An NMR-Based Similarity Metric for Higher Order Structure Quality Assessment Among U.S. Marketed Insulin Therapeutics
| Autor: | Cameron J. Smith, David A. Keire, John L. Leazer, Sharadrao M. Patil, Kang Chen, Deyun Wang, Junyong Park |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Drug
Magnetic Resonance Spectroscopy media_common.quotation_subject medicine.medical_treatment Pharmaceutical Science Insulin analog 02 engineering and technology Computational biology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Similarity (network science) Renal Dialysis medicine Insulin lispro Humans Insulin media_common Mathematics Mahalanobis distance Insulin glargine Proteins Biosimilar 021001 nanoscience & nanotechnology Magnetic Resonance Imaging 0210 nano-technology medicine.drug |
| Zdroj: | Journal of pharmaceutical sciences. 109(4) |
| ISSN: | 1520-6017 |
| Popis: | Protein or peptide higher order structure (HOS) is a quality attribute that could affect therapeutic efficacy and safety. Where appropriate, the HOS similarity between a proposed follow-on product and the reference listed drug should be demonstrated during regulatory assessment. Establishing quantitative HOS similarity for 2 drug substances, manufactured by different processes, has been challenging. Herein, HOS differences among U.S. marketed insulin drug products (DPs) were quantified using nuclear magnetic resonance spectra and principal component analysis (PCA). Then, the unitless Mahalanobis distance (DM) in PCA space was calculated between insulin analog reference listed drugs and their recently approved follow-on products, and all DM values were 3.29 or less. By contrast, a larger DM value of 20.5 was obtained between the 2 insulin human DPs independently approved. However, upon mass-balanced and reversible dialysis of the 2 insulin human DPs against the same buffers, the DM value was reduced to 1.19 or less. Thus, the observed range of nuclear magnetic resonance-PCA-derived DM values can be used as a robust and sensitive measure of HOS similarity. Overall, the DM values of 3.3 for DP and 1.2 for drug substances using insulin therapeutics represented realistic and achievable similarity metrics for developing generic or biosimilar drugs, quality assurance, or control. |
| Databáze: | OpenAIRE |
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