Comparison of the higher-order structure of biosimilar and innovator biotherapeutic drugs using automated circular dichroism: a novel approach to validation, measurement and analysis by Applied Photophysics Limited

Eight of the predicted top-ten drugs by revenue in 2016 will be biotherapeutics and as early as 2014, 50% of the top-100 pharmaceutical products will be accounted for by vaccines and biotherapeutics. Understandably, pharmaceutical companies are competing to establish new biotherapeutic drug pipelines, both as innovator and generic manufacturers. The societal benefit through improved treatment of any number of conditions by these new drugs cannot be over-stated.
The FDA and the EMA are demanding that companies provide evidence of equivalence of higher order structure (HOS), not only for biosimilars when compared with innovator
products but also for any licensed biotherapeutic where the process is changed, e.g. on scaleup or where some manufacturing efficiency improvement is sought. There are very few tools that provide HOS information in a manner that is amenable to rapid and routine analysis: the recent introduction by APL of a highly innovative, fully automated circular dichroism (CD) spectrometer has opened the door for CD to take on that role.
Automated CD has been used for early-stage characterisation and formulation studies but a wider, unmet need is for routine, quantitative and robust comparison of HOS in innovator and generic products. Two key barriers stand in the way of using CD in this role:
1. An absence of primary certified reference materials for CD and hence a lack of
traceability of the CD measurement, which lowers confidence in comparing data measured in different places on different instruments, or even the same instrument at different times.
2. An absence of defined analytical methods, particularly in the analysis and
presentation of data in a simple, meaningful manner that is accepted industry-wide
The key aims of this proposal are to deliver novel methods for the calibration and validation of CD instruments and to develop statistical analytical methods to provide a solution to the comparison of protein HOS.