生命科学

制药制造中的破坏技术

As pharma shows robust global growth of 2.48%, the strength of the industry is reflected in its continued innovation and breaking

由于Pharma显示出强劲的全球增长率为2.48%,因此该行业的实力反映在其持续的创新和破坏技术中,从而提高了制造效率并扩大了潜在的治疗目标的范围。莎拉·哈丁(Sarah Harding)博士,来自CPHI Worldwide的报道。
全球CPHI - 全球最大的制药活动 - 2019年11月5日至7日,有45,000名游客聚集在德国法兰克福。参观者来自160多个国家 /地区,目的是无与伦比的洞察力,以了解制药的最新趋势和发展。与活动同时,CPHI推出了今年的年度报告,包括对制药行业的评估,该行业表明2019年全球增长率为2.48%。这种健康的增长被解释为表明对全球市场的信心增强,并得到了广泛的创新,破坏技术和数字化的支持。
Demand for enhanced productivity, cost efficiency and sustainability are driving many of the disruptive technologies in pharma manufacturing. This is especially pertinent in light of the emerging model of personalized medicine, which is creating significant changes in the market, advised Peter Solkner, Managing Director ofVetter Pharma International。As many new drugs are developed for targeted population cohorts, the market sizes for those drugs are likely to shrink. As a result, explained Stuart Needleman, Chief Commercial Officer atPiramal Pharma Solutions,以患者为中心是制药行业的重点。
“大容量产品仍然有很多空间,”全球营销领导者Dago Caceres评论说DuPont。“但是个性化医学的市场正在增长 - 通常用于孤儿的适应症,全球大约有7,000种产品。对于这些更为重点的疗法,我们需要确保在解决较小量的同时保持效率。”
毫无疑问,新的医疗保健模型以及针对目标人群的较小量疗法的转变可能会对制药供应链产生深远的影响。未来可能需要更加灵活的制造,必须尽可能高效,因为增强生产的解决方案有助于该行业维持其增长,并确保全世界患者的负担得起,可及的医疗保健。
Formulating solutions
A common solution is the implementation of ‘green chemistry’. Although the term was popularized in the 1990s due to an emerging awareness of chemical pollution and resource depletion, the basic principles of green chemistry – ensuring that chemical manufacturing is as efficient and economical as possible – have always been the basis of good chemical production. In other words, employing a green chemistry approach could add not just to a company’s sustainability credentials – it could also save money and increase a company’s manufacturing efficiency.
catsci, a global process research and development CRO headquartered in the UK, develops perfect-for-purpose chemical processes that are economically and environmentally sustainable, using innovative thinking and applying extensive experience to explore new reactions and routes.
珍妮·沃利斯(Jenny Wallis),业务发展经理catsci, commented that “In the fast-paced and evolving pharmaceutical industry, drug discovery and development is getting more and more complex while demanding shorter timelines. Using our consultative approach, we work closely with our customers to efficiently navigate this challenging landscape and become their preferred partner for process research and development of small molecule therapeutics. Our award-winning chemistry services ensure that our customers can deliver affordable, best-in-class small molecule therapeutics.”
纳米型,今年CPHI卓越的获胜者制药奖, are addressing several of the pharma industry’s issues with one innovative approach. The company’s technology increases the active surface area of API particles, enabling significant improvements in dissolution rates and bioavailability. This, explained Edward Haeggström,纳米型首席执行官目前应对制药行业面临的许多挑战。
  1. 如果低生物利用度是疗效的障碍,可能会增加进入市场的药物数量并降低总体开发成本(目前包括9/10的“失败”药物),则可能会挽救“失败”药物。
  2. Increased bioavailability means that lower doses – by up to ten-fold – might achieve equivalent efficacy to ‘normal’ formulations, potentially reducing the overall drug load and minimizing side effects.
  3. 随着API变得越来越有效(由于生物利用度较高),所需的较低负载可能导致较小的药物制造量,减少环境影响和较小的占地面积。
“而不是使用立方吨的CO2,制造商只需要立方升。”Haeggström说。“与其需要大型植物进行毒品生产,他们只需要一个房间。”
Other novel solutions for enhancing efficiency includeDuPont’snew METHOCEL cellulose ethers (hydroxypropyl methylcellulose; HPMC), which enable formulators to create reliable formulas for tablet coatings, granulation, controlled release, extrusion, moulding and for controlled viscosity in liquid formulations. These cellulose ethers make the manufacturing of tablets more efficient, eliminating the need for water and making them 60% faster to produce, explained Dago Caceres, Global Marketing Leader atDuPont
约翰逊 马特斯((JM), in the meantime, has expanded its portfolio of homogeneous ester hydrogenation catalysts with the addition of another ‘Gusev’ catalyst. Compared with other agents used for these core reactions, said Kevin Gwilliam, Marketing Manager atJM, Gusev technology offers milder reaction conditions (temperature and pressure), which allow for a broader substrate与各种官能团范围的范围和兼容性。
Gwilliam说:“ Gusev催化剂的产生(通常是危险)的废物比异质替代品少。”“它们更具成本效益,更可持续。”
For the second time in three years,Cambrex赢得了CPHI API开发奖的卓越奖结晶筛选和过程开发服务。The service has bridged the gap between the bench and manufacturing platform, providing controlled, robust and scalable crystallization processes.
Go with the flow
在制药制造中,针对当前效率和灵活性挑战的另一个经常引用的解决方案是使用流动化学。持续的处理,广受赞誉,提供“流程强化”。
“It uses less water and less solvents, and produces less waste,” said Pierre Giuliano, Managing Director ofLa 梅斯塔, a custom manufacturing company located in France. “Continuous pathways can provide better safety and productivity. It also gives us the ability to make compounds that simply could not be made with batch processing.”
“Flow chemistry certainly is a big focus,” agreed Stephen Drake, Manager of Marketing and Development at卡内卡, a Japanese international CDMO based in Osaka. “It allows us to deliver more projects in less time,” added Alan Walker, the company’s Vice President – Marketing and Development. In fact, Drake and Walker explained,卡内卡近年来,日本赢得了两项流动化学奖,​​并且刚刚在新加坡获得了GMP认证的公吨连续加工设施。
07 CPHI评论图像-Innosyn.jpg.png

流动技术的终极由InnoSyn这是一家以其在新的和现有化学过程的研究和开发方面的最新技术而闻名的公司。
“ 3D打印反应堆是最有效的方法,因为您可以设计反应堆来完成您想要做的事情,”项目负责人Jan Brummund解释说InnoSyn。“我们设计了渠道的方式签订eral temperature probes can be implemented over the length of the reactor and enable an optimal process control.”
但是,新的独特功能Cryoflowskid技术(如图),解释说,AndréDeVriesInnoSyn,是整个设置由直观的触摸屏控制。流速,压力,温度和其他参数均使用从每个传感器和输入点收集的数据进行数字化数字化。
“我们可以测量通道内部的温度,并监测每个反应器模块上的差压力,” De Vries强调。“该系统会提醒我们,如果违反了集合限制,然后将触摸屏手动纠正任何问题,然后才会引起化学过程问题。”
de vries继续解释了新设备,Cryoflowskidwhich was developed in partnership与De Dietrich流程系统一起提供三个反应步骤在一个系统和公关oduces up to 5 kg product/hour under cryogenic conditions. The equipment – which has a very small footprint – will be ready for operation with a ‘plug & produce’ concept and can produce a comparable volume of product as a 1600L batch reactor in one day.
Healthy planet
此外,人们越来越意识到,以及提供成本,效率和安全利益,以及在批处理处理中无法实现的化学性能,流动化学具有环境优势,例如,使用较少的溶剂和减少浪费。
“Technological innovations such as flow chemistry are vital for designing pharmaceutical processes with a lower environmental and economic impact,” said Roger Kilburn, Chief Executive Officer atArcinova, a multi-service CDMO based in the UK. “The greater speed and efficiency, alongside the reduced amount of initial material required, makes flow chemistry a perfect tool for increasing sustainability in the pharmaceutical industry.”
“这是更绿色的化学反应,比批处理处理更小。”卡内卡’sStephen Drake.
This is important because the pharma industry is having to balance the demand for more and more drugs with an increasing recognition that this must be achieved with less and less environmental impact. Realising both of those goals might seem like an insurmountable challenge, but it’s one that many companies are already striving to overcome.
Referring toJM’s营销经理凯文·格里亚姆(Kevin Gwilliam)扩大了Gusev Catalysts的投资组合,指出,使用更环保的替代方案可以大大减少化学过程的足迹,例如,就废物而言。

格里亚姆断言:“在制药空间中,肯定有更绿色的替代品的应用。”“我们只是用我们可以提供的东西刮擦表面,但基本上我们可以将酶放入一系列分子模型中以改善化学性质。对于制药公司来说,可持续性将成为越来越重要的驱动力。

“制药的可持续性是越来越重要的重点,” Pharma -Pharma的Matthew Dickman说Azelis,专业化学品的全球领先分销商。“Azelisis proactively involved in reviewing our raw materials and our partners to ensure that we are a market leader in this important process.”
“我们上周在纽约实现了可持续性目标,”全球领导者Rina Chokshi说,DuPont。“作为一家公司,我们认为自己处于可持续性的最前沿,我们当然将其应用于制药公司,与行业分享我们的经验,并支持我们的制药客户以其自身的可持续性目标……绿色化学是我们的支柱之一;我们非常了解我们的材料和流程。”
c²制药, a Luxembourg-based pharmaceutical group that manufactures and distributes APls and complex compounds obtained from natural and synthetic origins, is a key sponsor of thePartnerships for a Better Worldprogram that ensures sustainable, traceable and fair-trade harvesting and sourcing of raw materials.
Andrew Badrot, Chief Executive Officer ofc²制药, communicates a refreshingly sincere wish to run his company in a manner that benefits his staff, his customers and partners, and the world in which we all live.

Similarly, “Our Chairman’s personal vision is reflected in our logo – the ‘wings of happiness’,” said Patrick Park, Vice President – Business Development atSK pharmteco, the newly consolidated contract manufacturing organization (CMO) combining the former business entities ofSK BiotekandAmpac Fine Chemicals。“SK专注于员工,邻居,客户和股东的幸福,其中包括考虑我们的环境影响。通过专注于KPI的幸福,SK将有效地运行并迅速发展,而不会损害我们生活和工作的环境。”
Digital world
“制药公司被锁定在一场永久性的竞赛中,与时间进行创新,并尽快,成本效益,将新药疗法推向市场,” Bikash Chatterjee说。Pharmatech 同事in this year’sCPhI Annual Report。在Chatterjee(我怀疑,许多其他人的观点)中,解决方案在于创造工程师和运营商所需的情报,以做出更明智的决策,以提高运营效率,并提高产量和生产力。
Gareth Jenkins, Chief Scientific Officer atArcinova,指出:“合成生物学提供了一系列技术,使化学家能够对自然界进行的无数转化进行数据挖掘。这导致了一个短得多的制造工艺,通过工业生物技术和化学的最终修饰产生了复杂的中间体,从而消除了对稀缺的珍贵金属催化和减少石化溶剂的依赖。”
“Digitalization is a huge part of theSK公司,以及我们的增长列之一。”SK pharmteco’s帕特里克公园。“我们生成了很多数据,挖掘这些数据对于报告和效率至关重要。我们的重点是内部流程和程序,以提高性能并减少生产时间。”
“我们的流程控制和植物都将尽可能数字化,”营销和开发经理Stephen Drake在卡内卡
“We have implemented a ‘Big Q Initiative’ at our manufacturing plants for ensuring consistency and quality control,” said Rina Chokshi, Global Leader – Regional Product & Field Marketing Leader atDuPont。“It gives a promise of reliability to our customers.”
Marina Kaptein,小组传播总监Azelis,从分销商的角度讲话,但她的评论可能引起了许多其他行业中许多其他“数字之旅”的共鸣。她说:“几年前,数字化是一个流行语,但没有人真正理解它的真正含义。Azelishas always had data-centric business model, a lot of work has gone into it and now is the time to capture the benefits and implement digital transformational, which will increase efficiency and improve our services to customers and principals.”
Conclusion
Various pressures upon the pharma industry are forcing it to become more efficient. Although cost has always been a motivating factor, additional pressures relating to increased flexibility, efficiency and sustainability are further driving the need for ‘better’ manufacturing.
The pharma industry is responding to these demands with a range of novel technologies. These technologies, and the digitalization of pharma, should go some way to addressing the challenges at hand. However, in order to ensure affordable and accessible healthcare in the future, greener processes, smarter route synthesis, novel formulation techniques, flow chemistry and digital solutions all need to be more widespread.
历史向我们表明,制药行业是一种灵活而创新的野兽。我毫不怀疑,它将再次面临这些新挑战。我的好奇心仅在于看到哪些技术最终将对达到这些目标产生最大的影响。