ABSTRACT
In contrast, NMR is fairly underutilized beyond the discovery phase of the biopharmaceutical product development, mainly because the sensitivity and resolution of NMR for macromolecules such as proteins are much lower than those for small molecules. The characterization of a protein product and its variants is a critical part of a protein-based pharmaceutical product development program. The determination of a protein structure using NMR, while providing extremely valuable information, is not trivial and not always feasible. Thus, NMR has not been used often in biopharmaceutical product characterization studies. However, there are still many analytical issues that can readily be addressed by NMR in a biopharmaceutical product development program. For example, process validation studies, as required by the regulatory agencies, must be conducted to demonstrate that impurities (often small molecules) from the cell culture fluids and process buffers used in the manufacturing process are removed from the final product. In addition, the manufacturing process must not cause objectionable levels of extractables from process equipment (filters, columns, gaskets, etc.).7 Many of these process-related impurities can be easily detected by fairly simple and general NMR methods.
