Two Grand Challenges for Pharma

The growing, aging, and increasingly comorbid population is relying on the pharma industry for more personalized medicines and advanced treatments, all at lower costs. New approaches to manufacturing and supply will be essential. 

In the UK, partners across industry, government, and academia have come together to form the Medicines Manufacturing Innovation Centre. As part of a collaboration between CPI, the University of Strathclyde, GSK, AstraZeneca, and with funding from UK Research and Innovation and Scottish Enterprise, the center has set out two ‘Grand Challenges’ to address in medicines manufacturing: producing tablets more efficiently using continuous direct compression, and reducing waste and improving agility in clinical supply with a “just-in-time” approach.

Here, we speak with John Robertson, Principal Investigator at CMAC Future Manufacturing Research Hub, about the development phase of Grand Challenge 1. And we chat with CPI’s Dave Berry – Grand Challenge 2 lead – to find out how exciting new initiatives could transform the future of drug manufacturing. 

Tell us about the two Grand Challenges…

John Robertson: Grand Challenge 1 involves the creation of a continuous direct compression (CDC) platform that will enable oral solid dosage medicines to be formulated more easily. When compared with traditional “batch” manufacturing, continuous manufacturing allows for more efficient use of time and expensive materials due to the flow of production without interruption. We will further build on this process efficiency by developing a digitally-twinned CDC platform and workflow, enabling scientists to better understand and optimize their formulations in a digital space. Existing CDC models are often inflexible and specific for individual equipment manufacturers; the digital twin will help us adapt and improve processes, while reducing development times.

Dave Berry: Grand Challenge 2 will deliver just-in-time medicines supply for clinical trials through an automated supply chain system, which we call the Pharmacy Automation for Clinical Efficiency (PACE) platform. The PACE platform consists of a collection of robots connected digitally to a dashboard that provides quality information to qualified persons who certify batches of medicines and send them to patients. The platform will enable multiple medicines to be produced on a single line, along with individualized packaging and real-time quality checks.

Grand Challenge 1 and 2 were officially announced in 2019. What are the updates since then?

JR: One of the most exciting updates over the last year has been the addition of several new partners to help support the Grand Challenges, including Siemens, Perceptive Engineering, and Process Systems Enterprise (PSE). Over the past year, we have also been working on the development and evaluation of the digital twin, which will allow us to understand and optimize the CDC platform in a digital space. 

In October 2020, we officially broke ground on the Medicines Manufacturing Innovation Centre building in Renfrewshire, UK. 

DB: As John said, the addition of these new partners is certainly exciting. Siemens will also be providing digital manufacturing support to Grand Challenge 2, along with Applied Materials, which will be integrating its SmartFactory Rx automation software into the PACE platform.

We are also pleased to report that the PACE platform is now 90 percent built, and we are on track to finish in 2021. Originally, the plan was to finish the PACE platform in the new Medicines Manufacturing Innovation Centre building, which is the state-of-the-art facility that will house the Grand Challenges and future programs. However, COVID-19 forced construction to pause on the center. Interestingly, however, this hurdle has forced us to think more critically about the platform’s portability. Through this disruption, we realized that some of the design features and IT infrastructure should be incorporated into the platform, rather than into the building, to allow the platform to be transferred with more ease – theoretically, across the world to be used for clinical studies.

How were the first two Grand Challenges chosen?

DB: The challenges were selected and defined to tackle areas of medicines manufacturing where there are known inefficiencies – and because of the potential of advanced technology to reduce the waste associated with current processes. 

JR: Despite improvements in medicines manufacturing, the way we make tablets has remained static for about a century. Grand Challenge 1 looks at how we can improve one of the simplest ways of making tablets: direct compression. The first step of Grand Challenge 1 looks to address the direct compression process itself; the second step incorporates continuous manufacturing into the process. By leveraging continuous manufacturing, we can reduce waste while also reducing batch-to-batch variability. With these improvements, we hope to reduce drug waste from 30 percent – associated with today’s manufacturing methods – to less than 5 percent. Not only can this offer a huge economic benefit, but reduced development times and API consumption can also provide significant environmental benefits.

DB: The manufacturing of medicines for clinical trials represents a significant – but essential – investment for drug manufacturers. The way we produce this supply currently relies on a ‘just in case’ approach. This means that requirements are predicted up to two years in advance to allow for lead times, and drugs are often over-produced to ensure sufficient supply. Delayed or cancelled trials can also result in expired drugs that will not be used. Creating a more agile and responsive supply chain will allow a shift to ‘just in time’ manufacturing, minimising the need for excess drug production. This approach will improve efficiency and reduce some of the costs associated with producing medicines for clinical trials. Making clinical trials cheaper and more effective will create a cascade of positive effects for both pharma companies and patients.

How could these initiatives help accelerate the adoption of personalized medicines?

DB: Grand Challenge 2’s PACE platform includes a number of features that allow for the creation and distribution of personalized medicines that are made just in time for clinical trials. The design of the platform allows for multiple drugs to be packaged on the same line without cross-contamination. Additionally, bottles can be filled with custom amounts of drug compounds, and then sealed and sorted with customized barcodes for rapid labeling and distribution. The platform enables the flexible production of clinical supply, produced for specific trials and even specific patients.

JR: The CDC platform associated with Grand Challenge 1 occupies a slightly larger scale than the PACE platform. At the moment, it cannot tailor medicines to individual patients. Instead, the Grand Challenge 1 technology will be able to respond to and tailor medicines for specific patient groups – e.g., pediatric or geriatric dosing regimens – through improved manufacturing processes. The improved speed and agility will allow for shorter runs, enabling pharmaceutical companies to better respond to differing patient needs.  

Why are partnerships such a fundamental aspect of the Medicines Manufacturing Innovation Centre?

JR: Partnerships are the building blocks that enable us to de-risk the adoption of innovative technologies into pharmaceutical manufacturing. For industry partners like GSK and AstraZeneca, incorporating new, advanced, and unproven technologies into medicines manufacturing often presents too much risk, outweighing potential benefits. 

DB: One of the most exciting parts of this collaboration is getting together with all of the partners in a pre-competitive environment. We are all able to collectively use our cross-sector expertise to advance the field. These partnerships have continued to evolve over the last few years. And we have now started introducing new partners that can contribute their expert technology, services, or know-how to the Grand Challenges. This includes companies who have expertise in fields seemingly “outside” of pharmaceutical manufacturing. Their knowledge and technology will enable us to accelerate advancements in our own industry. 

What are the next steps for the Medicines Manufacturing Innovation Centre?

JR: Right now, we continue to work on the projects, but we are also thinking about new Grand Challenges, including Grand Challenge 3, which will focus on the development of oligonucleotides. Overall, the goal of the Grand Challenges is to improve medicines manufacturing, not just within the silo of the Medicines Manufacturing Innovation Centre or in the UK, but to help the entire global pharma sector.

DB: My hope is that we can revolutionize medicine manufacturing as a whole. In the long run, the introduction of advanced technology into medicines manufacturing is going to have lasting positive effects that will change the way we make medicines for the better.