Formulation and Quality – Biomolecular
2019 PharmSci 360
Demonstrating equivalence of protein higher order structure (HOS) between a generic or biosimilar product to its RLD is an important consideration for drug approval. Herein, HOS differences among insulins were quantified using NMR spectra, PCA and the unitless Mahalanobis distances (DM). The resulting DM value in PCA space between insulin lispro RLD and the 2017 approved follow-on product was 3.3. Another DM value of 1.6 was obtained between insulin glargine RLD and the 2015 approved follow-on product. A larger DM value of 21 was obtained between two insulin regular brands that differed in formulation. However, upon mass-balanced and reversible dialysis of the two insulin regular brands to the same buffer, the DM value was reduced to 1.2 and less. Thus, the observed range of DM values can be used as a robust and sensitive measure for HOS similarity. The DM values of 3.3 for DP and 1.2 for DS using the US marketed insulin therapeutics represented realistic and achievable similarity metrics, useful for evaluation of generic or biosimilar drugs.