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Biochemical Engineering

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Macromolecular Bioprocessing

The focus is on the creation of scalable processes for the cost-effective manufacture of macromolecular therapies. This is achieved by using advanced high throughput engineering tools for bioprocess design and scale-up.

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Research in Macromolecular Bioprocessing is headed by the £6M EPSRC Centre for Innovative Manufacture in Emergent Macromolecular Therapies, and an associated EPSRC Centre for Doctoral Training, hosted in the Department of Biochemical Engineering with collaborations from across UCL (Schools of Pharmacy, Dept. of Chemical Engineering, Dept. Public Health Economics) and from Imperial College (Dept. Chemical Engineering). The focus is to create a set of methods and tools by which early identification of a new molecule’s ease of manufacture can be assessed alongside clinical effectiveness and costs of manufacture and also the cost of formulation and delivery to the patient. The ultimate objective is to achieve efficient conversion of potent new therapies to the patient at a cost which the NHS can afford. Centre studies are complemented by work to consider the ways in which bioprocesses are developed for the manufacture of complex and highly specific next-generation biopharmaceuticals.

Figure 1: The macromolecules we study are complex in nature and understanding their behaviour under processing conditions is often crucial

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Activities include host cell engineering to overcome process bottlenecks, the creation and use of automated microscale bioprocessing techniques and modelling tools for intelligent experimentation and rapid bioprocess optimisation. Additional studies include the assessment of alternative manufacturing strategies for the production of new molecules and embrace options such as continuous processing and the application of single use routes to industrial practice. The use of advanced facilities to examine scale-translations underpins the work in the research group.Integration of USD approaches with advanced engineering of bacterial (with Warwick University) and mammalian (with Kent University) expression systems through £3.7M of joint BBSRC-EPSRC Bioprocessing Research Industry Club (BRIC) awards.

Figure 2: Advanced robotics are used to collect process data at miniaturised scales of operation

  • Ultra Scale-Down (USD) of key unit operations for the recovery & purification of micromolecules
  • Microwell methods for the rapid screening of process options
  • Advanced methods for assay deployment and for efficient experimental design
  • Decisional tools for the better integration of business and process decision making
  • Assessment of manufacturing alternatives including life cycle analysis
  • Biophysical characterisation of protein heterogeneity and aggregation mechanisms
  • Formulation and protein engineering to maximise product shelf-life

Allmendinger R, Simaria AS, and Farid SS. (2014) Multiobjective evolutionary optimization in antibody purification process design. Biochem Eng J, 91, 250-264. doi: 10.1016/j.bej.2014.08.016

Allmendinger R, Simaria AS, Turner R and Farid SS. (2014) Closed-loop optimization of chromatography column sizing strategies in biopharmaceutical manufacture. J Chem Tech Biotechnol, 89 (10), 1481–1490. doi:10.1002/jctb.4267

Aucamp JP, Davies R, Hallet D, Weiss A and Titchener-Hooker NJ. (2014) Integration of host strain bioengineering and bioprocess development using ultra-scale down studies to select the optimum combination: An antibody fragment primary recovery case study. Biotechnol Bioeng., Vol 111, Issue 10, 1971-81, doi:10.1002/bit.25259

Siganporia CC, Ghosh S, Daszkowski T, Papageorgiou LG, Farid SS. (2014) Capacity planning for batch and perfusion bioprocesses across multiple biopharmaceutical facilities Biotechnol Prog, 30 (3), 594-606. doi:10.1002/btpr.1860

Velayudhan A. (2014) Continuous antibody purification using precipitation: An important step forward. Biotechnol., Volume 9, Issue 6, 717–718. doi:10.1002/biot.201400098

Yang Y, Farid SS, Thornhill NF. (2014) Data mining for rapid prediction of facility fit and debottlenecking of biomanufacturing facilities. Journal of Biotechnology, 179, 17-25. doi:10.1016/j.jbiotec.2014.03.004

Gerontas S, Lan T, and Titchener-Hooker NJ. (2013) Evaluation of a structural mechanics model to predict the effect of inserts in the bed support of chromatographic columns, Abstracts of papers of the American Chemical Society, 245.

Konstantinidis S, Kong S, and Titchener-Hooker NJ. (2013) Identifying analytics for high throughput bioprocess development studies. Biotechnol Bioeng, 110 (7), 1924–1935, doi:10.1002/bit.24850

Ramasamy S, Titchener-Hooker NJ, and Lettieri, P. (2013) Challenges of developing decision-support LCA tools in the biopharmaceutical industry. Proceedings of the Fourteenth International Waste Management and Landfill Symposium, S. Margherita di Pula, Cagliari, Sardinia, Italy; 30 September – 4 October

Tetteh E and Morris S. (2013) Systematic review of drug administration costs and implications for biopharmaceutical manufacturing. Applied Health Economics and Health Policy, Oct; 11(5):445-56. doi:10.1007/s40258-013-0045-x

Grant Y, Matejtschuk P, Bird C, Wadhwa M, and Dalby PA. (2012) Freeze drying formulation using microscale and design of experiment approaches: a case study using granulocyte colony-stimulating factor. Biotech Lett, 34 (4), 641– 648. doi:10.1007/s10529-011-0822-2