Meeting New Manufacturing Demands by Investing in Flexibility

A fundamental, digitally driven overhaul of bio/pharmaceutical manufacturing models are needed to meet the demands of current global supply chain pressures and rising complexity of novel therapeutics.

Various global and market-specific trends are transforming the bio/pharmaceutical industry, leading to the need for new strategies and investment across the full value chain. From geopolitical uncertainty and supply chain disruptions to an increased focus on digitalization and precision medicine, bio/pharmaceutical companies are being faced with both challenges and opportunities, particularly in relation to manufacturing.

Fundamental Adjustments Required

As industry increases focus on precision/personalized medicines, a bilateral adaptation will be necessary, confirms Miguel Forte, ISCT President, ARM Board Member, and CEO, Kiji Therapeutics. “On one side manufacturing processes for smaller batches will indeed be needed and management of the impact on processes and cost will need to be a focus. At the same time the platform concept, both in regulatory approval but also in manufacturing, will have to be developed so that shared parts of manufacturing, in between specific patient’s tailoring production, can be used for multiple slightly different and personalised products,” he states.

“The growth of advanced and precision medicines is forcing a fundamental rethink in how we design and operate manufacturing facilities,” asserts Jason Jones, Head of Global Business Development, Cellular Origins. “The traditional model, built for long and predictable production campaigns, is simply not configured for the short, variable and highly personalized workflows that define these new modalities.”

A primary challenge for manufacturers is adaptability, Jones continues. “To meet [this challenge], manufacturers need to move toward systems that are inherently flexible, where digital orchestration, modular automation, and robotics work together to manage complexity without introducing risk,” he says.

“What matters most is preserving the integrity and biology of the therapeutic product. The manufacturing technology should adapt to the therapy, not the other way around,” Jones adds.

“Legacy manufacturers must fundamentally reimagine facility design and operating models to keep pace with precision medicine’s fragmented, high-value pipelines — where it is relevant to their business, which is and will not always be the case,” remarks Max Baumann, Co-Founder, Treehill Partners. “The commercial viability of a new drug is tied directly to how manufacturing can enable rapid and scalable production for smaller patient cohorts — this demands operational agility that supports commercial success.”

For Sharyn Farnsworth, Director Upstream Process Development, FUJIFILM Biotechnologies, significant adjustments to facility designs and operating models are necessary for manufacturers to be able to achieve the agility required for advanced and personalized medicines. Using her company’s approach as an example, she points out that single-use facilities are useful modular options that enable adaptability for various products and scales.

“Utilizing single-use systems allows for optimizing operational workflows, rapid setup, tech transfer, and scale-out which in the end offers enhanced responsiveness and efficiency in production processes,” Farnsworth says. “This flexibility supports smaller batch sizes, swift product changeovers, and varied production requirements while also allowing for scalability that can be rapidly set up and adjusted according to production demands.”

There needs to be a shift from the fixed, large-scale systems over to modular, single-use bioprocessing suites that can easily switch between different client programs with minimal downtime, confirms Minni Aswath, VP of Process Development, PD Downstream, Bionova Scientific. “Operationally, this means embedding cross-functional project teams, automated scheduling systems, and real-time process analytics to maintain agility. The focus shifts from maximizing volume to maximizing responsiveness, quality, and client value,” she notes.

Investing in Flexibility

“Flexibility in manufacturing must go beyond facility layout. It requires an operational model that can be reconfigured, replicated, and redeployed without needing to start from first principles each time,” Jones reveals. “The use of modular systems and mobile robotics allows manufacturers to decouple production from fixed infrastructure, while a single orchestration layer provides digital consistency across sites.”

By employing this approach, it is possible to have a process validated in one location and then reproduce that process at another location by using the same digital blueprint, Jones specifies. “This approach also allows organizations to scale capacity incrementally, rather than through large, one and done investments,” he says. “For developers of advanced therapies, this creates a realistic path to global access without compromising process fidelity.”

A framework for such a standardized and modular approach has been developed by FUJIFILM Biotechnologies, Farnsworth points out. The kojoX framework incorporates a standardized and modular approach to constructing and operating manufacturing facilities to ensure consistency and flexibility throughout a global network, she confirms.

Such standardized facilities “ensure a resilient supply chain, enabling faster market entry and maintaining consistent quality standards, while reducing the risks and delays associated with constructing new facilities from scratch,” Farnsworth continues. “This approach also enhances operational efficiency, providing the ability to manufacture identical products uniformly and predictably across any site in the network.”

Standardization, while important, is often neglected during the early stages of new technology development, Forte notes. “Standardization helps and contributes to modularity and easier relocation and scaling, and digitalization, prospectively AI [artificial intelligence], helps to ensure monitorization, control, and cost-efficient production,” he says.

“New investments should incorporate standardized utility connections, plug-and-play equipment platforms, and portable cleanroom units that can be replicated or relocated across sites or geographies,” agrees Aswath. “For CDMOs serving a global client base, this modularity supports fast deployment of capacity in response to evolving project pipelines or regional demand shifts, reducing both time and capital risk.”

For companies seeking commercial agility amid shifting demand, a key priority is investing in manufacturing capacity that has been structured for flexibility, specifies Baumann. While platform technologies “theoretically offer lower capex and enable drug programs with uncertain volumes to remain commercially viable,” Baumann wonders whether expected results of such an approach will be achieved in the future, given the evolving nature of the industry.

“Improvements to manufacturing technologies are essential to ensure modular, scalable approaches that can be used across multiple clinical pipelines. More importantly, investment into new automated, technologies that can meet the clinical, financial, and regulatory needs is essential and currently lacking,” asserts Jon Ellis, CEO Trenchant BioSystems. “Legacy technologies that are largely manual, operator dependent, and lack digital integration still predominate. The implementation of truly automated, digitized platforms, that can control both manufacturing and analytics ought to be a call to action for the industry.”

Value Creation of Automation

“Implementing a fully digital ecosystem, encompassing electronic batch records (EBR), advanced data analytics, and digital twins, represents a significant upfront investment,” stresses Aswath. “The return on investment is best measured not just in cost savings, but in time-to-batch reduction, deviation prevention, and yield optimization.”

The upfront cost of automation is significant, but the real discussion should be about value creation, iterates Jones. “The return on investment is now increasingly quantifiable, and it comes through three primary levers: productivity, predictability, and scalability,” he says.

Measurable, data-backed improvements that can be gained through the use of robotics and automation include reduced manual touch time, better use of cleanroom space with closed, mobile systems, and lower cost of goods as a result of having fewer interventions and deviations, Jones adds.

“The metric [used to measure return on investment] is always the comprehensive cost of goods of the product. Digitalization, despite the investment, will optimize the costs by both reducing direct costs of manufacturing and indirect costs through optimal monitorization,” stresses Forte.

“Reduced cycle times and labor costs, coupled with minimized batch failures, create plausible links between digital upgrades and commercial margin improvements,” agrees Baumann. “For that, real-time analytics, measures of overall equipment effectiveness, and yield tracking often frame the business case for digitalization, providing tangible performance boosts against legacy integration costs.”

Measurement of the return on investment of digitalization is possible through tangible operational improvements, such as higher yields, faster batch release, reduced deviations, and shorter downtime, adds Rashid Mijumbi, Global Vice President — Data, Analytics & AI, FUJIFILM Biotechnologies. It is possible to achieve such improvements through the use of “data, advanced analytics, and AI platforms to optimize batch performance, reduce waste, and accelerate batch release,” he points out.

“In addition, as an industry we can accelerate regulatory compliance with automated data integrity checks, audit-ready documentation, and digitally enforced compliance to streamline regulatory workflows. These efficiencies translate into faster market access and reduced overhead,” Mijumbi says.

“Legacy systems have proven to be inefficient and difficult to scale, so it is the cost of not being able to ensure patients can access therapies and the commercial challenges that should be weighed against implementing digitization,” confirms Ellis. “Automation in both novel manufacturing solutions and data capture and analysis are both critical to ensure sustainability.”

While there has been much investment into AI within industry lately, such advanced technology is “redundant if manufacturing is still paper driven and operator dependent,” Ellis specifies. “Simply, the short-term financial burden to embrace digitization and automation is insignificant compared to the necessity to ensure clinical and commercial viability,” he states.

“The most strategic benefit [of automation and digitalization] lies in time,” comments Jones. “A fully integrated, digitally connected environment can take a therapy from clinical to commercial readiness faster, without the need to redevelop the process. That acceleration, achieved without compromising quality or compliance, is where the business case for digital and robotic manufacturing is most compelling.”

Implement Green Practices Early On

Improving automation and digitalization of manufacturing can also allow companies to become more environmentally friendly; however, sustainability is not something that should be retrofitted into an established process, Jones cautions. “[Sustainability] should be designed in from the earliest stages of process development,” he says.

“Closed systems, digital control, and automation all play a part in achieving this by reducing facility energy demands, minimizing material waste and improving reproducibility. When processes are digital, they become measurable, and that visibility is what enables continuous improvement,” Jones explains. “Metrics such as process mass intensity (PMI) and energy consumption per batch are no longer theoretical; they can be tracked and optimized in real time.”

Aswath concurs that companies should integrate green chemistry principles and PMI metrics, such as solvent reduction, water and energy minimization, and optimized buffer management, from the earliest stages of process development. Using Bionova as an example, she highlights how scientists can evaluate environmental impact alongside process performance to select materials and conditions that improve both yield and sustainability.

“Through the translation process, product development should always be done with the end in mind. This ensures product suitability to commercial success,” says Forte. “The sustainability aspect is no different and conforming to product and process specifications it should also be a focus from early steps of development.”

In addition to starting PMI as early as possible, Ellis reveals that companies should incorporate standard tools and frameworks for green chemistry, implement lifecycle perspective to meet environmental objectives, and should document all actions to facilitate regulatory acceptance and further process optimization.

“The connection between sustainable design and efficient design is direct,” notes Jones. “A flexible, automated facility not only reduces environmental impact but also creates more reliable, more scalable production.”

Achieving Economic Sustainability

Current geopolitical uncertainty is reshaping manufacturing strategies and location decisions. “Geopolitical uncertainty makes location strategy a central design consideration,” comments Farnsworth. “By strategically investing in technologies and adopting optimized operating models, organizations can strengthen resilience, protect supply chains, and enhance security amid shifting geopolitical dynamics.”

In light of the current global instability, supply chain security is of critical importance to ensure life-saving medicines are delivered to patients, remarks Ellis. “There needs to be collaboration between manufacturers, owners and developers to mitigate supply chain risk and reduce the financial burden,” he says. “Where proprietary reagents and materials are used, domestic supply or contingency storage is essential. The cost of securing individual reagents makes up a relatively small part of COGs, and the risk of not being able to supply patients in critical need of therapies and the commercial impact far outweighs such a cost increase.”

There has been an acceleration in reshoring or near-shoring efforts to secure supply chains as a result of recent geopolitical dynamics, adds Aswath. “While this can raise production costs by 10–25% due to higher labor and infrastructure expenses, companies, such as Bionova, offset these increases through process intensification, automation, and lean operational models,” she says.

Forming and leveraging strategic partnerships can also help companies to access a broader global network, shared resources, localized expertise, and harmonized quality systems that can help to mitigate regional cost pressures, Aswath specifies. “The key is balancing security with efficiency: designing right-sized, high-yield processes that reduce the total cost per gram or per dose, even within higher-cost regions,” she explains.

“The strategy of manufacturing location and geographical distribution will be driven by the availability of talent and resources as well as business and political forces,” specifies Forte.

“Reshoring and regionalization have become increasingly important themes in the global pharmaceutical supply chain, and they bring both opportunities and challenges,” emphasizes Jones. “The clear benefit is resilience, reducing dependency on long, complex supply routes and enabling production closer to the point of care.”

However, the labor and operating costs associated with such strategies are often higher, Jones asserts. “The key to making [these strategies] economically sustainable lies in automation and standardization,” he states.

“By reducing the dependency on manual operations and optimizing facility utilization, companies can offset the additional regional costs and maintain competitiveness,” Jones summarizes. “In effect, automation changes the economics of location. It allows reshoring to become not only a policy decision but an opportunity, with more investment put into viable, efficient, long-term production stability.”