Industrial Doctorate Centre: Biopharmaceutical Process Development

生物制药制造业继续发展，越来越重视支持科学和工程。在整个产品生命周期中有效地运用科学和工程方面的当代知识，将有助于提高生物制药的生产效率和遵守法规。这种范式转变的根本是推动采用以科学和工程原则为基础的综合系统方法，以评估和减轻与不良产品和工艺质量有关的风险。由于监管当局引入了一种新的基于风险的药品质量保证系统，这些变化已经成为可能。传统的制造方法是将产品的可变性纳入规格，并固定操作策略以确保重复性。测量技术的发展促使运营战略发生变化。这一修订的方法基于设计质量(QBD)的应用，以过程分析技术(PAT)为基础，以产生更严格的质量和更有保证的安全性的产品。QBD被定义为科学地设计产品和过程性能特性以满足特定目标的手段。因此，实际的改进需要一个科学和工程理解的知识库，以确定变量之间的相互关系，并将学习整合到不同的制造场景中。该中心的重点是应对这一范式转变带来的挑战，并培养新一代学生，使他们具备商业生物制药工艺开发的所有阶段的能力。关键是要确保他们具备在生物系统开发、高级上游工艺工程以及下游工艺的工程和开发领域的学科接口工作的技能。培训将围绕三个要素制定，这三个要素构成了加强对这一进程的了解的支柱。这三个要素是：(1)计量、数据和知识管理；(2)增加现有知识；(3)更有效地利用知识。正在采用的办法的力量在于，它同样适用于以微生物和动物细胞培养为基础的既定生物过程，以及包括干细胞、海洋生物技术和生物纳米技术在内的新兴领域。建议在这一领域建立一个中心的理由是为了解决一个公认的问题，即缺乏受过适当培训的人员，他们将提供下一代生物制药开发。这些问题在一系列报告中都有明确阐述。Semta报告说，超过四分之一的生物科学公司没有足够的科学技能。39%的生物科学/制药公司有长期空缺；22%的公司在科学领域存在技能短缺(是其他部门的五倍)。塞恩斯伯里勋爵担心生物科学业务的性质迅速变化，成立了BIGT并委托生物科学2015年。提出的一个强烈信息是，训练有素的工作人员严重短缺。此外，BioProcessUK对进入该部门的训练有素的人员所需增加的数量进行了量化评估。他们估计，在目前每年毕业的150名博士生的基础上，还需要增加100名训练有素的人员。这不仅仅是增加训练有素的人的数量的问题。该中心还将解决目前对工程师、化学家和生物学家进行UG培训的局限性，这种培训没有使他们做好准备，以应对以学科接口为特色的工艺开发工作的挑战。拟议方案将解决战略上的不足，并培养出具有适当跨学科技能的新一代毕业生，以推动研究议程和将基本概念转化为产业的知识。

Biopharmaceutical manufacturing continues to evolve with an increased emphasis on underpinning science and engineering. Effective deployment of contemporary knowledge in science and engineering throughout the product life cycle will facilitate manufacturing efficiencies and regulatory adherence for biopharmaceuticals. Fundamental to this paradigm shift has been the drive to adopt an integrated systems approach based on science and engineering principles for assessing and mitigating risks related to poor product and process quality. Changes have been enabled as a consequence of the regulatory authorities introducing a new risk-based pharmaceutical quality assurance system. The traditional approach to manufacture has been to accommodate product variability into the specifications and fix operational strategies to ensure repeatability. Developments in measurement technology have invited changes in operational strategy. This revised approach is based on the application of Quality by Design (QbD), underpinned by process analytical technology (PAT) to yield products of tighter quality and more assured safety. QbD is defined as the means by which product and process performance characteristics are scientifically designed to meet specific objectives. Practical improvements therefore demand a knowledge base of science and engineering understanding to identify the interrelationship between variables and integrate the learning into different manufacturing scenarios. The focus of the Centre is to address the challenges emerging from this paradigm shift and to train a new generation of students with competencies in all stages of commercial biopharmaceutical process development. Critical to this is to ensure they have the skills to work at the discipline interfaces in the areas of biosystem development, upscaled upstream process engineering, and the engineering and development of downstream processing. The training will be formulated around three elements that form the backbone of achieving an enhanced understanding of the process. The three elements are (i) Measurement, Data and Knowledge Management, (ii) Enhance Available Knowledge and (iii) Use Knowledge More Effectively. The power of the approach being adopted is that it is equally applicable to established bioprocesses based on microbial and animal cell culture, as well as emerging areas including stem cells, marine biotechnology and bio-nanotechnology. The rationale for proposing a Centre in this area is to address a well recognised problem, a lack of appropriately trained personnel, who will deliver the next generation of biopharmaceutical development. These issues have been clearly articulated in a series of reports. SEMTA reported that over a quarter of bioscience companies do not have sufficient science skills. 39% of bioscience/pharmaceutical companies have long-term vacancies; with 22% having skill shortages in the science arena (five times that for other sectors). Lord Sainsbury, concerned at the rapidly changing nature of the bioscience business, set up the BIGT and commissioned Bioscience 2015. One of the strong messages raised was the serious shortfall in trained staff. Furthermore a quantitative assessment of the increase needed of trained people entering the sector was made by bioProcessUK. They estimated an increase of 100 trained personnel was required on top of the current 150 doctoral level candidates graduating per year. It is not simply a matter of increasing the number of trained persons. The Centre will also address the limitations of the current UG training of engineers, chemists and biologists which does not prepare them for the challenge of working in process development distinguished by disciplinary interfaces. The proposed programme will address a strategic shortfall and produce a new generation of graduates with the appropriate inter-disciplinary skills to drive both the research agenda and knowledge transfer of underlying concepts into industry.