FUTURE TARGETED HEALTHCARE …...10 Future Targeted Healthcare Manufacturing Hub THE HUB IN NUMBERS Hub: UCL Spokes: Imperial, Warwick, Manchester, Nottingham, LoughboroughUser Steering

ANNUAL REPORT 2018FUTURE TARGETED HEALTHCARE MANUFACTURING HUB

Grant Ref: EP/P006485/1

www.ucl.ac.uk/biochemeng/hub

http://www.ucl.ac.uk/biochemical-engineering/research/research-and-training-centres/future-targeted-healthcare-manufacturing-hub

2 Future Targeted Healthcare Manufacturing Hub

Annual Report 2018 3

CONTENTS

CONTENTS

FOREWORD ............................................................................ 5

EXECUTIVE SUMMARY ................................................................ 6

THE HUB IN NUMBERS ................................................................ 8

THE HUB: VISION & RATIONALE ..................................................... 9

SHAPING THE FUTURE OF THE DEVELOPMENT OF TARGETED BIOLOGICAL MEDICINES ...........................................11

USER ENGAGEMENT AND PATHWAYS TO IMPACT ..............................13

UPDATE FROM THE SPECIALIST WORKING GROUPS (SWGs) .................14Cell-Free Synthesis ...................................................................................14Decisional Tools ........................................................................................14Formulation ...............................................................................................14T-cell Processing .......................................................................................15Healthcare Regulation & Reimbursement ................................................15

PATHWAYS TO IMPACT ..............................................................16

RESEARCH INNOVATION .............................................................17

KNOWLEDGE TRANSFER ............................................................18The Translation Sub-Committee: ..............................................................18User Feasibility Studies: ..........................................................................19Knowledge Transfer Partnerships (KTP): .................................................20Secondments: ............................................................................................20Patents: .....................................................................................................20

SKILLS PROVISION ...................................................................21

POLICY SETTING ......................................................................22

PUBLIC ENGAGEMENT & VISIBILITY ...............................................24

VIEWS FROM THE HUB COMMUNITY ..............................................26

GRAND CHALLENGE RESEARCH THEMES .........................................28

GRAND CHALLENGE 1: TRANSFORMING SUPPLY CHAIN MANAGEMENT AND ECONOMICS FOR TARGETED MEDICINES ................31

GRAND CHALLENGE 2: SUSTAINABLE MANUFACTURING FOR FUTURE TARGETED MEDICINES ..............................................33

PLANNING FOR THE FUTURE .......................................................35

THE HUB & ITS SPOKES .............................................................37

HUB EVENTS 2018 ....................................................................50

SELECTED HUB PUBLICATIONS .............................................................. 51

CONFERENCE PRESENTATIONS ....................................................62

FINANCES ..............................................................................70


CONTENTS


FOREWORD

“the Hub has developed a strong international presence and a unique consortium”

FOREWORD

This past year has been a hugely exciting one for the Hub. As Chair of the Hub Advisory Board, it has been a massive pleasure to watch the activity grow in all dimensions. It is clear that the Hub has developed a strong international presence and a unique consortium, focused on some incredibly important strategic issues. Ringing endorsement of that vision and of the unparalleled support the Hub has secured have been constant themes of the year. I think we all knew that this was an exciting area but nothing had quite prepared me for just how timely the discussions and debates the Hub has generated would prove to be!

Of course at the very heart of the Hub are the researchers and over the past year it has been a particular joy to see them come together as a coherent team and for them to rise to the challenge of managing their programme of cutting-edge research. I am particularly proud of them and excited to see what they will produce for the Hub and our community over the next phase of the programme. It certainly promises to be a fascinating journey.

Dr Stuart West Chair, Hub Advisory Board


EXECUTIVE SUMMARY

“…we have made significant advances in our scientific understanding and technology innovations, and we are now working closely with our user community…”

EXECUTIVE SUMMARY

The Hub has embarked on an ambitious set of strategic research targets, closely informed by a strong industry and regulatory consortium. Our focus is to develop and examine technological solutions for the rapid realization of targeted healthcare and include: pioneering studies in the utility of cell-free synthesis for just-in-time manufacture of valuable therapeutics; engineering characterization of novel bioreactor geometries for effective process development and delivery of cell and gene therapy products; as well as advanced software tools to help in decision-making for the industry.

The benefits of the Hub extend beyond the users who co-developed the strategic agenda. Our innovations will move the reality of targeted healthcare forward significantly, by identifying the technological and logistical solutions necessary. Targeted interventions will provide a step change for many patients in terms of widened access to new treatments. The range of targets is huge and includes treatments for cancers and the re-programming of degenerative disorders such as dementia. This is a radical new opportunity for the industry. The Hub approach offers the possibility of rapid and effective development for new clinical medicines and promises a new horizon for the sector. The Hub represents a radical departure from existing research activities.

Over the past year, we have made significant advances in our scientific understanding and technology innovations, and we are now working closely with our user community to deliver user feasibility studies, which are designed to test our methods, and to gauge the utility of new approaches in an industrial setting. Already we have the first batch of nine such studies defined and approved for execution within the next year. The results of these studies will be used to inform new research directions and to further our understanding of the evolving manufacturing landscape. This close integration with industry means that our progress makes a defined impact on manufacturing practice. Since launch, we have grown the user base by over a third and also brought in Cancer Research UK, and the newly formed Medicines Manufacturing Innovation Centre (MMIC).

Close working with the regulatory agencies has enabled us to understand better new regulatory pathways to help innovation both in general and in the targeted/advanced therapies areas. We have noted significant differences between Europe and the United States (e.g. data needed for accessing facilitating pathways and marketing applications reviewing times), which will inform manufacturing models going forward.

A route to manufacturing of nanoparticles has been established that is able to control their morphology and size distribution, and then also to encapsulate biologics and deliver them into macrophages. The impact of co-formulating multiple proteins on their stability to aggregation and fragmentation has also been revealed. New biophysical techniques have enabled the analysis of degradation in these protein mixtures.


EXECUTIVE SUMMARY

Prof Nigel Titchener-Hooker Hub Director

Prof Suzanne Farid Hub Co-Director

Prof Paul Dalby Hub Co-Director

We have made excellent progress in the mapping of existing supply chains and workflows through activity-based costing and scheduling models and curated supply chain optimisation tools covering optimised variants of supply chains with new manufacturing platforms. These can handle larger problem instances and more complex real-world aspects such as uncertain trial duration or varying number of clinical sites for a trial.

Key insights have been gained specifically to improved T-cell process and product understanding, including a risk ranking of key process and culture variables. Our work is particularly relevant for autologous, patient-specific T-cell immunotherapy development, whereby patient starting cellular material may be of variable quality and limited in terms of cell number. These findings have been discussed with key Hub users and have been corroborated by studies they have separately undertaken.

The Hub has been the first to demonstrate primary T-cell ex vivo manufacture in an automated stirred-tank bioreactor system and the findings have the potential to be applied to multiple other cell candidates for advanced therapy applications. These findings have potentially significant commercial implications and ultimately de-risk these processes whilst simultaneously expediting commercial R&D activity.

In parallel we have developed multivariate statistical models able to capture the dynamics of generic batch processes. Results suggest that they are able to improve the consistency and productivity of batch processes and are suitable for application to the operation of T-cell and cell-free synthesis processes.

Another notable success includes our work with Sutro on the capacity to adopt cell-free synthesis to facilitate manufacture of targeted therapies. Staff secondment has enabled us to secure the technical, in-depth knowledge needed to broaden the scope of this method for manufacture. In addition, our close co-operation with Sutro has given us unparalleled access to their proprietary cell lines and reagents, ensuring that our studies remain focused and industrially relevant.

Our scientific successes have been matched by impressive progress both in the development of the Hub as a national focus, and in the training and experience we are providing for our PDRAs and the associated doctoral students. The growth of the Hub, and the continuing breadth of that, demonstrates the relevance and the quality of what we deliver for the sector. The success of our researchers in publicity, conference and career advancement all point to the effectiveness of the EPSRC Hub mechanism, based around a focused and managed cohort, to deliver for the UK.


THE HUB IN NUMBERS

THE HUB IN NUMBERS

April 2019

Academic Researchers Across 6 Leading Universities

Conference Presentations

Partnering Companies & Organisations

Publications

Aligned PhDs/EngDs

User Feasibility Studies

Meetings, Workshops & Networking Events

Leveraged Funding

27

3050

12 £10.3M

39

20

78


THE HUB: VISION & RATIONALE

“By 2025 targeted biological medicines, personalised and stratified, will transform the precision of healthcare prescription, improve patient care and quality of life”

THE HUB: VISION & RATIONALE

VisionBy 2025 targeted biological medicines, personalised and stratified, will transform the precision of healthcare prescription, improve patient care and quality of life. Novel manufacturing solutions have to be created if this is to happen. We have created a Hub and Spoke mechanism to align and coordinate a network of users and academics to provide strong support for UK industry. The Hub is a unique resource for the creation, delivery and dissemination of innovative manufacturing research, driving forward the national agenda. It is the first globally recognised consortium in targeted healthcare manufacturing, and acts as a powerful factor for encouraging inward UK investment, attracting the best researchers worldwide, accelerating SME development and facilitating NHS deployment. Our vision is based on an unrivalled track record of delivery.

Rationale The current “one-size-fits-all” approach to drug development is challenged by the ability to treat patients as individuals. Stratified medicine identifies populations for treatment by genetic pre-screening and diagnostics linked to a companion drug molecule. For some indications truly personalised medicines will be offered. Without significant manufacturing innovations the promise of targeted healthcare will remain inaccessible for many via an NHS under extreme financial pressure. The implications for health and UK society well-being are profound.

Deliverables The Hub is providing the manufacturing infrastructure and capabilities needed to enable UK manufacturers to exploit fully medical precision advances, through new technologies, skilled personnel, IP and spin-outs. Two grand challenges create and combine decisional tools and manufacturing innovations to achieve sustainable healthcare and enhanced UK competitiveness in this new era. We have a platform of activities to network academics, industrial users and regulators to deliver outreach and impact broadly. Society will benefit from increased access to affordable treatments.

Mode of Operation Engineers, scientists, and economists from leading UK universities and user industries are driving research excellence and shaping the national research landscape. Collaborations with academic research spokes, EPSRC Hubs, and stakeholders (Catapult-led translational spokes and industry), via feasibility studies and leveraged funding (e.g. Innovate UK), will sustain innovation and accelerate impact to deliver the timely vision.


THE HUB IN NUMBERS

Hub: UCL Spokes: Imperial, Warwick, Manchester, Nottingham, Loughborough

User Steering Committee*. *Signed or in the process of signing the Collaboration agreement as of April 2019

Companies: 3M, Adaptimmune Therapeutics, Aglaris, Albumedix, Allergan, AstraZeneca, Autolus, BIA Separations, Biologic B, BioPharm Services, Cell Medica, deltaDOT, Eli Lilly, Francis BioPharm Consulting, Fujifilm Diosynth Biotechnologies, GSK, Ipsen, Lonza, Oxford BioMedica, Pall, Perceptive, Puridify, Purolite, Rare Access, ReNeuron, Sartorius, SSC Bio, Sutro BioPharma, Tillingbourne Consulting, TrakCel, West Pharmaceutical Services, Wyatt Technology. Industry/Govt Associations, Charities: ABPI, BIA, Cancer Research UK, KTN, LGC, MMIP, NIBSC. Translational Spokes: Cell and Gene Therapy Catapult, Centre for Process Innovation/NBMC

Hub Operations & Support

Grand Challenge researchCore research deliverables

75.5 PDRA FTEs in Hub and Spoke model

Grand Challenge 1

Transforming supply chain management and economics for tartgeted medicines

Grand Challenge 2

Sustainable manufacturing for future targeted medicines

Pathways to impactBuilding national & international network

• Academic feasibility studies

• CDT doctoral studies

• Policy and Health Economics studies

Accelerating adoption of Hub outputs

• User-led feasibility and EngD studies

• Catapult demonstrators of Hub tools

• New CoE and spin outs

Traditional One-Size-Fits-All Medicines Targeted: Stratified Medicines Targeted: Personalised Medicines

Number of drug products

Number of patients per group

FIGURE 1: Moving from one-size-fits-all to targeted medicines (stratified and personalised)

FIGURE 2: Future Targeted Healthcare Manufacturing Hub structure

User Growth: Since launch, we have grown the user base of partnering companies (including SMEs) and also brought in Cancer Research UK and the newly formed Medicines Manufacturing Innovation Centre (MMIC).

Moving from “one-size-fits-all” to “targeted” medicines…

How can stratified biologics and personalised cell therapies achieve success in manufacturing and business?


SHAPING THE FUTURE OF THE DEVELOPMENT OF TARGETED BIOLOGICAL MEDICINES

“Developing these products is a multi-disciplinary activity and the Hub is particularly well placed and networked to address these challenges”

SHAPING THE FUTURE OF THE DEVELOPMENT OF TARGETED BIOLOGICAL MEDICINESThe invention and rapid development of better, cheaper and more effective new medicines and therapies is vital to the economic and societal health of the UK. The Life Science Industry is one of the most important, productive and globally competitive parts of our economy generating a combined estimated annual turnover of ~£70 billion, employing more than 240,000 people and comprising nearly 6000 businesses. Its success is founded on high quality science and engineering research in industry and in academia. It depends on the flow of ideas between the two, on the development of relevant skills in the future and current workforce and in the establishment and nurturing of dynamic and interactive communities and networks.

We face many challenges to bring personalised and stratified medicines to patient and to market successfully. They are often based on molecules, cells and processes of greater complexity than conventional drugs and biologics and can be more difficult to develop, make, analyse and control. Many also require the development of new, shorter, more agile supply chains and pose novel quality control, quality assurance and regulatory challenges. The highly personalised nature of some life changing therapies will ultimately require that they are developed more quickly and manufactured more cost effectively. These step changes pose significant obstacles to success and require sustained research and collaboration to address them.

The successful development of targeted biological medicines is fundamentally dependent on continuing and consistent support for research in the bio-processing (bio-manufacturing), analytical and digital sciences by Government, Industry and Charitable Foundations. This support is needed to underpin the entire processes of product and process invention, process development and product manufacture. It is critical to bringing product to patient. It is crucially dependent also on the continuing flow of relevant skills and trained professionals into industry and academia.

Developing these products is a multi-disciplinary activity and the EPSRC Future Targeted Healthcare Manufacturing Hub is particularly well placed and networked to address these challenges. Many future solutions and insights will flow from the combination of new bio-processing and analytical approaches with novel modelling, digital, machine learning and AI methodologies. This has great potential not only through automation of development and manufacturing processes but in the development of real time AI enabled analysis that would assure product quality in complex products as they are made.

Both Government and industry have recognised the importance of supporting the life sciences in the past and continuing investment in research will be fundamental to underpin the leading position that the UK has established in the bio-processing sciences as new therapies with new development and manufacturing challenges are developed.


SHAPING THE FUTURE OF THE DEVELOPMENT OF TARGETED BIOLOGICAL MEDICINES

The global life sciences sector is expected to reach >$2 trillion in gross value by 2023 and is of critical importance to the future growth of the UK economy. It is a market of enormous opportunity for UK bioscience and one in which we can be highly successful if we continue to invest in the bio-processing research needed and train the people the sector requires. Strategic investments by UKRI and the research councils in the likes of the EPSRC Future Targeted Healthcare Manufacturing Hub are paving the way for what should be a bright future for all of us.

Dr Mark Carver

Chair, Hub User Steering Committee


USER ENGAGEMENT AND PATHWAYS TO IMPACT

“The diversity of users is reflected in the fact that the make-up includes not only multina-tionals, SMEs, contract manufact-urers, and suppliers, but also industry associations”

USER ENGAGEMENT AND PATHWAYS TO IMPACT

The Hub has 39 users who have helped to shape and drive the Hub’s research programme. The diversity of users is reflected in the fact that the make-up includes not only multinationals, SMEs, contract manufacturers, and suppliers, but also industry associations, Catapult Translational Spokes – Cell and Gene Therapy (CGT) and CPI’s National Biologics Manufacturing Centre (NBMC). The Hub also incorporates a national network of academics in the Research Spokes who are part of the national research agenda. The Hub has identified two Grand Challenges to address over the duration of the grant: to transform the supply and to enable sustainable manufacturing of targeted medicines. These challenges can only be met with full engagement of our users, in a variety of mechanisms (see Figure 4).

The direction of the Hub is guided by the User Steering Committee (USC). This committee meets twice a year in a one-day event combining update reports, formal keynote talks, and workshops. These meetings are an invaluable mechanism to engage users in the formulation of plans for future research.

Significantly, the User Steering Committee (USC) has been instrumental in the formation and success of our five Specialist Working Groups (SWGs). The SWGs are the groupings for the specific work areas, cutting across our 2 Grand Challenges, delivering focused work streams. The SWG meetings have also enable invited experts to contribute to the discussions. For instance, representatives of the NHS and MHRA have provided excellent input to our Healthcare SWG. SWG meetings are also held twice a year and enable a less formal, technical interaction between the researchers and users. Typically, the SWG meetings provide a springboard for other points of engagement, including User Feasibility Studies (UFS), specific research studies identified by users and decided by competition. These studies, the first tranche of 9 are under way, are supported by up to 3 months of a Post-Doctoral Research Associate’s (PDRA) time over a period of up to 12 months. In addition, undergraduate or MSc projects can be supported. Longer term engagement can be facilitated in a variety of ways, including EngD projects (4 years), Knowledge Transfer Partnerships (KTPs) which promote in-company research, InnovateUK-funded collaborative research programmes, Company Centres of Excellence which may run over a number of research areas, and Impact Acceleration Awards (IAAs).


UPDATE FROM THE SPECIALIST WORKING GROUPS (SWGs)

UPDATE FROM THE SPECIALIST WORKING GROUPS (SWGS)

Cell-Free SynthesisThis group is concerned with the use of cell free synthesis (CFS) for biotherapeutic manufacture. It covers the selection and design of host cells for the production of cell free extracts, and the implications of CFS use for product quality and downstream processing. It also explores opportunities arising from CFS for process modularisation and distributed manufacture, and the use of decisional tools to understand the potential impact of CFS on different product classes and supply chain models.

Decisional ToolsThis group addresses the application of Decisional Tools to identify cost-effective routes forward for the development, manufacture and supply chain of targeted therapies. Hub PDRAs present their latest insights and industry talks fuel roundtable discussions to help shape future directions for both autologous CAR T-cell therapies and stratified proteins. More specifically, the Decisional Tools SWGs have discussed the supply chain gaps and point-of-care manufacturing business models for autologous CAR T-cell therapies, targets for cell-free synthesis to enable feasible business models for stratified proteins (e.g. ADCs), optimal conditions that incentivize companies to pursue companion diagnostics and datamining tools to aid biomarker stratification. Finally we have been examining the lessons that can be learnt between cell therapies and proteins.

FormulationThis group has continued to assess the strategic research direction for formulation work within the Hub, and also ensured that it is addressing the key challenges within stratified protein therapy industry. The group has identified several emerging areas to consider in the plans for future research directions, including opportunities for collaboration, and working across the different modalities of stratified proteins, peptides, cell therapies, viral vectors, and non-viral gene delivery.


UPDATE FROM THE SPECIALIST WORKING GROUPS (SWGs)

T-cell ProcessingThis group focusses on innovative approaches to manufacturing being developed in the Hub’s T-cell processing team. The meetings have been used to introduce the SWG to the wide range of T cell projects underway in the Hub via a series of short presentations from post docs and PhD/EngDs. They also include 3-4 focused technical discussions. The output from this meeting is establishing better interaction between SWG members and the Hub’s T-cell processing team on a number of focused technical projects.

Healthcare Regulation & ReimbursementThis group explores the current realities and future challenges and opportunities in the areas of reimbursement and regulation of targeted protein- and cell-based therapies. The meetings update on the work being conducted in the Hub on reimbursement and regulation. Roundtable discussions are used to explore key questions introduced in the session. The aim of this meeting is to facilitate communication and knowledge sharing between different stakeholders, and has promoted a mutual understanding of the field and better integration of the engineering perspective in the ongoing discussion.


PATHWAYS TO IMPACT

Knowledge Transfer

Research Innovation

Skills Provision

Policy Setting

Public Engagement & Visibility

Initiating research translation and wider engagement

Developing strategy

Coordinating equipment resource

Building a community

Influencingpolicy

Acting for thenational good

Maintaining visibility and reputation

Providinginformation

PATHWAYS TO IMPACT

The mechanisms for pathways to impact are outlined in Figure 3, and discussed in more detail below. The Hub has created and leads the national research and innovation landscape in this sector by engaging with the entire value chain including translational stakeholders (Innovate UK and Catapults) through to industry to ensure acceleration of impact.

FIGURE 3: Schematic of the framework for Hub outreach

Bioprocess conference with sector partners

In2 Science & Headstart

BPUK exhibition

Secondments

Creativity at home

Access to Centre facilities

Website

R&D Workshops

Feasibility Project Competition

Company Feasibility studies

EngD awards for SMEs

MBI content

Spin outs of licences

PDRAs in academic posts

Impact acceleration project

Catapult demonstrator

Company Centre of Excellence

International grant activity

Collab R&D grants

Doctoral projects

MHRA engagement

MMIP engagement

BIA: MAC, SIAC, GTAC

Translation sub committee

Workshops with KTN

PDRA public engagement training

EPSRC emerging healthcare

BBSRC network bioprocessing

Writing competition

Refresh public engagement strategy


RESEARCH INNOVATION

RESEARCH INNOVATION

The Hub has begun to deliver the scientific and engineering advances required for manufacturing biological targeted medicines. New processes and tools have been developed to guide selection of processes and manufacturing options that will enable the sector to commercialise targeted medicines more effectively. The Hub operates at the early stages of the development pathway chain, innovating the process operations, monitoring and control techniques to allow new medicines targeted to stratified patient groups or even individuals to be manufactured rapidly, economically, and in response to demand.

Academic feasibility studies are currently being planned with the first call to go live in December 2019. These will aim to establish collaborations with the wider academic community, and enable a strategic evaluation of emerging technologies that have the potential to address the key manufacturing research challenges of the Hub.

International collaborations have been forged via the Global Challenges Research Fund (GCRF) to establish antibody therapeutic manufacturing in Thailand at their National Biopharmaceutical Facility, and also vaccine manufacturing at their BIOTEC Virology and Cell Technology Laboratory. Hub PI, Dan Bracewell has also agreed to be a member of the Scientific Advisory Group in India, which is helping to review domestic grant applications as part of a $250 million National Biopharma Mission activity.


KNOWLEDGE TRANSFER

KNOWLEDGE TRANSFER

User companies have defined the original Hub research programme remit, and in User Steering Committees (6 monthly), and biannual meetings across five Specialist Working Groups in decisional tools, formulation, cell-free processing, T cell processing and healthcare. Via these, users have continued to steer the research direction into the most strategic areas, and to provide materials, data, and advice. Several mechanisms have been established to provide opportunities for further User Engagement as summarised in Figure 4. The first two years’ operation of the Hub has seen the establishment of the User Steering Committee, Specialist Working Groups, a Translation and Impact Committee, Hub-aligned EngD programmes, and the first User Feasibility Studies. Over the next year, it is hoped that further Knowledge Transfer Partnerships and Impact Acceleration Awards, currently under discussion, will be initiated.

FIGURE 4. MECHANISMS THROUGH WHICH USERS CAN ENGAGE WITH THE HUB.

The Translation and Impact Committee:The Translation and Impact Committee was formed in Yr2, and will meet biannually to review and prioritise resourcing and identify appropriate activities to accelerate translation of research to adoption and exploitation. This group first met in January 2019, chaired by one of our Catapult partners and comprises 3 Hub academics and 3 users. A key role of the Translation and Impact Committee is to track potential IP generation and define a plan for exploitation and impact in each case.

User Steering Committee

Specialist Working Groups (SWGs)

UG & MSc Projects

User Feasibility

Study

EngD

Impact Acceleration

Award

Company Centre of

Excellence

InnovateUK Collab R&D

KTP

Company Commitment

Teec

hnol

ogy

Read

ines

s

x2 per y

x2 per yS SWGs

4–22 weeksSupervised by PDRA/Doctoral researcher

~ 3 months Allocated PDRA time

Knowledge exchange / Discovery to use

scheme

~1-3 y

~1-3 y

Strategic partnership with portfolio of

EngDs and dedicated PORA(s)

4 y company-focused Up to 75% time at

company


KNOWLEDGE TRANSFER

User Feasibility Studies: The User Steering and Specialist Working Group meetings have helped to define key opportunities for knowledge transfer, and promoted applications from Users with competitive bids for User Feasibility Projects. These were prioritised by the newly Formed Translation and Impact Committee (comprising four industry/Catapult members), and 9 User Feasibility Projects were funded in the first round in February 2019 (Table 1). The funded projects span aspects of process control, formulation, cell-free synthesis, supply chain optimisation, economic evaluation, and T-cell manufacturing process modelling, and involve 8 user companies, the Cell and Gene Therapy Catapult, UCL, and four of the Spoke universities.

TABLE 1: User Feasibility Studies being supported in 2019

Company Lead(s) & HEI partner

Topic

Aglaris Historical batch analysis and trajectory optimisation for T-cell expansion process controlUniversity of Manchester

Albumedix Formulating recombinant human albumin as nanoparticle scaffold and assessing the potential for drug delivery

University of Nottingham

BIA, Oxford Biomedica Economic analysis to highlight the challenges with going for cheaper US subsidised vector suppliers for early phase manufacture of academic clinical material

University College London

Cell & Gene Therapy Catapult Mechanistic modelling for immunotherapy manufacture

Loughborough University

FujiFilm Diosynth Biotechnologies Testing and developing established cell-free synthesis protocols for 3 classes of productUniversity College London

Ipsen Techno-economic evaluation of a cell-free synthesis (CFS) system for the expression of recombinant toxinUnivesity College London

MedImmune Real-time process analysis and control of continuous chromatographyUniversity College London

TrakCel Comparing freeze-thaw performance of vials vs bags for the containment of T-cellsImperial College London

West Pharmaceutical Services Development of supply chain optimization models for autologous CAR T cellsUniversity College London


KNOWLEDGE TRANSFER

Knowledge Transfer Partnerships (KTP): Hub activities have led to several KTP projects including with Sartorius Stedim UK to develop a new bioreactor vessel for adherent and suspension cell culture. KTP projects with Biovault Technical have developed a scalable and consistent bioprocess for umbilical cord tissue (UCT) human stem cell production, while another has just started to develop a scalable and consistent process for exosome production from UCT-hMSCs.

Secondments:The Hub has supported secondments of PDRAs into industry settings, to enable more efficient knowledge transfer. For example, Olotu Ogonah spent 2 weeks at Sutro learning methodologies already established in industry, and then defining key challenges in cell-free synthesis of biopharmaceuticals.

In addition, one of our Hub CoIs, Dan Bracewell, is currently undertaking a secondment at the CPI National Centre for Biologics Manufacture (NBMC).

Patents: IP is currently being filed by UCL Business in a novel analytical technique to monitor protein co-formulations.


SKILLS PROVISION

“Over 64 manufacturing and process specialists are currently being trained to PhD/EngD level in the new ways of working required for targeted medicines”

SKILLS PROVISION

Fifteen Hub and Spoke PDRA researchers have been trained to have the skills and experience in new ways of working required by industry to transfer and implement our new technologies in practice. Three PDRAs have since gone onto new higher-level roles in academia or industry. Elvan Gokalp (Warwick) started in a Teaching Fellowship position at the Univesity of Warwick, while Xiaonan Wang (Imperial) started a new lecturer position at the National University of Singapore (NUS) in Chemical and Biomolecular Engineering. One of our other PDRAs, Olotu Ogonah has now accepted a post at Oxford Biomedica.

Over 64 manufacturing and process specialists are currently being trained to PhD/EngD level in the new ways of working required for targeted medicines, and most will seek jobs in the sector. In addition, we have graduated 14 trained PhD/EngD students in Hub methods and innovations. All 37 EPSRC CDT in EMT PhD students starting from 2016 were aligned to the Hub vision. 18 of these were based at external institutions, bringing these collaborating universities into the Hub’s extended research community. Since 2016, 27 EPSRC CDT in Bioprocess leadership EngD students have also been aligned to the Hub vision. Year 1 and Year 3 students have presented posters at each of the bi-annual User Steering Committee meetings, while selected final year students have presented orally.

CPD training for industry: Hub methods and innovations have already begun to be disseminated via our MBI training modules attended by industry. For example, the new ‘Antibody Targeted Therapies’ MBI addresses the emerging Antibody-drug conjugate (ADC) class of therapies, while the Cell and Gene Therapy Bioprocessing and Manufacture MBI has adopted aspects of regulation and distributed manufacturing concepts.


POLICY SETTING

POLICY SETTING

The Hub is highly active in policy setting, and has continued to engage with key sector policy forming and roadmapping bodies:

BioIndustry Association (BIA): Our USC Chair, Mark Carver is also Chair of the BioIndustry Association’s Science and Innovation Advisory Committee (SIAC), and provides a link to the sector roadmapping exercise that he is coordinating to define the current UK capabilities, challenges and gaps in sector funding.

Association of British Pharmaceutical Industries (ABPI):Hub Advisory Board member Bryan Deane represents ABPI and is providing two-way communication on sector needs.

Medicines Manufacturing Industry Partnership (MMIP):The MMIP provides a single UK industry voice and point of engagement with government to facilitate the growth in medicines manufacture in the UK. We have engaged in a number of meetings with MMIP, the associated and newly commissioned MMIC, and their partners CMAC, to build future links in areas of mutual interest.


POLICY SETTING

Public Policy and regulatory bodies:The UCL Hub team has established a dialogue with the MHRA Innovation Office on the regulatory implications of the emerging technology by the Hub partner, by the UCL Department of Science, Technology, Engineering and Public Policy (STEaPP). This has already informed the direction of research to adapt to the regulatory barriers, and also defined more long-term challenges particularly for the proposition emerging from industry in the use of combinatorial therapies, which cannot be licensed under the current processes, except for with defined combinations the are taken through clinical trials. To boost this area, the Hub has jointly funded (with the Vaccines Hub) a Policy Advisor position within STEaPP to engage Whitehall and the regulatory agencies directly, and create the landscape required to bring these new therapies to market.

The Hub’s Healthcare Specialist Working Group has also met four times (every 6 months), and has included representatives from NHS providers, MHRA, NIBSC and industry. This has evaluated the current regulatory landscape and areas of regulation that will potentially need to change to enable some new therapies onto the market.

BioProNET: Paul Dalby (Hub Co-Director) is a committee member of this BBSRC-funded Network which addresses the Bioprocessing sector from the life sciences perspective. With over 500 members across the UK academic and industrial community, it plays a key role in roadmapping the capabilities and challenges of the bioprocessing sector in terms of biological engineering. It is also closely linked into the roadmapping activity being carried out by Mark Carver on behalf of the BIA.


PUBLIC ENGAGEMENT & VISIBILITY


Outreach activities are a key part of the Hub strategy.

The main aims are:• To provide clear communication with the Hub Users and Academic

Communities on Hub progress, outputs, and key dates.• To facilitate early contact with school pupils and teachers to raise

awareness of biochemical engineering and promote the world-class reputation of the Hub.

• To attract the very best students into the biochemical engineering sector.

The current range of activities is summarised below:a. Science & engineering fairs and festivals. Hub associated

staff participate in a number of events to engage with young audiences and share the impact biochemical engineers make in the world. For example, the the “Big Algae Experiment” (led by Dr Brenda Parker) has developed an open source algae bioreactor and a phone app to enable members of the public, schools and universities to participate in data collection on outdoor microalgal growth in multiple locations across the UK. This has been rolled out with school groups at the New Scientist Festival, the Latitude Festival and elsewhere. An installation entitled “Engineer your Future” at the London Science Museum promoted biochemical engineering to a wider audience. A microbrewery event at the UCL Institute of Making produced a Biochemical Engineering beer, and this activity will now be expanded in future plans for the UCL East Development.

b. School visits and teaching material for schools. Our researchers are involved in a range of outreach activities organised by the UCL Faculty of Engineering and Hub Widening Participation. For example, Dr Olotu Ogonah recently created and delivered 2 programmes (e.g. “How Many Engineers Does it take to make Ice Cream?”) to encourage pupils aged 11-16 from under-represented, minority backgrounds from state schools to pursue a career in the engineering sciences.

c. In2Science and Nuffield charities. Hub researchers have worked with the In2Science and Nuffield charities to offer work experience for Year 12 students. Both schemes are open to pupils from low-income backgrounds with an interest in STEM subjects. We have hosted 4-6 students per year for two to six weeks in Summer. Pupils work in our state-of-the-art facilities alongside researchers in order to understand at first-hand the challenges of biochemical engineering. In addition we have hosted a further 5-7 pupils (Year 11 /12) over 1-2 weeks each Summer, who have approached us directly.



d. Taster Day Courses at UCL. Hub staff have coordinated Taster Days as part of the University of London Taster Day initiative and with UCL Widening Participation. Year 12 students with an interest in Biochemical Engineering met current students and lecturers, to learn about the subject, work on an interactive exercise with presentations and visit our laboratory teaching facilities. Hub staff and researchers have also taken part in the UCL Engineering “Engineers save lives” Masterclass series in collaboration with the Royal Institution. The aim of these sessions is to introduce year 9 pupils to the wide range of engineering disciplines at an early state in order to inspire them and attempt to move away from the hard hat, bridge building stereotype of engineering.

e. Online presence. The Hub website, LinkedIn and Twitter feeds have helped to further increase awareness of Hub activities, outputs and opportunities.

f. Annual workshops have been held on core Hub topics including one on Manufacturing ATMPs in colloboration with the KTN on 18th September 2018, which engaged the wider academic community for dissemination, as well as to build collaborative partnerships in new Hub research activities. The Hub was also an event partner with MIT and CMAC for the 3rd International Symposium on Continuous Manufacturing of Pharmaceuticals (ISCMP) in London on 3-4October 2018. Hub PDRAs also co-organised Entrepreneurship Essentials for Researchers (SPERO) workshop in London on 26-28 September 2018, in colloaboration with UCL Innovation and Enterprise, and sponsored by Santander.

g. Newsletters: The Hub has sent out two newsletters to its User and academic network, as a key mechanism for updating on Hub progress, and raising awareness of key dates and calls for the User Feasibility Studies.


VIEWS FROM THE HUB COMMUNITY

VIEWS FROM THE HUB COMMUNITY

“The Hub is a unique UK resource that brings together academia, industry and service providers and sets the agenda for research and innovation in future targeted healthcare and the associated manufacturing needs. It has helped shape some exciting research challenges for us in the field of effective supply chains to deliver personalised medicine ”Professor Nilay Shah, Department of Chemical Engineering, Imperial College

“The Hub brings together researchers with a range of expertise across different disciplines, creating a unique capability for the UK. For the research team at the University of Manchester it provides us with the opportunity to determine whether the control systems that we have designed over the last few years are able to address the complex challenges that are introduced in the production of personalised medicines. ”Professor Barry Lennox, School of Electrical and Electronic Engineering, University of Manchester

“Through the User Steering Group researchers gain insight of key industry needs and then help in the development of holistic solutions that translate new ideas from benchtop to bedside ” Dr Veeren Chauhan, University of Nottingham

“The Hub has helped me realise my career goals ”Dr Olotu Ogonah, now at Oxford Biomedica

“Working in the Hub was a total privilege for me. After working in the Hub, I have obtained a permanent position at a very prestigious research institution: Warwick Manufacturing Group. ” Dr Elvan Gokalp, University of Warwick

“The Hub provides an opportunity for interaction and networking with both people in industry and leading academic groups that are interested in continuously strengthening the UK’s position in this sector. When we look into the future at what we need in 5-10 years, we can look to influence and steer the Hub’s research agenda. ” Dr Bo Kara, Head of Process Development of Cell & Gene Therapy Platform Chemistry, Manufacturing and Controls, GSK

“The Hub will work to help the sector bridge the gap from academia to industry and drive forward with bioprocessing technologies and get them into industrial applications. ”Dr Oliver Hardick, CEO and Founder, Puridify Ltd


GRAND CHALLENGES:

GRAND CHALLENGES: Grand Challenge Research Themes

GC1: TRANSFORMING SUPPLY CHAIN MANAGEMENT AND ECONOMICS FOR TARGETED MEDICINES

GC2: SUSTAINABLE MANUFACTURING FOR FUTURE TARGETED

MEDICINES

PLANNING FOR THE FUTURE

GC


GRAND CHALLENGE RESEARCH THEMES


GC1

ADDRESSING THE MANUFACTURING CHALLENGES FACING OUR USERS: The Hub comprises two Grand Challenges research themes.

Grand Challenge 1 (GC1): Transforming supply chain management and economics for targeted medicines investigates the business potential of game- changing technologies for commercial feasibility and affordability for healthcare systems.

Grand Challenge 2 (GC2): Sustainable manufacturing for future targeted medicines is establishing new technologies with the potential for radical re-design of manufacture. GC1 is setting the performance targets required to achieve significant reductions in development time and cost (>50%) as well as manufacturing costs (>25%). GC2 is establishing novel technologies capable of achieving these quantified targets. A programme of Platform activities, including research, training, networking, and knowledge transfer, has been established to maximise the impact of EPSRC investment over the Hub lifetime and create sustainability. This is helping the sector respond effectively to the shifting innovation landscape.



NOVEL NATURE OF THE MANUFACTURING RESEARCH: The Hub enables an integration of disciplines that could not be delivered by separate projects. TRL2-4 research is delivering: new paradigms for rapid manufacture and analytics, including cell-free synthesis and continuous operation; how product type and demand impacts choice; how manufacture can be configured to fit with radically altered models of clinical trials and regulation following pre-screening and targeting; and create and test novel supply chain concepts. Decision-support methods are enabling business managers to evaluate opportunities and risks of alternative manufacturing options, and relate improvements in the cost-effectiveness of targeted treatments to NICE thresholds. 65% of effort is being directed towards two user-driven Grand Challenges at TRL2-4. 35% is Platform, Operational and Pathways to Impact activities with feasibility studies at a network of UK university (TRL2), industry and Catapult collaborators (TRL3-6), and leading international centres, forming Spokes that link research and knowledge transfer to achieve a step change in the industry. Significant leverage is being exerted by the integration of these approaches, providing a novel link between product type, manufacturing strategy, supply and delivery for drugs targeted to the patient(s). This is providing an integrated enterprise and manufacturing perspective where the opportunity is to achieve radical innovation that greatly exceeds the sum of the isolated research areas. Insights help to ascertain the most promising manufacturing innovations and provide the capacity to “future-proof” supply chains for targeted medicines. The Hub grand challenges, and their technical work packages (GC1.1-1.4, GC2.1-2.4), are summarised in Figure 5.

GC1



FIGURE 5: Grand Challenge research themes and interactions

Optimal manufacturing technologies , scale and patient throughputPerformance targets. Acceptable control limits for process parameters

Process intensification required for optimal end-to-end cycle timesSupply chain robustness and pinch points

Cost-benefit of flexibility

New manufacturing technology features. Resource requirementsPerformance observed. Variability in critical quality attributesBatch durations required to achieve different yield levelsOperating window robustness observedIdeal level of flexibility

1.1 Techno-economic optimisation of novel mfg technologies

Nov

el re

sear

ch to

ols

1.2 Feasible business models and regulatory strategies

1.3 Clinical production planning and portfolio mgmt for stratified trials

Suzanne Farid, UCL BENigel Titchener-Hooker, UCL BEPaul Dalby, UCL BEFuture Spokes

PIs

Suzanne Farid, UCL BESteve Morris, UCL AHRIrina Brass, UCL STEaPP Future Spokes

Juergen Branke, Warwick Bus SchSuzanne Farid, UCL BENilay Shah, Imperial CEFuture Spokes

1.4 Commercial supply chain logistics for personalised therapies

Nilay Shah, Imperial CESuzanne Farid, UCL BEJuergen Branke, Warwick Bus SchFuture Spokes

Scoping analysisCOG v cost of devtReimbursement strategiesRegulatory pathways

Capacity planningDiagnostic-driven trialsPortfolio selectionDealing with uncertainty

Patient-centric supply Make-to-orderTrack-and-traceLocal v centralised mfg

Manufacturing/facility level Process economicsFinancial v operational objTechnical innovation targets

Manufacturing strategy Process development Clinical portfolio Market supply

Grand Challenge 1 (Lead: Prof Suzanne Farid, UCL)Transforming supply chain management and economics for targeted medicines

Christos Stamatis, UCL BE

PDRA

s

Christos Stamatis, UCL BEYang Yang, UCL BENishma Patel, UCL AHRGiovanni de Grandis, UCL STEaPP

Elvan Gokalp, Warwick Bus SchXin Fei, Warwick Bus Sch

Maria Papathanasiou, Imperial CE

2.1 Manufacturing proteins for targeted populations

Nov

el re

sear

ch to

ols

2.2 Formulation of stratified protein medicines

2.3 Manufacture and analytics for autologous cell therapies

Dan Bracewell, UCL BEPaul Dalby, UCL BENigel Titchener-Hooker, UCL BEFuture Spokes

PIs

Paul Dalby, UCL BEJonathan Aylott, Nottingham PharmFuture Spokes

Farlan Veraitch, UCL BENicolas Szita, UCL BEQasim Rafiq, UCL BERobert Thomas, L’borough M&MEFuture Spokes

2.4 Process control using advanced data-mining

Barry Lennox, Manchester E&EEPaul Dalby, UCL BEQasim Rafiq, UCL BESuzanne Farid, UCL BEFuture Spokes

Combination formulationsFormulation analyticsNanoencapsulationCo-crystallisation

T-cell reprogramming T-cell expansion Potency and quality assaysBioreactor platform design

Cell-free synthesis controlFormulation controlT-cell process controlMultivariate data analysis

Cell-free synthesis AutomationDSP integrationTransient transfection

Novel manufacture, formulation , analytics and advanced control

Grand Challenge 2 (Lead: Prof Paul Dalby, UCL)Sustainable manufacturing for future targeted medicines

Olotu Ogonah, UCL BE

PDRA

s

Hongyu Zhang, UCL BEVeeren Chauhan, Nottingham Pharm

Igor Andreyev, UCL BEShimaz Hashimdeen, UCL BEMaryam Sariatzadeh, L’borough M&ME

Carlos Duran Villalobos, Manchester E&EE


GRAND CHALLENGE 1: TRANSFORMING SUPPLY CHAIN MANAGEMENT AND ECONOMICS FOR TARGETED MEDICINES


Novel manufacturing- and enterprise-level computational tools are being created to determine the technical, regulatory and supply chain innovation required to enable commercial feasibility of targeted medicines, whilst ensuring affordability for the benefit of society. The tools will span and drive decision-making across process development, clinical manufacturing and market supply for both stratified protein and personalised cell therapy medicines.

Research and Impact Highlights from GC1:• Cell-free synthesis economics: Case studies have highlighted

the differences in cost of goods and performance targets for cell-free synthesis compared to traditional mammalian processes for antibody-drug conjugates.

• CAR T-cell process and supply chain economics: Decisional tools have identified the current cost of goods (COG) of CAR T-cell therapies, which manufacturing platforms are most cost-effective at different dose scenarios, the key cost drivers, and the risk-reward trade-offs between centralised manufacture versus GMP-in-a-box configurations.

• CAR T-cell supply chain optimisation: Existing supply chains have been characterized and likely future supply chain workflows have been proposed.

• Regulation: Significant differences between Europe and the United States have been found for regulatory pathways of cell and gene therapies related to factors such as marketing application review times and flexibility around CMC and post-marketing requirements.

• Reimbursement: NICE’s approach to appraising CAR T-cell therapies Yescarta® (axicabtagene ciloleucel) and Kymriah® (tisagenlecleucel) has been mapped out and analysed for its longer-term feasibility.

• Clinical production planning of stratified proteins: An economic model has been constructed to understand incentivization mechanisms for the development of companion diagnostics for stratified proteins.

• Data analytics for biomarker stratification: Datamining tools have been developed to help clinicians make personalised decisions on aspects such as follow-up timelines.

GC1



• Data analytics for protein aggregation prediction: Novel predictive models have rapidly detected early aggregation signals and predicted the potential aggregation level and the impact of key attributes.

• Continuous chromatography monitoring: A tool for real-time analysis and monitoring of continuous bioprocesses with adaptive control methods has been developed and tested with user data.

User engagement highlights from GC1:Several roundtable discussions have been organized at the User Steering Committee events and Specialist Working Group meetings (Decisional Tools, Cell-free synthesis, Healthcare Regulation and Reimbursement) to help with this work. Further specific user engagement includes:

• Sutro Biopharma offered critical insights on the cell-free synthesis process for biopharmaceuticals (mAbs and ADCs) and helped develop the appropriate design correlations

• Ipsen provided a better understanding of small-scale, low throughput biomanufacturing facilities. A user feasibility study with Ipsen and UCL (Farid) has been approved to evaluate the CFS process as an alternative for more potent molecules (recombinant toxins).

• Interviews have been performed with Autolus to enhance our understanding on the manufacture, supply chain and regulation of autologous cell therapies.

• BioIndustry Association Manufacturing Advisory Committee (BIA MAC) and the MMIP ATMP workstream members on the process and business evaluation of viral vectors for in vivo and ex vivo applications. A user feasibility study with BIA MAC and Oxford Biomedica working with UCL (Farid) has been approved to evaluate the challenges and risks associated with changes in the supply chain of the viral vector at different stages of the development pathway.

• ABPI and Cell and Gene Therapy Catapult on reimbursement strategy discussions.

• Several semi-structured interviews with various stakeholders and experts on regulatory pathways for targeted medicines (including industry, regulatory bodies, patients’ groups, university hospitals, regulatory consultancies).

• Trakcel discussions have helped sanity check likely future supply chains for CAR T-cell therapies and led to a user-feasibility study between Trakcel and Imperial (Shah). GC

1


GRAND CHALLENGE 2: SUSTAINABLE MANUFACTURING FOR FUTURE TARGETED MEDICINES


Sustainable manufacturing for future targeted medicines continues to establish new technologies with the potential for radical re-design of manufacture. Novel bioprocesses, analytics and control algorithms are thus being created that enable robust, safe and cost-effective manufacturing and formulation of stratified protein and personalised cell medicines. Together these provide the flexibility and speed to produce medicines for small patient populations or individuals in response to clinical diagnostic data.

Research and Impact Highlights from GC2:• Formulation: New biophysical analysis methods have been

developed that are able to monitor the degradation of protein mixtures. The co-formulation of multiple proteins can lead to improved stability of proteins to aggregation and fragmentation.

• Nanoencapsulation: Novel nanoparticle manufacturing has been established that is able to encapsulate and co-formulate multiple proteins.

• Cell-free synthesis protocols: Scalable cell-free synthesis with model proteins can be achieved consistently using in-house protocols and the formation of product-related impurities can be mitigated by altering the synthesis conditions.

• CAR T-cell manufacturing platforms: T-cells can be cultivated in an automated stirred-tank bioreactor system, and their growth has been shown to be consistently and significantly better than in T-flask static culture, with equivalent cell quality.

• CAR T-cell predictive models and control: T-cell cultures have been characterised by both mechanistic and multivariate statistical models, which enables improvements to the consistency and productivity of these processes.

• T-cell analytics: Digital Holography Microscopy provides a rapid analytical tool to discern activated from non-activated T-cells.

User engagement highlights from GC2:• Sutro Biopharma in San Francisco (the only company with a

therapeutic made by CFS in clinical trials). They have provided both training (a 2 week internship for the PDRA in this area) and materials to UCL.

GC2



• Impact studies have begun to translate cell-free manufacture to a wide range of user-donated proteins. Fujifilm Diosynth Biotechnologies have initiated a feasibility study with UCL (Bracewell) to examine the application of CFS to products they have interests in, such as antibody fragments.

• MedImmune supplied several antibodies of different types for co-formulation studies.

• A 6-month user feasibility study with Albumedix was started in March 2019 to investigate the use of albumin as a delivery adjunct for poorly soluble drugs, and to develop nanoencapsulation strategies for co-formulation using albumin as a carrier matrix.

• In collaboration with Medimmune, via a Hub user feasibility study, pH sensing nanoparticles will be evaluated by Nottingham (Aylott) to monitor the impact of pH shock used to remove viral contaminants during mAb bioprocessing.

• Different microfluidic device companies have been contacted, and a proof-of-concept study with Redbud Labs Inc in the US and UCL (Szita) is taking place to assess if their mixing technology might assist us in finding a way forward to maintain cells in culture in microliter volumes.

• CGTC have signed up to a user feasibility study with Loughborough (Thomas) that will supply data for testing and refining the model and general approach

GC2




The initial detailed planned research phase was for the first three years of the grant (2017 – 2020). We have begun to hold strategic meetings to put in place an appropriate process for planning the next four years of Grand Challenge research. This will build upon input from across the Specialist Working Groups that have begun already to discuss and identify key areas of research for the future, through roundtable discussions with Users. We shall decide upon our new agenda, designed to take the Hub forward. Invariably we will decide that some of our avenues of research are complete or now require different routes of funding. Our intention is to create a radical and challenging vision consistent with a national centre, and to locate the academic partners needed to deliver this.

The proposed plans will be shared with the users for further input via the User Steering Committees and ratified by the Hub Advisory Board.



User Steering Committee

Research SpokesTranslatio

nal S

poke

s

National BiologicsManufacturing Centre

Biomanufacturers

Vendors

Industry/Govt Associations


THE HUB & ITS SPOKES

THE HUB & ITS SPOKES

The following section provides brief overview of each of the Hub and Spoke members.

1. UCL Biochemical Engineering, Applied Health Research, Science, Technology, Engineering and Public Policy (STEaPP)

2. Imperial College London Chemical Engineering

3. Loughborough University Mechanical, Electrical and Manufacturing Engineering

4. University of Manchester Electrical & Electronic Engineering

5. University of Nottingham Pharmacy

6. The University of Warwick Warwick Business School

SPOK

ES



THE HUB @ UCL The Hub

UCL – BIOCHEMICAL ENGINEERING

Professor Nigel Titchener-Hooker HUB DIRECTOR

Professor of Biochemical Engineering, Dean of Faculty of Engineering Sciences

EXPERTISE: Creation of whole bioprocess models and the use of these to gain process insights and understanding.

WEBPAGE: http://iris.ucl.ac.uk/iris/browse/profile?upi=NJTIT16

DECISIONAL TOOLS RESEARCH

Prof Suzanne Farid HUB CO-DIRECTOR

Professor of Bioprocess Systems Engineering

EXPERTISE: Bioprocess Decisional Tools, Bioprocess Economics, Drug Development Cost Modelling, Capacity planning, Portfolio Management, Risk Analysis, Multi-Criteria Decision-Making, Multi-Objective Simulation & Optimisation, Chemometrics

WEBPAGE: http://iris.ucl.ac.uk/iris/browse/profile?upi=SFARI53

PDRA: Dr Chris Stamatis

TRAINING: Chemical Engineering (MEng), Biochemical Engineering (MSc, EngD)

EXPERTISE: Decisional tools, Process economics for mAbs and bispecifics, Chromatography process development

PDRA: Dr Yang Yang

TRAINING: Computer Science (BSc, MSc), Chemical Engineering (PhD)

EXPERTISE: Bioprocess modelling and simulation, multivariate data analysis for DSP, decisional tool development



CELL-FREE SYNTHESIS EXPERIMENTAL RESEARCH

Prof Daniel Bracewell

Professor of Bioprocess Analysis

EXPERTISE: Bioprocess analysis; Speed and capabilities of the analytical techniques used.

WEBPAGE: https://iris.ucl.ac.uk/iris/browse/profile?upi=DGBRA75

PDRA: Dr Olotu Ogonah.

Now at Oxford Biomedica

TRAINING: PhD in Biochemical Engineering

EXPERTISE: Early stage R&D – USP development for Manufacturing

“The Hub has helped me realise my career goals”

FORMULATION EXPERIMENTAL RESEARCH

Prof Paul Dalby HUB CO-DIRECTOR

Professor of Biochemical Engineering and Biotechnology

EXPERTISE: Routes to improve the stability and activity of biocatalytic enzymes and therapeutic proteins, for ease of manufacture, formulation and delivery to patients.

WEBPAGE: https://iris.ucl.ac.uk/iris/browse/profile?upi=PADAL59

PDRA: Dr Hongyu Zhang

TRAINING: Protein aggregation specialist

EXPERTISE: Chromatography, time-resolved fluorescence spectroscopy, single-molecule spectroscopy

The Hub



CELL THERAPY EXPERIMENTAL RESEARCH

Dr Farlan Veraitch

Senior Lecturer

EXPERTISE: Development of robust, reproducible and cost effective production processes in the emerging field of cell therapy.

WEBPAGE: https://iris.ucl.ac.uk/iris/browse/profile?upi=FSVER77

Prof Nicolas Szita

Professor of Bioprocess Microfluidics

EXPERTISE: Translation of bioprocessing concepts into microfluidic systems (or Lab-on-a-chip systems); Use of advanced microfabrication techniques for polymers (rapid prototyping), glass and silicon.

WEBPAGE: https://iris.ucl.ac.uk/iris/browse/profile?upi=NSZIT68

PDRA: Dr Igor Andreyev

TRAINING: MSc in Physics, PhD in Physical and Mathematical Sciences, postgraduate MSc in Laser Technics & Technologies and in Biotechnology

EXPERTISE: Biophysics, laser/optical instrumentation, atomic force microscopy, Raman spectroscopy, advanced statistics, optical tweezers and dielectrophoresis, cell sorting and manipulation, microsystem engineering and microfluidics, nanotechnology

Dr Qasim Rafiq

Senior Lecturer in Bioprocessing of Regenerative, Cellular and Gene Therapy

EXPERTISE: Challenges of taking advanced therapies from the laboratory scale to industrial/clinical scale.

WEBPAGE: https://iris.ucl.ac.uk/iris/browse/profile?upi=QARAF73

PDRA: Dr Shaikh Shimaz Hashimdeen

TRAINING: Tissue Engineering and Immunology

EXPERTISE: Flow cytometry, cell culture, functional assays

The Hub



Aligned PhD Researchers:

RESEARCHER: Redwood-Sawyerr, Chileab

PHD THESIS: Applying synthetic biology to upscale and de-risk biologics production by CHO cell transient transfection.

RESEARCHER: Machlouzarides, Marian

PHD THESIS: Engineering challenges in personalised cell therapies: applying fundamental engineering, ultra scale-down design and experimental flow dynamics approaches for the design of novel cell culture platforms.

RESEARCHER: Colant, Noelle

PHD THESIS: Cell free systems for the synthesis of advanced therapy medicinal products (ATMPs)

RESEARCHER: Teneb Lobos, Jamie

PHD THESIS: Elucidating factors that control expression and aggregation of proteins

UCL – APPLIED HEALTH RESEARCH

HEALTH ECONOMICS RESEARCH

Prof Steve Morris

Chair of Health Economics, Applied Health Research Institute of Epidemiology & Health, Faculty of Pop Health Sciences

EXPERTISE: Cost-effectiveness of interventions to improve health across a range of disease areas and population groups, and the determinants of health service use.

WEBPAGE: http://www.ucl.ac.uk/dahr/people/morris

PDRA: Miss Nishma Patel

TRAINING: Health Economist

EXPERTISE: Economic evaluation alongside clinical trials, economic literature search

“In terms of my research, the Hub has served as a catalyst in transfer of knowledge between academia and industry, providing me with access to relevant bodies. Working with a multi-disciplinary team has provided direction for my research, exposure to funding streams, training courses and industry partners”

The Hub

http://www.ucl.ac.uk/dahr/people/morris



UCL – SCIENCE, TECHNOLOGY, ENGINEERING AND PUBLIC POLICY (STEaPP)

REGULATORY STRATEGIES RESEARCH

Dr Irina Brass

Lecturer in Regulation, Innovation and Public Policy, STEaPP, Faculty of Engineering Science

EXPERTISE: Regulation of emerging technologies; managing emerging risks and uncertainty of disruptive innovation; public policy and governance

WEBPAGE: http://www.ucl.ac.uk/steapp/people/brass

PDRA: Dr Giovanni De Grandis

TRAINING: Philosophy (Ethics, Political Philosophy, Applied Ethics); Healthcare Policy

EXPERTISE: Value Analysis and Conflict of Values; Ethical, Legal and Social Aspects (ELSA) of Research; Qualitative Empirical Research

“In terms of my research, it has certainly forced me to work in a different way and to explore new methods and approaches. I think this is very good.”

The Hub



IMPERIAL COLLEGE LONDON Hub Spokes:

CHEMICAL ENGINEERING

SUPPLY CHAIN OPTIMISATION RESEARCH

Prof. Nilay Shah

Head of Department of Chemical Engineering

EXPERTISE: Supply chain design and optimisation; Process synthesis and development for fine chemicals, pharmaceutical and biochemical processes; Mathematical techniques to assess and improve process safety

WEBPAGE: http://www.imperial.ac.uk/people/n.shah

PDRA: Dr Maria Papathanasiou

TRAINING: Chemical Engineer, PhD

EXPERTISE: Decisional/computational tools, Process modelling/simulation/optimisation, Bioprocess modelling (bioreactors & separation processes)

“The network that the Hub has provided me with has helped me to get easy access to expert opinion on my research”

http://www.imperial.ac.uk/people/n.shah



LOUGHBOROUGH UNIVERSITY Hub Spokes:

MECHANICAL, ELECTRICAL AND MANUFACTURING ENGINEERING

CELL THERAPY 1st PRINCIPLES MODELLING RESEARCH

Prof Robert Thomas

Professor of Manufacturing for Cell and Gene Therapies

RCUK Academic Fellow (Biomanufacturing)

EXPERTISE: Production systems and processes for cell based products; Translation to commercial manufacture and clinical use; Automated and scaled production; Measurement systems for process control and quality release; defining indicators of cell product quality.

WEBPAGE: http://www.lboro.ac.uk/departments/meme/staff/robert-thomas/

PDRA: Dr Maryam Shariatzadeh

TRAINING: PharmD, Chem Eng, PhD

EXPERTISE: T cell manufacturing, Automated and scaled production, Cell therapies, Stem cell manufacturing, Regenerative medicine and tissue engineering

“The Hub gave me more visibility to our industrial partners and provided more opportunities for future collaborations. The Hub provided the opportunity to have a closer collaboration with both academia and industry compared to a conventional postdoc and I feel more supported as part of a bigger research group”


RESEARCHER: Diffey, Ben

PHD THESIS: Development of Strategies for Manufacturing Consistent T-cell Populations

http://www.lboro.ac.uk/departments/meme/staff/robert-thomas/

http://www.lboro.ac.uk/departments/meme/staff/robert-thomas/



UNIVERSITY OF MANCHESTER Hub Spokes:

ELECTRICAL & ELECTRONIC ENGINEERING

MONITORING AND CONTROL RESEARCH

Prof Barry Lennox

Professor of Applied Control in the School of Electrical & Electronic Engineering

EXPERTISE: Robotics for use in Nuclear Engineering Decommissioning; Leakage and blockage detection in pipelines; Multivariate statistical process control; Model predictive control; Control loop monitoring; Monitoring and control of batch processes.

WEBPAGE: https://www.research.manchester.ac.uk/portal/barry.lennox.html

PDRA: Dr Carlos Alberto Duran Villalobos

TRAINING: Electronics Engineer/ MSc Digital Signal Processing/ PhD Process Control

EXPERTISE: Process Control, Multivariate Analysis, Adaptive Control, Data-based Models

“By Joining the Hub, I have met colleagues and experts from academia and industry. This has allowed me to acquire skills and experience needed to collaborate in a multidisciplinary group. By Joining the Hub, I have an immense satisfaction knowing that my work could be part of technologies that could save lives”

https://www.research.manchester.ac.uk/portal/barry.lennox.html

https://www.research.manchester.ac.uk/portal/barry.lennox.html



UNIVERSITY OF NOTTINGHAM Hub Spokes:

PHARMACY

NANOENCAPSULATION FORMULATION RESEARCH

Dr Jonathan Aylott

Associate Professor in Analytical Bioscience, Faculty of Science

EXPERTISE: Design, development and implementation of miniaturized analytical devices

WEBPAGE: https://www.nottingham.ac.uk/Pharmacy/People/jon.aylott

PDRA: Dr Chauhan Veeren

TRAINING: Pharmacist (MPharm), Nanodiagnostics (PhD)

EXPERTISE: Nanoformulation, Analytical Chemistry and Spectroscopy, Microscopy

“Through the User Steering Committee, researchers gain insight of key industry needs and then help in the development of holistic solutions that translate new ideas from benchtop to bedside”


RESEARCHER Booth, Thomas

PHD THESIS: Scalable production of glassy protein therapeutics’

https://www.nottingham.ac.uk/Pharmacy/People/jon.aylott



THE UNIVERSITY OF WARWICK Hub Spokes:

WARWICK BUSINESS SCHOOL

PRODUCTION PLANNING RESEARCH

Prof. Jurgen Branke

Professor of Operational Research & Systems

EXPERTISE: Optimisation under Uncertainty

WEBPAGE: http://www.wbs.ac.uk/about/person/juergen-branke/

PDRA: Dr Xin Fei (incoming, 2019)

TRAINING: BSc. Physics, MSc. Financial Engineering, PhD. Operations Research & Management

EXPERTISE: Efficient information collection in stochastic optimization

http://www.wbs.ac.uk/about/person/juergen-branke/



OPERATIONAL SUPPORT TEAM

Dr Eleanor Bonnist

Hub Project Manager

Prof Vaughan Thomas

Hub Outreach Consultant

Miss Laura Pascual Buffone

Research Finance Administrator

FORMER TEAM MEMBERS

Dr Xiaonan Wang

PDRA on Supply Chain Optimization Research

Destination: Assistant Professor, Department of Chemical and Biomolecular Engineering, National University of Singapore

Dr Adam Collins

PDRA on Cell Therapy First-Principles Modelling Research

Destination: LabX Software Specialist, Mettler-Toledo International

Dr Elvan Gokalp

PDRA on Production Planning Research

Destination: Teaching Fellow, Warwick Manufacturing Group, University of Warwick


THE HUB EVENTS, PUBLICATIONS AND PRESENTATIONS

THE HUB EVENTS, PUBLICATIONS AND PRESENTATIONS


HUB EVENTS 2018

HUB EVENTS 2018

The Hub events are listed below. These invite users to hear updates on the progress of the research and to input and interact with the project.

15 February Regulatory Scenarios Workshop

13 March Decisional Tools Specialist Working Group

28 March Formulation Specialist Working Group

25 April Regulation & Reimbursement Specialist Working Group

2 May Networking Event at the Science Innovation Union meeting

4 May Cell-Free Synthesis Specialist Working Group

15 May User Steering Committee Meeting

16 May Hub Advisory Board Meeting

29 May T-Cell Processing Specialist Working Group

18 September Manufacturing ATMPs Event, in partnership with the KTN

3 October International Symposium on Continuous Manufacturing of Pharmaceuticals (partner)

16 October Regulation & Reimbursement Specialist Working Group

17 October T-Cell Processing Specialist Working Group

18 October Formulation Specialist Working Group

23 October Decisional Tools Specialist Working Group

25 October Cell-Free Synthesis Specialist Working Group

6 November User Steering Committee Meeting

7 November Hub Advisory Board Meeting


SELECTED HUB PUBLICATIONS


Underlining denotes members of the dedicated Hub Research Associate team

2019An expanded conformation of an antibody Fab region by X-ray scattering, molecular dynamics and smFRET identifies an aggregation mechanism. Codina N, Hilton D, Zhang C, Chakroun N, Ahmad SS, Perkins SJ, Dalby PA Journal of Molecular Biology, 2019; 431, 1409-1425, doi:10.1016/j.jmb.2019.02.009

Fast genetic algorithm approaches to solving discrete-time mixed integer linear programming problems of capacity planning and scheduling of biopharmaceutical manufacture Jankauskas K, Papageorgiou LG, Farid SS Computers and Chemical Engineering, 2019; 121, 212-223, doi:10.1016/j.compchemeng.2018.09.019

Rapid and scale-independent microfluidic manufacture of liposomes entrapping protein incorporating in-line purification and at-line size monitoring Forbes N, Hussain MT, Briuglia ML, Edwards DY, Horst JHT, Szita N, Perrie Y International Journal of Pharmaceutics, 2019; 556,68-81, doi:10.1016/j.ijpharm.2018.11.060

Selective stabilisation and destabilisation of protein domains in tissue-type plasminogen activator using formulation excipients Robinson MJ, Matejtschuk P, Longstaff C, Dalby PA Molecular Pharmaceutics, 2019; 16(2), 744-755, doi:10.1021/acs.molpharmaceut.8b01024

Intracellular processing of silica-coated superparamagnetic iron nanoparticles in human mesenchymal stem cells Harrison RP, Chauhan VM, Onion D, Aylott JW, Sottilie V RSC Advances, 2019;9, 3176-3184, doi: 10.1039/C8RA09089K

New generation of bioreactors that advance extracellular matrix modelling and tissue engineering Ahmed S, Chauhan VM, Ghaemmaghami AM, Aylott JW Biotechnology Letters, 2019; 41(1), 1-25, doi:10.10Nano07/s10529-018-2611-7

Collagen gel cell encapsulation to study the effect of fluid flow on mechanotransduction Shariatzadeh M in Multiscale Mechanobiology in Tissue Engineering, Springer, 2019, doi: 10.1007/978-981-10-8075-3



Potential of continuous manufacturing for liposomal drug products Worsham RD, Thomas V, Farid SS Biotechnology Journal, 2019; 14(2), e1700740, doi:10.1002/biot.201700740

Integrated Continuous Biomanufacturing: Industrialization on the Horizon Farid SS Biotechnology Journal, 2019; 14(2), 1800722, doi:10.1002/biot.201800722

Dynamic scheduling of multi-product continuous biopharmaceutical facilities: a hyper-heuristic framework Oyebolu FB, Allmendinger R, Farid SS, Branke J Computers & Chemical Engineering, 2019; 125, 71-88, doi:10.1016/j.compchemeng.2019.03.002

2018Evaluation of fluorescent dyes to measure protein aggregation within mammalian cell culture supernatants Oshinbolu S, Shah R, Finka G, Molloy M, Uden M, Bracewell DG Journal of Chemical Technology and Biotechnology, 2018; 93(3): 909-917, doi:10.1002/jctb.5519

Flocculation on a chip: a novel screening approach to determine floc growth rates and select flocculating agents Radhakrishnan ANP, Marques MPC, Davies MJ, O’Sullivan B, Bracewell DG, Szita N Lab on a Chip, 2018; 18, 585-594, doi:10.1039/C7LC00793K

Bioprocesses for Cell Therapies Farid SS, Jenkins MJ In Biopharmaceutical Processing: Development, Design and Implementation of Manufacturing Processes, 2018; Ch. 44, 899-930, pub. Elsevier, doi:10.1016/B978-0-08-100623-8.00044-X

On-line control of glucose concentration in high-yielding mammalian cell cultures enabled through oxygen transfer rate measurements Goldrick S, Lee K, Spencer C, Holmes W, Kuiper M, Turner R, Farid SS Biotechnology Journal, 2018; 13(4), doi:10.1002/biot.201700607



A guide to manufacturing CAR T cell therapies Vormittag P, Gunn R, Ghorashian S, Veraitch FS Current Opinion in Biotechnology, 2018; 53, 164–181, doi:10.1016/j.copbio.2018.01.025

Experimentally integrated dynamic modelling for intuitive optimisation of cell based processes and manufacture Stacey AJ, Cheeseman EA, Glen KE, Moore RLL, Thomas RJ Biochemical Engineering Journal, 2018; 132, 130–138, doi:10.1016/j.bej.2018.01.012

Effect of Mechanical Loading on Osteogenesis of Human Embryonic Stem Cell-Derived Mesenchymal Progenitors within Collagen Microspheres Shariatzadeh M, Baldit A, Perrault CM, Lacroix D Journal of Biotechnology and Biomedicine, 2018; 1(1), 001-020.

Stiffness of cell micro-environment guides long term cell growth in cell seeded collagen microspheres Shariatzadeh M, Perrault, CM, Lacroix, D Archives of Clinical and Biomedical Research, 2018; 2(5), 167-182, doi:10.26502/acbr.50170056

Tm-Values and Unfolded Fraction Can Predict Aggregation Rates for Granulocyte Colony Stimulating Factor Variant Formulations but Not under Predominantly Native Conditions Robinson MJ, Matejtschuk P, Bristow AF, Dalby PA Molecular Pharmaceutics, 2018; 15(1), 256-267, doi: 10.1021/acs.molpharmaceut.7b00876

Dynamic modelling of aqueous two-phase systems to quantify the impact of bioprocess design, operation and variability Patel N, Bracewell DG, Sorensen E Food and Bioproducts Processing, 2018; 107, 10-24, doi:10.1016/j.fbp.2017.10.005

Lifetime and Aging of Chromatography Resins during Biopharmaceutical Manufacture Nweke MC, Rathore AS, Bracewell DG Trends in Biotechnology, 2018; 36 (10), 992-995, doi:10.1016/j.tibtech.2018.01.001

Manufacturing Exosomes: A Promising Therapeutic Platform Colao IL, Corteling R, Bracewell D, Wall I Trends in Molecular Medicine, 2018; 24 (3), 242-256, doi:10.1016/j.molmed.2018.01.006

Precipitation as an Enabling Technology for the Intensification of Biopharmaceutical Manufacture Martinez M, Spitali M, Norrant EL, Bracewell DG Trends in Biotechnology, 2018; in press, doi:10.1016/j.tibtech.2018.09.001



Protein A Chromatography Resin Lifetime - Impact of Feed Composition Pathak M, Lintern K, Bracewell DG, Rathore AS Biotechnology Progress, 2018; 34 (2), 412-419, doi:10.1002/btpr.2608

The effect of feed quality due to clarification strategy on the design and performance of protein A periodic counter-current chromatography El-Sabbahy H, Ward D, Ogonah O, Deakin L, Jellum GM, Bracewell DG Biotechnology Progress, 2018; 34(6), 1380-1392, doi:10.1002/btpr.2709

Three dimensional characterisation of chromatography bead internal structure using X-ray computed tomography and focused ion beam microscopy Johnson TF, Bailey JJ, Iacoviello F, Welsh JH, Levison PR, Shearing PR, Bracewell DG Journal of Chromatography A, 2018; 1566, 79-88, doi:10.1016/j.chroma.2018.06.054

Ultra scale-down approaches to study the centrifugal harvest for viral vaccine production Melinek BJ, Dessoy, S, Wright B, Bracewell DG, Mukhopadhyay TK Biotechnology and bioengineering, 2018;115 (5), 1226-1238, doi:10.1002/bit.26546

Dual Data-Independent Acquisition Approach Combining Global HCP Profiling and Absolute Quantification of Key Impurities during Bioprocess Development Husson G, Delangle A, O’Hara J, Cianferani S, Gervais A, Van Dorsselaer A, Bracewell D, Carapito C Analytical chemistry, 2018; 90(2), 1241-1247, doi: 10.1021/acs.analchem.7b03965

An Evaluation of the Potential of NMR Spectroscopy and Computational Modelling Methods to Inform Biopharmaceutical Formulations Pandya A, Howard MJ, Zloh M, Dalby PA Pharmaceutics, 2018; 10 (4), 165, doi:10.3390/pharmaceutics10040165

Computational Design To Reduce Conformational Flexibility and Aggregation Rates of an Antibody Fab Fragment Zhang C, Samad M, Yu H, Chakroun N, Hilton D, Dalby PA Molecular Pharmaceutics, 2018;15(8), 3079-3092, doi:10.1021/acs.molpharmaceut.8b00186



Coupled molecular dynamics mediate long- and short-range epistasis between mutations that affect stability and aggregation kinetics Yu H, Dalby P Proceedings of the National Academy of Sciences,2018; 115 (47), E11043-E11052, doi:10.1073/pnas.1810324115

Exploiting correlated molecular-dynamics networks to counteract enzyme activity–stability trade-off Yu H, Dalby P Proceedings of the National Academy of Sciences,2018;115 (52), E12192-E12200, doi:10.1073/pnas.1812204115

Frontiers and opportunities: highlights of the 2nd annual conference of the Chinese Antibody Society Zhang H, Deng M, Lin P, Liu J, Liu C,Strohl WR, Wang S,Ho M Antibody Therapeutics, 2018; 1(2), 27-36, doi:10.1093/abt/tby009

Cost-effective bioprocess design for the manufacture of allogeneic CAR-T cell therapies using a decisional tool with multi-attribute decision-making analysis Jenkins MJ, Farid SS Biochemical Engineering Journal, 2018; 137, 192-204, doi:10.1016/j.bej.2018.05.014

Impact of allogeneic stem cell manufacturing decisions on cost of goods, process robustness and reimbursement Pereira Chilima TD, Moncaubeig F, Farid SS Biochemical Engineering Journal, 2018; 137, 132-151, doi:10.1016/j.bej.2018.04.017

Technologies for large-scale umbilical cord-derived MSC expansion: Experimental performance and cost of goods analysis Mizukami A, Pereira Chilima TD, Orellana MD, Neto MA, Covas DT, Farid SS, Swiech K Biochemical Engineering Journal, 2018; 135, 36-48, doi:10.1016/j.bej.2018.02.018

Development of a process control strategy for the serum-free microcarrier expansion of human mesenchymal stem cells towards cost-effective and commercially viable manufacturing Heathman TRJ, Nienow AW, Rafiq QA, Coopman K, Kara B, Hewitt CJ Biochemical Engineering Journal, 2019; 141, 200-209, doi:10.1016/j.bej.2018.10.018



Agitation and aeration of stirred-bioreactors for the microcarrier culture of human mesenchymal stem cells and potential implications for large-scale bioprocess development Heathman TRJ, Nienow AW, Rafiq QA, Coopman K, Kara B, Hewitt CJ Biochemical Engineering Journal, 2018; 136, 9-17, doi:10.1016/j.bej.2018.04.011

Cell therapy-processing economics: Small-scale microfactories as a stepping stone toward large-scale macrofactories Harrison RP, Medcalf N, Rafiq QA Regenerative Medicine, 2018; 13 (2), 159-173, doi:10.2217/rme-2017-0103

Centralised versus decentralised manufacturing and the delivery of healthcare products: A United Kingdom exemplar Harrison RP, Rafiq QA, Medcalf N Cytotherapy, 2018; 20(6), 873-890, doi:10.1016/j.jcyt.2018.05.003

Qualitative and quantitative demonstration of bead-to-bead transfer with bone marrow-derived human mesenchymal stem cells on microcarriers: Utilising the phenomenon to improve culture performance Rafiq QA, Ruck S, Hanga MP, Heathman TRJ, Coopman K, Nienow AW, Williams DJ, Hewitt CJ Biochemical Engineering Journal, 2018; 135, 11-21, doi:10.1016/j.bej.2017.11.005

An automated microfluidic perfusion device for adherent cell reprogramming, expansion and culture condition monitoring Szita N, Veraitch F, Raimes W, Kumar V, Marques M New Biotechnology, 2018; 44, S14, doi:10.1016/j.nbt.2018.05.168

Long-Term Retinal Differentiation of Human Induced Pluripotent Stem Cells in a Continuously Perfused Microfluidic Culture Device Abdolvand N, Tostoes R, Raimes W, Kumar V, Szita N, Veraitch F Biotechnology Journal, 2018; doi:10.1002/biot.201800323

Precision healthcare supply chain desing through multi-objective stochastic programming Wang X, Kong Q, Papathanasiou MM, Shah N Computer Aided Chemical Engineering, 2018;44, 2137-2142, doi: 10.1016/B978-0-444-64241-7.50351-7

Chapter 6- Computational tools in the assistance of personalized healthcare Papathanasiou MM, Onel M, Nascu I,Pistikopoulos EN Computer Aided Chemical Engineering, 2018; 42, 139-209, doi:10.1016/B978-0-444-63964-6.00006-4



Advances in enabling smart technologies across the cell therapy supply chain (Interview) in Management Part 2: creating a logistics strategy for commercialization Papathanasiou M Cell & Gene Therapy Insights; 2018; 4(5), 495-500, doi: 10.18609/cgti.2018.050

Enhanced distance-dependent fluorescence quenching using size tuneable core shell silica nanoparticles Elsutohy MM, Selo A, Chauhan VM, Tendler SJB, Aylott JW RSC Advances, 2018;8, 33840-35848, doi: 10.1039/C8RA05929B

Augmented automated analytics using fluorescent nanosensors Chauhan VM Cell & Gene Therapy Insights, 2018; 4(9), 837-850, doi: 10.18609/cgti.2018.085

Enhancing cell and gene therapy manufacture through the application of advanced fluorescent optical sensors (Review) Harrison RP, Chauhan VM Biointerphases,2018;13, 01A301, doi: 10.1116/1.5013335

The promises and perils of biotech in personalised healthcare: can new regulatory pathways protect the vulnerable? DeGrandis G, Brass I, Petersen, A Risk and Regulation Magazine, 2018;36, 21-23, www.lse.ac.uk/accounting/carr/publications/Risk-Regulation-Magazine

Lancet Commission: stem cells and regenerative medicine Cossu G, Birchall M, Brown T, De Coppi P, Culme-Seymour E, Gibbon S, Hitchcock J, Mason C, Montgomery J, Morris S, Muntoni Napier D, Owji N, Prasad A, Round J, Saprai P, Stilgoe J, Thrasher A Wilson, J The Lancet, 2018, 391(10123), 883-910, doi: 10.1016/S0140-6736(17)31366-1

Cost-effectiveness and benefit-to-harm ratio of risk-stratified screening for breast cancer: a life-table model Pashayan N, Morris S, Gilbert FJ, Pharoah PDP JAMA oncology, 2018; 4(11), 1504-1510, doi:10.1001/jamaoncol.2018.1901

Influence of incident wavelength and detector material selection on fluorescence in the application of Raman spectroscopy to a fungal fermentation Process Goldrick S, Lovett D, Montague G, Lennox B Bioengineering, 2018, 5(4), 79, doi: 10.3390/bioengineering5040079

http://dx.doi.org/10.1001/jamaoncol.2018.1901



2017Formation and purification of tailored liposomes for drug delivery using a module-based micro continuous-flow system Dimov N, Kastner E, Hussain M, Perrie Y, Szita N Nature Scientific Reports, 2017; 7(1), doi:10.1038/s41598-017-11533-1 and 10.1038/s41598-018-25217-x

Predicting performance of constant flow depth filtration using constant pressure filtration data Goldrick S, Joseph A, Mollet M, Turner R, Gruber D, Farid SS, Titchener-Hooker NJ Journal of Membrane Science, 2017; 531, 138-147, doi:10.1016/j.memsci.2017.03.002

Decentralized manufacturing of cell and gene therapies: Overcoming challenges and identifying opportunities Harrison RP, Ruck S, Medcalf N, Rafiq QA Cytotherapy, 2017; 19(10), 1140-1151, doi:10.1016/j.jcyt.2017.07.005

X-ray computed tomography of packed bed chromatography columns for three dimensional imaging and analysis Johnson TF, Levison PR, Shearing PR, Bracewell DG Journal of Chromatography A, 2017; 1487, 108-115, doi:10.1016/j.chroma.2017.01.013

An automated laboratory-scale methodology for the generation of sheared mammalian cell culture samples Joseph A, Goldrick S, Mollet M, Turner R, Bender J, Gruber D, Farid SS, Titchener-Hooker N Biotechnology Journal, 2017; 12(5), doi:10.1002/biot.201600730

Effects of bed compression on protein separation on gel filtration chromatography at bench and pilot scale Kong D YC, Gerontas S, McCluckie RA, Mewies M, Gruber D, Titchener-Hooker NJ Journal of Chemical Technology and Biotechnology, 2017; doi:10.1002/jctb.5411

Bioprocess microfluidics: applying microfluidic devices for bioprocessing Marques MP, Szita N Current Opinion in Chemical Engineering, 2017; 18, 61-68, doi:10.1016/j.coche.2017.09.004

Integration and application of optical chemical sensors in microbioreactors Gruber P, Marques MPC, Szita N, Mayr T Lab on a chip, 2017; 17(16), 2693-2712, doi: 10.1039/C7LC00538E



Neutron reflectivity measurement of protein A–antibody complex at the solid-liquid interface Mazzer AR, Clifton LA, Perevozchikova T, Butler PD, Roberts CJ, Bracewell DG Journal of Chromatography A, 2017; 1499, 118-131, doi:10.1016/j.chroma.2017.03.084

Effects of lysosomal biotherapeutic recombinant protein expression on cell stress and protease and general host cell protein (HCP) release in Chinese hamster ovary cells Migani D, Smales CM, & Bracewell DG Biotechnology Progress, 2017; 33(3), 666-676, doi:10.1002/btpr.2455

Mechanical characterisation of agarose-based chromatography resins for biopharmaceutical manufacture Nweke MC, McCartney RG, Bracewell DG Journal of Chromatography A, 2017; 1530, 129-137, doi:10.1016/j.chroma.2017.11.038

Drying techniques for the visualisation of agarose-based chromatography media by scanning electron microscopy Nweke MC, Turmaine M, McCartney RG, Bracewell DG Biotechnology journal, 2017; 12(3), 1600583, doi:10.1002/biot.201600583

Measurement of impurities to support process development and manufacture of biopharmaceuticals Oshinbolu S, Wilson LJ, Lewis W, Shah R, Bracewell DG TrAC- Trends in Analytical Chemistry, 2017; 101, 120-128, doi:10.1016/j.trac.2017.10.026

Fluorescence based real time monitoring of fouling in process chromatography Pathak M, Lintern K, Chopda V, Bracewell DG, Rathore AS Scientific reports,2017;7, 45640, doi: 10.1038/srep45640

Downstream Processing for Cell-Based Therapies Rafiq QA, Masri F BioPharm International, 2017; 30(4), 22-26, doi: n/a, www.biopharminternational.com

Two strategies to engineer flexible loops for improved enzyme thermostability Yu H, Yan Y, Zhang C, Dalby PA Nature Scientific Reports, 2017; 7, art. 41212, doi:10.1038/srep41212



Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations Yang Y, Velayudhan A, Thornhill NF, Farid SS Biotechnology and Bioengineering, 2017; 114(9), 2043–2056, doi:10.1002/bit.26329

An integrated experimental and economic evaluation of cell therapy affinity purification technologies Weil BD, Jenkins MJ, Uddin S, Bracewell DG, Wellings D, Farid SS, Veraitch F Regenerative Medicine, 2017; 12(4), 397–417, doi:10.2217/rme-2016-0156

Integrated continuous bioprocessing: Economic, operational, and environmental feasibility for clinical and commercial antibody manufacture Pollock J, Coffman J, Ho SV, Farid SS Biotechnology Progress, 2017; 33(4), 854–866, doi:10.1002/btpr.2492

A new lot sizing and scheduling heuristic for multi-site biopharmaceutical production Oyebolu FB, Van Lidth De Jeude J, Siganporia C, Farid SS, Allmendinger R, Branke J Journal of Heuristics, 2017; 23(4), 231–256, doi:10.1007/s10732-017-9338-9

A roadmap for cost-of-goods planning to guide economic production of cell therapy products Lipsitz YY, Milligan WD, Fitzpatrick I, Stalmeijer E, Farid SS, Tan KY, Smith D, Perry R, Carmen J, Chen A, Mooney C, Fink J Cytotherapy, 2017; 19(12), 1383–1391, doi:10.1016/j.jcyt.2017.06.009

Cell free protein synthesis: a viable option for stratified medicines manufacturing? Ogonah OW, Polizzi KM, Bracewell DG Current Opinion in Chemical Engineering, 2017; 18, 77–83, doi: 10.1016/j.coche.2017.10.003

Emerging automated approaches for cell and gene therapy manufacture: critical role of automation in the manufacture of cell & gene therapies Rafiq QA Cell Gene Therapy Insights, 2018, 4(9), 911-914, doi: 10.18609/cgti.2018.070



Process development of human multipotent stromal cell microcarrier culture using an automated high-throughput microbioreactor Rafiq QA, Hanga MP, Heathman TRJ, Coopman K, Nienow AW, Williams DJ, Hewitt CJ Biotechnology and Bioengineering, 2017, 114(10), 2253-2266, doi: 10.1002/bit.26359

2016Industry 4.0 a vision for personalized medicine supply chains? Branke J, Farid SS, Shah N Cell & Gene Therapy Insights, 2016; 2(2), 263-270, doi:10.18609/cgti.2016.027


CONFERENCE PRESENTATIONS


2019Paul Dalby Analysis, control and engineering of protein dynamics, stability and aggregation CASSS 8th International Symposium on Higher Order Structure of Protein Therapeutics 8-10 April 2019, San Francisco CA, USA

Suzanne Farid Decisional tools for predictive data-mining & cost-effective design for biopharma facilities of the future (keynote) 257th American Chemical Society (ACS) Meeting, March 31-April 4 2019, Orlando, FL, USA

Jonathan Aylott Sensing inside the cell with miniaturised analytical devices MediLink East Midlands Sensing and Imaging for diagnostics, detection and monitoring 28 February 2019, Nottingham, UK

Qasim Rafiq Process Development and Manufacturing Strategies CART-TCR Summit Europe Meeting 25-27 February 2019, London, UK

Robert Thomas Efficient model driven design of cell-based product manufacturing ECI Advancing Manufacture of Cell and Gene Therapies VI 27-31 January 2019, Coronado CA, USA

Veeren Chauhan Augmenting automated analytics using fluorescent nanosensors Phacilitate Leaders World and the World Stem Cell Summit 22-25 January 2019, Miami, Florida, USA

Jonathan Aylott Nanosensors and measurement of biological material in situ and in real time ESACT-UK Annual Scientific Meeting 9-10 January 2019, Tamworth, UK

2018Robert Thomas Cost and control in cell therapy process development and manufacture GMP Manufacturing, Scale-Up and Challenges of ATMPs 14-15 November 2018, Galway, Ireland



Daniel Bracewell Cell-free synthesis: a liberating technology to meet the demands of targeted therapeutics? BioProcessing Asia 12-15 November 2018, Langkawi, Malaysia

Suzanne Farid Cost of goods and supply chain analysis for cell therapy manufacture BioProcessing Asia 12-15 November 2018, Langkawi, Malaysia

Maria Papathanasiou Autologous Cancer Therapies: How can we handle the complexity of the supply chain? AIChE Annual Meeting 28 October-2 November 2018, Pittsburgh PA, USA

Qasim Rafiq Process development and control strategies for advanced therapy manufacture 5th Annual Stem Cell & Regenerative Medicine Congress 25-26 October 2018, London, UK

Qasim Rafiq Automated approaches for the process development and manufacture of CAR-T Therapies Parenteral Drug Association Meeting 15-17 October 2018, Washington DC, USA

Paul Dalby Analysis and control of protein dynamics and stability: downstream to formulation 5th Annual BioProNet conference 10-11 October 2018, London, UK

Nigel Titchener-Hooker Human plasma fractionation: a 75-year journey of innovation, ingenuity and a degree of serendipity Recovery of Biological Products XVIII 6-12 October 2018, Asheville NC, USA

Christos Stamatis Integrating high-throughput experimentation with advanced decision-support tools for chromatography process development Recovery of Biological Products XVIII 6-12 October 2018, Ashville NC, USA



Suzanne Farid Process economics perspectives of continuous manufacture for mAbs and vaccines 3rd International Symposium on Continuous Manufacturing of Pharmaceuticals 3-4 October 2018, London, UK

Maria Papathanasiou Decision tools in the assistance of the CAR T-cell industry Cell Therapies and Bioengineering Conference (SBE, AIChE) 20-22 September 2018, San Francisco CA, USA

Robert Thomas Step 3: How much process risk am I carrying forward into clinical stage production? Phacilitate Leaders Europe 11-12 September 2018, London UK

Qasim Rafiq Panel discussion: future of bioprocessing and manufacture for ATMPs Phacilitate Europe Cell and Gene Therapy 11-12 September 2018, London UK

Christos Stamatis Process economics of cell-free synthesis for targeted biologics manufacture European Society of Biochemical Engineering Sciences (ESBES) 9-12 September 2018, Lisbon, Portugal

Carlos-Alberto Duran-Villalobos Fault tolerant MPC for Fed-batch Penicillin Production UKACC 12th International Conference on Control 5-7 September 2018, Sheffield, UK

Daniel Bracewell Cell-free synthesis: a highly disruptive technology for manufacture of personalised/targeted medicines 10th Annual Bioprocessing Summit 13-17 August 2018, Boston MA, USA

Elvan Gokalp Integrated clinical production planning and portfolio management models for stratified medicines European Conference on Operational Research 8-11 July 2018, Valencia, Spain



Maria Papathanasiou Precision healthcare supply chain design through multi-objective stochastic programming 13th International Symposium on Process Systems Engineering (PSE 2018) 1-5 July 2018, San Diego CA, USA

Veeren Chauhan Advanced fluorescent pH-sensitive PLGA particles for controlled targeted therapeutic delivery and mapping microenvironmental biochemical parameters Controlled Release Society conference 22-25 June 2018, New York, USA

Giovanni De Grandis Beyond Adaptive Regulations: What remains to be done to get innovative therapies to patients? Parenteral Drug Association (PDA) Europe Conference on Advanced Therapy Medicinal Products (ATMPs) 5-6 June 2018, Amsterdam, The Netherlands

Christos Stamatis Assessing feasible business models for commercialisation of cell therapies Parenteral Drug Association (PDA) Europe Conference on Advanced Therapy Medicinal Products (ATMPs) 5-6 June 2018, Amsterdam, The Netherlands

Suzanne Farid Cost of goods and supply chain economics analysis for allogeneic and autologous cell therapies Parenteral Drug Association (PDA) Europe Conference on Advanced Therapy Medicinal Products (ATMPs) 5-6 June 2018, Amsterdam, The Netherlands

Veeren Chauhan Harnessing the benefits of fluorescent PGLA United Kingdom and Republic of Ireland Controlled Release Society Conference (UKICRS) 4-5 June 2018, Belfast, UK

Maria Papathanasiou Towards the development of decisional tools to support supply chain logistics in the CAR T-cell industry 3rd Annual Bioprocessing of Advanced Cellular Therapies Congress 29-30 May 2018, Frankfurt, Germany



Robert Thomas Dynamic mechanistic modelling for optimisation of cell therapy process development and manufacture 3rd Annual Bioprocessing of Advanced Cellular Therapies Congress 29-30 May 2018, Frankfurt, Germany

Qasim Rafiq The commercial scale manufacturing strategies of ATMPs World Advanced Therapy & Regenerative Medicine Congress Meeting 16-18 May 2018, London, UK

Suzanne Farid Process economics for successful commercialisation of universal and personalised cell therapies World Advanced Therapy & Regenerative Medicine Congress Meeting 16-18 May 2018, London, UK

Qasim Rafiq Automated approaches for the process development and manufacture of cell and gene therapies International society for Cell and Gene Therapy (ISCT) 2-5 May 2018, Montreal, Canada

Giovanni De Grandis Real World Patients Sharing Data Safely: Data Sharing Meeting of the European Federation of Allergy and Airways Diseases Patients’ Association (EFA) 16-17 April 2018, Lisbon, Portugal

Robert Thomas Dynamic mechanistic modelling for optimisation of cell therapy process development and manufacture: delivering sufficient certainty with limited resource Bioprocessing Summit Europe 20- 22nd March 2018, Lisbon, Portugal

Suzanne Farid Streamlining biopharmaceutical decision-making: designing for manufacturability, facility fit and cost-effectiveness Parenteral Drug Association Annual Meeting (Agile Manufacturing Strategies: Driving Change to Meet Evolving Needs) 19-21 March 2018, Orlando FL, USA

Suzanne Farid Successful commercialization of CAR T-cell therapies: COG versus reimbursement perspectives Parenteral Drug Association Annual Meeting (Agile Manufacturing Strategies: Driving Change to Meet Evolving Needs) 19-21 March 2018, Orlando FL, USA



Maria Papathanasiou Decision tools in the assistance of the CAR T-cell industry CART-TCR Summit Europe Meeting 25-27 February 2018, London, UK

2017Suzanne Farid UCL Bioprocess Decisional Tools: Financial and operational evaluation of continuous bioprocesses for clinical and commercial mAb manufacture European Summit of Industrial Biotechnology (esib) 14-16 November 2017, Graz, Austria

Paul Dalby Impact of protein mutational variability upon formulation designs PEGS Summit Europe 12-16 November 2017, Lisbon, Portugal

Robert Thomas Dymanic and mechanistic modelling for optimisation of cell therapy process development and manufacture BioProcess International Conference & Exhibition 25-28 September 2017, Boston MA, USA

Yang Yang Time-Series Data Mining For Continuous Bioprocess Analysis ECI Integrated Continuous Biomanufacturing III 17-21 September2017, Cascais, Portugal

Suzanne Farid Autologous and allogeneic cell therapy process economics for successful commercialization World Advanced Therapies & Regenerative Medicine Congress 17-19 May 2017, London, UK

Suzanne Farid Successful commercialisation of autologous & allogeneic cell therapies: Cost of goods versus reimbursement perspectives International Society for Cell & Gene Therapy 3-6 May 2017, London, UK

Paul Dalby Computationally-guided protein and formulation engineering Biophysical Analysis of Biotherapeutics meeting at the 13th Annual PEGS conference 1-5 May 2017, Boston MA, USA



Paul Dalby Computationally-guided protein and formulation engineering Oxford Global 10th Annual Protein, Antibodies & Biotherapeutics Congress 24-25 April 2017, London, UK

Suzanne Farid Streamlining biopharmaceutical decision-making: designing for manufacturability, facility fit and cost-effectiveness (keynote) 253rd American Chemical Society (ACS) National Meeting 2-6 April 2017, San Francisco CA, USA

Yang Yang High-throughput data analysis for rapid ranking of high-concentration monoclonal antibody formulations using manufacturability indices 253rd American Chemical Society (ACS) National Meeting 2-6 April 2017, San Francisco CA, USA


Finances

FINANCES

£


FINANCES

FINANCES

Leveraged Funding

EPSRC Hub Core Funding£2.9M

Other UKRI£5.27M

Industry (non Hub)£2.44M

EPSRC (non Hub)£0.83M

EU£0.74M

Government Agency£0.73M

Charity£0.08M

Hub Consortium: Cash£0.28M

FIGURE 6: Cumulative value of the Hub grant & leveraged funds awarded by Year 2

Source, Funder Amount/£M

Hub Consortium: Cash 0.28

Industry (non-Hub) 2.44

Other UKRI 5.27

EPSRC (non-Hub) 0.83

EU 0.74

Government Agency 0.73

Charity 0.08

External sources total 10.38

TABLE 2: Cumulative value of leveraged funds awarded by Year 2

Growth of the grant portfolio associated with the Hub is an important metric of success. We have pursued a number of different avenues, including companies, government agencies and UKRI. The Hub has secured approximately £10M from external sources, which complements the £2.9M EPSRC core funding for the first two years of the Hub. In addition to this, Users have pledged in-kind contributions to the value of £2.6M.

For more information on the Hub, collaboration and how to join the industrial User Group please contact:

Dr. Naveraj Gill, Strategic Alliance Director, Deputy Head of Department (Enterprise)

e: [email protected]

t: +44 (0) 203 549 5619

UCL HUB LEADERSHIP

Hub Director

Prof. Nigel Titchener-Hooker, FREngExecutive Dean of the UCL Faculty of Engineering Sciences

Hub Co-Director (User Engagement & Translation)

Prof. Suzanne Farid, FIChemE Professor of Bioprocess Systems Engineering

Deputy Head of Department (Education)

Hub Co-Director (Community Engagement & Training)Prof. Paul Dalby, FRSCProfessor of Biochemical Engineering & Biotechnology

Deputy Head of Department (Research) Director of the Centre for Doctoral Training

Grant Ref: EP/P006485/1

www.ucl.ac.uk/biochemeng/hub

Documents

FUTURE TARGETED HEALTHCARE …...10 Future Targeted Healthcare Manufacturing Hub THE HUB IN NUMBERS Hub: UCL Spokes: Imperial, Warwick, Manchester, Nottingham, LoughboroughUser Steering