Investigation of Cleaning in Place for Fermentation
Based Processes

Charlotte Atwell’s EngD Biopharmaceutical Process Development research project will be in collaboration with Heineken, the UK's leading beer and cider business.

The project will initially investigate the cleaning benefits analysis tool for application within the brewery environment. While this will be a relatively short task it will introduce Charlotte to the process detail and allow her to understand the scope of the task across the brewery and also the transferability between sites.

Alongside this she will develop predictive models of the cleaning progression on selected unit operations within the brewery. In doing so, it will be necessary to encapsulate a measure of variation to get a confidence indication of the prediction. Other tasks will include the building of a predictive model within a control / optimization strategy. This will exploit the financial indicators from the benefits analysis to specify the objective function of the optimization.

Decisions made will potentially change cleaning policy to maximize benefit while accounting for process variation. Finally a number of case study trials on brewery equipment to consider effectiveness and transferability between brewery sites.

Bioprocessing of Lipid Rich Microalgae: Novel Approaches to Whole Process Modelling and Optimisation

Chelsea Brain is undertaking her EngD Biopharmaceutical Process Development project jointly between the Dove Marine Laboratory and Scottish Bioenergy. The project will draw on the challenges raised by Scottish Bioenergy who are currently developing algal photobioreactors for bioremediation of whisky distillery waste.

The early stages of the project will be concentrate on the optimisation of the existing commercial algae biosystem. This will include modelling the relationship of waste water throughput with growth rate, calculating optimal configurations of modular reactors and the effect on carbon dioxide capture from flue gas, and calculating how much waste water and at what BOD can be treated without killing
the algae.

The work will be mainly carried out at the research laboratories at the Dove Marine Laboratory and the Biopharmaceutical Bioprocessing Technology Centre at Newcastle University where mathematical modelling and chemical engineering principles will be applied in a 'whole systems' approach. In parallel to data analysis and modelling, the project will explore the potential of algal strains relevant to the production of high-value oils, with a view to ultimately introducing these new strains into the commercial system at the Glenturret Distillery.

Comparative Genomics of the Human Mucosal Microbiota

Matthew Collinson’s EngD Biopharmaceutical Process Development project is in collaboration with GlaxoSmithKline (Stevenage) and the School of Computing Science. The underlying research will be based around the use of grid computing to analyze metagenomic data and study gene expression in the gut microbiome at different states
of health.

This project builds on recent developments in DNA sequencing technologies which have made genomic data much more accessible through projects like the human genome and human microbiome projects. He will be using a computational infrastructure ‘MicroBase’ developed at Newcastle University for analysis and it is anticipated that the project will move towards future applications in terms of manipulating the microbiome for medical advances.

Process Control of Spray Drying Towers

Mark Crosby’s EngD Biopharmaceutical Process Development research project is in collaboration with Procter & Gamble (Longbenton, Newcastle). P&G dry laundry business is rapidly increasing volume in our developing markets where capacity will be doubled in the next 10 years.

There is therefore the need to develop smart ways to increase plant capacity via optimization of operation. At the same time, formulations are evolving towards narrow processing windows originating this traditional process becomes more sensitive to changes on the properties of intermediate products such as blown powder. Accordingly an improved control of the properties of the powder will have impact on some of the reliability issues that occurs with higher frequency on the traditional process such as; over packing, segregation and emissions.

From the 52 current recognized outputs coming from the spray drying process moisture, density and particle size distribution of the blown powder has been identified as some of the critical properties that will influence the opportunities highlighted above. Accordingly the following objectives have been defined for the following project on process control strategy: (i) reduce time to reach production of acceptable quality product and (ii) improve control of output variables during steady state (Accuracy, standard deviation).

Realising the Benefits of Advanced Process Monitoring in Biopharmaceutical Manufacturing

Stephen Goldrick is sponsored for the EngD Biopharmaceutical Process Development by Perceptive Engineering Ltd, who are based in Warrington in the UK. They are a monitoring and control systems vendor and consultancy company who specialise in applications within the process and utility sectors. In the EngD programme Stephen is tackling a number of case study problems for pharmaceutical manufacturing clients of Perceptive Engineering where improved process monitoring and control will lead to process quality improvements.

The first case study for a biopharmaceutical manufacturer in the North West of England commenced by contrasting the capabilities of commercial process monitoring software and is comparing this against application need, with specific reference to the issues raised in biomanufacturing. Subsequent studies will build on this to consider aspects where generic approaches suffice and where application specific approaches are required.

The Challenges of Scale Up of Bioprocesses

Kerem’s EngD Biopharmaceutical Process Development project is in collaboration with Pall Life Sciences, based in Portsmouth. An array of bioreactors will underpin the project and the aim will be assess scalability to stir tank reactors and larger reaction vessels. The goal is to investigate the health of the system and the associated environment and to identify if the parameters are scalable.

The basis of the approach will be through the collection and interpretation of data generated under a variety of conditions. Kerem will be engaged in both the undertaking of the experiments to understand how the data was generated and the associated issues as well undertake the subsequent analyses.

There would also be the opportunity to introduce new sensors to capture additional information that would assist in the characterization of the process. In the longer term there would potentially be the opportunity to assess the impact of a process on the subsequent purification process.

Purification and Analysis of Novel Antibiotics
from Actinomycetes

Bernhard Kepplinger’s EngD Biopharmaceutical Process Development project is with Demuris a spin-out company from Newcastle University. The objective is to find lead compounds, in particular antibiotics, from Actinomycetes.

The project will involve the purificationof the Antibiotics from the supernatant at a smallscale with a variety of chromatography methods, followed by chemical characterisation and biological analysis of novel antibiotics in order to face to future demand for antimicrobials with a new mode of action. The research is being undertaken in collaboration with staff at Newcastle University Medical School.

Full-scale Multistage Batch Chemical Synthesis, Process Standardisation & Optimisation

The EngD Biopharmaceutical Process Development project that Matthew Molloy is working on offers the opportunity to study an Active Pharmaceutical Ingredient (API) process with a view to identifying routes to a sustained improvement in product yield.

The research project is in collaboration with Piramal Healthcare. The goal is to develop approaches to reducing the variability in the multi-stage batch chemical synthesis, of the active pharmaceutical compound.The aim is to identify the causes of variability and therefore develop automatic controls, trips/alarms and preventative/corrective measures to keep the process running at the optimal point.

More specifically the aim is to assess the current state of the process with respect to process standardisation and mass balance, assessment of the causes of yield loss based on testing anecdotal evidence and analysis of data; identify critical operating parameters upon which to standardise the process and implement improvement projects to support improved manufacture.

Advanced Process Control for Continuous
Pharmaceutical Production

John Palmer’s project, Advanced Process Control for Continuous Pharmaceutical Production, will be in collaboration with GEA Pharma Systems Technology group in Eastleigh.

The project will be looking at applying process systems approaches to a continuous tablet production process. It will involve the modelling of the process with different tablet formulations and the design of advanced control systems on the process. He will have the opportunity to work and implement his research on both pilot scale equipment and also full scale production.

The key outputs in the first instance will include process models to improve process observation and process control based on engineering understanding of the process.

The Application of Multivariate Analysis Techniques in Biopharmaceutical Development

Elspeth Ritchie’s EngD Biopharmaceutical Process Development project is in collaboration with the industrial sponsor Lonza Biologics. Her research project will comprise a variety of related subprojects employing the development and application of multivariate statistical data analysis and other analytical techniques across a range of production steps.

More specifically the project will be an umbrella encapsulating a number of smaller projects all applying key process analysis techniques to Lonza’s processes for the production of recombinant proteins in mammalian cells. It is expected that these smaller projects will include studies in areas such as instrumentation, multivariate analysis of historical process data and the use of design of experiment techniques for process development and process robustness assessment.

Fundamental Understanding of the Underlying Science of Plant Cleaning

The EngD Biopharmaceutical Process Development research project that will be undertaken by Wendy Carr will be in collaboration with Britest Ltd. Britest is a leading not-for-profit company, acknowledged internationally for its expertise in delivering tangible benefits to member companies through the successful development and structured deployment of innovative process solutions.

The focus of research project will be pharmaceutical plant cleaning as this is an area that has been identified by Britest member companies as an area where Britest methodological approaches will add value. There are significant costs associated with plant cleaning (lost opportunity, use of solvent, manpower, etc). This project aims to reduce these costs by developing a scientific understanding of plant cleaning and a methodology to develop “right first time” cleaning protocols.

Wendy graduated from Sunderland University with a BSc in Applied Biology. Following this she worked within the biopharmaceutical sector for a variety of companies including MSD Billingham, Millipore and Cobra biomanufacturing now known as Recipharm. The EngD project will be looking into plant cleaning methodologies and understanding the science behind them.