Flexsafe® - New PE Film. New Benchmark.

Sartorius has developed a new polyethylene film and bioprocessing bags to facilitate the way towards the single-use facility of the future. Flexsafe® meets the most stringent needs for safer bioprocessing.

Cell Growth

Flexsafe® bags ensure excellent and reproducible growth behavior of the most sensitive production cell lines. The optimization of the resin formulation and the complete control of our raw materials, the extrusion process and the bag assembly guarantee a consistent lot-to-lot cell growth performance.

Optimized Resin and Additive Formulation

To avoid cell growth issues that have been reported by several users of single-use bags1,2 and to ensure batch to-batch consistency, it is important to optimize and control the concentration of antioxidants. In close collaboration with polymer, additive and film suppliers, we developed a new polyethylene film, called S80. Applying a standardized cell growth assay3,4, the raw material composition and film formulation was optimized especially for critical upstream applications.

As a result, Flexsafe® bags are designed to excel thanks to:

Optimized antioxidant package

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Excellent cell growth of the most sensitive cells

Use of pharmacopeia-listed antioxidants only

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Simplified toxicology assessment

Zero slipping agents

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No risk of interference due to these agents

Mechanical anti-blocking

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Reduces stickiness, facilitates extrusion and bag handling

Meaningful specifications and process control from polymer resin to finished bag

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Reliable and reproducible growth performance, well-characterized extractables profile


1Gammell P., et al. The impact of lot-to-lot variability of disposable cell culture bags on cell growth during the scale-up of a mammalian production cell line. Cell Culture Engineering XIII, April 2012. 
2Hammond M., et al. Identification of a Leachable Compound Detrimental to Cell Growth in Single-Use Bioprocess Containers. PDA J. Pharm. Sci. and Tech. 67 (2) 2013: 123-134.
3Jurkiewicz E., et al. Verification of a New Biocompatible Single-Use Film Formulation with Optimized Additive Content for Multiple Bioprocess Applications. Biotechnology Progress Early View. doi/10.1002/btpr.1934, first published 30 May 2014 
4Fenge C., et al. Consistently superior cell growth achieved with new polyethylene film formulation. Bioprocess International Supplement, September 2014

Full Control of Manufacturing Process

The current industry practice of using resins or films based on trade names does not provide true control of polymer and additive formulations. Therefore, we established a strong collaboration with leading polymer, additive and film manufacturers to access and control the formulation of our polymer and additive package and to define and control the operating ranges for extrusion, welding and gamma-irradiation processes.

Flexsafe® is the first bag on the market that underlies complete control and traceability of all resins, additives and the entire manufacturing process:

  1. Film Polymers
  2. Additives
  3. Extrusion Process
  4. Gamma Irradiation
  5. Assembly

Excellent Cell Growth and Lot-to-Lot Consistency

Based on our unprecedented material science and process control approach, you can rely on excellent and reproducible growth behavior, even for your most sensitive cell lines. This has been confirmed by the recently published Dechema study* and biopharma companies worldwide using their specific cell lines. Further, no residual amounts of bDtBPP, a cytotoxic leachable, was identified in WFI extracts of Flexsafe® bags.

  • Consistent growth and no aging effects after gamma irradiation
  • Reliable growth performance of serum and protein-free media stored in Flexsafe® bags


* Eibl R., et al. Recommendation for leachable studies - Standardized cell culture test for the early identification of critical films for CHO cell lines in chemically defined culture media. DECHEMA Jan 2014

Robustness

Flexsafe® meets your requirements for outstanding robustness and ease of use at all steps of your manufacturing process. The film’s strength and flexibility provide consistent performance and easy handling – even in the most stringent applications like cell culture, long-term storage or shipping of drug products.

Superior Strength and Flexibility

The thickness, strength and flexibility of the new S80 film enhances the mechanical robustness of Flexsafe® bags, making it ideal for all bioprocessing applications. The strength of Flexsafe® bags significantly reduces the risk of accidental damage to the bag due to inappropriate handling. Its flexibility enables convenient installation and self-deployment of the bag in its container.

Watch the Video:
To test the strength of our Flexsafe® bag, we performed an in-house water burst test

Flexsafe® 3D Bags | Safe and Easy-to-use for Storage applications

Due to its well-characterized and consistent extractable profile, the use of Flexsafe® 3D Bags allows a safe long-term storage for all fluids from upstream, to downstream and final filling steps.

Thanks to the combination of the flexibility of the S80 film and the self-deploying accessory, the bag can be filled to its full volume with no operator manipulation.

Watch the Video:
Self-deploying solutions from 100L to 1,000L

The excellent flexibility of each layer of our new polyethylene film and a total thickness of 400 μm provide extraordinary robustness. To qualify the extraordinary strength and flex

Standard flex durability film

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Highly resistant to fatigue and pinhole formation

Tensile strength

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Strength of film and welds

Elongation and energy at break

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Flexibility, ease of installation and use

In-house water burst test

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Strength of bag

Extensive worst-case testing in actual use

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Robustness of Flexsafe in stirred tanks, in rocking motion bioreactors and under actual shipping conditions

Flexsafe® 3D Bags | Safe & Robust Liquid Shipping

Our Flexsafe® 3D shipping system is successfully qualified under a selection of ASTM D4169 tests. The test sequences have been chosen after real transportation trips and ASTM D4169 laboratory trials.

The comparison of real shipping values with ASTM D4169 shows a substantial safety margin, thus providing extensive qualification and giving reassurance of security during fluid shipment.

Watch the Video:
Liquid Shipping Applications from 100L to 500L

Filled Flexsafe® shipping bags in Palletank® passed the most stringent shipping validation test according to ASTM D4169.

Assurance of Supply

To meet the highest business continuity requirements, we have a robust contingency plan for our Flexsafe® bags in place. The uninterrupted film supply is based on redundant resin crackers, film extrusion lines and multiple manufacturing sites.

  • Established resin specifications
  • Design space for film extrusion
  • Full traceability of resins and additives
  • 10-year contract with film manufacturer
  • 2-year customer change notification period
  • Last-time buy option for a minimum of 2 years resin demand
  • Backup resin crackers and film extruders
  • Two-year supply of safety stocks of resin and film
  • Multiple bag manufacturing and sterilization sites
  • Own bags, filters and connectors
  • Strategic partnerships for tubing and sensors

One for All

The complete range of scalable Flexsafe® bags enables you to implement single-use bioprocessing throughout all steps of drug manufacture, from process development to production – all using just one film.

Bags in All Volumes for All Bioprocessing Steps

Flexsafe® bags are fully scalable, ranging from 20 mL to 3,000 L. Furthermore, you can use Flexsafe® bags for all bioprocessing steps:

  • Reduce time and expense for process validation, extractables and leachables studies, toxicology assessment and stability studies
  • Benefit from robustness, consistent quality and assurance of supply
  • Ensure worry-free operations, quality and supply chain

Consistent Extractables Profile

Flexsafe® delivers a well-characterized, consistent extractables profile due to raw material and process controls:

  • Facilitate leachables validation and toxicology assessment
  • Obtain sustainable, reproducible and reliable process validation data

Sartorius Flexsafe® bags are an integral part of our total solution offering for single-use manufacturing.

Get inspired by our single-use factory concept:

Watch our video of a cell-based vaccine production process concept, relying completely on single-use technologies.
This example shows how you can implement Flexsafe® bags throughout an entire process from seed production to final filling.

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