Rapid Identification of Biotherapeutics with Label-Free Raman Spectroscopy

Product identification is a critical
and required analysis for
biotheraputics. In addition to regulatory requirements for identity
testing on final drug products, in-process identity testing is implemented
to reduce business risks associated with fill operations and can also
be used as a tool against counterfeiting. Biotherapeutics, in particular
monoclonal antibodies, represent a challenging cohort for identity
determination because of their similarity in chemical structure. Traditional
methods used for product identification can be time and labor intensive,
creating a need for quick, inexpensive and reliable methods of drug
identification. Here, driven by its molecular-specific and nonperturbative
nature, we present Raman spectroscopy as an alternate analytical tool
for identity testing. By exploiting subtle differences in vibrational
modes of the biologics, we have developed partial least-squares-discriminant
analysis derived decision algorithms that offer excellent differentiation
capability using spontaneous Raman spectra as well as label-free plasmon-enhanced
Raman spectra. Coupled with the robustness to spurious correlations
due to its high information content, our results highlight the potential
of Raman spectroscopy as a powerful method for rapid, on-site biotherapeutic
product identification.