Lucie Clavel, Dr. Paolo Saccà and Mathias Taillebois, fill and finish experts at Sartorius explain how single-use solutions are reshaping final formulation and filling — from regulatory compliance to operational agility.
Sartorius
Changing regulations are reshaping final formulation and filling
Regulatory standards are evolving, and with them, the expectations for final formulation and filling operations. The revision of EU GMP Annex 1 has caused a significant shift in how sterile drug products must be filled. For example, manufacturers are clearly advised to use rapid transfer ports (RTPs), and pre-use post-sterilisation integrity testing (PUPSIT) should be incorporated as a standard process step.
Pharmaceutical manufacturers are now under pressure to close the gap between their current operations and new regulatory requirements. For some, this means upgrading legacy stainless-steel filling systems; for others, the more viable path is to outsource their fill and finish activities.
As a result, CMO/CDMOs are managing a surge in new projects, each with its own customers, products, and process requirements. Traditional stainless-steel equipment poses limitations for these operations: each product typically requires dedicated installations, extensive cleaning and validation, and enough footprint to prevent crosscontamination. As such, logistics are becoming more complex, and legacy systems alone are rarely equipped to keep up.
In parallel with these regulatory pressures, the broader biopharmaceutical landscape is also shifting. The rise of next generation therapeutics is driving demand for high-value, smallvolume production. Injectable formats are also on the rise — in 2024, the FDA approved 50 new drugs, half of which were injectables. Since 2019, the installed base of fill & finish lines for ready-to-use (RTU) containers has more than doubled, reflecting this shift toward faster changeovers and flexible manufacturing. At the same time, multi-product facilities are becoming increasingly important, and the industry continues to globalize, with outsourcing playing a larger role in development and manufacturing strategies. Together, these trends are accelerating the move toward single-use (SU) technologies.
Benefits of SU technology in final formulation and filling
SU technology offers a practical and future-proof solution to the challenges facing today’s final formulation and filling operations. It eliminates many of the obstacles associated with traditional stainless steel equipment: no cleaning or sterilisation steps, reduced risk of cross-contamination, and no need for productspecific installations. This simplification enables more agile manufacturing, especially in facilities managing a wide variety of products and batch sizes.
Operational agility
The advantages of switching to SU solutions are particularly pronounced in environments with high complexity, such as CDMOs managing a wide range of projects or OEMs developing equipment to meet diverse fill and finish specifications. Compact single-use assemblies can easily accommodate different formats without requiring major infrastructure changes, streamlining operations and improving adaptability.
Faster setup
SU equipment also accelerates facility and process setups. Traditional final formulation and filling equipment can only be qualified after it has been installed and integrated into the cleanroom environment, delaying timelines and increasing risk. In contrast, SU systems can be prequalified, and a significant portion of the qualification work can be completed in parallel with filling equipment installation, shortening the path to production.
Shared responsibility
Importantly, the accountability for system validation begins earlier and shifts to the SU provider. Annex 1, Section 8.123 states that “The selection, design, qualification, maintenance, and monitoring of such systems [single-use systems] should be appropriately documented and justified. Where parts of the manufacturing process are outsourced, the responsibilities of the contract giver and contract acceptor must be clearly defined in a written contract.” Leading suppliers deliver comprehensive validation data, compatibility testing, and audit-ready documentation as part of their offering. As such, the supplier assumes critical parts of the compliance burden, giving customers confidence in the integrity of their systems.
“In today’s fast-evolving pharmaceutical market, flexibility in managing different dosing technologies is essential. With a trusted partner like Sartorius, IMA Life is able to meet customers’ needs efficiently and effectively.”
Eng. Roberto Montuschi - product manager at IMA Life
Operational efficiency
Beyond regulatory compliance, SU solutions also offer significant advantages for operational efficiency. By reducing or eliminating tasks like cleaning, sterilisation, and tubing preparation, facilities can allocate skilled labor to higher-value steps, such as monitoring the final formulation and filling process or quality control.
Reduced costs
Indirect costs tied to utilities and waste management are converted into predictable, direct costs, an advantage particularly valued by CDMOs managing lean margins. In greenfield projects, the economic benefit is even more pronounced. Adopting a SU approach from the start can reduce capital investment by up to 30%, while also minimising facility footprint. This efficiency enables more productive use of cleanroom space and supports modular facility design.
Beyond cost savings, these efficiencies also increase speed to market and improve sustainability. They reduce downtime, batch changeover, and campaign cleaning evaluation between different drug products, allowing drug manufacturers to respond more quickly to changing demands and easing drug product transfer.
Overcoming skepticism in the shift to single-use technology
Despite the clear advantages, adoption of SU technology is not without its barriers. The most common obstacle is hesitation about reliability, cost, and long-term viability, particularly among teams accustomed to stainless steel.
Critics sometimes dismiss singleuse as environmentally wasteful or superficially expensive. But this perception overlooks hidden burdens in stainless-steel systems: water consumption, detergent use, energy demand, and extensive human labour. When these factors are considered, the lifecycle footprint of SU tools can be significantly lower.
Moreover, each SU component — from tubing and bags to filters and connectors — must meet stringent standards for bioburden, endotoxins, and extractables. This is particularly crucial in final formulation and filling operations, where batches can be worth millions of euros and are often destined directly for patients. In this context, a seemingly “simple” SU assembly is actually a rigorously engineered, highly validated system.
Stainless-steel equipment is typically embedded within the facility infrastructure, with piping routed through false ceilings and interstitial spaces. These concealed sanitary connections are difficult to inspect and control, especially during repeated CIP/SIP cycles. Over time, continuous temperature excursions can lead to undetected leaks — posing both contamination risks and maintenance challenges. Rigid architectures also create long transfer pathways and dead volumes, leading to unnecessary product loss.
In contrast, SU assemblies are designed to minimise dead volume and ensure all product transfers remain visible and controlled. There is no need for CIP/SIP, eliminating risks associated with cleaning failures or thermal stress on connections.
For some, the compromise is a “combo line” — hybrid systems that combine elements of singleand multi-use systems. While this can offer reassurance, these systems often preserve much of the complexity they were meant to avoid. As projects advance, issues such as cleaning validation, qualification delays, and infrastructure constraints frequently prompt teams to reassess. Many ultimately move to full SU configurations once they experience the efficiency and flexibility firsthand.
Real world adoption of SU technologies for final formulation and filling
Below, we share some examples of challenges that we were able to solve with flexible SU solutions alongside design and installation support.
Developing a next-gen fill and finish environment
An Italian manufacturer of filling lines with gloveless isolators required tailoredmade single-use solutions to equip their small-footprint, fully automated, robotic lines. Sartorius co-developed two integrated Single-Use System (SUS) kits, enhancing sterility and process control. The RTP beta-bag kit, combining Sartorius’ standard needle with the manufacturer’s patented transfer system, enables sterile, automated needle insertion into the isolator. The PUPSIT filtration kit, customised to client needs, ensures reliable product filtration close to the filling point.
“Thanks to its strong commitment to developing customized systems, Sartorius is a leading reference in innovative single-use technologies that seamlessly integrate with emerging solutions such as robotics in aseptic pharmaceutical production. Sartorius delivers flexible solutions that empower the transition to fully automated human-less production systems.”
Eng. Andrea Masiello - project manager at Pharma Integration
Lack of experience with SU systems
A Korean biopharmaceutical company performing final formulation and filling in-house had limited experience with SU systems. We provided hands-on training, design collaboration, and on-site demos, helping them confidently adopt fit-for-purpose single-use filling sets.
Handling high potency products
A US-based biopharmaceutical company needed a solution for the safe handling of toxic waste during their final formulation and filling process. We provided a closed, gamma-irradiated beta-bag system that protected operators while maintaining sterility during waste disposal from the isolator.
Demanding formulation processes
A CDMO in Italy was handling a challenging formulation process for one of its clients. We supported them by integrating advanced mixing technology, allowing them to achieve consistent, scalable formulations with simplified handling.
Product quality issues
An fill and finish component OEM in Germany required support to define visible particle control, as there are no regulations available today. Sartorius provided quality risk management based on decades of manufacturing knowledge to set up stringent specifications to improve product quality
Installing an automated PUPSIT
A pharmaceutical company in Germany and its isolator manufacturer were discussing the optimal location for installing their PUPSIT skid (inside or outside the isolator). Sartorius supported the evaluation and helped identify a solution that ensured Annex 1 compliance while reducing the risk of SU system misuse. The final setup places the automated PUPSIT unit in front of the main isolator, enclosed within a RABS to maintain aseptic integrity and simplify operation.
Conclusion: The future demands flexibility
Being successful in final formulation and filling requires responding to diverse manufacturing demands while also keeping up with changing regulations. Single-use solutions offer a clear path forward, helping manufacturers overcome legacy constraints, improve product recovery (and thus process yields), achieve compliance, reduce cost, mitigate process risk, and operate with greater speed and agility.
Realising these benefits relies on effective implementation, supported by fit-for-purpose design and technical expertise. Sartorius enables this through configurable solutions and shared responsibility for qualification and documentation — giving our customers peace of mind during the critical stages of system deployment. This approach helps ensure that final formulation and filling systems are compliant, efficient, and adaptable to future needs.