LIFE SCIENCES & HEALTHCARE

The scientific basis to deliver sustainable outcomes in Life Sciences and Healthcare

SUSTAINABLE PHARMACEUTICAL MANUFACTURING WITH THE VIRTUAL TWIN EXPERIENCE

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A TIME FOR CHANGE

The growing global demand for pharmaceuticals due to longer, more affluent living, presents many challenges for the industry.

While the Life Sciences and Healthcare industry aims to improve the quality of our longer lives, there is a growing recognition that the pharmaceutical sector must do more to improve its sustainability performance.

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DISRUPTIVE, CORRECTIVE ACTION

"The reality is that greenhouse gas (GHG) emissions are locked in for decades at the time they’re emitted, which means that if you want to be climate neutral in 2050, you have to halve or completely neutralize your emissions by 2030—that’s right now, essentially,” explains Alice Steenland, Dassault Systèmes’ Chief Sustainability Officer.

"This is why it’s such an urgent situation, because we don’t know today how to completely transform our consumption and manufacturing processes. And, usually, these processes take decades, if not centuries, to change.

"This is an innovation challenge for all industries, and that includes pharmaceuticals because it is a massive manufacturing industry globally that’s very energy-intensive.

"The urgent need for action requires us to move away from incremental improvements in climate change and emissions and really shifting towards radical, disruptive change.

"This means completely rethinking how you make things and completely rethinking where energy comes from. That’s what we need to do, and we need to do it in the next few years. So this presents a massive innovation challenge for pharmaceuticals,” added Alice.

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To meet the high demands of sustainability, traditional ways of innovating will not effect manufacturing sustainability quickly or effectively enough.

Instead, manufacturers need to leverage the power of the virtual twin to optimize their real-world impact before building their plants and supply network.

But, what is a virtual twin? A virtual twin is a virtual model of a physical system that can be created from scratch or from a pre-existing system in a digital environment.

Virtual twins adhere to the principles of science across multiple scales and business contexts. With this technology, innovators can model and simulate the behavior of the microscopic, down to the level of molecules, all the way up to entire cities, to determine how transportation, utilities, health monitoring and power generation converge in a complex environment.

Virtual twins are a crucial solution to solve complex pharmaceutical manufacturing sustainability challenges, such as achieving zero carbon and integrating more closely with the circular economy.

ACCELERATING PHARMACEUTICAL MANUFACTURING INNOVATION WITH THE VIRTUAL TWIN

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The capabilities provided by virtual twins need to be utilized by all innovation stakeholders on the same collaboration platform to accelerate the innovation process.

In this ebook, we will discuss how virtual twins are also now assets which need to be managed to enable sustainable innovations in pharmaceutical manufacturing that can impact:

• Society, which demands access to safe, effective and affordable therapies.• The environment to reduce or eliminate GHG emissions and natural resource utilization during the manufacturing process and post-consumption scenarios.• Pharmaceutical businesses in realizing ethical and sustainable practices to thrive in an industry beset by divergent, multivariable and competing demands through risk management and by reducing unknowns.

Pharmaceutical manufacturing is replete with scientific data stored in silos—data that’s hard to access, aggregate and contextualize. Too much time is wasted trying to combine pharmaceutical metadata, which can be used to actualize sustainability improvements.

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Manufacturing cost pressures to deliver affordable therapies globally

Volatile markets make it difficult to determine the quantity of products needed in a given country

Growing global demand for pharmaceuticals

Governments want production sovereignty, requiring new, distributed and localized lines to open

New classes of products with the rise of biologics, smaller batches and personalization

More complex supply chains, including a growing need for cold chains

Serialization to combat the risk of counterfeiting

Virtual twins on the right collaboration platform provide multidisciplinary stakeholderswith a scientific basis to quickly tackle global pharmaceutical manufacturing challenges together 6

CHAPTER 1

SAFE, ACCESSIBLE AND AFFORDABLE TARGETED THERAPIES FOR SOCIETY 7

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Increasing affluence results in longer lifespans, and with it comes an increasing need to develop more targeted therapies to cure complex diseases.

"Because the virtual twin delivers scientific awareness, stakeholders can, for example, determine the lowest operating temperature possible or minimize the number of days for culture growth with minimal impact on the yield, or optimize the therapy’s effectiveness while meeting quality and cost considerations,” revealed Dr. Daniela Jansen, BIOVIA’s Brand Marketing Director.

The ability to define the optimal range of parameters helps to optimize the manufacturing of costly targeted active pharmaceutical ingredients (APIs), which is critical for precision medicine.

The virtual twin gives stakeholders the visibility to monitor and control the production process, enabling them to apply corrective and preventive action. This avoids losing entire batches of pharmaceuticals—thereby ensuring high quality, reducing cost and improving sustainability.

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ACCELERATING PRECISION MEDICINES COLLABORATIVELY

"In the area of oncology, for example, it’s clear that only a fraction of the population will respond to a certain treatment. That is why precision medicines speak directly to sustainability because pharmaceutical manufacturers will develop the right drugs that the right people can take at the right time. In response, pharmaceutical manufacturers need the right tools to help them design, develop and manufacture these therapies at speed," added Dr. Jansen.

As the virtual twin can model the pharmaceutical company’s entire operations, its role in the manufacturing phase is to facilitate data flow from the earlier stages, where these therapeutics were developed with the help of in silico experiments. Then, pharmaceutical development stakeholders can use this data and collaborate to devise the manufacturing processes to bring these therapeutics for precision medicine to fruition.

The virtual twin unites scientific and patient data and science-based tools to help organizations determine a therapy’s suitability for defined patient groups. They can be confident that a therapy will work before figuring out how to deliver it to patients safely and cost-effectively.

The global nature of manufacturing today requires the use of the virtual twin to help manufacturers manage and control distributed manufacturing sites. Many companies and stakeholders are collaborating within the extended development and manufacturing network. The virtual twin can be leveraged to qualify and profile these stakeholders and ensure that production can meet global therapeutic goals—be it a specific demographic needs, cost or accessibility. This will support efficient manufacturing and speed time-to-patient for targeted therapeutics.

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INNOVATIVE THERAPIES TO MEET GLOBAL NEEDS

"Pharmaceutical companies are hesitant to innovate and change tried-and-tested manufacturing processes because of the intense effort needed to pass regulatory approval. But, a science-based virtual twin offers much-improved process understanding and data as well as decision traceability," offered Dr. Barbara Holtz, a Life Sciences and Healthcare Industry Value Expert with Dassault Systèmes.

"This is the edge that can help pharmaceutical companies quickly transition from processes in batch facilities to smaller, more agile facilities. It can help them do away with large multipurpose equipment in favor of new hardware to realize small batch production and precision medicines.

"This is where the collaboration platform is key because it bridges pharmaceutical companies with the technical partners who will build these assets. The platform facilitates the transmission of specifications to these partners who can then iterate solutions quickly with a pharmaceutical company’s chemical, biotech, process and mechanical engineers," added Dr. Holtz.

The virtual twin is the application that helps these actors understand scientific and engineering data. They can then engage with that data to assess impacts and analyze risks if they change or combine something.

The modeling and simulation capabilities of the virtual twin of the process extend from end to end. For example, in the manufacturing of pills, this includes, but is not limited to, crystallization, particle size reduction, blending, granulations, drying, compaction, and coating.

These digital models can optimize the speed at which the pill is formed, the pressure the material is subjected to, and the exact sequence and timing of operations that ultimately result in a perfectly formed pill with no chips, spalls, splitting and performance against specifications.

Simulation can validate that a pill has enough integrity to survive the stresses of its lifecycle, from its delivery to pharmacies and distribution centers to dispensing and finally into a medicine cabinet—proving that when you take it out of the bottle, it will still be completely intact.

Collaboratively, manufacturing stakeholders can evaluate subtle variations in formulation and how a variation in formulation will affect the final product or its price.

"Suppose we’re formulating a new ingredient for use in Asia. And we know that the water quality in an area is such that we need to slightly increase the pH of our product," suggested Dr. Stuart Wright, an Emerging Industries Industry Process Expert at SIMULIA.

"Now the challenge to the formulation team is how do we increase the pH of our final product? And what will be the impact on the price of that product per ton?

"Can it be a positive impact, or will it be a negative impact? We need to optimize the price, but there’s a lot of tweaking to the recipe for that formulation because of the influence of the pH level.

"Simulation can be used here quite effectively, where if we know the relationship between ingredients and the final product’s qualities, we can use optimization techniques to explore thousands of subtly varying alternatives and identify the most cost effective, the most ‘green’, the best performing, etc." he explained.

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CHAPTER 2

THE COLLABORATIVE AND SCIENTIFIC BASIS TO A BETTER ENVIRONMENT

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The virtual twin’s modeling and simulation capabilities are based on a strong adherence to scientific principles. With the virtual twin, pharmaceutical companies can innovate the pharmaceuticals themselves, the packaging and devices they come in, and the production lines they’re made with, to achieve more desired environmental sustainability outcomes.

The impact of virtual twins is achieved with a multiscale and multidisciplinary collaborative approach to turn the variety of scientific data and information generated into innovative ways of engaging with the system under investigation while reducing waste and emissions.

"As a result of the COVID-19 pandemic, we have witnessed the acceleration from relatively rigid and difficult-to-change supply chains to dynamic supply networks consisting of a range of contract manufacturers, engineers, service providers, biotech companies and clinical research organizations," said Claire Biot, Vice-President of the Life Sciences and Healthcare Industry at Dassault Systèmes.

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IMPROVING REAL-WORLD ENVIRONMENTAL IMPACT

This accelerated supply chain transformation requires a collaboration platform to manage these virtual twins as assets, which are subject to change, regulatory compliance and intellectual property protection. Collaborators can then—on this platform—design and engineer the complex processes and operations that result in more sustainable manufacturing.

PharmaceuticalsAs pharmaceutical companies endeavor to deliver novel therapies for complex diseases such as cancer, they need the right scientific tools to understand and contextualize biological ingredients like monoclonal antibodies, antibody fragments, recombinant proteins or cell and gene therapies.

The virtual twin enables collaborators to investigate novel therapies at the molecular level and view a 3D representation of the protein, for example, to discover how its shape directly dictates its function and how environmental parameters can affect it. This data can be directly integrated with the manufacturing processes for these novel therapies so that manufacturing lines can be designed and simulated to ensure a low environmental impact.

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Packaging and devicesModern therapies are being administered through increasingly sophisticated delivery mechanisms that improve patient experience and adherence, but this also increases manufacturing complexity.

Additionally, these new therapies are more sensitive to the environment, especially temperature and light, which has further logistical consequences. But, with the virtual twin, Life Sciences and Healthcare innovators can simulate the performance of packaging and devices to satisfy these conditions in various use scenarios before investing in their production.

Supply chain actors can work together to optimize packaging and device design to improve its logistical impact through lightweighting to reduce transportation cost, weight and environmental impact while ensuring its efficacy at the point of consumption.

However, this process isn’t static. As pharmaceutical manufacturers collect more data and learn more about their production processes’ environmental impact, they can turn that data into actionable plans to, for example, develop and manufacture reusable injectors that only require cartridge changes rather than single-use devices.

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Production plantsAs pharmaceutical manufacturing accelerates towards small batch production, modularity is becoming an increasingly crucial aspect of production plant design. Virtual twins enable production plant designers and engineers to visualize and realize more flexible plug-and-play architectures where processes can be quickly assembled, rather than built from scratch, every time a new product or slight change is introduced in the manufacturing process.

Within these new, modular plants, virtual twins can also be used to validate thermal cycling, as heat can significantly strain any component’s life expectancy within a production line. Designers and engineers can conduct such evaluations during production line development to limit or reduce any single component’s fatigue during its lifespan.

They can also determine parts' and assemblies’ geometries and convert a 3D representation of those parts and assemblies into an appropriate mathematical model to verify real-world performance by, for example, employing finite element modeling to test for stress and strain or kinematic modeling to determine the speed of motion or vibration.

The process can be simulated and optimized virtually, improving the process understanding and the critical process parameters (CPPs).

Additionally, they can optimize batch changeovers by shifting away from stainless steel manufacturing assets to single-use ones built with different materials that can be repurposed or recycled. This improves capacity utilization by reducing the cleaning and sterilization times and, consequently, reduces heat and water consumption at each changeover to realize better lifecycle assessments.

Virtual twins are particularly useful during the development and realization of continuous manufacturing to overcome the start-stop challenges between manufacturing steps to improve manufacturing inventory management and reduce the need for the energy and water-intensive cleaning phases.

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Through the product’s lifecycle, new data sources from real-world manufacturing operations are added to maintain the virtual twin’s status, such as transaction information, maintenance records, and real-time sensor data.

The key value add is that the virtual twin retains all the information associated with it—the original requirements are still connected to the current virtual prototype, as are original design decisions and simulation results. As the real-world twin ages, the virtual twin ages with it; the virtual twin is both the digital replica of the product itself and its history and evolution.

Furthermore, dialogue is not exclusive to the virtual twin and its real-life counterpart but can also function between two virtual twins.

After all, virtual twins do not exist in a vacuum; it is when the data from one virtual twin can interface and interact with the data from other virtual twins (a factory twin interfacing with a production line twin) that true value can be generated.

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CHAPTER 3

INNOVATING BUSINESS MODELS FOR SUSTAINABLE PHARMACEUTICALS

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To keep the business viable, pharmaceutical companies need to actualize new business models that deliver more value with less resources. These business models can also enable pharmaceutical companies to integrate more closely with the circular economy and demonstrate their progress towards achieving their sustainability goals.

A shift to the circular economy involves creating value without pushing more pharmaceutical consumption.

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PROVING NEXT-GENERATION FACILITIES ARE POSSIBLE

Because the virtual twin accurately models a company’s entire operations, it simplifies how management stakeholders can factor business processes, KPIs, strategies, assets, value networks and more, into their business’ decision-making process.

Alice shared, "I was speaking with a customer who is building one of the world’s first large-scale electric glass plants with a coalition of manufacturers—melting and recycling the glass and then producing it, but using almost entirely renewable energy.

"The customer said it very clearly: ‘If you told people you were going to build a glass facility that did not run on fossil fuels, and you told them that even just five years ago, they never would have believed you that it could be done because nobody thought it was possible.

"They didn’t believe you could get to the levels of heat needed or control the levels of heat in the process with renewable energy. The customer explained that if you hadn’t been able to actually design the plant and simulate its functions with the virtual twin to prove that it was possible from a scientific perspective, you never could have gotten the coalition of actors, the EU subsidies or huge amount of capital necessary to build this facility. That’s where we are in history, which is that we have to start doing things that nobody believes is possible—and one of the only ways to prove it is to do it virtually. And to show them scientifically that it can happen, it that it is possible.

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VIRTUAL TWINS FOR BUSINESS TRANSPARENCY

Creating sustainable pharmaceutical manufacturing assets, processes and products requires the transparency afforded by the virtual twin.

The ability to monitor everything, utilizing sensors and IoT systems, in real time, helps companies to demonstrate what’s happening in their operations and to make this information accessible to experts or people who are not manufacturing specialists.

Since the regulatory mandate for pharmaceutical companies involves having good process understanding and control—also known as continued process verification—organizations can leverage the virtual twin to demonstrate process understanding and aggregate all data necessary to submit regulatory documentation. In doing so, pharmaceutical companies adhere to regulatory mandates and work more efficiently and cost-effectively by avoiding waste and batch losses.

Mastery of continuous process verification also enables actors to take pre-emptive action if the process is going out of trend—it de-risks pharmaceutical manufacturing and reduces waste.

In collaboration with society and regulators, pharmaceutical companies can determine how best to optimize their manufacturing for sustainability. This builds trust between such partners and stakeholders who can trust that the pharmaceutical company is on course to deliver value over the long term, well before legislation compels the industry to do it.

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Essentially, the business case for sustainable pharmaceutical companies is that

‘sustainability’ is a proxy for good management, which means that you are not operating your company on a one-year time horizon; you are operating it as if it will be here in 50 years.”

— Alice Steenland

Our 3DEXPERIENCE® platform powers our brand applications, serving 11 industries, and provides a rich portfolio of industry solution experiences. Dassault Systèmes, the 3DEXPERIENCE Company, is a catalyst for human progress. We provide business and people with collaborative virtual environments to imagine sustainable innovations. By creating ‘virtual experience twins’ of the real world with our 3DEXPERIENCE platform and applications, our customers push the boundaries of innovation, learning and production.

Dassault Systèmes’ 20,000 employees are bringing value to more than 270,000 customers of all sizes, in all industries, in more than 140 countries. For more information, visit www.3ds.com.

Europe/Middle East/AfricaDassault Systèmes10, rue Marcel DassaultCS 4050178946 Vélizy-Villacoublay CedexFrance

AmericasDassault Systèmes175 Wyman StreetWaltham, Massachusetts02451-1223USA

Asia-PacificDassault Systèmes K.K.ThinkPark Tower2-1-1 Osaki, Shinagawa-kuTokyo 141-6020Japan ©

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ACCELERATING THE JOURNEY TO SUSTAINABLE PHARMACEUTICALS

The virtual twin delivers the scientific capabilities for pharmaceutical manufacturers to operate more sustainably and create highly effective therapies to meet society’s growing demands.

The pharmaceutical industry is science-driven. Science drives continuous technological progress, which increases complexity at all stages. The industry therefore needs agility to be able to respond sustainably. That is why we propose 3D experiences on our platform and virtual twin solutions that work on a scientific basis.

The virtual twin offers an accurate replication of your pharmaceutical operations, helping you identify potential therapy candidates more quickly and reduce the time needed to optimize or develop the processes and hardware to manufacture these new therapies.

Together, innovation stakeholders can collaborate on the 3DEXPERIENCE® platform to realize new ways of working via innovative manufacturing processes.

Manufacturing networks can realize more sustainable outcomes by combining human knowledge, approach, expertise, and experience to aggregate, contextualize and understand scientific data.

In this ebook, we’ve only barely started on what virtual twins can do for your business—which is why we invite you to get in touch with us to jointly build the vision to pursue sustainable Life Sciences and Healthcare with virtual twins at 3ds.com/life-sciences.