(12j) Predicting the Aggregation Behaviour in Biopharmaceuticals

Profile

Sarah Hedberg

Imperial College London and Fujifilm Diosynth Biotechnologies

Academic advisers: Dr Daryl Williams and Dr Jerry Heng

PhD Thesis:

Predicting and Controlling Aggregation for mAbs During Bioprocessing, 2016

Research Interests:

My principal area of research is to develop an improved fundamental understanding of the role of protein phase behaviour that can be utilised in downstream bioprocess engineering. Potential research activities would include:

i) Studying the impact of protein aggregation in the downstream processing of biopharmaceuticals (primarily chromatography) and the formulation process;

(ii) The development and improvement of experimental techniques that can be used to predict protein aggregation and estimate the osmotic second virial coefficient (e.g. self-interaction chromatography and cross-interaction chromatography);

(iii) The development of robust crystallisation approaches for proteins using the second virial coefficient data;

(iv) To employ modelling tools for predictioning and control of these biopharmaceutical downstream operations.

My research has always been driven by the needs of the biopharmaceutical industry, with a current focus on controlling protein aggregation, which is critical in order to avoid immunogenicity issues in biopharmaceuticals. Problems with protein aggregation and other impurities would have the greatest impact on the downstream and formulation process. Previous research has shown that the second virial coefficient, describing the thermodynamics of the protein-protein interactions in solution, can be a useful tool for predicting the aggregation propensity of proteins. Automatic, high-throughput techniques requiring minimal proteins such as self-interaction chromatography, cross-interaction chromatography and dynamic light scattering have previously demonstrated to be very successful in determining the second virial coefficient or the interaction parameter that can be helpful in predicting protein aggregation.

My research work has always been in collaboration with industry and the industry partners for my current research are Fujifilm Diosynth Biotechnologies and JML Biotechnology Consulting. The research undertaken has later been directly implemented by these companies. I am planning to maintain these industrial links in my research and to work with these companies in my future research career.

My research vision is that we need to look closer at the thermodynamics governing the protein-protein interactions and approaching the problem from a physical chemical viewpoint. This may then help us gain a better understanding as well as being able to predict and control protein phase behaviour, protein stability and aggregation, protein crystallisation as well as performance for formulation and downstream operations.

Teaching Interests:

My current teaching interests lies within the biochemical engineering/ bioprocess engineering field. I am interested in promoting more biochemical engineering and biological engineering within the traditional chemical engineering teaching environment. I am especially hoping to teach and incorporate more of the downstream purification process and formulation process courses on biopharmaceuticals into the chemical engineering curriculum.

I have previously been part of designing, planning, teaching and marking a wide range of subjects in Chemical Engineering for the past 4 years, in my Department at Imperial College, but also at Tsinghua University, as a summer school course leader, and University College London, as a teaching associate. This teaching has ranged from fundamental chemistry, separation unit operations and chromatography to sustainable development (with a chemical engineering outlook). I have obtained a teaching recognition as an Associate Fellow of the Higher Education Academy (AFHEA) from the Higher Education Academy in the UK.

Publications

Hou, Y., Hedberg, S. & Schneider, I. C. Differences in Adhesion and Protrusion Properties Correlate with Differences in Migration Speed under EGF Stimulation. BMC Biophysics,2012, 5: 1-12.

Hedberg, S.H.M., Heng, J.Y.Y., Williams, D.R., and Liddell, J.M. Self-Interaction Chromatography of MAbs: Accurate Measurement of Dead Volumes.Pharmaceutical Research, 2015, 32(12): p. 3975-3985.

Hedberg, S.H.M., Heng, J.Y.Y., Williams, D.R., and Liddell, J.M. Micro Scale Self-Interaction Chromatography of Proteins: A MAb Case-Study.Journal of Chromatography A, 2016, 1434: p. 57-63.

Hedberg, S.H.M., Brown L., Heng, J.Y.Y., Williams, D.R., Optimised Protein Immobilisation Reactions and Immobilisation Kinetics for Chromatography Media, submitted to Colloids and Surfaces B, 2016.

Hedberg, S.H.M., Heng, J.Y.Y., Williams, D.R., Kinetics and Thermodynamics of Protein Aggregation, in preparation 2016.