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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/8/2087 |
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| author | Kakon Nag Enamul Haq Sarker Samir Kumar Sourav Chakraborty Maksusdur Rahman Khan Mashfiqur Rahman Chowdhury Rony Roy Ratan Roy Bipul Kumar Biswas Emrul Hasan Bappi Mohammad Mohiuddin Naznin Sultana |
| author_facet | Kakon Nag Enamul Haq Sarker Samir Kumar Sourav Chakraborty Maksusdur Rahman Khan Mashfiqur Rahman Chowdhury Rony Roy Ratan Roy Bipul Kumar Biswas Emrul Hasan Bappi Mohammad Mohiuddin Naznin Sultana |
| author_sort | Kakon Nag |
| collection | DOAJ |
| 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 (<i>p</i> > 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. |
| first_indexed | 2024-03-10T23:39:14Z |
| format | Article |
| id | doaj.art-10e419586d3946b98e8a88780e1960ef |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T23:39:14Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-10e419586d3946b98e8a88780e1960ef2023-11-19T02:36:36ZengMDPI AGPharmaceutics1999-49232023-08-01158208710.3390/pharmaceutics15082087Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process EngineeringKakon Nag0Enamul Haq Sarker1Samir Kumar2Sourav Chakraborty3Maksusdur Rahman Khan4Mashfiqur Rahman Chowdhury5Rony Roy6Ratan Roy7Bipul Kumar Biswas8Emrul Hasan Bappi9Mohammad Mohiuddin10Naznin Sultana11Globe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshGlobe Biotech Limited, 3/Ka (New), Tejgaon I/A, Dhaka 1208, BangladeshWell-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 (<i>p</i> > 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.https://www.mdpi.com/1999-4923/15/8/2087erythropoietinbiosimilarcritical process parameter (CPP)design of experiment (DoE)purificationquality by design (QbD) |
| spellingShingle | Kakon Nag Enamul Haq Sarker Samir Kumar Sourav Chakraborty Maksusdur Rahman Khan Mashfiqur Rahman Chowdhury Rony Roy Ratan Roy Bipul Kumar Biswas Emrul Hasan Bappi Mohammad Mohiuddin Naznin Sultana Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering Pharmaceutics erythropoietin biosimilar critical process parameter (CPP) design of experiment (DoE) purification quality by design (QbD) |
| 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 | erythropoietin biosimilar critical process parameter (CPP) design of experiment (DoE) purification quality by design (QbD) |
| url | https://www.mdpi.com/1999-4923/15/8/2087 |
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