The biomanufacturing industry is experiencing a fundamental shift as single-use technologies (SUTs) gain widespread adoption. These innovative systems offer distinct advantages over traditional stainless steel infrastructure—from reduced contamination risks and faster turnaround times to lower capital investments and enhanced operational flexibility. However, SUTs also have limitations that must be considered to minimize issues that could impact manufacturing and product transport.
Organizations must implement a comprehensive and robust risk management program that anticipates, evaluates, and mitigates the unique variables inherent to SUTs throughout every project phase—from initial clinical studies through process qualification and to full commercial production. When executed strategically, this approach enables companies to harness the full potential of single-use systems, streamlining biologics production while maintaining the highest quality standards and reducing costs.
While stainless steel systems remain the traditional approach, they present specific operational challenges: high capital costs, contamination risks from stagnant flow areas, and extensive cleaning requirements that extend changeover times between products.
Single-use technologies (SUTs) address these issues directly. Pre-sterilized, disposable components reduce contamination risks and cross-contamination between batches. Installation, validation, and changeover processes that once took days or weeks can now be completed in hours—ideal for multi-product facilities and clinical manufacturing.
Today, leading biomanufacturers are equipping facilities with both single-use and stainless steel manufacturing lines, a strategic approach that provides the flexibility to meet the demands of specific applications or project phases. For example, manufacturers can implement flexible scale-out strategies by utilizing multiple single-use bioreactors in parallel to quickly produce test batches during development, then transfer production to larger stainless steel lines for commercial-scale manufacturing. This strategic flexibility also enables manufacturers to optimize technical performance and costs for each product.
While single-use technologies offer compelling operational advantages, their successful implementation hinges on robust risk management strategies that ensure process reliability, product quality, and regulatory compliance throughout the entire product lifecycle.
The shift to single-use systems introduces unique challenges that require specific consideration. Supply chain dependencies become more complex with SUTs, as manufacturers must rely on external suppliers for critical components while maintaining strict quality standards. Material compatibility is a concern, as different drug products may interact differently with polymer surfaces. Extractables and leachables require comprehensive testing and monitoring to ensure patient safety, particularly as regulatory agencies like the FDA and EMA continue to refine their expectations around contaminants.
Compliance with ICH guidelines requires organizations to demonstrate that their SUTs meet the same rigorous standards as traditional stainless steel systems. These challenges underscore the need for structured, phase-appropriate risk assessments that evolve with each stage of product development—from early clinical phases where flexibility is needed to commercial manufacturing where consistency and reliability are essential. Without this systematic approach, the very advantages that make SUTs attractive can become liabilities.
Effective implementation of single-use technology requires a multi-stage approach, with evaluations conducted at key points throughout product development. At AGC Biologics, we have implemented a streamlined three-tiered approach to risk assessment: pre-process characterization, before process performance qualification (PPQ), and during commercial readiness review (Figure 1). These evaluation points create opportunities to adjust strategies using real-world analytical data before advancing to the next development stage.
Manufacturers must also conduct targeted assessments in key areas to ensure effective workflows and consistent product quality:
Process Parameter Risk Assessment employs streamlined parameter classification and testing protocols to identify critical control points.
Raw Material Risk Assessment utilizes a two-stage process for traceability and criticality scoring, helping identify high-risk materials while optimizing costs and safeguarding project timelines.
Extractables & Leachables Assessment implements risk-based testing strategies that consider product proximity, exposure times, operating temperatures, and material compatibility factors.
Nitrosamine Risk Assessment ensures proactive compliance with ICH M7 guidelines, mitigating risks associated with potentially carcinogenic impurities.
Elemental Impurity Assessment addresses ICH Q3D compliance requirements.
Shipping Risk Assessment applies FMEA analysis methodologies to evaluate global distribution scenarios, ensuring product integrity is maintained even under worst-case shipping conditions.
Successful risk management requires strategic alignment of assessments with specific development phases—such as conducting raw material evaluations during early process development when changes are least disruptive. Organizations should employ risk scoring to prioritize testing efforts, implement iterative review processes that adapt to emerging data, and focus on qualifying reliable supply chain partners that support long-term operations.
Single-use technologies offer significant advantages when properly implemented, but success requires deep expertise in comprehensive risk management. When selecting a manufacturing partner, consider CDMOs with proven track records in multi-stage risk assessment for SUT biologics manufacturing.
AGC Biologics conducts a comprehensive risk assessment for each product to optimize production yield and cost-efficiency. Using our globally coordinated three-tiered approach, proven SUT processes, and a reliable global supplier network that ensures consistency and quality, AGC Biologics is positioned as a leading advanced therapeutics CDMO.
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To further explore this approach, read our article “Risk Management in Biologics Manufacturing: Strategies for Adaptive Biomanufacturing and Excellence in Single-Use Technologies,” and contact us to discuss partnering on your next project.