The evaluation of a peptide-based therapeutic’s higher order structure (HOS) by NMR is a useful assessment of “sameness” when comparing Reference Listed Drug Products (RLDs) to up and coming generic drug products. However, small differences in average pH and pH variability has been shown to cause failures to meet the recommended benchmarks for drug product similarity [Figure 1]. Minor adjustments in pH prior to NMR analysis allows for a more accurate comparison of peptide HOS sameness. A detailed study on the effects of pH on HOS sameness has been published by our team in The AAPS Journal, in late 2024, demonstrating the readily reversible changes to the NMR spectra of peptide therapeutics with respect to minute differences in pH.