Single-use technologies (SUT) are well-suited for modular production environments and represent a valuable solution in today’s ever-evolving biologics development landscape. Though SUTs have been increasingly adopted across various applications, their use requires thorough risk assessment to identify, address, and minimize any issues that may arise during manufacturing and transport.
Conducting a comprehensive risk assessment that is tailored to each phase of the project — clinical, process qualification, and commercial—is essential to fully understand and manage the impact of SUTs at every stage of the process, thereby ensuring their optimal value for unique molecules and manufacturing strategies.
Given the unique considerations associated with disposable systems, such as material compatibility, E&L, and supply chain dependencies, comprehensive risk assessment is not just a formality but a strategic imperative. To meet these demands, some CDMOs apply a tiered, multi-stage risk assessment model across development milestones, ensuring that potential risks are identified early and refined through each phase of the process lifecycle.
Tiered Risk Management Strategies
Effective risk management begins at the earliest stages of process integration and continues through to commercialization. Key foundational steps include thorough facility fit evaluations and supplier qualification processes to verify that components meet necessary performance and compliance standards. However, the cornerstone of an effective risk strategy lies in the implementation of a structured, stage-gated assessment model.
This model typically involves multiple formal risk assessments tailored to different phases of the process life cycle. For example, AGC Biologics employs a three-tiered risk assessment strategy, conducting structured evaluations at key points: prior to process characterization, post-characterization, and before process performance qualification (PPQ), and again after PPQ before commercialization. This approach helps ensure that risk management evolves alongside process understanding and regulatory demands
This tiered approach ensures that risk assessments are iterative but not redundant, streamlining timelines, avoiding duplication of effort, and maintaining cost efficiency. Moreover, it allows teams to revisit and refine assessments as variables evolve or as new information emerges, ensuring that the process remains resilient under real-world conditions. These structured checkpoints can be used not only to identify and mitigate risk but also to streamline regulatory submissions and reduce testing burdens, supporting accelerated development without compromising quality.
Key Risk Assessments Across the Process Lifecycle
By embedding risk evaluation into each crucial milestone, manufacturers can better anticipate challenges, reduce operational disruptions, and support the successful implementation of single-use systems at every scale. Effective mitigation of risk relies on a suite of targeted assessments conducted at strategic phases of the development life cycle.
A few key risk assessment strategies crucial to effective process workflow integration include:
- Process parameter Risk Assessment (PRA)
- Raw Material Risk Assessment
- E&L Risk Assessment
- Nitrosamine Risk Assessment
- Elemental Impurity Risk Assessment
- Shipping Risk Assessment
Risk assessments are strategically timed to align with the evolving complexity and regulatory demands of a bioprocessing workflow. Raw material risk assessments are initiated during early process development to guide material selection and sourcing strategy. As development advances into clinical manufacturing, these assessments are complemented by single-use system evaluations to ensure integration with upstream and downstream operations. Throughout scale-up and tech transfer, reassessments are conducted to validate process robustness and compatibility across manufacturing platforms. Finally, during commercial readiness and post-approval stages, life cycle-based risk reviews ensure continuity in quality and supply, accounting for changes in vendors, regulations, or product specifications.
Conclusion
The adoption of single-use technologies has become a strategic imperative for biomanufacturers. Unlocking their full potential, however, depends on robust, phase-appropriate risk management strategies that proactively address challenges such as material compatibility, extractables and leachables, and supply chain variability.
Equally important is access to experienced partners who understand the nuanced requirements of SUT implementation. The right CDMO brings not only the infrastructure, but also the technical and regulatory expertise to evaluate, validate, and deploy single-use systems effectively across different development stages. This level of support is critical to de-risking deployment, accelerating timelines, and ensuring consistent, high-quality output from early development through commercial launch.
Through a globally coordinated supply chain network, a good CDMO should minimize raw material and consumable supply risks from the outset of each project. A tiered strategy, such as AGC Biologics’ approach, prioritizes conducting process risk assessments at three distinct points: prior to process characterization, post-characterization, and post-process performance qualification, thereby ensuring greater precision, reducing testing burdens, and improving timelines. By leveraging methodologies like Failure Mode, Effects, and Criticality Analysis, teams can identify and prioritize critical parameters early, streamline resources, and enhance product quality. This methodical, data-informed framework enables the delivery of highly robust, commercially viable processes with greater cost-efficiency.
Ultimately, harnessing the full potential of SUTs is intrinsically linked to the ability to anticipate, evaluate, and mitigate these new variables, making a robust risk management framework an indispensable component of any modern bioprocessing strategy.