The Phoenix of Process Innovation

Imperial Chemical Industries (ICI) once employed as many as 30,000 people in Teesside in the North East of England. The company’s history dated back to the 1920s and the demolition of its three 100 m cooling towers in 2012 signaled the end of an era for a region – and a community – defined by their industrial heritage.
 
Similar stories can be seen the world over. From the US “Rust Belt” to the industrial heartlands of Southern Ontario, Canada, to Bergslagen, Sweden, globalization has led to industrial decline, which can, in turn, influence social and economic issues.
 
Globalization is arguably one of the defining political issues of our time, with governments across the developed world thinking about how to reduce geographic inequality and create stable jobs in former industrial regions. One big hope for advanced economies is creating jobs in high value, high productivity industries, such as pharmaceutical manufacturing. The big stumbling block? The inherent risk of innovation.

Waste into worth

In the UK, CPI is an example of how older industrial sites can be given a new lease of life, benefiting the local economy, the country, innovation and, ultimately, patients worldwide. Since its establishment, CPI has worked on a number of pharma-related projects, including the BioStreamline project to optimize the development of novel biotherapeutics, and PROSPECT CP (Prove Real-world Scalable Predictive Tools/Technologies for Complex Particles) project, which involves the creation of a facility for continuous wet granulation.

CPI was born in Teesside out of different parts of ICI. “At one time, ICI at Wilton was the epicenter of the world’s chemical industry,” explains Graeme Cruickshank, CPI’s Chief Technology and Innovation Officer. “When ICI was broken up and sold to various other companies, there was a question of what the best opportunity was for some of the existing infrastructure in Wilton. At the time, people said that if the scale-up reactors were closed, we’d never break the problem of turning waste into worth because they can’t be reopened.”

One NorthEast, the regional development agency for North East England, stepped in to keep parts of the facility open and CPI was established in 2004 as a not-for-profit focusing on process innovation. It received an initial £0.6 million in UK government funding and then in 2011 became a founding member of the government’s network of High Value Manufacturing Catapult centers. These centers are designed to aid the future growth and success of manufacturing in the UK.

According to Cruickshank, CPI’s goal is to act as a “catalyst” that brings together academia, businesses, government and investors to “translate bright ideas and research into the marketplace,” and provide access to the right experts, equipment, facilities, networks, and funding. “While we are mainly located in the North East of England and have contributed significantly to regenerating local industry in this region, we also provide innovation services to multi-national companies, as well as companies across the whole of the UK,” he adds.

Today, CPI works across a number of high-value markets, including pharmaceuticals (small molecules, biopharmaceuticals and complex medicines), medtech, speciality chemicals and materials, electronics, automotive and more. It operates seven facilities – many of which target the pharma industry (see sidebar: Innovation Network).

The valley of death

According to Cruickshank, many good inventions are not successfully commercialized because there are several steps in between inventing something and selling it – all of which require investment in money, people and time. “This is called the ‘valley of death’. The width of the valley is how long it takes to make the decision and the depth is the capital required. Our role is to help people make decisions faster by spending less money,” says Cruickshank. “One of our unique selling points is that we allow companies to test out ideas without interfering with current production lines or having to invest in new infrastructure.”

As scientists often focus on the product without considering the manufacturing scale required once commercialized, cost of goods evaluation is a useful technique to help prioritize practical work. “One thing CPI often asks first is ‘how much product do you need to make?' I’ve had some interesting answers to that question!” says Harvey Branton, Biologics Chief Technologist at CPI. He adds that some companies have estimated they’ll need to manufacture tons of product going beyond the scale of most CMOs, once current process yields are taken into account. “This highlights that people don’t always understand how commercial manufacturing works and what is required for successful scale up! Manufacturing volumes can vary wildly from project to project and we advise accordingly. For example, even though the manufacturing methods are similar, the approach to support a vaccine (where 20 litres may represent a year’s supply) is very different to a commodity product requiring tons of product annually. Final manufacturing processes need to be robust and additional experiments may be required to ensure that the product can be cost effectively manufactured.”

According to Nick Johnson, Commercial Director at CPI, there are two main kinds of innovation CPI is poised to help with: incremental and disruptive. “Incremental innovation is quite routine for large organizations. A big pharma company might have an existing manufacturing practice and be interested in how they can make incremental improvements, for example, and some companies also ask us how we can augment their R&D capabilities,” he explains. “Disruptive innovations are more the preserve of small companies and SMEs often come to CPI with a great idea, but without the R&D infrastructure, nor the technical expertise, to make it a reality. We can help them optimize their innovation and get it to the market. We also do a lot of work with universities looking to spin out their technologies.”

CPI can also advise companies on how to access government funding. “There are all kinds of government support programs available to help with innovation,” says Johnson. “And getting the right funds at the right time can be absolutely critical for SMEs. We have a group that looks at the funding landscape and engages with industry around how to apply and secure those funds. “Increasingly, we are speaking with the investor space to help marry up people with funds they wish to distribute with the right companies and organizations.”

Innovation reborn

CPI has been involved in a number of ground-breaking pharma projects. “Cell-free expression is just one example of how we can contribute. This isn’t something that’s widely used yet, but we have customers with processes that could really benefit from this emerging technology,” says Branton. CPI are actively involved in a range of special interest groups which regularly bring academics and industry together to discuss disruptive manufacturing approaches. Some of these include novel expression platforms, directed evolution and automated approaches.

More recently, CPI has been involved with PROSPECT CP in collaboration with AstraZeneca and GlaxoSmithKline. The continuous wet granulation facility is due to be completed in Q3 2020 and will be available as a national, open access center for contract development. “Continuous granulation is receiving enormous attention from pharma manufacturers. Solid oral dosage forms are still the most prevalent delivery method, so innovations have a correspondingly significant effect. Wet granulation was chosen as inherently it is a unit operation used to deliver tablets, particularly those for drug substances with challenging processing properties,” says Jacquin Wilford-Brown, a Principal Scientist at CPI involved in PROSPECT CP. “Some molecules are simply not amenable to direct compression approaches (e.g., products containing high doses of APIs), so delivering a solution to help the challenging molecules in a portfolio has a substantial impact.”

This capability also compliments the newest CPI center, the recently-announced Medicines Manufacturing Innovation Centre, which will be located in Scotland and is a collaboration between CPI, AstraZeneca, GlaxoSmithKline, the University of Strathclyde, Innovate UK and Scottish Enterprise. The facility aims to help with the development of  next generation pharmaceutical manufacturing technologies.

The shutdown of manufacturing facilities often fills media headlines, but the history of CPI shows that old facilities can be given a new lease of life to benefit local communities and economies. “As a direct result from working with CPI, a number of companies have gone on to invest in assets and innovation within the Tees Valley in the North East region of England. Fifteen companies have also co-located with CPI’s innovation and incubation facilities at NETPark and Newton Aycliffe,” says Johnson. “This allows companies access to our facilities, whilst attracting skills to the local area. CPI employs over 430 highly skilled members of staff. Over 40 percent hold a PhD or equivalent and 90 percent of CPI staff live in the North East of England.”

And reinvigorating local manufacturing hubs can have a huge impact on a country. The North East of England, for example, currently produces around a third of the UK’s GDP in terms of pharmaceutical manufacturing, and the International Monetary Fund found that a 40 percent increase in R&D spending by the private sector could increase GDP by around five percent in the long term in advanced economies such as the UK (1).

“This year, we are celebrating the 15th birthday of CPI! We’ve come a long way!” says Cruickshank. “The really funny thing about our work is that when we do our job well, our customers go away! If I help a company to be successful then they may not need us anymore! And that’s a really rewarding thing to see.”