Single-use technology: accelerating agile bioprocess development

Biopharmaceutical manufacturing faces a dual challenge: accelerating time-to-market while maintaining compliance and product quality. Traditional stainless-steel systems, though proven, impose long lead times, cleaning validation cycles, and rigid capacity constraints.

Single-use technology (SUT) enables a flexbile facility design by decoupling capacity and product mix from fixed infrastructure. Beyond accelerating development, it allows rapid adaption to market demand through variable batch sizes, fast changeovers and parallel production. This increases facility productivity and utilization while lowering cost of production by reducing downtime. For engineers, the question is not if SUT works, but how to implement it without compromising sterility, scalability and data integrity.

While eliminating CIP/SIP reduces development timelines, the primary value of single-use systems lies in operational flexibility and facility efficiency. Modular, disposable assemblies enable rapid changeovers, multi-product operation and parallel workflows without reconfiguring fixed infrastructure. Reduced hold-up volumes improve yield, while compact equipment layouts lower facility footprint and utility demand. Together, these factors increase throughput and asset utilization, enabling agile manufacturing with a lower and more predictable cost of production.

With disposable components, engineers can design flexible workflows that adapt to varying batch sizes and product portfolios, without the bottlenecks of fixed infrastructure. This agility transforms bioprocess development from a linear, resource-heavy endeavor into a dynamic, iterative cycle that supports rapid scale-up and scale-out strategies.

While upstream operations are often designed as closed and sterile systems, downstream processing typically operates under controlled bioburden conditions; throughout this article, “closed processing” refers to minimizing contamination risk and manual intervention rather than implying full aseptic operation across all unit operations.

Constructing a stainless-steel biopharmaceutical facility typically involves hundreds of millions in upfront capital, long lead times, and a rigid infrastructure that limits adaptability. For process engineers, this creates a high-risk environment where any change in product mix or capacity requires costly retrofits.

Single-use technology fundamentally changes the facility cost and risk profile by reducing dependence on fixed stainless-steel assets and utility-intensive infrastructure. Instead of committing early to large, rigid installations, manufacturers can deploy standardized, modular units that support incremental capacity expansion and evolving product portfolios. This design flexibility lowers upfront CAPEX, shortens time-to-operation and enables facilities to adapt to pipeline uncertainty without costly retrofits

Early-stage process development is often constrained less by science than by infrastructure availability and rigidity. Traditional stainless-steel setups tie experimentation to fixed assets, long preparation cycles and limited parallelization. Single-use systems (SUS) remove these constraints by enabling modular, rapidly reconfigurable process setups that support fast iteration, early scalability assessment and smoother tech transfer – while maintaining GMP-compliant process control.

In process development, progress depends on how quickly engineers can test, adjust and repeat. Single-use assemblies support this by allowing rapid reconfiguration of upstream and downstream workflows without infrastructure-driven downtime. Pre-assembled, disposable flow paths enable:

• Parameter refinement to optimize yield and robustness
• Early scalability validation wihtout committing to fixed equipment
• Parallel experimentation to compare process variants and accelerate selection

By reducing dependency on shared assets and fixed layouts, SUS shorten the path to clinical readiness – without locking processes into premature facility designs.

The same modularity, standardized flow paths and rapid reconfiguration that accelerate process development also form the foundation for continuous processing.

Speed is irrelevant if sterility fails. Early-stage batches are highly sensitive to contamination, which can derail timelines and inflate costs. Closed single-use assemblies mitigate this risk by:

• Using pre-sterilized components to minimize human intervention
• Ensuring secure fluid transfers and sampling under GMP conditions
• Reducing contamination risk through validated connection technologies

Integrating these controls into PD workflows safeguards against batch failures and supports consistent quality, enabling faster progression from concept to clinic without compromising compliance.

Scaling from a 50 L pilot run to a 2,000 L commercial batch is more than a simple volume increase; It is a complex engineering challenge where consistency in product quality, yield, and compliance must be strictly maintained across every stage of the lifecycle. While single-use bioreactors (SUBs) simplify infrastructure requirements and accelerate tech transfer, success depends on the precision of design and control. Validating fluid dynamics, mass transfer, and sensor performance is essential to ensuring that the process behaves predictably as it moves toward commercial scale.

In downstream processing, the value of single-use systems lies not in aseptic operation, but in closed, well-controlled flow paths that support bioburden control and process consistency. Disposable assemblies reduce manual handling and open manipulations while enabling standardized unit operations across scales. For DSP, engineering priorities shift toward minimizing hold-up volumes, ensuring consistent flow dynamics and integrating scalable inline sensors. These factors directly influence yield, flushing requirements and product quality, making flow path and sensor design critical for reliable scale-up and robust cost of production.

The challenge: Maintaining process fidelity across scales

Scaling a bioprocess is rarely a linear task. Maintaining geometric similarity between bioreactor sizes is essential to replicate mixing patterns and mitigate cell-damaging shear stress. However, physical geometry alone does not guarantee process fidelity. If analytical probes deliver inconsistent data as you move from lab-scale to production-scale bags, your process fingerprint becomes fragmented. This inconsistency forces engineers into reactive troubleshooting, delaying tech transfer and risking batch loss.

The solution: Standardizing data with scalable sensing

Standardized digital sensors address the scaling gap by prioritizing sensor transferability. By utilizing standardized, digital measurement technologies, we ensure that the analytical performance in a 2,000 L commercial run is ensured to be consistent with smaller scales. In-line monitoring acts as a key safeguard, enabling real-time feedback necessary for tight process control and GMP compliance during scale-up.

Engineering priorities for successful scale-up:

• Secure data linearity: Deploy standardized sensor technology to ensure probe accuracy and calibration-free operation across all vessel volumes
• Validate process dynamics: Confirm that fluids behavior are predictable through CFD modelling, consistent design or empirical testing
• Automate data integrity: Indicate monitoring systems that support continuous data integrity

These attributes are equally critical for continuous processing, where stable operations depends on consistent process dynamics, uninterrupted and comparable data streams and automated data integrity to maintain control without batch-based resets or manual intervention.

The benefit: Predictable and faster tech transfer

When your sensors “talk the same language” at every scale, the transition from development to manufacturing becomes predictable. While ensuring the highest standards of product quality this means:

• Reduced validation cycles
• Fewer process deviations
• Faster path to clinical readiness

As working volumes increase, oxygen transfer, nutrient distribution, and mixing efficiency become harder to control. Engineers must optimize:

• Impeller design and agitation speed to maintain homogeneity
• Sparger configuration for consistent gas distribution
• Sensor placement for accurate real-time feedback

Advanced in-line monitoring and single-use sensors allow early detection of deviations and reducing risk during tech transfer. Combined with robust modeling and validation, these measures ensure that scale-up delivers the same performance as pilot runs, without compromising product quality or compliance.

Managing extractables and leachables in single-use environments

Single‑use systems require strict control of extractables and leachables (E&L) for safety and compliance. All contact materials must be assessed for chemical compatibility and migration risks.

An effective E&L framework should involve:

• Material characterization: Understanding all components and manufacturing additives to ensure compatibility across process conditions.
• Risk‑based strategy: Assessing components by process criticality, testing worst-case scenarios, and ensuring toxicological safety; robust change-control is essential as material or process changes affect E&L.
• Regulatory alignment: Meeting global standards such as USP <665>/<1665>, ICH, and FDA/EMA guidelines, and maintaining traceable documentation through development to GMP manufacturing.

Early E&L integration reduces validation risks and supports quality and regulatory readiness.

Implementing single‑use technology shifts GMP compliance focus from cleaning validation to managing change control, supplier oversight, and documentation.

Key aspects include:

• Component change control: Any modifications can impact E&L and performance, so engineers need timely supplier updates and impact assessments.
• Validation documentation: Pre‑assembled systems still require proof of sterility, integrity, and suitability, plus clear material traceability.
• Supplier qualification: Reliable suppliers are vital; formal agreements, audits, and access to data facilitate risk management and lifecycle control.

Early planning in change control and validation streamlines tech transfer and strengthens GMP compliance as production expands.

Horizontal scaling is a key strategy for achieving agility in modern biopharmaceutical manufacturing. Instead of relying on a single large-scale bioreactor, multi-product facilities increasingly adopt modular designs that enable parallel production lines. Without the constraints of fixed stainless-steel infrastructure this approach also has definite advantages such as:

• Operational risk reduction
• Support faster changeovers
• Allow simultaneous clinical batch production for multiple therapies

Single-use systems make this possible by providing standardized, disposable assemblies that can be deployed quickly and replicated across multiple lines.

Scaling out is more than duplicating vessels; It requires a standardized infrastructure that ensures consistency and compliance across all lines. Using multiple 2,000 L single-use bioreactors instead of one large tank distributes risk and increases throughput. Each fluid path must be equipped with validated instrumentation for:

• Pressure control and overpressure protection
• Accurate level monitoring
• Reliable flow measurement for critical additions

In downstream processing, the same standardized instrumentation across parallel lines is critical to control flow distribution, minimize hold-up volumes and ensure consistent purification performance, directly impacting yield, flushing efficiency and deviation risk.

Standardization across these elements ensures process integrity and simplifies qualification for GMP compliance.

The challenge: The campaign bottleneck in multi-product environments

In multi-product environments, the transition between different drugs candidates such as switching a line from Monoclonal Antibodies (mAbs), is traditionally a major bottleneck.

In stainless-steel facilities, the requirement for extensive Clean-in-Place (CIP) and Steam-in Place (SIP) validation adds days of downtime to production schedules and introduces significant cross-contamination risks. This rigidity limits a facility’s ability to respond to shifting pipeline demands.

The solution: Parallel flexibility through scaling out

By scaling out with modular single-use assemblies, manufacturers can eliminate the cleaning bottleneck entirely. Because each fluid path is a dedicated, disposable closed system, the risk of carryover is engineered out of the process. This allows for a “zero-carryover” with key engineering advantages for rapid transitions:

• Zero-carryover assurance: Pre-sterilized, disposable components enable rapid product changeovers, ensuring that no residue from a previous campaign can contaminate the next batch
• Closed-system integrity: validated connectors and single-use assemblies maintain sterility during transitions, minimizing the need for cleanroom re-classification
• Hours, not days: The elimination of CIP/ SIP allows manufacturers to switch between different mAbs or vaccines in hours rather than days, maximizing facility utilization and equipment uptime

The benefits: High-velocity multi-product pipelines

This capability transforms the facility into an agile manufacturing hub. Scaling out with disposable ensures that switching between different therapies is a standard operational procedure rather than a high-risk engineering project. The result is a more resilient supply chain and the ability to support diverse pipelines without compromising GMP standards.

Agility in biopharmaceutical manufacturing must be paired with compliance and traceability. As processes scale from development to GMP production, maintaining a continuous digital thread ensures that every data point, from early experiments to commercial batches, remains accurate, secure, and regulatory-ready.

Tech transfer is often where process continuity breaks down. If analytical methods or sensor technologies differ between development and GMP environments, data comparability suffers - impacting validation and regulatory confidence.

To avoid this, engineers should:

• Deploy standardized sensor technology across all scales
• Integrate in-line monitoring for real-time parameter tracking
• Ensure critical measurements (pH, DO, flow, pressure) remain consistent from lab to the plant

This approach captures a precise process fingerprint during development and maintains it through scale-up, accelerating validation and reducing risk during tech transfer.

In single-use environments, fluid management becomes a critical success factor for process integrity and regulatory compliance. Using low-accuracy sensors introduces measurement variability that can cascade into yield losses and quality deviations. For high-value biologics making high-precision measurement is essential from development through commercial production.

In an agile manufacturing environment, speed is only as valuable as precision. When scaling up, even small inaccuracies in mass flow measurement can lead to significant deviations in critical additions or harvest volumes.

Many traditional single-use flow sensors provide only approximate values, which are highly sensitive to changes in fluid density, temperature, or the presence of micro-bubbles. These “approximate” values represent a critical bottleneck for Engineers: if the measurement is unreliable, the entire automated sequence for dosing or harvest must be paused for manual verification.

The solution: Mass flow precision with the Coriolis principle

Rather than relying on volumetric estimations that fluctuate with temperature or pressure, this bottleneck can be removed by applying the Coriolis principle in single-use systems. Direct measurement transforms the workflow with:

• Property-agnostic performance: Direct mass flow measurement without reliance on volumetric estimates. Achieve absolute accuracy regardless of changes in media density or viscosity. This ensures that a buffer addition at the start of a campaign is just as precise as the harvest flow at the end.
• Calibration-free reliability: Pre-calibrated sensors that eliminate the downtime of on-site setup, supporting rapid “plug-and-play" transitions, to ensure accuracy for mass flow, density, and temperature
• Actionable digital data: Real-time feedback data for closed-loop control and compliance, ensuring that manufacturers’ automation architecture can react instantly to process changes

In bioprocessing, low measurement accuracy directly affects separation efficiency, forcing operators to compromise between product loss and impurity carryover – ultimately reducing yield and increasing COP through reprocessing, extended flushing or batch deviation risk. Reliable measurement also reduces extended paperwork for cGMP compliance.

This approach removes guesswork and ensures that agile workflows remain efficient and GMP-compliant at every scale.

The benefit: Scaling out without uncertainty

Current single-use sensors are largely derived from laboratory designs, driven by material availability and cost rather than GMP requirements. As a result, robustness, long-term stability and process reliability are not always sufficiently addressed. The next generation must adopt an industrial design approach - translating proven principles into single-use formats while maintaining accuracy, reliability and cost efficiency.

By moving from “estimation” to “execution”, your facility avoids the rework and yield losses associated with dosing errors. This precision ensures that as you scale out your multi-products lines, your measurement technology is an accelerator, not a constraint.

The challenge: Bridging the accuracy gap

Historically, engineers had to choose between the flexibility of single-use and the precision of stainless-steel Coriolis meters. This "accuracy gap" often led to process deviations during tech transfer, as the measurements used in the lab didn't match the performance of the production floor.

The solution: consistent Coriolis measurement across scales

Advanced single-use Coriolis meters, such as those designed for biopharma applications like the Proline Promas U 500, bring the same level of accuracy expected in stainless steel systems into disposable environments. Key engineering benefits:

• Total consistency across scales: From small-batch PD to large-volume commercial harvest
• Traceable data integrity: Full integration with digital monitoring systems ensures audit readiness and automated batch reporting
• High-resolution feedback: Reduces the risk of process deviations by identifying flow inconsistencies before they impact product quality

The benefit: Scalability without compromise

By incorporating high-precision flow control into single-use assemblies, engineers create a seamless link between agility and precision, critical for maintaining product quality during scale-up and scale-out.

Single-use technology has fundamentally changed biopharmaceutical manufacturing by replacing rigid stainless-steel infrastructure with modular, disposable systems that enable rapid scale-up and scale-out. But agility only works when supported by precise measurement, standardized sensing, and strong data integrity. By combining SUT with reliable analytical instrumentation and digital traceability, manufacturers can scale with confidence while maintaining quality and compliance.

Taken together, these developments point towards a clear technical direction: fully closed, interconnected processing architecture that can ultimately support continuous operation. Achieving this requires more than disposable hardware – it depends on standardized flow paths, reliable inline measurement, robust control strategies and end-to-end data integrity. While adoption will remain hybrid and stepwise, these foundations enable manufacturers to move from isolated batch steps toward integrated, controlled process trains that reduce manual intervention, variability and operational risk.