Revolution in pharma

Steam was the force behind the original Industrial Revolution. Electricity powered the second. During the Third, or Digital Revolution, advances in electronics and computing resulted in the widespread automation of industrial processes. And intelligent computing is behind the Fourth Industrial Revolution, which, in the pharmaceutical industry, goes by a slightly different name: Pharma 4.0.

The term was trademarked by the International Society for Pharmaceutical Engineering (ISPE) and essentially, it refers to the roadmap for pharmaceutical companies to embrace the power of digital transformation. This involves not only the adoption of advanced technology such as artificial intelligence (AI), big data, cloud computing, robotics and the Internet of Things (IoT) to optimise processes, reduce costs, improve quality, enhance customer satisfaction and foster innovation, but the cultural, organisational and operational changes required to make these changes stick.

“It’s not just an IT project; it’s everything that goes along with that,” stresses Ryan Thompson, a senior specialist of Industry 4.0 at CRB Group, a full-service facility design, engineering, construction and consulting firm for the life sciences and food and beverage industries. “But, crucially, it is also a revolution. Companies shouldn’t expect marginal or incremental gains. They can expect order of magnitude gains in productivity, quality, flexibility and speed. All of these technologies working together can be more than the sum of their parts.”

Demonstrating the ROI

However, while research firms are predicting doubledigit growth in the market for Pharma 4.0 technologies over the next decade, there are still significant barriers preventing their widespread adoption. During a recent webinar hosted by CRB Group, which works closely with pharmaceutical companies to help them implement Pharma 4.0 systems, the host asked participants what their greatest challenges were when it came to implementing intelligent technologies.

The bar for ‘budget/ROI’ shot up before their eyes. Second place was company culture. This anecdotal evidence is supported by more in-depth research, published in CRB’s 2023 Life Sciences Report, which cited ‘lack of evidence of ROI’ as the biggest barrier for data and AI projects, with security and cybersecurity coming in second.

As Thompson explains, this comes back to his point about Pharma 4.0 being about much more than the technology alone. “There are tangible and intangible return on investment considerations,” he notes. “While the costs are generally easy to calculate, the benefits often require a bit more work. For example, will you actually increase efficiency?”

Here, he says using a discrete event simulation model to analyse the benefits can be very impactful. “A simulation of how the entire business operates – people, warehouse, labs, quality, manufacturing, maintenance, supply chain, and so on – can be evaluated in ‘as-found’ and ‘to-be’ states with assumptions and benefits that can be quantified (along with risks),” he explains.

The intangible part is even more difficult. “What type of business do we want to be? What is the value of being a digital-first company? What does it mean to attract creative people who want to use technology to solve these problems? What new business offerings will this unlock? What creativity will it spark? These are very difficult questions to answer and quantify and speak to the culture of a company – but they should be considered when evaluating investments as well,” he advises.

New ways of working

When organisations begin to implement Pharma 4.0 initiatives, their current ways of working also need to be evaluated and potentially adjusted, according to Yvonne Duckworth, a fellow of digital technology at CRB Group, who is also the co-chair of the Pharma 4.0 Community of Practice. And that doesn’t just mean hiring a new cohort of tech and data whizzes. She says the key skills for Pharma 4.0 can be divided into three categories: leadership skills, such as decision-making, motivating staff and facilitating culture change; business skills, such as critical thinking, system integration and knowledge management; and technical skills, including data science literacy and data visualisation.

“Implementing new technologies and updating processes may require upskilling current positions or re-skilling positions,” she says. “In addition, training your personnel to acquire the skills and knowledge needed to operate, maintain, and analyse the new technologies and data sources will probably be required.

“In addition, it is very useful to have new sources of data, but all that data needs to be managed, and this could require hiring new roles such as data scientists and data analysts. Plus, it is important to focus on supporting new ways of working, advancing technologies and the flow of information and knowledge.”

Playing the long game

For Thompson, the biggest mistake organisations make when trying to evaluate ROI is that they often fail to separate the infrastructure investment from a specific technology project. “Many digitalisation projects have higher upfront costs because infrastructure is also needed. But when done properly, that infrastructure will lay the groundwork and allow for scaling projects into the future,” he explains.

“It’s not uncommon to have a project that may have an infrastructure cost that adds a lot of value for future projects, but it still has to shoulder the high costs to pilot. How do you measure the ROI on that? The real value is the ability to scale that pilot project and leverage the investment you made.”

For this reason, Duckworth always makes a point of brainstorming with her clients at the early stages of a project to find out what digital technologies they might be considering not only for day one, but also down the road. “That way, we can incorporate these aspects into the facility design and hopefully prevent them from having to re-design the facility down the road,” she says. This could be as complex as upgrades to network infrastructure or as simple as widening hallways or doorways to ensure technologies like robotics or AGVs can be added later.

The reality, however, is that many projects get stopped at or before the proof of concept (PoC) phase because the ROI is considered too long. “Or, even if the project makes it through PoC, it might be stopped shortly after simply because the benefits at scale weren’t explained well enough,” Thompson notes. “It’s crucial to separate infrastructure and demonstrate what it will provide in the future – namely, reduced costs to future projects with quicker execution.”

Which technologies can deliver the best ROI?

Unsurprisingly, it is almost impossible to come up with a definitive answer to the question: Which Pharma 4.0 technologies can deliver the best ROI? “The best ROI is going to vary from company to company, facility to facility, and even what time horizon you are looking at,” Thompson says.

Although he can be drawn on one point: “Everyone wants to immediately start taking advantage of artificial intelligence – but getting there is a journey and requires significant infrastructure and data science. That said, this will probably have the best long-term ROI, looking five years into the future,” he acknowledges.

For example, developments in AI image analysis have led to improved defect detection and reduced engineering costs for some ISPE members, reducing false rejects and rework by up to 90%, according to one of the organisation’s use cases, and lowering engineering costs by 30 to 50%.

As well as AI, CRB’s recent webinar also highlighted use cases that demonstrated the benefits of virtual reality (VR) and reality capture technologies. Implementing VR training for clean room and isolator environments was shown to reduce training time and improve overall equipment effectiveness (OEE) for pharma companies, due to higher equipment availability. VR can also be used to assist with engineering design, allowing, say, operations staff to enter a virtual environment and check clearances and clashes much more efficiently.

In a similar vein, reality capture using 360-degree cameras can improve engineering efficiency and reduce travel time and disruption to operations, while progressive reality capture uses 360-degree video to automatically track construction progress, reducing the time spent manually tracking and improving tracking accuracy.

In each case, there’s a learning curve to contend with and a culture change to navigate. “Key stakeholders must be involved to increase the acceptance of new technologies like these,” Duckworth stresses.

Thompson recommends pharma companies to use a maturity model to help figure out where to get started. BioPhorum offers one with a life science focus – the Digital Plant Maturity Model. Another option is the Smart Industry Readiness Index developed by the International Center for Industrial Transformation, which is industry agnostic but comprises a suite of frameworks of tools to help manufacturers identify areas to target, scale and sustain their digital transformation.

Help is at hand

Every year, the ISPE Pharma 4.0 Community of Practice conducts a survey to find out where pharma companies are in their digital journeys. For Duckworth, the most recent one made for encouraging reading, showing a significant drop in the number of companies that have not started Pharma 4.0 implementation along with an increase in the number that have started or have systematic, ongoing actions.

However, on top of concerns around ROI, respondents cited other obstacles, including lack of skills, complexity of integration, regulatory uncertainty and cultural resistance to change, which are hindering their progress. The message both Duckworth and Thompson are keen to hammer home is that they are not alone.

“Regulatory agencies are on board with Pharma 4.0TM; they are not trying to fight this,” Thompson stresses. There are also industry guidelines and programs out there to help, including the FDA’s Emerging Technology Program and the EMA’s Quality Innovation Group, where representatives from academia, industry, the regulatory network and the QIG get together to discuss innovative approaches for the development, manufacture and quality control of medicines.

Most importantly, Thompson concludes, it’s crucial to remember that embracing Pharma 4.0 is not just about adding new technologies to your business or installing a new piece of software; to achieve measurable gains, intelligent technology must be combined with organisational and operational changes.

“Everyone is trying to figure out how this fits their business. But it’s those who embrace culture change who will truly reap the benefits,” he says. “Empowering teams, incorporating agile methodologies and a fail-fast mentality tend to be the most effective for successfully implementing Pharma 4.0 technologies. Oftentimes, business processes that discourage change get in the way of life sciences companies making true progress.”