Structural change is monitored during antibody manufacture
LGC scientists, working with GlaxoSmithKline, UCB, Nottingham University and the National Physical Laboratory, are for the first time in the UK using novel hydrogen deuterium exchange to provide automated high-speed and high-resolution information on structure and structural change during the manufacture of monoclonal antibodies (mAbs) and pegylated fragmented antibodies (fAbs).
The application of this technique enables Teddington, Middlesex-based LGC, an international science-based company and leader in chemical and biological analytical services and reference materials, to analyse mAb and fAb stability faster than traditional methods. It also enables biopharmaceutical companies to improve the manufacture of therapeutic mAbs and improve the prediction of their immunogenicity and stability once they enter the human body as a therapeutic agent.
Pharmaceutical and biopharma companies such as GlaxoSmithKline and UCB are able to enhance the therapeutic properties of these antibodies through recombinant DNA technology.
LGC scientists use deuterium, a heavier form of hydrogen, to measure the rate of exchange of hydrogen atoms present on the protein to provide an insight into the structural changes a protein undergoes when exposed to different chemical stresses.
Therapeutic mAb products are complex to manufacture and are susceptible to physiochemical modifications which can impact the manufacturability of the product and its stability, resulting in unacceptable batch-to-batch variation, decrease in yield or unknown immunogenicity. It is anticipated that application of this technique will reduce total biopharmaceutical development time by at least six months. Without the additional costs associated with batch failure and repeated clinical trials, patients will gain access to new medicines quicker and at a lower cost, says LGC.
LGC’s Dr Gavin O’Connor, principal scientist, Organic Mass Spectrometry, said: ‘This project marks a significant step forward in providing information to UK biopharmaceutical scientists experiencing problems in manufacturing biologicals and in predicting the long-term stability of their product. Improving analytical methods for determining higher order protein structures is an extremely valuable development.’
This work was part-funded by the UK’s Technology Strategy Board.
LGC employs 1,500 staff in 28 laboratories and centres across Europe and at sites in India, China and the US. The firm was founded almost 170 years ago as the Laboratory of the Government Chemist - a statutory function maintained by LGC today.