Collaborative Research/GOALI: Fully Continuous Downstream Processing Enabled by Coupled Precipitation-Filtration Capture Operations

该研究项目的目标是开发一种用于治疗性生物药物的高效纯化方法，该方法有可能促进生物制造行业从批量加工向连续加工的过渡。连续加工的使用具有改善产品均匀性、降低药物生产成本和更灵活的生产操作的潜力。该研究项目涉及设计，建造，运营，评估和优化生物制药纯化的综合示范过程。 该研究是与工业合作伙伴合作进行的，因此该项目为研究生提供了一个独特的培训环境，并应有助于成功进入国内生物制药行业。此外，从研究项目中获得的知识可以迅速转移到工业中。外联工作正在利用大学现有的计划，开发，部署和评估生物分离学习模块和实验室实验，用于中学化学课程。该研究项目的目标是开发一种连续耦合的沉淀过滤生物制造过程，用于蛋白质治疗，相对于传统的基于柱色谱的捕获，具有显着的性能和成本优势。该纯化工艺基于静态混合器和中空纤维过滤器的分级配对，用于目标产品的有效脱水、洗涤和再溶解。使用协同和可推广的交联和排除体积沉淀剂对导致在低沉淀剂浓度下的可逆的、非变性的沉淀，减轻沉淀的传统限制。正在开发和验证蛋白质溶解度、沉淀动力学和沉淀形态的数据驱动模型，以提供沉淀过程的定量描述。该研究项目正在与工业合作伙伴合作执行，该合作伙伴与项目研究人员一起设计、构建、运营、评估和优化生物制药纯化的综合示范工艺。 因此，从研究项目中获得的知识可以迅速转移到工业中。

The goal of this research project is to develop a highly efficient purification method for therapeutic biopharmaceuticals that has the potential to facilitate the transition of the biomanufacturing industry from batch to continuous processing. The use of continuous processing has the potential for improved product uniformity, lower cost production of drugs, and more flexible manufacturing operations. The research project involves designing, building, operating, evaluating, and optimizing an integrated demonstration process for biopharmaceutical purification. The research is being performed in collaboration with an industrial partner, so the project is providing a unique training environment for graduate students and should facilitate successful career entry into the domestic biopharmaceutical industry. Additionally, knowledge gained from the research project can be rapidly transferred to industry. Outreach efforts are leveraging an existing program at the university to develop, deploy and assess bioseparations learning modules and lab experiments for use in secondary school chemistry curricula.The goal of this research project is the development of a continuous coupled precipitation-filtration biomanufacturing process for protein therapeutics that offers significant performance and cost advantages relative to traditional column chromatography-based capture. This purification process is based on staged pairings of static mixers and hollow fiber filters for efficient dewatering, washing, and re-dissolution of the target product. The use of synergistic and generalizable cross-linking and excluded volume precipitant pairs results in reversible, non-denatured precipitates at low precipitant concentrations, relieving the traditional limitations of precipitation. Data-driven models are being developed and validated for protein solubility, precipitation kinetics, and precipitate morphology to provide a quantitative description of the precipitation process. This research project is being performed in collaboration with an industrial partner who, in conjunction with the project researchers, are designing, building, operating, evaluating, and optimizing an integrated demonstration process for biopharmaceutical purification. Consequently, knowledge gained from the research project can be rapidly transferred to industry.