Seeding and Continuous Biopharmaceutical Crystallisation (SCoBiC)

生物技术在理解人类基因组学和蛋白质组学方面取得了重大进展，并为医学诊断、预防和治疗带来了革命性的变化。以目标为导向的生物技术研究的进展和突破已被用来加强一些具有商业意义的产品的合成。据报道，目前有超过6,000种生物药物正在开发中，潜在价值超过1,000‘S亿美元(2012年为1450亿GB)。尽管在发现基于蛋白质的药物方面取得了越来越大的成功，但以具有成本效益和可靠的方式生产这些药物仍然是一个重大的工业挑战，目前限制了生物制药行业向患者提供解决方案的能力。这里的愿景是制定一项计划，通过实施种子和连续生物药物结晶(SCoBiC)，实现下游生物处理(DSB)的过程强化和消除瓶颈，以分离和纯化生物药物。这个拟议项目的雄心是开发连续生物结晶过程的策略，包括通过播种直接从多组分发酵液中选择性结晶整个抗体和抗体片段。目标是降低制造成本，提供更简单的工艺，同时获得可通过多步骤层析获得的高纯度材料。这一雄心壮志是因为人们意识到，分离和纯化过程是商业生物制药产品制造过程中最耗时、最耗费成本的下游操作之一。这项提议将开发一个连续的生物结晶平台，作为传统DSB的替代方案，提供可制造性的改进，实现更高的生产能力，降低产品成本，提高产品质量和稳定性，包括获得新配方和技术的机会。

Biotechnology has made significant advancements in the understanding of human genomics and proteomics revolutionising medical diagnosis, prevention and treatment. Advances and breakthroughs in target-oriented biotechnology research have been used to enhance the synthesis of a number of commercially significant products. It has been reported that there are over 6000 biopharmaceuticals currently in development, potentially worth in excess of $100's bn (£145bn in 2012). Despite the increasing successes in discovering protein-based medicines, their manufacture in a cost effective and reliable fashion remains a major industrial challenge, which currently limits the ability of the biopharmaceutical industry to deliver solutions to patients. The vision here is to develop a programme for process intensification and de-bottleneck of downstream bioprocessing (DSB), by implementation of Seeding and Continuous Biopharmaceutical Crystallisation (SCoBiC), for the separation and purification of biopharmaceuticals. The ambition of this proposed project to develop strategies for a continuous biocrystallisation process, including selective crystallisation directly from multicomponent fermentation broths by seeding, for whole antibodies and antibody fragments. The goal is to reduce manufacturing costs, provide for simpler processes while achieving the high purity of material achievable from multi step chromatography. This ambition is driven by the awareness that separation and purification processes represent one of the most time and cost-intense downstream operations in the manufacture of commercial biopharmaceutical products. This proposal will develop a continuous biocrystallisation platform as an alternative to conventional DSB, offering improvements to manufacturability, enabling higher throughput, lowering the product costs, an increase in product quality and stability, including opportunities for novel formulations and technologies.