A Practical Guide to Scaling Up Production in Pharma and Biopharma Companies

The Covid-19 vaccination programme was one of the greatest scientific success stories in recent history – an example of what can be done when the entire industry, from R&D to manufacturing and distribution, pools all its resources and collaborates effectively.

Pfizer, AstraZeneca, Moderna, Johnson & Johnson and others achieved the impossible task of delivering a safe and effective vaccine, running clinical trials concurrently and starting production before vaccines had even been approved.

The pandemic shone a light on all aspects of the pharmaceuticals supply chain, from the availability of drugs used to treat patients with Covid-19, to drug discovery, production capacity and cold chain distribution. When the vaccine program ramped up, pharmaceuticals companies rose to the challenge – carefully managing new and complex processes, which would normally take years to refine, in order to meet the terms of their government contracts.

Manufacturers demonstrated tremendous flexibility and resilience during the crisis, quickly adapting the workflows in response to global demand. While the circumstances were exceptional, the genie is now out of the bottle and there’s no going back to how things were.

There’s an appetite to realize the potential of new technologies with innovative new treatments that address long-standing health problems. Public expectations have shifted irreversibly, and manufacturers will clearly need to embrace lean manufacturing and Six Sigma in order to make the most of new opportunities in life sciences.

Optimizing your planning and scheduling processes is one of the most powerful ways to deliver stronger ROI on new treatments. It allows you to rapidly scale up production while maintaining validated processes, and maximize capacity. Across the US and Europe, pharmaceuticals and biopharmaceuticals companies are now focused on scaling up, building operational resilience and realizing their digital transformation projects. Wherever you are now, our guide will show you how to future-proof your manufacturing operations for success.

Drug manufacturing today

US pharmaceuticals and biopharmaceuticals companies lead the way on drug development and pioneer the complex manufacturing processes required to get these new treatments to market.

Quality employees, infrastructure, favorable tax environments and access to capital are among the reasons why the country ranks so highly – but it is also important to note the market’s maturity is no barrier to future growth.[1]

One of the most important growth areas is biopharma manufacturing, which according to one article, delivers the ‘cutting-edge medicines developed hand-in-glove within the R&D ecosystem, providing high-wage STEM jobs, a growing source of exports and sustained investment and productivity gains.’ [2]

The author goes on to say that ‘process innovations are as important as product innovations’, and manufacturers ‘constantly research, develop and adopt new technologies and processes, such as continuous manufacturing, high-volume cell processing, and advanced purification, preservation and distribution modes.’[3]

But while continuous manufacturing has been adopted in some solid dose facilities, experts stress there are still a number of challenges to overcome if it is to be applied to biopharma.[4]

We’re finding that growing numbers of industry professionals recognize that poor scheduling methods are a barrier to growth. Planners want to iron out inefficiencies at an operational level, while senior leaders are pressing ahead with digital transformation projects to support strategic plans.

When working at the same capacity, it is possible (albeit difficult) to schedule hundreds of tasks in a specific sequence using spreadsheets. But as soon as you start to increase capacity, or introduce new products, traditional planning and scheduling methods are no longer fit-for-purpose.

This is important given the shifts taking place in the industry at the moment. As companies move away from ‘blockbuster drugs for large numbers of patients to more focused products targeting smaller populations’, facilities will have to be capable of producing more than one treatment.[5]

Demand for new therapies is only going to gain momentum over the coming years – driven partly by an ageing population and associated comorbidities in the US and other developed nations, and a push towards small-batch personalized medicines.

Drug companies must continue to invest in new therapies for cancer, diabetes, heart disease and other conditions and the stakes are high.

While the median cost of developing a new drug between 2009 and 2018 stood at $985million, the median for oncology and immuno-modulatory drugs was $2.8billion.[6]

In the aftermath of the pandemic, we saw digital transformation become a key priority for biopharmaceuticals companies, alongside global market growth and strengthening R&D.[7]

Data-driven technologies, including AI and machine learning, Internet of Things (IoT), advanced analytics and predictive modeling, are transforming pharmaceuticals manufacturing, driving forward improvements with powerful data-driven insights. In other words, they ‘have the potential to create value across manufacturing, the supply chain, and the entire healthcare ecosystem.’[8]

Scaling up with confidence

It is testament to the strength of the pharmaceuticals industry that it responded so quickly to the Covid-19 pandemic. The major vaccine manufacturers moved quickly to increase capacity across their supply chain network, with teams working around the clock to meet demand.

Scaling up outside an emergency doesn’t come with the same urgency but the agility, resilience and innovative thinking many demonstrated during the crisis will stand them in good stead for future success. But what exactly should they strive for when expanding their operations to include new products with evermore complex manufacturing processes?

Speed

Whereas it might ordinarily take a decade or more to get a vaccine to market, the first Covid-19 vaccine was administered in the US in late 2020 – less than a year after the pandemic emerged. This was only possible due to substantial government support but the speed at which the vaccine was developed, manufactured and approved has paved the way for new ways of working.

The vaccine itself is likely to be a catalyst for investment in mRNA technologies, so ‘the industry may look for novel ways to rapidly increase this capacity as well as repurpose existing capacity.’ [9]

Before Covid-19, FDA Commissioner Scott Gottlieb said efforts to streamline product development ‘can be frustrated by legacy business models that discourage collaboration and data sharing, and the adoption of disruptive technologies that make clinical research more effective.’ This, he suggests, results in missed opportunities to lower costs and validate new drugs.[10]

A dynamic approach to planning and scheduling is crucial for reducing delivery times and batch footprint. When everyone is working to a single live plan, automatically updated and optimized, they reduce the time spent on handovers, updates and reporting. You’ll also see whether there are opportunities to run tasks concurrently, speeding up production without investing additional resources or impacting other processes.

Capacity

During the pandemic, drug companies had to rapidly increase capacity to meet demand for vaccines. It reminded us that the threat of a global health emergency is never far away, but questions remain about what will happen to this additional capacity after the pandemic – how will it be used, will it still be needed and who will pay for it?[11]

What’s important is that manufacturers are able to identify and make use of excess capacity before making critical decisions about whether to invest in a new plant or equipment. A flexible approach to capacity planning is required, with detailed analysis of where equipment is being under-utilized before further resources are deployed.

Collaboration

As well as collaboration within production teams, and the wider organization, strategic partnerships are essential for growth. Ambitious start-ups have long been partnering with multi-national pharma companies in order to get their drugs to market, and the development of the Covid-19 vaccines shows just what can be achieved when researchers and manufacturers collaborate closely. But the benefits of collaboration extend beyond the life sciences, with the tech industry being touted as a key partner – partly because tech can help pharma companies to leverage their data more effectively.[12]

Location and costs

We’ve seen how supply chain disruption could quickly threaten the availability of life-saving drugs.

This is why, according to one report, the focus is moving away from landed costs towards the costs associated with location risk. As a result of the pandemic, we may see manufacturing move to lower-risk countries or closer to end markets.[13]

However, one of the strengths of the pharma industry is that it is truly global. Joint agreements will enable companies to collaborate and scale up production capacity quickly, wherever they are located.

Digital transformation

The way medicines are developed, manufactured and delivered is also changing thanks to advances in technology.

Wearables, for instance, could improve the speed and accuracy of clinical trials by monitoring participants remotely using ‘real-time, real-world’ data.

Real-time production data supports optimal planning and scheduling but can also be used for detailed what-if analysis before manufacturing begins – enabling planners to understand the impact of taking on new orders and senior managers to determine whether investment in a new facility would pay off. Manually-produced spreadsheets and Gantt charts might traditionally be used for this task – but they have their limitations. Not only are they time consuming to produce, they do not always offer the right insights to support decision making.

When production data is stored on a single secure site, available to all authorized personnel wherever they’re based, collaboration improves too. When we spoke with Dr Jennifer Pancorbo, Director of Industry Programs and Research at the Biomanufacturing Training and Education Center (BTEC) in Raleigh, part of NC State University, she told us:

One of the biggest changes [following Covid-19] is the need for flexible infrastructure that allows people to collaborate and manufacturing to take place across multiple territories, and gives them remote access to data and production plans.

Moving towards advanced planning and scheduling

As companies expand their range of new and innovative therapies, planners need to have a clear understanding of the complex processes involved in large-scale production and deliver ultra-efficiently.

In biopharma, a single batch could have as many as 1,000 operations, while processes may not follow a linear sequence. The challenge is to schedule these tasks to make the most of capacity, without causing bottlenecks. Production teams who already use Six Sigma or lean methodologies are well placed to make the kind of process improvements necessary for growth.

Advanced planning and scheduling (APS), facilitated by the right software, assists with both day-to-day planning and capacity planning on a large scale. It supports what-if? analysis too, so planners can see how taking on new contracts would impact their existing commitments at each site.

It is worth remembering that while few would have capacity to meet global demand, it is not uncommon for pharmaceuticals manufacturers to have unused capacity. As an analogy, a highway may only run at full capacity during rush hour and holiday season – while it stays relatively empty at other times, planners must consider the maximum number of vehicles it needs to hold.

Planners need full visibility across their facility and other sites around the world, wherever they are working, in order to create the master schedule. There is no point loading all tasks into the schedule on a Monday morning, putting a strain on resources and potentially causing bottlenecks. Similarly, there’s no point machinery or people sitting around idle.

What does good planning and scheduling look like?

Advanced planning and scheduling allows teams to work together effectively, wherever they are based. In short, they’re able to achieve the following:

Co-ordinate

Understand what resources and capacity you have and use automated scheduling to optimize every task. With so many complex processes involved in making a single batch, planners depend on actionable insights to support better resource planning and run tasks concurrently.

Communicate

A single live schedule, visible to all authorized personnel, ensures everyone knows what tasks need to be actioned and all updates are communicated. It also makes reporting to senior managers quicker, easier and more consistent.

Collaborate

Spending less time on manual scheduling means experts are freed up to add more value to work and collaborate closely with colleagues, both within their production team and at other sites. What does good planning and scheduling look like?

Visibility of every action and process is paramount. When teams are working 24-hours a day, communicating the latest plan and actions via a shared planning platform will ensure there are no unnecessary hold-ups, nor lengthy handovers. In other words, it promotes a spirit of collaboration that is difficult to achieve when people are siloed and working from spreadsheets. Since the plan is regularly and automatically updated, they also have confidence in the data they use.

Co-operate

All this promotes co-operation across the production team and beyond, as everyone works together to achieve the same outcome. Next, we’ll see how one biopharmaceutical manufacturer is on track to save time, reduce costs and increase the number of batches produced using advanced planning and scheduling methods.

Engineering growth at a US biopharmaceuticals plant

Maximizing capacity is a priority for any pharmaceutical company with commercial ambitions.

Inefficiencies in planning and scheduling mean that companies will struggle to increase their through-put without incurring higher costs, which impacts profitability.

This was certainly the case for one of our customers, a major biopharmaceuticals manufacturer based in North Carolina. It had realized that a system of spreadsheets and flip boards meant it lost valuable time – for example, when staff had to decontaminate every time they left and re-entered a sterile area to check a chart. Moreover, tasks like machine maintenance were not included in the schedule, which could potentially disrupt production.

It is important to remember that even the smallest inefficiencies add up over time. At this particular company, shop floor employees were spending several hours on manual scheduling every week and it was difficult to adapt the schedule if changes occurred.

But an independent study showed that the planning team would see significant time savings and be able to make evidence-based decisions if they moved to an automated web-based schedule.

A single schedule, visible to all authorized personnel, could reduce decontamination and scheduling times, while improving communication across the production team and with senior managers.

The study also found that, had the production team made process improvements via APS, they could have produced 4.65% more batches last year. Now, with an APS system in place, the site has capacity to produce almost 28% more batches in a full year. As well as putting the company on track to significantly increase revenue, data from the APS system also showed they could make major cost savings by rescheduling the cleaning crew to work only day shifts, not 24/7.

Conclusion

The coming years will prove critical as more pharma and biopharma companies realize their digital transformation projects, which took on a new sense of urgency during the Covid-19 crisis.

We should see technology being used to drastically speed up clinical trials and improve patient outcomes. The ‘research triangle’ of North Carolina, and the UK’s ‘golden triangle’ of London, Cambridge and Oxford, are both expected to grow – presenting new opportunities for manufacturers to make new innovations a commercial reality. Complex production processes demand a new approach to planning and scheduling, which supports transparency, collaboration and the ability to scale up.

Whether you want to understand capacity at existing facilities, or one not yet built, advanced planning and scheduling methods allow you to make decisions with confidence. Technology is not designed to replace years of expertise but to remove the manual calculations, reporting and updating of spreadsheets that currently take up valuable production time.

Scheduling is even more critical than before, and greater efficiency not only benefits the production team. Increased savings and revenue both help to offset the high costs associated with R&D and manufacturing complex therapies, not to mention the cost of clinical trials and approvals.

Source 1: www.news-medical.net/news/20191206/US-pharmaceutical-industry-continues-to-shine-according-toCPhI-2019-Annual-Report.aspx

Source 2: https://catalyst.phrma.org/new-report-advanced-manufacturing-powering-innovative-biopharmaceuticals

Source 3: Ibid

Source 4: https://www.scienceboard.net/index.aspx?sec=sup&sub=can&pag=dis&ItemID=536

Source 5: JAMA, cited in www.biopharmadive.com/news/new-drug-cost-research-development-market-jama-study 

Source 6: www.deloitte.com/us/en/insights/industry/life-sciences/pharmaceutical-industry-trends.html  

Source 7: www.deloitte.com/content/dam/Deloitte/ce/Documents/about-deloitte/ce_2020_global_life_sciences_outlook.pdf  

Source 8: www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/pharmaoperations-the-path-to-recovery-and-the-next-normal

Source 9: www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-mdnew-strategies-modernize-clinical-trials-advance

Source 10: www.pharmaceutical-technology.com/features/big-tech-big-pharma-collaboration-recipe-for-success

Source 11: www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/pharmaoperations-the-path-to-recovery-and-the-next-normal