High-Strength Single-use Assemblies for Bulk Liquid Transport

Section Overview

• Single-Use Assemblies for Fluid Management and Transport
• A Next-Generation Single-Use Film for Bioprocessing
• Ultimus^® Film Outperforms Commercially Available Film
• Shipping Qualification and Transport Simulation Testing
• Transport Simulation Testing
• Case Study: Transportation Qualification of Ultimus^® Film for Bulk Liquid Transport
• Buffer Stability Testing for Long-Term Storage
• Extractables Testing
• Dossier Specifically for Single-Use Assemblies
• Conclusion
• Related Products

Single-Use Assemblies for Fluid Management and Transport

Mobius^® single-use assemblies provide efficient and scalable fluid management across the entire bioprocessing workflow from media and buffer preparation to final fill applications. The Mobius^® portfolio includes 2D assemblies for small-scale storage, liquid handling, and frozen liquid transport, as well as 3D assemblies for transport, storage bins and mixers, and their complementary hardware bins.

Bioprocessing films are the foundation of single-use processing and are a driver in selecting single-use assemblies. PureFlex™ film has been a trusted solution for single-use applications for decades and is ideal for handling volumes of liquid less than 100 L. This film has a proven track record of reliability and is particularly well-suited for small-scale and 2D applications. By contrast, Ultimus^® film delivers exceptional strength and durability and was designed for larger-scale applications exceeding 100 L in volume. This superior damage resistance ensures reliable, leak-free performance under the most challenging conditions. Together, PureFlex™ and Ultimus^® films provide a comprehensive solution for a wide range of single-use processing applications.

This article discusses how Ultimus^® film enhances process efficiency due to its superior strength and leak resistance compared to other single-use films. It also provides an overview of key considerations for shipping qualification and transport simulation testing.

A Next-Generation Single-Use Film for Bioprocessing

Ultimus^® film represents a new benchmark for single-use films, combining exceptional strength, leak resistance, and operational benefits with innovative multi-layer technology making it the preferred choice for demanding applications in pharma and biopharma production. This film delivers several key benefits including:

• Exceptional Durability: Ultimus^® film offers superior strength and leak resistance, minimizing disruptions caused by product failures and reducing the potential for costly product losses.
• Healthy Cell Growth: Ultimus^® film is free of the antioxidant Irgafos^® 168, a design choice that supports healthy cell growth by eliminating potential contaminants.
• Enhanced Operational Efficiency: By mitigating the risk of leaks and minimizing downtime, Ultimus^® film helps streamline processes, boosting productivity and reducing operational costs.
• Comprehensive Datasets: A robust data package accompanies assemblies made from Ultimus^® film and includes detailed testing data on robustness, extractable profiles, and compatibility with solvents such as DMSO and DMAc.

The portfolio of products made from Ultimus^® film includes fluid management assemblies >100 L, Mobius^® Mix and Power Mix assemblies, Mobius^® iFlex bioreactor assemblies, and a range of Mobius^® ADC reactor assemblies for antibody-drug conjugate production.

Ultimus^® Film Outperforms Commercially Available Film

When evaluating film quality, standards published by the American Society for Testing and Materials (ASTM) play a crucial role in determining performance and reliability. Figure 1 shows the results of ASTM testing applied to Ultimus^® film and seven other commercially available films. Results are summarized below:

• Tensile Strength: Ultimus^® film had approximately 3x higher tensile strength than tested commercially avilable films. This exceptional durability ensures long-lasting reliability, even under challenging conditions.
• Abrasion Resistance: Measured by abrasion cycles to failure, Ultimus^® film had 10x higher film integrity compared to other tested films. This superior resistance ensures the film maintains its structural integrity over time.
• Puncture Force: Ultimus^® film had a 2x greater penetration resistance than tested commercially available films. This added strength provides unmatched protection against physical impacts.
• Gelbo Flex Crack Test: In this test of flexibility and robustness, Ultimus^® film had zero pinholes after being twisted and crushed repeatedly.

Shipping Qualification and Transport Simulation Testing

Liquids that may be transported during the bioprocess workflow include buffers, cell culture media, process intermediates, and bulk drug substances. During transportation product sterility and stability must be maintained, operator safety should be ensured and the transportation process should align with logistic operations.

Ensuring safe and efficient transport of liquids requires a rigorous approach to shipping qualification and simulation testing should confirm the hardware and assembly strength, integrity, and resilience against transport hazards. This ensures that materials will reach their destination safely, and that product quality and performance for critical applications is not compromised. Robust carriers and assemblies must be selected and thoroughly tested to validate their performance under real-world conditions. Below is a summary of related considerations and testing protocols.

When selecting  hardware bins for your shipping needs, several factors must be considered¹:

• Durability: The bins must withstand expected use conditions to ensure consistent performance
• Cleanliness: A clean bin eliminates the presence of particles and minimizes contamination risks
• Surface Finish: The hardware finish must meet quality and performance standards
• Weight: Lightweight bins enhance ease of handling while maintaining structural integrity
• Usage Requirements: Features like stacking and collapsibility may be desired for efficient storage and transport

A stainless-steel rigid carrier addresses these factors and offers superior durability, cleanliness, and compatibility with advanced assemblies, making it an ideal choice for bioprocessing applications.

Key factors to evaluate for single-use assemblies include:

• Film Robustness: Ensures safe transport and product protection
• Extractables Profile: Maintains product quality and patient safety
• Closed System Design: Essential for sterility and safety during transport
• Carrier Compatibility: The assembly must seamlessly fit within the selected bin
• Testing Excellence: Ultimus^® film has undergone ASTM standard testing for tensile strength, abrasion resistance, puncture resistance, and absence of pinholes. These rigorous evaluations confirm its ability to handle demanding transport scenarios

Transport Simulation Testing

Shipping qualification is incomplete without validating the packaging through established testing guidelines, such as those provided by ASTM and ISTA.

Among the relevant tests are ASTM D4169 which includes different levels of severity for simulated transport conditions and ISTA Series 3 which includes simulations for vibration, drop, and shipment scenarios. Within ISTA Series 3, ISTA 3E and 3H series tests provide robust simulation relevant to bioprocessing; 3E is tailored for truckload shipments and ISTA 3H covers multiple transport modes such as truck and rail¹. A combination of ISTA 3E, 3H, and ASTM testing can be used depending on the risk presented by transportation.

When designing a testing strategy, several factors should be considered including:

• Shipping routes and environmental conditions throughout the lifecycle
• Handling requirements and potential shocks, vibrations, or other hazards
• The number of samples and acceptance criteria for validation

The selected tests, whether from ASTM or ISTA protocols, should be performed at certified testing facilities to ensure compliance and reliability².

We conducted testing of Ultimus^® film assemblies and carriers using ISTA 3E tests. Mobius^® 3D assemblies made with Ultimus^® film in stainless steel carriers were filled to 500 L and 200 L and evaluated at ambient temperature and 2 °C, respectively. Visual inspections were performed after each test to identify any immediate issues and after testing, every bag underwent a pressure decay test to check for leaks and assess their structural integrity.

All tests passed for both assemblies and carriers, establishing a robust baseline qualification (Table 1). This information provides a foundation for customers to inform their own qualification processes.

Case Study: Transportation Qualification of Ultimus^® Film for Bulk Liquid Transport

To further test the robustness of assemblies made with Ultimus^® film at 1000 L scale, extensive simulation testing was performed on five single-use assemblies. The goal was to assess the integrity and durability of the assemblies during bulk liquid storage and transport across multiple manufacturing sites via truck using worst-case scenario testing. Conditions were simulated using ISTA 3E/H random vibration testing to replicate 2,400 miles of truck transport.

To push the limits of the assemblies, an extreme scenario was created:

• The 1000 L Mobius^® assemblies made with Ultimus^® film were placed in collapsible bins. While stainless steel bins are the recommended solution, this setup maximized the challenge of plastic-on-plastic abrasion
• Assemblies were gamma-irradiated and tested at room temperature with fill volumes of 650, 765, and 960 L. One test omitted the bin liner for additional stress on the film
• Assemblies were subjected to eight hours of hydraulic shaking, replicating the vibrations of long-haul transportation

Before testing, bags were visually checked for leaks or damage and pressure decay testing was performed to assess the internal pressure stability. After testing, a soapy water test was performed to identify potential leaks through bubble formation under pressure.

The assemblies made with Ultimus^® film demonstrated exceptional durability: no leaks were observed after 2,400 miles of simulated transport and even the most challenging test, performed without a bin liner, successfully passed, underscoring the robust performance of these assemblies.

Buffer Stability Testing for Long-Term Storage

Ultimus^® film assemblies were also evaluated for their impact on buffer stability over 60 days. pH and conductivity of various buffers stored in Ultimus^® containers were measured and compared to buffers stored in glass containers. As shown in Figure 2, no significant changes in pH or conductivity were observed, confirming that the film did not affect buffer stability. These data support the stability extended buffer storage (>60 days) and long transportation routes in containers made from Ultimus^® film.

Extractables Testing

The Emprove^® Program provides convenient online access to comprehensive documentation needed for implementation of single-use systems in pharmaceutical manufacturing. Detailed product information contained within the Emprove^® Dossiers reduces the time and investment typically needed to gather and/or prepare documentation and enables more agile, risk-based decisions. The Emprove^® Program includes single-use components, filters, connectors, and films, as well as a wide range of other products used in bioprocessing such as chromatography resins, cell culture media and chemicals. The description for the filter and single-use dossiers are below:

• The Emprove^® Material Qualification Dossiers (MQD) include product test specifications, release criteria, and regulatory information for the components as well as materials used for component qualification.
• The Emprove^® Quality Management Dossiers (QMD) includes quality and validation information including site qualification, irradiation sterilization process and packaging validations and site qualification.
• The Emprove^® Operational Excellence Dossier (OED) includes extractables data following BioPhorum and USP <665> guidance to support patient safety evaluation. OED’s are available for individual filters.
• The Emprove^® Component Extractable Reports includes extractables data following USP <665> to support patient safety evaluation. The reports are for single-use components made by third-party suppliers.

Dossier specifically for single-use assemblies

The Emprove^® Advanced Qualification Dossier (AQD) was developed to provide biomanufacturers with the information they need to support risk assessments on single-use assemblies containing multiple components. This first-of-its-kind dossier supports custom and configurable assemblies and includes:

All available component qualification information along with extensive USP <665> extractables data for all the components in the assembly.

Information on extractables, bill of materials, regulatory statements, component surface area information, original manufacturer information, shelf-life statements, and customer-approved drawings of the assemblies.

The data needed for end users to conduct risk assessments and patient safety evaluations of their assemblies.

Conclusion

Mobius^® assemblies and containers made with Ultimus^® film offer innovative solutions for reliable transportation and storage of bioprocessing liquids, enabled by next-generation high-strength film technology. Extensive testing, including transport simulation, stable buffer hold, and comprehensive extractables datasets, ensure low risk and high performance of these assemblies.

By following best practices, assessing transportation risks, selecting the right products, and leveraging ASTM and ISTA test sequences, you can confidently qualify your shipping process with solutions designed to meet the highest standards.

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