Integrating Continuous Technologies Rapid Delivery of Cost Effective Biotherapeutics to Patients

高效、敏捷地生产高质量的生物制药是生物制药制造业的当务之急。将多个单元操作集成到一个连续过程中的优势已经在之前的一个基于CPI Darlington的财团项目中得到了证明。在这个项目中，3 / 4的终端用户参与公司已经开始开发自己的能力。英国需要继续发展这一领域的专业知识，以鼓励生物制药制造业的存在。该项目建立在之前项目中开发的概念验证系统的基础上，并增加了下一个所需级别的可配置性、自动化控制和过程智能：-*关键控制自动化和预测性能，以显示质量属性的实时连续性，并预测消耗品寿命和转换，以避免质量偏差（预测性维护）。下一代先进的过程控制和机器学习技术将得到发展。这些工具将创建一个独立于供应商/规模的智能控制解决方案。*优化单元操作接口的3d打印微流体的结合，以减少体积，因此停留时间分布。这些接口也是用于在线质量分析的卫生过程采样的关键点。*将系统产生的过程数据与制造成本、所需投资、环境成本、生产能力和生产设施要求同步。将积极评估这些因素，以便根据这些因素对进程进行优化。*扩展系统的上游能力，包括一个灌注生物反应器。该工艺将利用阿斯利康的单克隆抗体产品和工艺。宝尔生物技术将继续支持使用下游工艺中使用的设备和耗材。该项目汇集了5家生物技术产品公司，所有公司都在英国运营和弹射中心。在高价值制造弹射器开放访问中心主持的演示输出将确保集成制造技术的性能、设计、控制策略和商业价值的传播。

Efficient and agile production of high-quality biopharmaceuticals is of the highest priority to the biopharmaceutical manufacturing industry. The advantage of integrating multiple unit operations into a continuous process has been demonstrated by a previous consortium project, based at CPI Darlington. During that project, 3 out 4 of the end-user participant companies have moved to develop their own capabilities. The UK needs to continue to develop expertise in this area to encourage a biopharmaceutical manufacturing presence.This project builds on the proof-of-concept system developed in previous projects and adds the next required level of configurability, automation control and process intelligence:-* critical control automation and predictive performance to show real-time continuity of quality attributes and to predict consumable lifetime and changeover to avoid quality deviations (predictive maintenance). Next generation Advanced Process Control and Machine Learning techniques will be developed. These tools will create a vendor independent /scale independent intelligent control solution.* optimisation of unit operation interfaces by the incorporation of 3D-printed microfluidics to reduce volumes and therefore residence time distribution. These interfaces are also a critical point for hygienic process sampling for at-line quality analytics.* synchronising the process data generated by the system into manufacturing cost, investment required, environmental cost, production capacity and production facility requirements. These elements will be actively assessed to allow for the process to be optimised on these factors.* extending the upstream capabilities of the system to include a perfusion bioreactor. The process will utilise a monoclonal antibody product and process from AstraZeneca. Pall Biotech will continue to support the use of equipment and consumables used in the downstream process.The project brings together 5 biotech product companies, all with UK Operations and a Catapult centre. The output of a demonstrator hosted at a High Value Manufacturing Catapult open access centre will ensure dissemination of the performance, design, control strategies and business value of the integrated manufacturing technology.