As 2018 draws to a close, it’s been another exciting year in the area of biopharmaceuticals. We’ve seen further success from immunotherapy based approaches, new biopharmaceuticals have come to market in addition to approvals for the first biosimilars and I am sure we shall see data in the new year again showing that biopharmaceuticals have a dominant position in the top selling drugs charts.
One element that is constant though is that these biopharmaceuticals are complex to characterise. Characterisation is critical as even small modifications to the biomolecule can have dramatic effects on both efficacy and safety. Unlike small molecule drugs, which are chemically manufactured, large molecule, or biopharmaceutical drugs, are typically produced in cell culture using living organisms. Even what may seem a minute change in the cell culture conditions can cause quite major changes in the biopharmaceutical. What we are seeing in the industry is the adoption of a toolbox of different techniques and technologies to be able to perform this complete and comprehensive characterisation of biopharmaceuticals. These techniques include:
Peptide Mapping – This involves digesting the biopharmaceutical in to smaller peptides which can then be sequenced to ensure the protein sequence is as expected and there are no amino acid substitutions and gain a full picture of the biotherapeutic.
Aggregate Analysis – With monoclonal antibodies, there is the tendency for some to form aggregates of dimers, trimers, etc. This technique allows you to separate out, identify and quantify such aggregates. Why is this important? Aggregates are good at overstimulating the immune system which causes safety issues.
Charge Variant Analysis – Antibodies can also exist as multiple different charge variants which again have to be identified and quantified using this technique.
Glycan Analysis – Glycosylation is one of the most common post translational modifications and any changes to the glycan composition, pattern or attachment site can alter the biopharmaceutical. There are a variety of different techniques that can be employed to analyse glycans, for a review I recommend this article on glycan analysis strategies.
Intact and Subunit Analysis – Whilst peptide mapping is seen as a ‘bottom-up’ approach, this is an opposite ‘top-down’ approach characterising the whole, or large subunits, of the protein rather than peptides.
Multi Attribute Method (MAM) – This methodology uses peptide mapping and mass spectrometry to combine many of the analyses above into one single method.
As is evident from just these common characterisation techniques is that there are a wide choice of options available, and within each technique there are further options available such as different columns and chemistries to be used and which technology to utilise. However, it is essential to develop such a toolbox of analytical techniques to characterise biopharmaceuticals as each biomolecule represents a new challenge and in the background there is always the need to gain a deeper understanding and improve productivity.
To give more education and understanding on the techniques in this toolbox and the variety of different approaches you can employ in each technique, we have put together a series of on-demand webinars covering many of these techniques, delivered by experts in the field from both Thermo Fisher Scientific and NIBRT. These webinars can be viewed at your leisure here.
Biopharmaceuticals are complex and new entities are as, if not more, complex so it is vital that we develop and continually refine a toolbox of techniques and technologies to enable us to fully characterise whatever biomolecule is presented to us.
For more information on biopharmaceutical characterisation, please visit the Learning Centre
NIBRT and Thermo Fisher Scientific are collaborating to develop analytical solutions for the characterisation of complex biopharmaceuticals. Click here to learn more about the collaboration and the resulting applications.