The Biopharmaceutical Bioprocessing Technology Centre (BBTC) was founded in 2008 in response to the demand for highly skilled staff in the bioprocessing industry and the requirement for a deeper understanding of process behaviour. We decided to use an approach that focus on whole processes to enable consistently high quality production. Quality by Design (QbD) underpinned by Process Analytical Technology (PAT) offers the ideal solution.

Over the past 9 years we trained a new generation of EngD students with competencies in all stages of commercial biopharmaceutical and process development. We make use of the strong research reputation of Newcastle University in biological, engineering and medical sciences aligned to the bio and processing industry.

Quality by design (QbD) concept as presented by U.S. Food and Drug Administration (FDA) 2

Pharma and Industrial Biotechnology – Whole Process ABB Eesha Raut Astra Zeneca Keeley Burke Britest Kirsty McLachlan Fujifilm Diosynth Biotechnologies Amy Green GlaxoSmithKline Emma Craughan Lonza Elspeth Ritchie Perceptive Engineering Stephen Goldrick Piramal Pharma Solutions Matthew Molloy Pharma and Industrial Biotechnology – Up Stream CPI - Centre for Process Innovation Matthew Abbott Green Biologics Victoria Outram Lonza Ruth Rowland-Jones Novartis Pharmaceuticals UK Ltd Antonia Sofikiti Pall Life Science Kerem Irfan Perceptive Engineering Grace Oppong ScotBio Chelsea Brain Pharma and Industrial Biotechnology – Down Stream Accelyo Andrew Tait GlaxoSmithKline Charlotte Bell GlaxoSmithKline Chris Davis GlaxoSmithKline Rory MacDonald Pfizer Aatika Rizvi UCB Nicholas Whitelock Pharma and Industrial Biotechnology – Product Development Alcyomics Juliana Haggerty Demuris Bernhard Kepplinger Demuris Olga Chrobak Demuris Nicola Taylor GlaxoSmithKline Matthew Collison High Force Research Jennifer Wallis Onyx Scientific Ltd Gillian Moore

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Cell & Gene Therapy Arthritis Research UK Steven Wilkinson Arthritis Research UK Kimberley Green Athersys William Milligan Oxford Biomedica Jakub Krakowiak Oxford Biomedica Kirstie Pemberto Tower Cold Chain Solutions Ltd Fabio D'Agostino Cleaning and Emission Control Aesica James Hendry Britest Wendy Carr Heineken Charlotte Atwell Shasun Daniel Mullen Food & Consumer Goods British Bakels Angela Barone Croda Jodie Symington Procter & Gamble Mark Crosby Procter & Gamble Sean Clifford Unilever Joana Figueiredo Process Industry: Oil & Gas BOC Richard Adamson Intertek Group Plc Frederick Stubbin Compact GTL Ben Dannatt

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3 4

Pharma and Industrial Biotechnology – Whole Process

Application of Multivariate Data Analysis to Improve and Optimise

Industrial Processes

Host Company: ABB Student: Eesha Raut

Andrew worked with the small start-up company Accelyo. Accelyo are developing a scaleable continuous manufacturing platform to produce high value products, such as hierarchically structured nanomaterials, biologics, low solubility pharmaceuticals, and high surface area catalysts, by lyophilisation. Andrew worked on the development of a proof of concept unit which allows to intensify the lyophilisation process by increasing the heat and masstransfer capabilities through reducing the volume to nanolitre scale. To assure uniform product quality a numerical model was developed and a computational fluid dynamics study carried out for predicting product characteristics, determining process parameter boundaries, and understanding equipment limitations. Andrew designed an on-line Process Analytical Technology (PAT) device for the monitoring and control of the lyophilisation process.

5 6

The Use of Statistics in Understanding Pharmaceutical Manufacturing Processes Host Company: AstraZeneca Student: Keely Burke

Process Understanding and Design

Methodology for Industrial Biotechnology

Host Company: Britest Student: Kirsty McLachlan

AstraZeneca is one of the leading global biopharmaceutical companies. Keeley worked with AstraZeneca to help to get a better process understanding of the manufacturing of active pharmaceutical ingredients (API). Based on historic data she developed a new Bayesian method to calculate process capability. The process capability indices are informative tools to estimate the risk of a process failing the required specifications. Keeley proved the feasibility of the method in real life case studies.

Britest is a not-for-profit, membership-based organisation working with the chemical, pharma and biotech industries. Britest developed a range of tools designed to highlight the knowledge gaps within chemical and physical processes and to promote innovative process design solutions. The tools can help to identify areas where optimisation may be possible and also increase the understanding of the process as a whole across a range of disciplines. Kirsty joined Britest to investigate usability of existing tools in the bioprocessing industry looking at processes like monoclonal antibody production, insulin production, waste water treatment and penicillin production. To complement the existing tools Kirsty developed two new tools that specifically implement the Quality by Design approach in bioprocessing.

7 8

Model Based Process Design for a Monoclonal Antibody-producing Cell Line Optimisation: Using Hybrid Modelling and an Agent Based System Host Company: Fujifilm Diosynth Student: Amy Green

Development of Cost Effective Biosynthetic Processes for the Production of Small Molecule

Pharmaceutical Compounds

Host Company: GlaxoSmithKline

Student: Emma Craughan

Fujifilm Diosynth is a world leading cGMP Contract Development and Manufacturing Organization (CDMO) working with partners in the biopharmaceutical industry. They support the development and production of biologic, vaccines and advanced therapies. Amy’s work at Fujifilm Diosynth is a typical example for the implementation of Quality by Design and Process Analytical Technologies. She used a whole system approach to optimise processes. She developed models for cell cultivation and for ion exchange chromatography; finally she used an agent based modelling approach to combine the two models allowing overall process optimisation. The work proves the potential of agent based modelling for the bioprocessing industry to optimise processes and reach continuous high quality.

GlaxoSmithKline (GSK) is one of the leading global healthcare companies with 18 sites across the UK including its headquarter and four R&D sites. GSK focusses on three business areas: pharmaceuticals, vaccines and consumer healthcare. Emma worked in the Biotechnology and Environmental Shared Services a unit optimising biosynthetic processes for the production of pharmaceutical compounds, like antibiotics. She is looking at the whole process improving the strain screening, protein expression and purification. To complement the in laboratory optimisation she is doing cost analysis.

9 10

Application of Multivariate Data Analysis in Biopharmaceutical Production Host Company: Lonza Student: Elspeth Ritchie

Application of Multivariate Data Analysis and First Principle

Mathematical Modelling to the Biotechnology Industry

Host Company: Perceptive Engineering

Student: Stephen Goldrick

Lonza is one of the world’s leading suppliers to the pharmaceutical, biotech and specialty ingredients markets. Lonza is also offering integrated solutions. With the launch of the FDA’s Process Analytical Technology initiative companies are investing in the development of Multivariate Data Analysis methods. Elspeth developed software-based tools ranging from translation of high frequency online monitoring data as robust summary statistics with intuitive meaning to tools enabling potential reduction in confounding underlying variation in dataset structures through the use of alternative progression variables. Each tool was designed to fit into current and future planned ways of working at the sponsor company benefiting her host company.

Perceptive Engineering is a global company offering advanced automation and process control solutions. Stephen worked on the optimisation of upstream and downstream processing of biopharmaceutical facilities using first principal mathematical modelling and multivariate data analysis looking at the whole production process of a biopharmaceutical. Process Analytical Technologies were introduced at two points during the fermentation enabling on-line monitoring of critical parameters, i.e. glucose and product concentration. To improve control strategies further he performed a mathematical simulation of a fermentation based on historic data. In a similar manner he looked at the downstream processing implementing Design of Experiments. The optimisation lead to a significant increase in extraction yield. This projects shows the potential of Quality by Design to optimise whole bioprocesses.

11 12

A Framework for Enhancing Process Understanding Process Data using Multivariate Tools on Commercial Batch Process Data Host Company: Piramal Pharma Solutions Student: Matthew Molloy

Pharma and Industrial Biotechnology –

Up Stream

Piramal Pharma Solutions is a Contract Development and Manufacturing Organisation and offers end-to-end development and manufacturing solutions across the drug life cycle with facilities in North America, Europe and Asia. Matthew looked at historic batch data to develop a framework to gain insights into the process and to identify improvement potential. Today companies are using Quality by Design tools and Process Analytical Techniques in the development of new pharmaceutical. The same tools and techniques can be used to improve current production processes. Matthew’s framework uses multivariate modelling to identify steps that could be improved. He showed that small statistical differences can have an effect.

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Bioprocessing in Oscillatory Baffled Reactors (OBR): Enzymatic Saccharification Case Study Host Company: CPI - Centre for Process Innovation Student: Matthew Abbott

In Situ Product Recovery of Butanol from the Acetone Butanol Ethanol

Fermentation

Host Company: Green Biologics

Student: Victoria Outram

The CPI - Centre for Process Innovation is part of the Catapult network. Its open innovation model enables clients to develop products and prove processes with minimal risk. The CPI works in the areas biologics, industrial biotechnology, formulation, graphene and printable electronics. Matthew’s worked in the industrial biotechnology section investigating the use of oscillatory baffled reactors (OBR) in industrial settings. He modelled plug flow and OBR design to maximise functionality, established a protocol to maximise glucose production via enzymatic saccharification, proved the usability of OBRs for microalgae culture, and conducted a feasibility study on the use of OBRs for anaerobic digestion. Overall he established a range of potential commercial use of OBRs.

Green Biologics is a renewable specialty chemicals company focusing on developing differentiated, value-added products that are petroleum-based alternatives, e.g. acetone or butanol. The company uses solventogenic microbial strains which are used as biocatalysts as part of advanced fermentation processes. Many of the produced solvents are toxic for the cells. In situ product recovery can be applied in the fermentation process to counteract this. Many methods have been used in lab scale fermentation. Victoria looked into the application of the different methods at production scale. She performed a systematic techno-economic analysis taking into account the energy demand to identify the best method and performed optimisation of the most promising method.

15 16

Measuring, Monitoring and Control of Bioprocesses in Miniature Bioreactor Systems using Spectroscopy Technologies and Multivariate Data Analysis

Host Company: Lonza Student: Ruth Rowland-Jones

Application of Emerging Analytical Technologies for Characterisation of

Influenza Vaccines

Host Company: Novartis Pharmaceutical Student: Antonia Sofikiti

Lonza is one of the world’s leading suppliers to the pharmaceutical, biotech and specialty ingredients markets. Lonza is also offering integrated solutions. One area Lonza is working in is the production of biologics, like antibodies, expressed in mammalian cell cultures. Cell culture process development requires the screening of large numbers of cell lines and expression conditions. Ruth investigated the use of miniature bioreactors. Even though they allow screening of many cell lines and conditions they don’t allow monitoring during process due to the small volume. Ruth examined the use of spectroscopy technologies to resolve this limitation identifying one of those as a suitable method.

Novartis was founded in Switzerland is now one of the largest pharmaceutical companies. The company comprises three divisions: Innovative Medicines, Sandoz and Alcon. Antonia worked at Novartis Vaccine an egg-based influenza vaccine manufacturing site. Egg-based vaccine manufacturing is the most common production method. Antonia looked into the use of nanoparticle analysis to monitor the entire manufacturing process. She was able to identify the most suitable method and developed a novel application to determine virus growth in the allantonic fluid allowing monitoring at a very early stage.

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Carbon Dioxide Control in Bioreactors and the Application of Principal Component Analysis to Cell Culture Process Data Host Company: Pall Life Science Student: Kerem Irfan

Design of an Integrated Monitoring and Optimal Control System for

Supervisory Operation of Anaerobic Digesters

Host Company: Perceptive Engineering

Student: Grace Opong

Pall Life Sciences provides solutions for customers who discover, develop and produce biotech drugs, vaccines, cell therapies and classic pharmaceuticals. With an initial expertise in filtration and separation Pall Life Science moved into cell culture solutions. Kerem worked on the development of bioreactors. He investigated research into the effect of CO2 concentration on mammalian cell cultures, a critical process parameter that is not well understood. With a combination of laboratory experiments and multivariate data analysis he was able to gain in depth process understanding aiding scaling up of the cell culture and reactor design.

Perceptive Engineering is a global company offering advanced automation and process control solutions. Grace worked with 4 of Perceptive Engineering clients to optimise anaerobic digestion (AD). The lack of inline analytical instrumentation is a bottleneck in AD. The lack of online control leaves uncertainties that prevent efficient process optimisation. Grace could show the economic advantages of introducing process control mechanisms by performing a financial analysis. She was as well able to develop an inferential sensor based on real life data to measure volatile solids.

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Bioprocessing in Microalgae Host Company: ScotBio Student: Chelsea Brain

Pharma and Industrial Biotechnology –

Down Stream

ScotBio, formerly Scottish Bioenergy, is a small start-up company based in Scotland producing a natural food colourant. Chelsea joined the company when it was rethinking its business model. Based on a business analysis that Chelsea performed the company decided to move from making bioenergy from algae to producing natural food colourant. Practical work led to the development of a new protocol to overexpress the blue pigment in Spirulina by 250% making the process feasible for industrial scale production. The project gave a boost to the company, which is now breaking successfully into the natural food dye market.

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Continuous Spray Freeze Drying Host Company: Accelyo Student: Andrew Tait

Advanced Analytical and Microbial Methods for Biopharmaceutical and

Pharmaceutical Products and Processes

Host Company: GlaxoSmithKline

Student: Charlotte Bell

Andrew worked with the small start-up company Accelyo. Accelyo are developing a scaleable continuous manufacturing platform to produce high value products, such as hierarchically structured nanomaterials, biologics, low solubility pharmaceuticals, and high surface area catalysts, by lyophilisation. Andrew worked on the development of a proof of concept unit which allows to intensify the lyophilisation process by increasing the heat and masstransfer capabilities through reducing the volume to nanolitre scale. To assure uniform product quality a numerical model was developed and a computational fluid dynamics study carried out for predicting product characteristics, determining process parameter boundaries, and understanding equipment limitations. Andrew designed an on-line Process Analytical Technology (PAT) device for the monitoring and control of the lyophilisation process.

GlaxoSmithKline (GSK) is one of the leading global healthcare companies with 18 sites across the UK including its headquarter and four R&D sites. GSK focusses on three business areas: pharmaceuticals, vaccines and consumer healthcare. Charlotte focussed on advanced analytical and microbial methods, like Rapid Microbiology Methods to detect contaminants, stability testing to identify oxidative damage and container integrity testing. Her work plays an important role in the production, formulation and storage of biopharmaceuticals since the challenge here is to maintain the integrity of the protein structure.

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Improving the Process Understanding and Capability of the Filling Unit Operation within the Manufacturing Process for Multi Dose Powder Inhalers Host Company: GlaxoSmithKline Student: Chris Davies

Optimisation and Modelling of the Spiral Jet Mill

Host Company: GlaxoSmithKline

Student: Rory MacDonald

GlaxoSmithKline (GSK) is one of the leading global healthcare companies with 18 sites across the UK including its headquarter and four R&D sites. GSK focusses on three business areas: pharmaceuticals, vaccines and consumer healthcare. Dry powder inhalers are an important vehicle for many of GSK’s products. Chris investigated the combined effect of filling equipment parameters and powder formulation. Usually these two factors are looked at separately. Chris used, in line with the Quality by Design approach, a combination of lab scale experiments, commercial scale testing and multi variate data analysis. By better understanding the whole processes Chris was able to identify potential to speed up filling processes and make them more economic without scarifying the quality.

GlaxoSmithKline (GSK) is one of the leading global healthcare companies with 18 sites across the UK including it’s headquarter and four R&D sites. GSK focusses on three business areas: pharmaceuticals, vaccines and consumer healthcare. Jet mills are widely applied and robust apparatus to reduce the particle size of powders. GSK is using jet mills for a variety of their production processes. So far the scale up is poorly defined and mill design is sup-optimal in respect to energy efficiency. Rory developed a model to help to understand the interaction of different parameters during the milling process leading to a proposed scale up methodology. Using computational fluid dynamics analysis he was able to optimise the jet mill design.

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API Dissolution Kinetics: From Single Particle to Powder Behaviour Host Company: Pfizer Student: Aatika Rizvi

The Application of Statistical Concepts

and Methodology to the Solution of Practical Problems in Process

Characterisation, Modelling and Understanding

Host Company: UCB

Student: Nickolas Whitelock

Pfizer is a world leading biopharmaceutical companies, discovering, developing and providing over many medicines, vaccines and consumer healthcare products. The first step in drug uptake is dissolution. Thus dissolution is fundamentally important for the performance of pharmaceuticals. So far little attention has been paid to the crystal properties of organic/ bio-molecules. Aatika’s project focussed on the characterisation of organic, pharmaceutical active substances. Her work takes in the whole behaviour spectrum from single particle to powder behaviour using a variety of experimental and analytical methods. She focussed on a number of substances representative for the most common organic pharmaceuticals.

UCB is a global biopharmaceutical company, with a focus on neurology and immunology, active in manufacturing as well as R&D. Nicholas investigated the predictability of manufacturing scale of chromatography by microscale experiments. Liquid handling robots are playing an important role in the early stages of process development. They allow cost and time efficient testing of process conditions. There are essential difference between the robot and Fast Protein Liquid Chromatography (FPLC) as used during production, namely column symmetry, flow rate, flow pressure. Nickolas performed a range of small microscale experiments, which are the basis for a mechanistic model. This model takes into account scale, hydrodynamic and operational effects to predict large scale performance.

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Pharma and Industrial Biotechnology – Product Development

Computer Aided Classification of

Histopathological Damage in Images of Haematoxylin and Eosin Stained

Human Skin

Host Company: Alcyomics Student: Juliana Haggerty

Alcyomics is a Newcastle University spin out company that offers human in vitro pre-clinical safety testing to ensure drug safety and efficacy before first administration into man using Skimune®, a non-artificial human skin explant. Juliana worked on an automated computer based grading procedure. The approach combines expert knowledge with computational numerical capability and accuracy. Expert knowledge was used to identify features of interest. Similar to other BBTC projects historical data were used for model development. To design and optimise the process wrapper based feature selection and automated training of a classification model were employed. By automating the assay evaluation Skimune® the analysis time is reduced and the results are robust and reproducible.

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The Discovery and Characterisation of Novel Antibiotics from Amycolatopsis Isolate DEM30355 Host Company: Demuris Student: Bernhard Kepplinger

Approaches to Natural Product

Antibiotic Discovery from Actinomycetes

Host Company: Demuris

Student: Olga Chrobak

Demuris is a Newcastle University spin-out company with a focus on the discovery of natural products. The starting point for Demuris’ portfolio of new drug development lies in a vast collection of Actinomycete bacteria. Bernhard used the strain collection to identify new antibiotics. Actinomyces are the key source for natural antibiotics and most of the common antibiotics are synthetic derivatives of such. He isolated a strain that showed activity and was able to identify 3 new antibiotics. The compounds were characterised and genomic analysis lead to a proposed biosynthesis.

Demuris is a Newcastle University spin-out company with a focus on the discovery of natural products. The starting point for Demuris’ portfolio of new drug development lies in a vast collection of Actinomycete bacteria. Olga set out to investigate several approaches to identify new natural antibiotics to find the optimal method. She focussed on guided isolation, genome analysis, expression of orphan biosynthetic gene clusters, and an omics approach. All approaches led to the identification of new active components. Comparison of the methods concluded that there is not a one best approach to identify new antibiotics but that the different approaches complement each other.

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Application of Multivariate Data Analysis to Improve and Optimise Industrial Processes Host Company: Demuris Student: Nicola Taylor

Human-Microbiota Interactions in

Health and Disease: Bioinformatics Analyses of Gut Microbiome Datasets

Host Company: GlaxoSmithKline Student: Matthew Collison

Demuris is a Newcastle University spin-out company with a focus on the discovery of natural products. Nicola worked with a so far uncharacterised strain to identify new natural antibiotics. The strain she worked with is from an extreme environment. Already classical methods led to the identification of active compounds even though those were already known. Nicola then investigated new growth conditions for the strain that are closer to the natural conditions. Coculture screening of the strain with others showed promising results and several strain combinations are further investigated.

GlaxoSmithKline (GSK) is one of the leading global healthcare companies with 18 sites across the UK including its headquarter and four R&D sites. GSK focusses on three business areas: pharmaceuticals, vaccines and consumer healthcare. Matthew applied bioinformatics analysis of gut microbiome datasets. The gut microbiome is crucial for human health and chronic diseases often cause its dysfunctionality. Due to advances in culture independent metagenomic sequencing technologies vast amount of genomic data are available today. Matthew’s work is a way to make sense out of these data. He worked on 2 case studies: one focussed on the effect of antibody treatment the other one on the connection between protease frequency and glycan degradation. Both studies prove the practicability of this approach.

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Synthesis of Fluorescent Phosphorus Ligands and their Applications in Medical Imaging and Catalysis Host Company: High Force Research Student: Jennifer Wallis

The Design and Synthesis of Novel

APIs Based Upon Topiramate

Host Company: Onyx Scientific

Student: Gillian Moore

High Force Research is a chemical research and development company specialised in chemical synthesis and R&D for the pharmaceutical, biotechnology and fine chemicals industries. Jennifer worked on a novel fluorescent dyes, which is hoped will be able to be used as imaging agents to help potentially identify cancer cells. She proved that primary phosphines, which have a reputation of being toxic, can be used in this application.

Onyx Scientific is a chemistry contract research organisation. Onyx specialises in chemical and active pharmaceutical ingredients (API) manufacturing services to support life science clients. Gillian’s project was to identify new APIs hat are based on a known antiepileptic drug. This drug shows a complex activity pattern and derivates could be used to treat a range of other medical conditions. Gillian classified target activities and used extensive in silico modelling to identify potential new active components. Based on the modelling was the basis for chemical synthesis of the most promising candidates.

35 36

Cell & Gene Therapy

Novel Scaffolds to Support the Rejuvenation of Aged Cells for

Osteoarthritritis Therapy

Host Company: Arthritis Research UK Student: Kimberley Green

Kimberley worked at the Arthritis Research UK Tissue Engineering Centre based in York. The centre aims to develop treatment for earlier stages of arthritis, to slow down progression and defer the need for a joint replacement. She modelled the mass transfer of oxygen and glucose in a 3D cell culture system with the view to develop scaffold culture. 3D cell cultures are of great importance because they mimic real life conditions unlike the classical 2D cultures. Oxygen and glucose are essential for cell proliferation. Understanding their mass transfer is critical for the success of 3D cultures.

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Development and Characterisation of a Cytokine Supplemented Serum Free Medium Formulation for Bone Marrow Derived Mesenchymal Stromal Cells Host Company: Arthritis Research UK Student: Steven Wilkinson

Process Development for the Scalable Production of Human Multipotent

Adult Progenitor Cell

Host Company: Athersys

Student: William Milligan

Steven did his EngD at the Arthritis Research UK Tissue Engineering Centre based in Newcastle upon Tyne. The centre aims to develop treatment for earlier stages of arthritis, to slow down progression and defer the need for a joint replacement. Steven’s aim was to develop a defined, serum-free medium to expand Mesenchymal Stromal Cells. These cells can be isolated from bone marrow and used to reconstruct bone tissue in arthritis patients. The serum-free medium William developed is highly defined and low priced. The medium is an alternative to commercial media currently available for academic and commercial research.

Athersys is a medium size company, which developed a stem cell product platform for multiple disease indications in the areas of neurological, cardiovascular, inflammatory and immune disease areas. William’s project focused on the scalability of cell cultures. He investigated the use of microcarriers in suspension cultures of Multipotent Adult Progenitor Cells. He characterised growth behaviour in small scale suspension culture and performed correlation analysis to upscale to large scale cultures in bioreactors. The economic assessment showed the potential to save up to 83% production cost.

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Development of Predictive Modelling Approaches for Lentiviral Vector Process Development Host Company: OxfordBiomedica Student: Jakub Krakowiak

Characterisation of HEK293T Cells

Host Company: OxfordBiomedica

Student: Kirstie Pemberton

OxfordBiomedica is a dynamic SME. Based on their unique LentiVector® delivery platform, they created a portfolio of gene and cell therapy product candidates in the areas of oncology, ophthalmology and CNS disorders working with many national and international companies. Jakub used an approach combining MALDI-ToF and multivariate data analysis to analyse cell and lentivirus vector samples. By investigating different scales and different culture methods Jakub improved the characterisation of vectors and cells. This method can be used for accurate cell line prediction, accelerating cell line development, improving cell selection and reducing campaign time.

OxfordBiomedica is a dynamic SME. Based on their unique LentiVector® delivery platform, they created a portfolio of gene and cell therapy product candidates in the areas of oncology, ophthalmology and CNS disorders working with many national and international companies. Kirstie’s research project is focussing on the characterisation of lentiviral vector production from HEK293T cells with regards to the cellular pathways and culture kinetics. The project looks at the impact of different cell lines, culture modes, process parameters, viral vector species and how they affect the productivities of both functional and non-functional vector particles. By developing a good understanding of what factors drive lentiviral vector production and ultimately how they can be manipulated to maximise vector yields towards the development of improved manufacturing processes for lentiviral vector-based gene therapies.

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Multifactorial Analysis of Mesenchymal Stem Cell Properties for Storage and Transportation Host Company: Tower Cold Chain Solutions Student: Fabio D’Agostino

Cleaning and Emission Control

Tower Cold Chain Solutions provides rental services of a range of passive, reusable temperature controlled containers for the specialised logistics industry. They as well develop new temperature controlled transport solution and perform qualification tests in their environmental chambers for customers. The development of living cells for cell therapy is causing a new challenge for the logistics industry and its suppliers. Fabio worked on a novel storage and transport solution that combines temperature control and variable oxygen tension over a specific shelf life time. He developed a predictive model that allows to identify the correct transport/ storage conditions for specific cell lines.

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Computational Fluid Dynamic Modelling of Benzene Abatement Using Cryogenic Condensation Host Company: Aesica Student: James Hendry

A New Method for the Analysis of

Pharmaceutical Plant Cleaning Strategies

Host Company: Britest

Student: Wendy Carr

Aesica is a leading pharmaceutical contract development and manufacturing organisation for active pharmaceutical ingredients (API) and finished dose forms with five development and manufacturing sites in the UK, Germany and Italy. James worked at the Cramlington site. The main focus of his work was to assess the applicability of cryogenic condensation to control the benzene emission. The advantage of this method in the environment of a pharmaceutical plant is that it can utilise the cooling potential of the existing nitrogen infrastructure. A fluid dynamics model using an Eulerian-Lagrangian (DPM) approach was used to identify if the method is suitable. James was able to show that 97% of benzene can be captured with 1% escaping as particulate. Together with an adsorption polishing step the company will be able to meet the emissions limit. This approach is energy efficient and cost saving.

Britest is a not-for-profit, membership-based organisation working with the chemical, pharma and biotech industries. One of the ways to help their members are the Britest tools. These tools are a suite of qualitative instruments and methods that help to identify areas where optimisation may be possible and also increase the understanding of the process as a whole across a range of disciplines. Originally focussed on the chemical and pharma industry Britest started working with the biotech industry around the time Wendy joined. She looked at plant cleaning in the pharmaceutical industry using Principle Component Analysis (PCA). Based on her analysis she developed a new tool to support the design of manufacturing processes taking cleaning into account from early stages of development. This tool complements Britest’s offer.

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Improvement and Optimisation of Industrial Process Cleaning in the Brewing Industry Host Company: Heineken Student: Charlotte Atwell

The Development of Sustainable Systems for Resource Efficiency

Host Company: Shasun

Student: Dan Mullen

Heineken is an international brewing company with 5 breweries and cider mills in the UK. Newcastle University and Heineken worked together as part of the Zero Emissions and Cleaning (ZEAL) consortium, a group of British companies and universities aiming to explore the benefits of the optimisation and reduction of Cleaning in Process (CIP). Charlotte’s worked build on this reation ship. She used classical Quality by Design tools to characterise and optimise the cleaning procedure and classify optimisation capacity in Heineken’s cider mill. Her work led to the reduction of chemical and water consumption, of effluent costs and of production down time. Her work demonstrated that real-time cleaning modelling is possible and is now implemented as part of a company-wide improvement project.

Shasun is formulations partner for the pharmaceutical industry. Its services include formulation research & development activities, analytical method development and validation, scale-up & technology transfer, and full scale commercial manufacturing of oral solid dosage forms. Emission control is an important factor in any manufacturing industry. Dan looked at opportunities to improve the wastewater qualification. He developed a dynamic mathematical model of the wastewater treatment plant to understand the effects of mixing, dilution and treatment of effluents. To complement the model he used a pilot scale rig. The work is now implemented in the company.

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Food & Consumer Goods

In-line Near-Infrared Spectroscopy as a Process Analytical Technology Tool for

Monitoring and Control in Food Processing

Host Company: British Bakels Student: Angela Barone

British Bakels is part of Bakels one of the leading manufacturers and distributers of high quality bakery ingredients to the global bakery market. Angela worked on a new quality control method that makes use of Near-Infra Red spectroscopy. This method is the first to allow quality control throughout the production process allowing to identify failed batches early on. She was able to implement the method for powder mixes and for the first time ever for caramel, something that seemed to be impossible due to the opaqueness of the caramel. Angela’s work led to economic savings for the company, minimisation of human error and higher customer satisfaction.

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Actinobacterial Fatty Acid Extracts are a Source of Cosmetic Active Ingredients that Modulate Peroxisome Proliferator Activated Receptor Y Host Company: Croda Student: Jodie Symington

Control of Detergent Properties in a Spray Dryer Process

Host Company: Procter & Gamble Student: Mark Crosby

Croda is a manufacturer of speciality chemicals that deliver real benefits to a range of diverse products including health and beauty, engine lubricants, plastics and many more. Jodie established a protocol to extract fatty acids that interact with a cellular receptor from actinobacteria. This particular receptor is involved in the adipogenic pathway of human cells and is controlling fatty acid uptake. Decrease of fatty acid uptake can result in a loss of hypodermal skin volume causing the skin to wrinkle and age. The protocol Jodie developed enables her host company to identify new natural products that can be used in the cosmetics industry.

Procter & Gamble (P&G) is a multi-national consumer goods company specialising in a wide range of personal health/consumer health, and personal care and hygiene products. P&G is also producing washing detergents. To produce washing powder spray dryers are commonly used. In his project Mark investigated the control of moister content, particle size and bulk density properties using a combination of pilot plant experiments and modelling. He generated a model for the whole process based on this. This model can be used to control the spray drying process and for simulation studies.

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Investigating Dry Powder Rheology within Large-scale, Counter-rotational, Intermeshing Twin-Screw Mixers (TSMs), via Digital Image Processing (DIP) and Positron Emission Particle Tracking (PEPT)

Host Company: Procter & Gamble Student: Sean Clifford

Improving Personal Care Product Quality using Innovative Data Analysis

and Measurement Techniques

Host Company: Unilever

Student: Joana Figueiredo

Procter & Gamble is a multi-national consumer goods company specialising in a wide range of personal/consumer health, and personal care and hygiene products. Solid mixing is an essential part of many processes in the consumer goods or pharmaceutical industry but mixing processes are often inefficient. Twin-screw mixing is a method that shows great promise. Sean investigated the dry powder transport phenomena in twin-screw mixers using Positron Emission Particle Tracking and Digital Image Processing. This is one of a few studies in this area and established a novel, robust framework for efficiently characterising powder rheology.

Unilever is a British-Dutch transnational consumer goods company. Its products include food and beverages, cleaning agents and personal care products. Joana investigated the feasibility of new analytical instrumentation in personal care production. Joana focussed on antiperspirant spray, antiperspirant aerosol and hair care products. She was able to determine quality control protocols for each of these products and identified process conditions that cause batch failure. Her work allows the company to improve production and to prevent product failure.

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Process Industry: Oil & Gas

Optimisation and Scheduling of

Industrial Gas Supply and Storage Networks

Host Company: BOC Student: Richard Adamson

BOC is part of the Linde Group and the UKs leading specialist gas supplier. Adam worked on one of BOC’s tonnage sites. These sites produce gases exclusively for major industrial complexes like steelworks allowing round-the-clock supply of oxygen, nitrogen, argon, hydrogen and air. Tonnage sites are highly complex and often organically grown. The challenge is to run these sites energy and financially efficient while fulfilling the customer’s demand. Richard developed a system to optimise the production across the entire tonnage site in accordance with the customer demand. He took process disturbances, power price fluctuations and machine availability into account and focussed on the use of renewable energy. The new control system led to savings for BOC and raised customer satisfaction.

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Integrated Small Scale Gas to Liquids: Bridging the Gap for Oilfield Development Host Company: CompactGTL Student: Ben Dannatt

Addressing the Challenges of Crude Oil Processing Utilising Chemometric

Approaches

Host Company: Intertek Student: Frederick Stubbins

Compact GTL is a company offering solutions to convert problematic gas into high value liquids at the point of production. Dealing with associated gas at remote locations poses fundamental challenges to oil companies, where there is no commercially viable or technically feasible market for the gas or disposal methods. Ben worked on the process development for a modular Gas-to-Liquid process. By using a hybrid approach he improved the process understanding needed in the design phase of this complex process. He also developed a model to recommend the ideal flue gas filtration for biogas production taking into account performance, maintenance and economic benefit. Flue gas filtration is often overlooked as an opportunity for process improvement.

Intertek is a leading Total Quality Assurance provider to industries worldwide covering a wide range of sectors. Fredericks study addresses crude oil processing issues. The work can be divided into three areas: enhancing the understanding of crude oil quality, hydrocarbon stability in crude oil blends, and utilisation of process data for a better understanding of the process. Frederick adopted a classical Quality by Design approach for the oil industry. By using inline control methods, based on Near Infra-Red spectroscopy, he was able to generate tools for predicting physical properties of crude oil and plant fouling.

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BBTC Impact

Student Employment The BBTC educated students to work on the interface between biology, chemistry and engineering to develop better decisions and design tools for more efficient, cost effective (bio)processes. Most of the BBTC students and alumni are now in fulltime employment and the majority works in a relevant sector as engineer, scientist or manager using the skills they developed during their doctorate:

14 work in the process and pharma industry as engineer or scientist

7 students are in managerial or consultant roles in the processing industry or engineering consultancy sector

8 students are still with their host company; out of those 6 continue their EngD work and 2 moved into a managerial role

6 students stayed in academia and are currently Research Associates or Teaching Fellows

Top employers of the BBTC students are GSK, Centre for Process Innovation, Fujifilm Diosynth and AstraZeneca

The BBTC researchers left a lasting effect at their host company by:

helping to improve processes and increase product quality

influencing technical standards and protocols in the industry

impacting business performance leading to financial benefits

having an impact on the environment or society by reducing pollution and making products more affordable

Originally focussing on the pharma and consumable industries over time we started working with other processing industries. Our approach stayed the same: understand, measure, model, interpret and hence manipulate the biological and/or process system.

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Newcastle University

Contact Us

For more information contact:

Dr. Iris Lüke Bioprocessing & Biotechnology Centre - School of Engineering – Merz Court Newcastle NE1 7RU, United Kingdom

Phone: 0044 191 208 5958 Email: ceambbtc@newcastle.ac.uk Or visit our homepage: www.ncl.ac.uk/bbtc

We at Newcastle University are committed to delivering pioneering research that makes a positive impact in the world. Our research tackles international challenges to improve lives and influence policy around the world. We have one of the largest European Union research portfolios in the UK. Our research partnerships span the globe, including strategic partnerships with Monash University in Australia and Groningen University in the Netherlands. Newcastle University researchers are also working with international partners to tackle global challenges such as ending poverty and cutting sugar consumption through our Global Challenges Academy.

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