EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies

在20世纪80年代，通过将定义人类蛋白质的基因放入酵母等简单生物体中，开始有可能生产出潜在无限量的人类蛋白质。由此产生了一种新型药物，能够治疗严重关节炎、血友病、生长缺陷和一些以前没有令人满意的治疗方法的癌症。除了具有巨大的临床价值外，由此产生的技术已成为制药工业中一个新的和增长最快的部分的基础，被称为生物制药。由于所涉及的分子是蛋白质，它们比阿司匹林等传统药物要大几个数量级，也更复杂，而且它们的加工要求也高得多。它们也是如此复杂，以至于除了与制造它们的方法有关外，一般不能精确地描述它们。这意味着精确定义这些过程的能力对临床安全和商业成功至关重要。这些工艺的全面试验成本高昂，只有在确定了临床前景后才能进行，但考虑到控制第一代产品加工的因素很多，经常会出现如此广泛的拖延，以至于延迟了患者的可用性。伦敦大学学院开创了微观尺度的方法，这种方法足够好地预测大规模性能的有效条件，而更少、更集中的大规模试验就足够了。这解决了部分问题，但一个更大的挑战正在出现。早期的生物制药通常是最容易生产的。最终的量表也相对温和。现在，下一代生物制药是更复杂的材料，随着需求的增长，规模要大得多，因此工艺推动了可能的边界。产品和过程的综合复杂性以及如此多的变量需要考虑，意味着管理者需要更好的系统手段来支持他们的决策。目前，开发一种生物制药的成本可能超过7亿美元，需要10年时间。随着更先进的生物制药，这些数字往往会上升，但世界各国政府正面临着老年人增多的医疗成本危机。因此，他们对公司施加压力，要求降低价格。由于公众希望拥有不构成风险的药物，因此法规变得越来越严格，因此它们是定义生物过程的主要因素。这也增加了管理人员需要在流程的详细工程基础上获得特定部门的决策支持援助。最后，现在有可能将分子工程应用于蛋白质和疫苗，以增强其治疗特性，但这也可能导致严重的生物加工问题。根据英国行业专家的详细投入开发的研究愿景将应用这些方法作为另一个步骤变化的基础，从而可以更快，更低成本地收集信息，并与先进的决策技术相结合，为管理人员提供更好的基础，以制定政策。来自英国一流大学的学术团队提供了评估新药生产难易程度、加工成本和交付给患者所需的必要技能。我们将与公司合作测试结果，以确保它们在用于新的生物制药之前得到充分证明。这将削减费用，使所有可能受益的病人都能得到这些服务，并在国民保健制度目前有限的预算范围内尽早得到这些服务。

In the 1980s it began to be possible to produce potentially unlimited quantities of human proteins by placing the gene defining them in a simple organism such as yeast. From this grew a new kind of medicine capable of treating conditions such as severe arthritis, haemophilia, growth deficiency, and some cancers that previously had no satisfactory treatments. As well as having great clinical value the resulting technology has become the basis of a new and fastest growing part of the pharmaceutical industry, described as biopharmaceuticals. Because the molecules involved are proteins, they are orders of magnitude larger and more complex than conventional drugs such as aspirin and their processing is much more demanding. They are also so complex that they cannot in general be characterised with precision except in relation to the methods by which they are made. That means the capacity to precisely define such processes is critical to clinical safety and commercial success. Full scale trials of the processes are so costly they can only be conducted once clinical promise is established but, given the number of factors governing processing of even first generation products, there have often been hold-ups so extensive as to delay availability to patients. UCL has pioneered micro scale methods that are sufficiently good at predicting efficient conditions for large scale performance that far fewer and better focussed large scale trials suffice. That resolves part of the problem but an even greater challenge is now emerging. The early biopharmaceuticals were in general the easiest ones to produce. The final scales were also relatively modest. Now, the next generation of biopharmaceuticals are more complex materials and with rising demand the scales are far larger so that processes push the boundaries of the possible. The combined complexity of the product and the process with so many variables to consider means that the managers need better systematic means of supporting their decisions. Already the cost of developing a single biopharmaceutical can exceed 0.7 billion and take 10 years. With more advanced biopharmaceuticals these figures tend to rise and yet the world's governments are facing a healthcare cost crisis with more older people. They therefore exert pressure on companies to reduce prices. Because the public wishes to have medicines that do not pose risks, regulations become ever more stringent so they are a major factor in defining the bioprocess. This also adds to the need for managers to have sector-specific decisional-support aids well grounded in the detailed engineering of the processes. Finally, it is now possible to apply molecular engineering to proteins and vaccines to enhance their therapeutic properties but this can also cause serious bioprocessing problems. The research vision developed with detailed input from UK industry experts will apply these methods as the foundation for another step change whereby much faster and lower cost information can be gathered and integrated with advanced decisional techniques to give managers a better foundation on which to base their policies. The academic team from leading UK universities provides the necessary continuum of skills needed to assess the ease of manufacture of novel drugs, the costs of processing and of delivery to patients. We will work with companies to test the outcomes to ensure they are well proven prior to use on new biopharmaceuticals. This will cut costs so that all the patients who might benefit can receive them and at the earliest possible date achieved within the severely restricted budgets now available to the NHS.