In-situ biophysical characterization of high-concentration protein formulations using wNMR
ABSTRACTHigh-concentration protein formulation is of paramount importance in patient-centric drug product development, but it also presents challenges due to the potential for enhanced aggregation and increased viscosity. The analysis of critical quality attributes often necessitates the transfer of...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2304624 |
| _version_ | 1797336243167559680 |
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| author | Jing Song Marc Taraban Y. Bruce Yu Lynn Lu Pallavi Guha Biswas Wei Xu Hanmi Xi Akhilesh Bhambhani Guangli Hu Yongchao Su |
| author_facet | Jing Song Marc Taraban Y. Bruce Yu Lynn Lu Pallavi Guha Biswas Wei Xu Hanmi Xi Akhilesh Bhambhani Guangli Hu Yongchao Su |
| author_sort | Jing Song |
| collection | DOAJ |
| description | ABSTRACTHigh-concentration protein formulation is of paramount importance in patient-centric drug product development, but it also presents challenges due to the potential for enhanced aggregation and increased viscosity. The analysis of critical quality attributes often necessitates the transfer of samples from their primary containers together with sample dilution. Therefore, there is a demand for noninvasive, in situ biophysical methods to assess protein drug products directly in primary sterile containers, such as prefilled syringes, without dilution. In this study, we introduce a novel application of water proton nuclear magnetic resonance (wNMR) to evaluate the aggregation propensity of a high-concentration drug product, Dupixent® (dupilumab), under stress conditions. wNMR results demonstrate a concentration-dependent, reversible association of dupilumab in the commercial formulation, as well as irreversible aggregation when exposed to accelerated thermal stress, but gradually reversible aggregation when exposed to freeze and thaw cycles. Importantly, these results show a strong correlation with data obtained from established biophysical analytical tools widely used in the pharmaceutical industry. The application of wNMR represents a promising approach for in situ noninvasive analysis of high-concentration protein formulations directly in their primary containers, providing valuable insights for drug development and quality assessment. |
| first_indexed | 2024-03-08T08:51:24Z |
| format | Article |
| id | doaj.art-8d8f3e96eb104bfea17977931edd4cd5 |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2024-03-08T08:51:24Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-8d8f3e96eb104bfea17977931edd4cd52024-02-01T10:24:27ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2304624In-situ biophysical characterization of high-concentration protein formulations using wNMRJing Song0Marc Taraban1Y. Bruce Yu2Lynn Lu3Pallavi Guha Biswas4Wei Xu5Hanmi Xi6Akhilesh Bhambhani7Guangli Hu8Yongchao Su9Analytical Research and Development, Merck & Co., Inc, Rahway, NJ, USAUniversity of Maryland School of Pharmacy and Institute for Bioscience and Biotechnology Research, Rockville, MD, USAUniversity of Maryland School of Pharmacy and Institute for Bioscience and Biotechnology Research, Rockville, MD, USAPharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, USAUniversity of Maryland School of Pharmacy and Institute for Bioscience and Biotechnology Research, Rockville, MD, USAAnalytical Research and Development, Merck & Co., Inc, Rahway, NJ, USAAnalytical Research and Development, Merck & Co., Inc, Rahway, NJ, USAPharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, USAPharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, USAAnalytical Research and Development, Merck & Co., Inc, Rahway, NJ, USAABSTRACTHigh-concentration protein formulation is of paramount importance in patient-centric drug product development, but it also presents challenges due to the potential for enhanced aggregation and increased viscosity. The analysis of critical quality attributes often necessitates the transfer of samples from their primary containers together with sample dilution. Therefore, there is a demand for noninvasive, in situ biophysical methods to assess protein drug products directly in primary sterile containers, such as prefilled syringes, without dilution. In this study, we introduce a novel application of water proton nuclear magnetic resonance (wNMR) to evaluate the aggregation propensity of a high-concentration drug product, Dupixent® (dupilumab), under stress conditions. wNMR results demonstrate a concentration-dependent, reversible association of dupilumab in the commercial formulation, as well as irreversible aggregation when exposed to accelerated thermal stress, but gradually reversible aggregation when exposed to freeze and thaw cycles. Importantly, these results show a strong correlation with data obtained from established biophysical analytical tools widely used in the pharmaceutical industry. The application of wNMR represents a promising approach for in situ noninvasive analysis of high-concentration protein formulations directly in their primary containers, providing valuable insights for drug development and quality assessment.https://www.tandfonline.com/doi/10.1080/19420862.2024.2304624Accelerated stressbiologicsdrug product stabilityhigh-concentration drug productmABsprotein aggregation |
| spellingShingle | Jing Song Marc Taraban Y. Bruce Yu Lynn Lu Pallavi Guha Biswas Wei Xu Hanmi Xi Akhilesh Bhambhani Guangli Hu Yongchao Su In-situ biophysical characterization of high-concentration protein formulations using wNMR mAbs Accelerated stress biologics drug product stability high-concentration drug product mABs protein aggregation |
| title | In-situ biophysical characterization of high-concentration protein formulations using wNMR |
| title_full | In-situ biophysical characterization of high-concentration protein formulations using wNMR |
| title_fullStr | In-situ biophysical characterization of high-concentration protein formulations using wNMR |
| title_full_unstemmed | In-situ biophysical characterization of high-concentration protein formulations using wNMR |
| title_short | In-situ biophysical characterization of high-concentration protein formulations using wNMR |
| title_sort | in situ biophysical characterization of high concentration protein formulations using wnmr |
| topic | Accelerated stress biologics drug product stability high-concentration drug product mABs protein aggregation |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2304624 |
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