As the biopharmaceutical industry moves towards hyper-personalised treatments for diseases, Barry Heavey asks what this means for manufacturing.
The World Economic Forum has placed particular focus on what it refers to as the fourth industrial revolution, which it describes as follows: “The first … used … steam power to mechanise … the second used electric power to create mass production. The third used electronics and information technology to automate … now a fourth industrial revolution is building on the third, the digital revolution …. characterised by a fusion of technologies that is blurring the lines between the physical, digital and biological spheres.”
This encompasses a vision where human-machine interface technologies, such as collaborative robotics and augmented reality, become the norm and data is sourced from all steps in the manufacturing process to support better decisions, to drive efficiencies, flexibility, and maintain the highest standards of product quality.
This will be particularly important and impactful in the biopharma industry, where the digitisation of manufacturing will be an important tool in dealing with the rapidly increasing complexity and personalisation that is being seen with the many wonderful new therapies coming through the industry pipeline. A new milestone was recently reached in the biopharma industry, which may have profound impact in increasing the urgency with which digitisation will be adopted in the biopharma industry.
On 30 August 2017, a novel therapy (called CTL019) was approved by the US Food and Drug Administration (FDA) and described as a “new frontier in medical innovation”. CTL019 (now to be marketed as Kymriah by Novartis) demonstrated extremely exciting results in clinical trials, with 83pc of the cancer patients treated showing complete remission.
Apart from the potentially enormous impact on patients, why is this development particularly interesting? It could be because CTL019/Kymriah is like no other treatment currently on the market. It is a treatment that is entirely customised to the individual patient.
The treatment involves taking a sample of the patient’s blood, modifying their immune cells in a sterile manufacturing environment, and shipping the modified blood cells back to the patient’s treatment centre for reinfusion. These purified and genetically enhanced immune cells are now ‘programmed’ to attack the patient’s tumours in a way that appears to be more effective than many existing therapies. A batch of this therapy is derived from the patient and prepared for the patient, and hence can be regarded as the ‘batch of you’.
Trends in therapeutic complexity
There has been a steady trend of new therapies becoming increasingly complex in recent years. This has been driven by the amazing developments in life sciences research in the past three decades, where our understanding of the mechanism of many diseases has greatly increased and therapies can be ‘designed’ in a more rational way.
Traditional chemical drugs have become more potent and targeted to specific biochemical pathways in the body. Biologic drugs (or biopharmaceuticals) are extremely complex drugs that have proven to be very successful in recent years. Eight of the top 10 blockbuster drugs are now biologics.
However, unlike CTL019/Kymriah, the current range of blockbuster biotech drugs are ‘off the shelf’ products. Essentially, one batch of drugs produced in a facility can be used to treat thousands of patients.
New challenges for manufacturing and supply chain
With all the excitement around the FDA approval of CTL019/Kymriah, industry experts have focused on a major issue – one which was specifically addressed in the FDA press release. It is the challenge that this new hyper-personalised therapy will pose for manufacturing and logistics.
In the past 10 years, there has been a huge increase in the approval of new, precision medicines for treating a relatively small group of patients. This has created some challenges for manufacturing in the increased range of products that need to be produced, and the increased speed with which new products can enter the manufacturing portfolio.
Eli Lilly’s manufacturing facility in Cork provides a great example of a company responding to product mix changes with manufacturing transformation. The site was traditionally focused on large-scale production of a small number of chemical drugs. In the past decade, it has transformed itself by developing the capability to make a variety of highly potent chemical drugs and utilise continuous manufacturing technology to enable this. The site has also diversified by investing in manufacturing capacity for biologic drugs.
Eli Lilly is not the only site to have achieved this and Ireland has seen more than €10bn in capital investment in biotech in the past 10 years.
Likewise, companies that supply into the biopharma supply chain are adapting to the trend towards diversified niche portfolios. An example of this is the decision by GE to invest in a BioPark in Cork, to support client companies to invest in a flexible way in adding additional capacity for manufacturing of biologic drugs while utilising GE equipment, products and services to minimise capital outlay and increase speed.
Hyper-personalised drugs such as Kymriah may require further transformation of the manufacturing paradigm. While Kymriah is the only product of its kind currently approved, the announcement of Novartis’s success provided a boon to other companies developing similar products. Only a few days the after announcement of Kymriah’s approval, drug-maker Gilead announced that it would acquire a company called Kite Pharma – which is developing a similarly complex product – for $11.9bn. This would suggest that we may be entering another wave of radical change in industry product portfolios and manufacturing requirements.
Digitising manufacturing: Industry X.0
As companies’ portfolios of products and pipeline assets continue to grow more complex, the internal complexity that companies will face in manufacturing and supply chain will increase exponentially. Digitisation of processes (capturing more process data, improving visualisation, analytics and adopting artificial intelligence) will play a vital role in helping companies address and manage this increasing complexity. This will help companies deal with the enormous number of variables they face in manufacturing and help them to make the changes that will release bottlenecks, improve yields, control cost, and increase speed and flexibility – all while maintaining the highest quality standards.
Accenture research published in June 2015 (Value creation through digitisation in the pharmaceutical industry, an Accenture strategy study by Jan Ising, Clemens Oertel, Christine Knackfuss and Isabelle Heiber) indicates that, for a $10bn pharmaceutical company, a partial digitisation strategy leveraging end-to-end capabilities of a digital supply chain helps enable upwards of $387m in cost take-out. In support of this thinking, Accenture uses the term ‘Industry X.0’ and is defined as the digital reinvention of industry.
Industry X.0 businesses embrace – and profit from – constant technological change. They move beyond experimenting with IT bundles or ‘SMAC’ (social, mobile, analytics, cloud) stacks, combining digital technologies to drive both top-line and bottom-line growth. Industry X.0 businesses incorporate core operational efficiencies that are focused internally and apply combinations of advanced digital technologies to continuously create new, personalised experiences and solutions in both a business-to-consumer and business-to-business context. Helping companies to develop the capability to manufacture radical, new and hyper-personalised products, such as Kymriah, as well as efficiently manufacture existing products, is a key element of the Industry X.0 vision.