1. Biopharmaceutical manufacturers across Asia are facing increasingly complex modalities, unpredictable demand and growing pressure to improve affordability. What are the biggest manufacturing challenges these shifts are creating today?
Cost pressures are particularly acute in developing markets, where affordability affects patient access. New modalities require changes in facility designs and geopolitical uncertainties result in vulnerabilities in supply chains and demands.
We have seen an increasing demand in larger scales stainless steel bioreactors and CDMO outsourcing to drive cost down and increase productivity. While opting for larger stainless steel capacities and CDMO outsourcing can be effective, they alone are insufficient in process flexibility and complicate process transfers between CDMOs. Process intensification (PI) is another way to improve on productivity while driving down costs. But maximising benefit of PI is not possible without an automated, modular Single-use facility design and retrofitting legacy stainless steel facilities is not the most straightforward without flexibility in data architecture already built in.
The biggest manufacturing challenges for our customers in Asia today is changing and pivoting without destabilising production. In a region defined by both exceptional opportunity and considerable complexity, change is constant and manufacturers must be ready to pivot not just to stay competitive but also capturing growth opportunities.
2. As manufacturers look to produce more with existing infrastructure, how can process intensification help them increase productivity, improve flexibility and make better use of manufacturing capacity?
PI aims to increase production and manufacturing flexibility without the corresponding need for additional footprint. This can be achieved in several ways, the first being increasing production duration and process continuity within individual operations such as perfusion bioreactors or multi-column chromatography. However, continuous bioprocessing of individual process steps becomes limiting if pre-integrated equipment of fixed volumes cannot keep up (for eg, harvest and inactivation tanks, pre-final filtration skids and mixers). Therefore, it is also important to incorporate modular Single-use (SU) production lines where systems and lines can be added or removed, optimising footprint.
It is also worth considering that PI is not simply reducing footprint, adding more lines and running process longer. Complexity in running, adding additional lines for longer increases exponentially and may, in some cases, be counterproductive. Process and systems that add and run in modular configurations, interchangeable, closed SU configurations and supply chains allow manufacturers to adapt capacity to different products and, where appropriate, multiple modalities. Scaled-down SU systems may also require less energy, water and supporting infrastructure, while closed and more integrated operations can improve safety and process control.
The real advantages of PI is not just higher output but the ability to respond to changing demand without repeatedly expanding physical facility. For manufacturers operating in space-constrained locations or upgrading existing plants, that flexibility can be particularly important.
3. What role can single-use technologies play in helping manufacturers respond more quickly to changing production requirements while reducing the complexity associated with traditional manufacturing setups?
Changes in process often requires modifications to manufacturing lines, systems, equipment and production steps. Any changes, big or small, to hard piped stainless steel facilities would mean downtime for revalidation and SIP/CIP. Single-use technologies (SUT) allow production lines to be flexible because validated product contact components can be changed without major structural modifications. Closed SUT also enable operations to take place in lower cleanroom classifications, where there can be flexible use of facility space for both critical and non-critical operations. Single-use flexible hoses and utility panels can be changed, added or replaced easily, supported by appropriate risk assessment and regulatory requirements where necessary. This modularity is especially useful when demand is uncertain or when a facility must accommodate several processes over its operating life.
4. How are advances in process development and manufacturing technologies helping companies shorten the journey from development to commercial production?
The greatest contributions are improved predictability, higher reproducibility and repeatability. Better analytical and scaled-down models allow R&D and MSAT teams understand and predict process behaviour at large scales earlier, select suitable cell lines and optimise processes before moving into pilot.
High-throughput systems are particularly valuable because they enable extensive DoE protocols, testing more process parameter combinations, putting more cell lines through selection. Such technologies also allow scientists to better understand the drug candidate during scale-up, with the amount of experiments and data generated with less time and materials. The significant advantage of having large amount of data sets has to be the building of AI models that can help predict outcomes and suggest improvements.
The availability of consistent raw materials and supply during R&D through to manufacturing stages is important in the elimination of unwanted surprises. When combined with advanced analytics, automation and representative scale-down models, these systems help scientists and manufacturers identify critical variables and define a robust operating space earlier in development.
5. Digitalisation is increasingly becoming part of biopharmaceutical manufacturing. Where do you see the greatest opportunities for digital technologies to improve process visibility, decision-making and operational efficiency?
Digitalisation is certainly where we see many Asian customers moving toward, with varying stages in building a smarter facility. Advance data analytics enable operators interpret raw data and discovering useful insights for better understanding and decision-making. Statistical process control will also be useful to quality and production teams where early detection and prevention of problems is possible. That being said, the foundation of digitalization is high-quality data, where process analytical technology should be implemented wherever it provides meaningful information on the process and product quality. The implementation of Process Analytical Tools (PAT) to measure and collect Critical Process Parameters (CPP) and Critical Quality Attributes (CQA), along with digitisation, converting physical or analogue information into a digital format, are important first steps before digitalisation can happen.
AI models built on data collected from the facility will become an increasingly useful part of this environment, however, human knowledge and judgement should remain. AI model outputs and prediction are only as reliable as the data, context and controls behind them so it is important to still rely on human expertise and judgement. Even with automation and AI models, manufacturers must avoid over-reliance on automatically generated conclusions and maintain strong scientific and operational oversight.
6. How can manufacturers balance the need for greater automation and digitalisation with the practical challenges of integrating new technologies into existing facilities and processes?
Manufacturers should begin with a clear aim of operating need rather than pressurised into introducing automation and digitalisation. The first investments into building a smart facility should address specific constraints, such as recurring deviations, manual data entry, slow changeovers or limited process visibility. Introducing and integrating new technologies while undergoing digital transformation can be challenging with different requirements between legacy instruments and new ones. New technologies that brings about process change (for eg, PI) can be difficult to manage at the same time. A staged approach in such transformation, be it digitisation followed by digitalisation, or replacing linearly connected systems into modular connections then followed by digitalisation, allows manufacturers to first demonstrate value, manage validation requirements and get some experience before expanding across the facility.
An important consideration to note is making sure to start with a sound data architecture. Legacy systems should be upgraded into a flexible platform ready for the introduction of new system. New equipment should use standard interfaces, universal and agnostic to suppliers, and be able to exchange information with legacy equipment, manufacturing systems and quality platforms. Such architecture, together with SUconnections further allow new technologies to be added modularly without constraints from piping connections, footprint or digital platforms.
Transformations must also account for cybersecurity, data integrity, regulatory compliance and change control from the outset. Just as importantly, employees need to understand and trust the technology. Training, process knowledge and clear accountability remain necessary even as more decisions and operations become automated. The objective should be a controlled transition that improves performance without placing ongoing production at unnecessary risk while building a facility that is truly ready for challenges in the future.
7. Asia's biopharmaceutical manufacturing landscape is highly diverse, with different levels of infrastructure, expertise and investment across markets. What approaches can help manufacturers scale advanced production capabilities across the region?
There needs to be a stronger culture of open and precompetitive collaboration between different companies with different production capabilities in order to scale advanced production capabilities across Asia. We see an increasing number of partnerships, collaborations and process transfers, where customers work together, bridge capability and resource gaps by pairing complementary strengths in solving complex operational, technical, or strategic challenges. We also think that collective willingness to share non-proprietary knowledge, experiences, tools and research more widely is an opportunity to growth the Industry further. This can mean developing common training programmes for young scientists, sharing testing guidance and reference standards with emerging markets. Manufacturers, Governments, Academic Institutions, Regulatory boards and technology providers all can have a role to play in advancing this goal together.
However, this does not mean giving up intellectual property or competitive advantages between Companies and Nations, but recognising the areas in which wider access to knowledge strengthens individual capabilities and creating additional opportunities to all partners in a partnership which in turn strengthens the entire ecosystem. One recent example from Sartorius was that we were part of a discussion with multiple manufactures, coming together to build a solution for a common pain point. Such open sharing and collaborations will benefit many others and also prevent repeating mistakes.
8. Regional collaboration is becoming increasingly important for strengthening pharmaceutical supply chains. How can closer collaboration between technology providers, manufacturers and other ecosystem partners contribute to greater supply resilience?
The growth of the Industry has given rise to innovations from providers, each with its own propriety designs, use, and advantages. This is particularly so in SUT where we saw an incremental number of competition in the past few years. However, when manufacturers use highly specific components connections and process configurations, materials cannot easily be substituted or shared during a shortage. Standardization of specific SUT and common components could give manufacturers more options when normal supply routes are disrupted. Building modularity with standard SUT assemblies at process design stage can help with supply agility where technically and regulatorily appropriate.
To take it further, regional collaboration between SUT suppliers can also mean maintaining certain stock levels of common designs that can be “shared” should disruptions occur. Longer shelf life validation, better demand visibility, coordinated forecasting and stock rotation will also benefit agility in supply and collectively, greater resilience built in the whole ecosystem based in interchangeability, transparency and timely access to supply.
9. With affordability becoming an increasingly important consideration, how can manufacturers pursue greater efficiency and capacity without compromising product quality or patient safety?
Quality and efficiency should not be treated as competing priorities. As with ideas elaborated above, production and efficiencies can be improved with implementing PI, SUT, data nalytics and modular process systems.
The rate of right-first-time is another way to making sure cost remains low. Batch failures and deviations consume capabilities, supply and cause delays which will have an effect in costs and quality. The use of real-time process monitoring and predictive models referencing “golden batches” can be an additional tool in recognising process conditions moving outside acceptable ranges. Such advanced data analytical tools improves dexterity in picking up abnormalities compared to manual investigations. Continuous and online process verification tools are also effective in saving time during batch releases. Such real-time release testing protocols will also allow for a faster turnover. The combination of these efforts will keep drive capacity up, cost down, while ensuring product quality.
10. Sustainability is another growing priority for biopharmaceutical manufacturers. Where can process intensification, single-use technologies and digitalisation make the most meaningful contribution to reducing the environmental footprint of manufacturing?
To make the most meaningful contribution in Sustainability, the reduction in environmental footprint should be considered early during process development and scale-up. Decisions made in process development determine the eventual demand for energy, water, raw materials and waste treatment. This is especially so when process development and initial protocols are not the most efficient nor optimised. Design process running on PI may reduce equipment size, facility infrastructure footprint and eventually resource consumption per unit of product.
Considerations for SUT is also important in reducing environmental footprint. The use of SUT reduces the need for cleaning water, chemicals and steam, all of which require energy to produce, transport, treat and dispose. Although plastic use and disposal has some negative impact on the environment, proper disposal and savings in energy outweighs impact. The use of smaller volumes in an SU intensified process can also increase trade-offs.
Also, Digitalisation and data analytics can contribute to reducing environmental footprint by monitoring resource consumption, optimise operating conditions, reduce deviations and prevent failed batches. Combining these technologies, manufacturers can achieve higher, more consistent production with fewer inputs and less waste.
11. What lessons can Asian manufacturers learn from markets or facilities that have successfully adopted more flexible, intensified or digitally enabled manufacturing models?
Asian manufactures can be conservative, adopting the wait-and-see approach when it comes to new technologies. This is partly due to the environment we are in where investment and business models reward the safe and tested. However, as we have also seen Asia manufacturers mature and become more knowledgeable, they are ready to test new technologies and be early adopters alongside their western counterparts and competitors. The environment has also changed. Asia is now becoming the hotbed of innovations, test and launch sites, in parallel or in some cases, ahead of the US and EU. Therefore, manufacturers should always be ready to pivot and evolve together with its pipeline (and modalities), which is becoming a need more than a strategic advantage.
12. For manufacturers planning new facilities or upgrading existing ones, what capabilities should they prioritise today to ensure their operations can adapt to future changes in modalities, demand and technology?
Digitisation, Digitalisation, Automation and a flexible data architecture should be treated as core elements when planning new facilities or upgrading existing ones. As we have seen previously, these capabilities allow facilities to understand processes better with data, predict and optimise operations, and be flexible enough to add, remove and change production capacities in meeting future needs while staying competitive.
13. Looking ahead, which technological or operational developments do you believe will have the greatest impact on the way biopharmaceutical medicines are manufactured in Asia over the next five to ten years?
Some of the greatest technology areas to watch are: AI-enabled drug discovery, AI-assisted cell line and process development, “Self-driving Labs” with unlimited continuous throughput, advancements in targeted treatments approaches, personalised and precision medicines with modalities such as CGT, mRNA and oligopeptides. Preventive and longevity medicines such as engineered nutrition and vaccines for cancers/ageing should also be exciting.
14. Ultimately, what will it take for Asia's biopharmaceutical manufacturing ecosystem to become faster, more resilient and more sustainable while consistently delivering high-quality medicines to patients?
For Asia’s biopharmaceutical manufacturing ecosystem to ultimately achieve greater speed, resilience, sustainability and quality, a coordinated evolution across core players must work together. Governments, Manufacturers, Innovators, Regulators, Societies, Clinical Development, Service providers, Technology Suppliers and Healthcare providers must be committed in addressing challenges in driving digitalisation, modular and flexible manufacturing, innovative technologies, sourcing agility, minimise geopolitical and supply chain vulnerabilities. Members of the Industry also have a part to play in ensuring compliance, a knowledgeable workforce and on top of it all, a sustainable industry that is as good as humankind as to our environment.
