2-D NMR Assesses Biosimilar Structure

Before a biosimilar version of a protein therapeutic drug can be approved, the manufacturer of the new product must demonstrate that its properties and activity are comparable to the original drug. Determining higher order protein structure is an important part of establishing biosimilarity. In an interlaboratory study, researchers at the U.S. Food & Drug Administration, Health Canada, the National Institute of Standards & Technology, and the Medical Products Agency of Sweden show that two-dimensional NMR is reliably precise enough for the job (Nat. Biotechnol. 2016, DOI: 10.1038/nbt.3474). The researchers visually compared the similarity of spectral patterns and also used statistical methods to compare the chemical shifts of each signal from 2-D NMR experiments run on different instruments for the brand-name drug Neupogen, generically known as filgrastim, and three biosimilar versions. The precision across six spectrometers in four labs was found to be better than 10 ppb and almost as good as the digital resolution of the measurement. The use of 2-D NMR to analyze original protein drugs and subsequent biosimilars will give regulatory authorities greater assurance of drug quality, the study’s authors note.