Paving a pathway to PAT and pharma 4.0

David Leitham, senior vice president and general manager at software company AspenTech looks at why process analytical technology (PAT) is essential for the journey to Pharma 4.0.

The world is currently going through its fourth industrial revolution where automation, artificial intelligence (AI), machine learning, and Internet of Things (IoT) connected machines communicate with one another to better predict and analyse data, improve productivity and profitability, and increase operational efficiencies.

Pharmaceutical manufacturers have been amongst the slowest in adopting and experiencing a wave of technological innovations which offer exciting new opportunities, have the potential to improve their resilience, and facilitate higher levels of quality in all their processes. They have historically found it difficult to embrace change as by necessity, they have well-established, often complex, proven validation processes in place which they understandably fear disrupting. In the past there has been great reluctance to further evaluate manufacturing pain-points, even after a technology has been through the cycle and proven to bring value.

The journey towards Pharma 4.0 had primarily been undertaken on a project-by-project basis until recently. The focus was on investigating point solutions across the product lifecycle, replacing paper processes, automating analytics, and generally developing competencies to start a digital transformation. However, over the past year, we have seen changes accelerate, the industry move closer to realising the dream of Pharma 4.0 and escape the loop of everlasting pilot activity. The Covid-19 pandemic has sped up broader Pharma 4.0 initiatives, particularly with regards to using innovative techniques and partnerships to bring a vaccine to market, supply chain and manufacture, and contract organisation integration.

Social distancing measures have made it more difficult for manufacturers to execute their existing manual processes. Therefore, we have begun to see a shift in the industry which is moving away from a conservatively academic outlook and on to applied innovation. In this context, many manufacturers are intensely concentrated on reducing supply chain disruption, increasing capacity of batch production and minimising batch losses. Reducing lifecycle maintenance costs and CAPEX remain high on the agenda too. Notwithstanding compliance and safety, manufacturing equipment availability is therefore a top priority.

To address this challenge, we have seen the evolution of predictive and prescriptive maintenance capabilities. The latest asset performance management (APM) solutions leverage such capabilities to enable pharmaceuticals companies to protect their supply chain, increase asset utilisation and avoid unplanned downtime by predicting when equipment anomalies will occur, understanding why they do and prescribing how to avoid potential failures.

Alongside APM, we are seeing solutions driving further efficiencies for pharmaceuticals manufacturers, enabling them to:

·        Increase collaboration, from lab to pilot plant to API manufacturing.

·        Simulate end-to-end batch processes with first-principle models, accelerating regulatory approval and scale-up to full production.

·        Identify factors impacting product quality and process efficiency using multivariate analytics.

The above capabilities offer ideal starting points for pharmaceuticals organisations looking to quickly gain value and reduce costs through digitalisation. However, in order for organisations to consolidate gains and continuously optimise processes over time, they need to start moving from achieving pockets of efficiency towards more coordinated and overarching closed loop solutions where accuracy is improved over time.

The journey to PAT

Predictive analytics for APM and multivariate analytics for monitoring process behaviours that impact batch quality will ultimately lead to closed loop Process Analytical Technology (PAT) solutions. PAT has been a well-reputed and promising approach to faster, better, and more integrated manufacturing processes in pharmaceuticals for the past 15 years. It ensures high quality through the process as opposed to testing for quality after completion.

The promises and visions associated with PAT have a lot in common with trends like Industry 4.0 and Internet of Things. While these new trends have placed themselves firmly on the management agenda, PAT has not so far achieved the same attention at the management level. The time is definitely now to change this, as PAT is very much an enabler for digital transformation and ultimately for Pharma 4.0 in the production and development department of pharmaceuticals manufacturers.

The main benefit of PAT is that it leverages real-time data and measurements, along with advanced analytics to better understand and to adjust operational processes in order to improve the end quality of the product itself. Moving forwards, it will increasingly become fundamental to the whole pharmaceuticals manufacturing process. 

We are already seeing PAT tools continuously get better, simpler, and more robust, which, in turn, helps to lower the threshold for implementation. As little as five years ago, a PAT project often ended up simply as a development project, with no immediate direct commercial benefit. Today, as long as the right application is chosen, a PAT project can be all about implementation, reducing project risk and saving pharmaceuticals manufacturers from a number of avoidable pitfalls and delays

Whether a manufacturer’s PAT project turns into an implementation or just a development project depends on the planning phase. Choosing the tools and technologies that scale-up and can integrate into existing infrastructure is a must. Next, organisations should also consider the future direction of PAT. To be future-proof, the business will need to choose a PAT system which supports a range of data source types for instance. Businesses implementing PAT, moreover, should never underestimate the need for early results to ensure that the benefit of their project is recognised.

Manufacturers will achieve quantifiable benefits they can build on and scale up over time by continuously measuring the results and ensuring a robust control environment, secure documentation, and full compliance. Ultimately, it is all about unlocking the value from using PAT in a future-proof commercial environment, which paves a successful pathway not only to PAT but to Pharma 4.0 as well. Manufacturers will have embedded digitalisation into their processes and will be well-placed to manage, monitor and control them to achieve optimum quality of the final manufactured product.