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Digital Tools and Rising Biopharma Manufacturing Costs: Q&A with Barry Heavey, Supply Chain Lead at Accenture

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Article

Heavey discusses how the industry can avoid having efforts to accelerate discovery and development be hampered by manufacturing concerns.

Barry Heavey

Barry Heavey
Supply chain lead
Accenture

For the pharmaceutical industry, the ability to produce drugs is just as important as the ability to develop new drugs. It doesn’t matter what drugs get developed if the industry can’t produce them to match the demand. Barry Heavey, supply chain lead at Accenture, spoke with Pharmaceutical Executive about how digital tools can help the manufacturing side keep up with the development side.

Pharmaceutical Executive: What would cause efforts to accelerate discovery and development to be hampered by clinical/commercial manufacturing?
Barry Heavey: New molecules moving quickly from discovery through clinical trial to launch may be difficult to manufacture at the pace required. For example, complex drugs like antibody drug conjugates have a multi-step manufacturing process with a limited number of sites globally with all the required technical capabilities. So, even though the volumes of drug required are not enormous as these drugs are extremely potent in treating cancer, there may still be manufacturing bottlenecks at certain steps in the process. This may drive a need to invest in new facilities and train staff while also navigating regulatory approval of new sites.

Many new modalities, such as CAR-T cell treatments for cancer, are very challenging to scale in terms of supply due to the one-patient-one-batch nature of the product and the highly manual nature of the manufacturing process. There is urgent need for re-engineering of the manufacturing processes for cell and gene therapy, including the use of robotics, to support scaling, but these new processes will require time to optimize and validate.

Other exciting new modalities like AAV gene therapy are showing promise in trials, but AAV is an example of a modality which will require very significant investment in research to boost productivity and consistency in the production processes. This is due to the complexity of making, purifying, and testing genetically modified viruses at high yield in GMP conditions.Several modalities that are showing success in R&D are currently competing for limited resources in global supply chains. For instance, the explosive growth in demand for mRNA during the pandemic and more recently the high demand for injectable peptides to treat obesity has created high demand for sterile manufacturing capacity. This can create challenges and/or bottlenecks for companies seeking capacity to manufacture other sterile modalities such as monoclonal antibodies, siRNA, ADCs and beyond. Adding capacity in sterile manufacturing is not a trivial investment. Specialized facilities, equipment, consumables, and staff trained in aseptic procedural adherence are all key to ensure patient access and safety.

PE: How can the pharma industry leverage digital tools in manufacturing to prevent these issues?
Heavey: The pharmaceutical industry can use digital tools from the start of the lifecycle of the drug to model (create a digital twin of) the manufacturing processes and run “in silico” experiments to accelerate the development of an optimal manufacturing process at the appropriate scale. Digital tools can also support knowledge management between the various teams responsible for running manufacturing over time and geographies.

Generative artificial intelligence (AI) can reduce the time needed to create complex documentation linked to manufacturing and quality, in particular the regulatory submissions associated with manufacturing processes (so called chemistry manufacturing and control (CMC) documentation.Advanced analytics can be utilized to predict problems in the supply chain or accelerate root cause analysis when there is a problem. This can aid day to day manufacturing and quality, as well as longer term planning and decision support.Workers can be guided through flawless execution of complex procedures using digital SOPs and extended reality tools for training and guided method execution.

Automation and AI can streamline manufacturing operations, automate repetitive tasks, and enhance overall productivity, reducing the time and resources required for manufacturing and quality checks. Digital tools can also provide real-time visibility and analytics for supply chain management, optimizing inventory management, reducing waste, and ensuring a steady supply of materials and products. Predictive maintenance enabled by digital tools can reduce downtime and improve overall equipment effectiveness, thereby preventing unexpected disruptions in the manufacturing process.

PE: Which digital tools are most likely to reduce manufacturing costs?
Heavey: Advanced modelling of key manufacturing processes and equipment are already in use in many pharmaceutical manufacturing plans, helping to better control the manufacturing process, reduce variability and losses of time or yield. I believe further investment in modelling/digital twins enhanced by AI will generate very significant value in reducing costs when they are applied to manufacturing processes that have a high degree of complexity and variability.

Biology-based processes, such as production of proteins, vaccines, cell therapy and gene therapy, have very high complexity and variability. There is enormous potential for cost-take out in these processes by use of digital twins to optimize yield and consistency.The industry has already seen greater than 100fold reduction in the cost to produce monoclonal antibodies in the last two decades, but we have the potential to see similar cost take out in new modalities, like cell and gene therapy, happening faster using digital twins.

With the integration of automation tools like Robotic Process Automation (RPA), businesses can minimize human errors and enhance productivity related to tasks such as documentation and compliance checking. A simple example being the process of batch record review which can be radically simplified by creation of electronic batch records and review by exception, saving time and costs in quality assurance. Many other such routine tasks can be automated allowing the highly qualified scientists, engineers in manufacturing, quality, regulatory affairs and supply chain to focus on more high value activities such as process improvements or new product introductions.

By implementing these digital tools, businesses can achieve substantial savings while improving efficiency and quality control throughout the supply chain. The pharmaceutical industry can leverage these tools to stay ahead of the competition and ensure continued success in a rapidly evolving market.

PE: What factors are causing a rise in manufacturing costs?
Heavey: Biopharma manufacturing costs are rising due to several factors. One is the increasing complexity of drugs like proteins, peptides, mRNA, viruses, and cells. The manufacturing process for these drugs often needs specialized, novel, patented and expensive equipment, materials, testing equipment and reagents.

Companies must build large teams of internal expertise but also utilize external expertise in the form of contract development and manufacturing organisations. Contract development and manufacturing organisations that have specialist expertise and capacity for development and production of novel modalities (such as ADCs of AAV) are in high demand and hence have supplier power which makes them more expensive.

Companies investing in discovery and development of new drugs must also invest in efforts to scale up manufacturing processes from the lab to commercial scale. This can take time, effort, and significant cost especially for more complex candidates, as some of which may be lost if the candidate drug fails during some stage of development. Ensuring consistency, quality, and efficiency at larger scales can require additional investments in equipment and process optimization. Process development and manufacturing can account for 20–25% of the total cost of bringing a new drug to market.

In many cases for novel modalities such as AAV, the industrial scale manufacturing processes are relatively immature and the industry may be several years, if not decades, from having the understanding and technology to maximise the yield from the processes. Therefore, many companies are producing these new modalities at the relatively low yield and high cost per dose that was seen in monoclonal antibody production in the 1990s.

Regulatory requirements to gain and maintain approval for manufacturing processes at multiple sites and for multiple markets is undoubtedly a major driver for cost in manufacturing. New and more complex modalities where the process understanding is somewhat less mature will inevitably attract more regulatory scrutiny, adding to the overall cost of manufacturing.

Hiring, training, and retaining a skilled workforce of scientists and engineers is also a significant cost factor. Developing and manufacturing complex drugs requires a skilled and experienced workforce with some veteran experts who have a deep understanding of the scientific and engineering fundamentals of the manufacturing processes and global regulatory constraints. Companies must augment these teams of experts with ability to support training and continuous development of a wider team of operatives in various steps in manufacturing and quality control.

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