutics by moving away from the existing 'one-size-fits-all' approach to a more personalised and targeted, distributed manufacturing, approach which is not only relevant for the clinical exemplar selected, but has the potential to be applied as a platform to a wide variety of clinical indications.

The project is also expected to deliver significant impact and align with the UK's advanced therapeutic R&D and manufacturing agenda. This will complement activity of existing UK infrastructure projects such as the Cell and Gene Therapy and Precision Medicines Catapults in addition to the UK-wide research activities in this sector including the UK Regenerative Medicine Platform, the EPSRC Targeted Manufacturing Healthcare Hub and the EPSRC-MRC Centres for Doctoral Training.

As identified in the academic beneficiaries summary, there is significant potential for the research outcomes from this project in addition to the extensive multidisciplinary approach adopted by the project investigators to create impact within the academic community. This will enhance existing research activity in this sector but, specifically, will redefine and create a new manufacturing, business model and supply chain paradigm for the production and delivery of advanced therapeutics. Similar to the redistributed manufacturing approach, this project will look to establish a manufacturing approach not just close to clinic, but on/at patient, utilising the body's innate ability and regenerative potential.

Key beneficiaries also include industry, not just the healthcare manufacturing sector, but also other sectors which can benefit from personalisation, enhanced biometrology, self-powered sensors and novel business, supply chain and manufacturing models. Specifically, if the project vision is realised, the microfactory platform will have significant impact on the manufacture and supply of advanced therapies and can act as a platform system for the isolation and delivery of other therapeutics. Such a system is likely to be of interest to large pharmaceutical and biopharmaceutical companies (i.e. GSK, Pfizer, Novartis), vendor companies (i.e. Sartorius, Pall and GE Healthcare), SMEs, both UK and international (i.e. Autolus, Excellthera and Orchard Therapeutics) and CMOs (i.e. PCT, FujiFilm Diosynth and Lonza).

Other beneficiaries include the NHS and clinicians and has the potential to alleviate pressures for frontline staff as well as resource requirements by reducing the burden of acute and chronic conditions. Moreover, through the use of automated monitoring and dose formulation/administration, the microfactory platform has the potential to significant reduce human error and improve consistency. It is also expected that the research will result in the creation of new research-led teaching and training material which can be provided to industry delegates (e.g. through UCL MBI industry courses) or to undergraduate and postgraduate students across the field of bioengineering, materials science, management and electronic and electrical engineering.