National Physical Laboratory

Pre-formulation studies and downstream processing optimisation

Pre-formulation Studies and Down Stream Processing optimisation

The lack of importance given to the biomolecule characterisation, in the early stages of the drug development process, has been identified as one of primary reasons why so many biologicals fail. Knowing the stability towards environmental variables (such as pH, temperature, type of salt, salt concentration, type and concentration of different buffers, etc.) is pivotal for rationally optimising the storage conditions or the purification process. A rational understanding of the system can, for example, suggest steps to take in order to avoid unwanted degradation pathways such as aggregation, deamidation or oxidation.

For complex systems like proteins, it is necessary to apply more than one technique to have a complete picture of their behaviour and the application of complementary techniques is the approach we use at NPL.

In the Biotechnology laboratories at NPL, we have access to a range of techniques that allow us to characterise proteins at different levels: primary sequence, secondary and tertiary structure and oligomerisation state (quaternary structure and aggregation).

Range of measurements we can perform:

  • Purity: Akta and HPLC (SEC, RP, IEX, HIC, etc.), MALDI-TOF, SDS-PAGE

  • Primary structure: ESI-MS, MALDI-TOF-TOF

  • Secondary structure: CD (far-UV) and FTIR

  • Tertiary structure: CD (near-UV), Intrinsic Fluorescence, fluorescence-quenching studies with different quenchers, dye binding (i.e. ANS)

  • Thermodynamic stability: Temperature Denaturation Measurements (CD, FTIR and DLS)

  • Colloidal stability: SLS and Zeta Potential measurements

  • Aggregation state: DLS, SEC –HPLC, SDS-PAGE, PAGE

  • Activity: Classical enzyme kinetics

  • Binding: ITC, Biacore, ELISA


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Last Updated: 18 Dec 2017
Created: 5 May 2009


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