An Optimized Safe Process from Bench to Pilot cGMP Production of API Eptifibatide Using a Multigram-Scale Microwave-Assisted Solid-Phase Peptide Synthesizer
| العنوان: | An Optimized Safe Process from Bench to Pilot cGMP Production of API Eptifibatide Using a Multigram-Scale Microwave-Assisted Solid-Phase Peptide Synthesizer |
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| المؤلفون: | Paolo Rovero, Alfredo Paio, Annunziata D’Ercole, Matteo Zini, Francesca Nuti, L. Pacini, Anna Maria Papini, Arianna Ribecai, Giuseppina Sabatino |
| المصدر: | Organic process research & development 25 (2021): 2754–2771. doi:10.1021/acs.oprd.1c00368 info:cnr-pdr/source/autori:D'Ercole, Annunziata; Pacini, Lorenzo; Sabatino, Giuseppina; Zini, Matteo; Nuti, Francesca; Ribecai, Arianna; Paio, Alfredo; Rovero, Paolo; Papini, Anna Maria/titolo:An Optimized Safe Process from Bench to Pilot cGMP Production of API Eptifibatide Using a Multigram-Scale Microwave-Assisted Solid-Phase Peptide Synthesizer/doi:10.1021%2Facs.oprd.1c00368/rivista:Organic process research & development/anno:2021/pagina_da:2754/pagina_a:2771/intervallo_pagine:2754–2771/volume:25 |
| بيانات النشر: | Royal Society of Chemistry, Cambridge, UK , Stati Uniti d'America, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | chemistry.chemical_classification, Materials science, Chromatography, technology transfer, Organic Chemistry, multigram-scale microwave-assisted peptide synthesis, Peptide, generic peptide drug, Microwave assisted, peptide production scale-up, peptide production pilot plant, chemistry, Phase (matter), generic peptide drug, peptide production scale-up, multigram-scale microwave-assisted peptide synthesis, technology transfer, peptide production pilot plant, Eptifibatide, medicine, Physical and Theoretical Chemistry, medicine.drug |
| الوصف: | A growing industrial interest toward the peptide drug market fueled the need for the development of effective and cGMP compliant manufacturing methods for these complex molecules. Solid-phase strategies are considered methods of election for medium-length peptide syntheses not only on the research scale but for multigram-scale production, as well. The possibility to use microwave-assisted technology on the multigram scale, recently introduced, prompted us to evaluate the possibility to conveniently set up a safe and fully cGMP-compliant pilot process to produce eptifibatide, a generic peptide active pharmaceutical ingredient. Accordingly, we developed an optimized process on the laboratory scale (1-5 mmol), which was subsequently successfully scaled up to 70 mmol, obtaining all the information required by regulatory agencies to validate the process and qualify the pilot scale plant. The process consists of 5 steps: (1) automated microwave-assisted solid-phase synthesis of eptifibatide linear precursor; (2) cleavage from the resin with concomitant amino acid side-chains deprotection; (3) disulfide-bond formation in solution; (4) purification by flash column chromatography; (5) ion-exchange solid-phase extraction. Since the direct scale-up of a multigram-scale cGMP compliant peptide API production procedure is a challenge that requires an accurate understanding of each involved step, we initially performed a quality management risk assessment, which enabled a smooth and effective achievement of a successful final result. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d29c2a766b49246c4ffd343dfd85a016 https://publications.cnr.it/doc/464122 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d29c2a766b49246c4ffd343dfd85a016 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |