BiologicsThe Centre for Process Innovation

Biologics

From innovation to commercialisation

The Centre for Process InnovationFrom innovation to commercialisation

CPI is the UK’s national technology and innovation centre for the process manufacturing industries. At the National Biologics Manufacturing Centre, CPI combines state of the art facilities and technical expertise to support the growth and development of the UK biologics industry and supply chain.

The UK has a strong history of academic research and a rich landscape of capability and infrastructure in biologics, but in the face of increasing global competition and investment, interventions are required to anchor this high value sector in the UK.

CPI collaborates with large corporates, SME’s, academia and charities to enable the delivery of innovative manufacturing solutions to accelerate the growth of new and emerging biologic medicines. Through these collaborations we

develop, prove and commercialise innovative new processes and technologies that enable the cost effective, safe and high quality manufacture of life changing biologic therapies.

CPI is focussed on three key themes:

• Innovative processes and technologies

• New and improved analytical technologies

• Process development for novel products and formulations

The High Value Manufacturing Catapult is a partnership between industry and government, which is a catalyst for the future growth and success of manufacturing in the UK. Its long-term goal is to stimulate growth in the manufacturing sector and grow the sector’s contribution to UK GDP to a level more commensurate with that of competitor economies. It does this by helping businesses accelerate new concepts (often started in research institutions) to commercial reality (where they can be funded through market sources). In doing so, the Catapult reduces companies’ risk in innovation, and it enables the UK to address market needs in key areas, making the country more competitive on the global stage.

The High Value Manufacturing Catapult combines the strengths of seven UK technology and innovation centres, each focusing on major underpinning manufacturing technologies. The Catapult brings these centres together to develop cross sector manufacturing capabilities, which can span from raw materials to finished processes. It also enables innovation to cut across sectors by bringing together businesses from diverse industries and giving them access to a pool of world-class expertise, equipment and processes invested and supported by UK government.

CPI established the UK’s National Biologics Manufacturing Centre in 2015 with funding from the Government’s Department for Business Innovation and Skills.

The state-of-the-art facility is equipped with advanced technologies for upstream and downstream processing, high throughput process development, comprehensive analytical characterisation and capabilities for formulation, fill and finish. The facility has over 700m2 of flexible laboratories designed to handle BSL1 and BSL2 organisms. We can run whole bioprocess development programmes in our laboratories as well as developing “GMP ready” processes in a series of GMP proving clean rooms. The flexible design of the facility enables equipment expansion and reconfiguration to support specific projects.

The CPI team bring significant expertise in all aspects of biopharmaceutical development and manufacture including mammalian and microbial process development, process scale-up and technology transfer, advanced bioanalytical development, new technology development and evaluation, advanced experimental design and multivariate data analysis.

CPI supports the UK biopharmaceutical industry by engaging in a variety of collaborative work programmes to support process innovation and facilitate the development and adoption of new manufacturing and analytical technologies. Our capabilities and expertise in high throughput and novel process development enables partners and clients to bring their products to market more quickly and with reduced risk. We support SMEs, large companies and universities to translate early, proof of concept stage research into industry and market-ready technologies. Clients can also access our facility and expertise on a fee for service basis.

The National Biologics Manufacturing Centre has been created to act as a central hub for the UK’s Biologics industry, hosting key events and research projects and providing a central facility to advance innovation in the industry.

Introduction

The highly experienced CPI team can help guide you from concept to finished product. We have scientists, engineers, scale up experts, process technologists and commercialisation specialists to take your project from early concepts through to robust manufacturing process packages and products.

Our services can be customised to meet your needs wherever you are in the development process and supply chain. We are delighted to work side by side with our clients to help them overcome the challenges of commercialisation of their products and processes. Our extensive industry experience means we can make recommendations accordingly in an effort to produce the best possible outcome.

We welcome all enquiries about our capabilities and equipment. It is our mission to help customers and partners maximise the potential of their products, accelerate speed-to-clinic and help reduce cost-of-goods. We pride ourselves on meeting our deliverables and adding considerable value to our partners’ and customers’ products and processes.

We offer services in the following areas:

• Upstream Processing

• Downstream Processing

• Analytical Testing and Development

• Fill and Finish

• Manufacturability, Process Modelling and Simulation

• Process Economics and Evaluation

• Commercialisation and Business Support including IP Landscaping

• Public – Private Project Funding Support

• Bespoke Training Packages

Services

We have upstream laboratory facilities equipped with state-of-the-art technologies to support the development, demonstration and scale-up of bioprocesses.

The micro-Matrix and ambr250 mini bioreactors allow scale-down, high-throughput evaluation and optimisation of critical process parameters. Optimised processes can be scaled-up and demonstrated at laboratory and pilot scale.

Our work is supported by a range of static and shaking CO

2 incubators for flask culture. We

have a Roche CEDEX HT bioanalyser, COBAS

blood gas analyser, ViCell™ automated cell counters and osmometers for in-process sample measurements. We also have -80°C freezers and liquid nitrogen cryobanks for long term storage of cell lines.

Upstream processing activities cover both mammalian and microbial cells as detailed in the respective sections.

Mammalian cell culture capabilities are focused on the use of customer and partner supplied cell lines to produce and optimise the production of a wide range of biopharmaceutical products, recombinant therapeutic proteins and attenuated viruses (eg AAV).

Microbial capabilities are based on the use of a variety of microbial systems for the production of recombinant proteins (soluble and insoluble).

• Establishment and storage of research cell banks

• Cell line/strain screening and evaluation

• Development of robust and scalable processes using QbD and DoE approaches

• Production and supply of pilot scale materials for downstream process development, analytical testing or other non-GMP studies

• Development of process models

Mammalian

Microbial

Combined Service OfferingUpstream Processing

Our downstream capabilities are focused around the development and optimisation of manufacturing ready processes for a variety of product types.

Examples of products encountered include recombinant therapeutic proteins, attenuated viruses (eg AAV), PEGylated proteins and complex biological nanopharmaceuticals. For microbial processes, purification can be optimised for both soluble products and those refolded from inclusion bodies.

Our flexible facilities are appropriately equipped to allow for both lab and pilot scale purification. We have high throughput screening capabilities based on the use of automated liquid handling work stations. We have developed methods for rapid experimental design that integrate with automated methods for high throughput investigation and development of downstream

unit operations such as protein refolding, precipitation and chromatographic purification. Integration with high throughput process development analytics, such as the LabChip® GXII, enables rapid analysis of product quality and yield. By using lab scale equipment such as tangential flow filtration (TFF) and traditional or continuous chromatography systems, unit operations can be

scaled for further optimisation or exploration of design space.

Systems can be used as standalone operations or integrated, with options for gravimetric quantification, temperature regulation and highly efficient mixing, to allow for semi-automated processing and analysis. We also have industry standard capabilities for semi-automated and fully automated pilot scale process demonstration including separations, normal flow filtration, depth filtration, microfiltration, tangential flow filtration and chromatography unit operations. Our single-use capabilities allow for disposable processing, including temperature regulated mixing systems and flexible filtration.

Downstream processing service offerings include:

• Development of robust and scalable processes including the following unit operations:

• Primary separation/recovery steps (eg cell broth clarification, cell disruption, inclusion body recovery, protein folding, precipitation, depth filtration)

• Filtration – normal flow (NFF) and tangential flow (TFF)

• Chromatography (batch and continuous)

• Conjugation or protein modification (eg PEGylation)

• Unit operation or full process scale–up for demonstration at laboratory or pilot scale

Downstream Processing

Analytical science underpins almost all aspects of biopharmaceutical development and manufacture and we ensure the latest developments in analytical science are translated into our customer’s projects.

Our extensive analytical suite supports investigation and optimisation of the various stages of biopharmaceutical development and manufacture, helping to optimise product yield and quality. We provide comprehensive characterisation of product quality attributes such as glycan profile, levels of aggregation, secondary structure and charge variant profile as well as high throughput screening of product purity, titre

and impurity clearance throughout downstream processing. We have Ion Torrent™ next generation sequencing capabilities to allow a genomics based approach to biopharmaceutical process optimisation, helping to identify important cellular features related to the performance of cell lines. CPI is also equipped with a Waters Synapt G2Si mass spectrometer to allow peptide mapping and comprehensive characterisation of

post translational modifications, plus hydrogen deuterium exchange for higher order structure studies.

In addition to applying our state of-the-art analytical tools to research and development projects, we also perform routine bioanalysis (cell count/viability, nutrients, metabolites, product titre, and product characterisation); stability testing; characterisation of reference standards; comparability testing (purity, potency and identity); method development, verification and transfer.

Analytical testing and development services include:

• Purity and identity measurements

• Impurity measurements

• Potency and higher order structure

• Formulation and stability studies including comprehensive characterisation of aggregation

• Development of process specific analytical methods

• Process analytical technologies

• Product characterisation

• Molecular characterisation

• Method development

• Method transfer and verification

Analytical

Our Fill and Finish capabilities are focused on improving the sterile filling, finish and lyophilisation of biologic drugs.

Fill and finish service offerings include:

• Handling a wide range of products (eg proteins, vaccines, DNA and viral vector solutions, viscous biopolymers and other nanoparticles)

• Filling volume ranging from 0.2-250ml

• Filling of up to 120 vials per hour

• Flexible bulk volume up to 20L

• Batch Lyophilisation covering: development of lyophilisation cycles in vials, flasks and bulk volumes; development and optimisation of multi-step lyophilisation cycles

Fill and Finish

...the future inspired.

To find out more about our full range of services visit: www.uk-cpi.com call: +44 (0)1642 455 340

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Centre for Process Innovation Wilton Centre, Wilton, Redcar, Cleveland, TS10 4RF, United Kingdom

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T: +44 (0)1642 455 340E: info@uk-cpi.comW: www.uk-cpi.com