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Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering
Well-characterized and scalable downstream processes for the purification of biologics are extremely demanding for delivering quality therapeutics to patients at a reasonable price. Erythropoietin (EPO) is a blockbuster biologic with diverse clinical applications, but its application is limited to f...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460001/ https://www.ncbi.nlm.nih.gov/pubmed/37631301 http://dx.doi.org/10.3390/pharmaceutics15082087 |
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author | Nag, Kakon Sarker, Enamul Haq Kumar, Samir Chakraborty, Sourav Khan, Maksusdur Rahman Chowdhury, Mashfiqur Rahman Roy, Rony Roy, Ratan Biswas, Bipul Kumar Bappi, Emrul Hasan Mohiuddin, Mohammad Sultana, Naznin |
author_facet | Nag, Kakon Sarker, Enamul Haq Kumar, Samir Chakraborty, Sourav Khan, Maksusdur Rahman Chowdhury, Mashfiqur Rahman Roy, Rony Roy, Ratan Biswas, Bipul Kumar Bappi, Emrul Hasan Mohiuddin, Mohammad Sultana, Naznin |
author_sort | Nag, Kakon |
collection | PubMed |
description | Well-characterized and scalable downstream processes for the purification of biologics are extremely demanding for delivering quality therapeutics to patients at a reasonable price. Erythropoietin (EPO) is a blockbuster biologic with diverse clinical applications, but its application is limited to financially well-off societies due to its high price. The high price of EPO is associated with the technical difficulties related to the purification challenge to obtain qualified products with a cost-effective defined process. Though there are reports for the purification of EPO there is no report of a well-characterized downstream process with critical process parameters (CPPs) that can deliver EPO consistently satisfying the quality target product profile (QTPP), which is a critical regulatory requirement. To advance the field, we applied the quality by design (QbD) principle and design of experiment (DoE) protocol to establish an effective process, which is scalable up to 100× batch size satisfying QTPP. We have successfully transformed the process from static mode to dynamic mode and validated it. Insignificant variation (p > 0.05) within and between 1×, 10×, and 100× batches showed that the process is reproducible and seamlessly scalable. The biochemical analysis along with the biofunctionality data ensures that the products from different scale batches were indifferent and comparable to a reference product. Our study thereby established a robust and scalable downstream process of EPO biosimilar satisfying QTPP. The technological scheme presented here can speed up the production of not only EPO but also many other life-saving biologics and make them available to the mass population at a reduced cost. |
format | Online Article Text |
id | pubmed-10460001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104600012023-08-27 Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering Nag, Kakon Sarker, Enamul Haq Kumar, Samir Chakraborty, Sourav Khan, Maksusdur Rahman Chowdhury, Mashfiqur Rahman Roy, Rony Roy, Ratan Biswas, Bipul Kumar Bappi, Emrul Hasan Mohiuddin, Mohammad Sultana, Naznin Pharmaceutics Article Well-characterized and scalable downstream processes for the purification of biologics are extremely demanding for delivering quality therapeutics to patients at a reasonable price. Erythropoietin (EPO) is a blockbuster biologic with diverse clinical applications, but its application is limited to financially well-off societies due to its high price. The high price of EPO is associated with the technical difficulties related to the purification challenge to obtain qualified products with a cost-effective defined process. Though there are reports for the purification of EPO there is no report of a well-characterized downstream process with critical process parameters (CPPs) that can deliver EPO consistently satisfying the quality target product profile (QTPP), which is a critical regulatory requirement. To advance the field, we applied the quality by design (QbD) principle and design of experiment (DoE) protocol to establish an effective process, which is scalable up to 100× batch size satisfying QTPP. We have successfully transformed the process from static mode to dynamic mode and validated it. Insignificant variation (p > 0.05) within and between 1×, 10×, and 100× batches showed that the process is reproducible and seamlessly scalable. The biochemical analysis along with the biofunctionality data ensures that the products from different scale batches were indifferent and comparable to a reference product. Our study thereby established a robust and scalable downstream process of EPO biosimilar satisfying QTPP. The technological scheme presented here can speed up the production of not only EPO but also many other life-saving biologics and make them available to the mass population at a reduced cost. MDPI 2023-08-04 /pmc/articles/PMC10460001/ /pubmed/37631301 http://dx.doi.org/10.3390/pharmaceutics15082087 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nag, Kakon Sarker, Enamul Haq Kumar, Samir Chakraborty, Sourav Khan, Maksusdur Rahman Chowdhury, Mashfiqur Rahman Roy, Rony Roy, Ratan Biswas, Bipul Kumar Bappi, Emrul Hasan Mohiuddin, Mohammad Sultana, Naznin Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering |
title | Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering |
title_full | Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering |
title_fullStr | Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering |
title_full_unstemmed | Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering |
title_short | Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering |
title_sort | satisfying qtpp of erythropoietin biosimilar by qbd through doe-derived downstream process engineering |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460001/ https://www.ncbi.nlm.nih.gov/pubmed/37631301 http://dx.doi.org/10.3390/pharmaceutics15082087 |
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