Enabling Total Biopharma Solutions

After a few decades of speculation and proof of concept, the biopharmaceutical industry has fully embraced the advantages of single-use technologies throughout all phases of drug production1. In particular, as industry interest shifts to continuous bioprocessing versus traditional batch methods, the flexibility of single-use technologies has once again emerged as an asset to industry advancement.
Whether using a batch or continuous process, biopharmaceutical developers want to make high quality products in a cost- and time-efficient manner. The ability to translate laboratory-scale processes to commercial, cGMP-compliant production is key to achieving this aim, and the best way of doing this is to use single-use technologies that are designed with scaleup in mind.
Being able to use larger working volumes is also important for efficiency focused manufacturers. This, combined with the desire for scalability, means that most forward-thinking developers favor technologies that can work across a range of volumes, from the laboratory through to commercial scale2.

Single-use scale-up
The Allegro™ suite of single-use technologies is specifically designed to allow biopharmaceutical companies to translate development-scale processes into commercial-scale production processes. This portfolio of single-use technologies is fully validated and robust, with easily integrated solutions for upstream and downstream processing, including cell culture, buffer and media prep, up to formulation and filling. Each technology comes with extensive validation packages, including strong manufacturing assembly validation. Users may also request custom validation of the technologies in line to meet specific needs.

Bioreactors and storage solutions
Allegro STR single-use bioreactors are designed for working volumes of 60 L to 2,000 L, making them suitable for process development through to commercial production. The systems are stirred tank reactors that have direct bottom-driven impellers, allowing power inputs up to 0.25 W/kg. This input level reduces mixing times and increases oxygen transfer rates – up to 40 h-1 – providing more consistent, scalable performance.
Each bioreactor includes advanced single-use and reusable sensors, with all data recorded in compliance with 21 CFR Part 11, and transmitted to the operator through a user-friendly interface. With clear handling instructions for simple operation, the overall ease of use is industry leading. Compact footprints (height below 3 m) also make the bioreactors a good fit for most cleanrooms.

Biocontainers
The Allegro range also features 2D (50 mL to 50 L) and 3D (50 L to 3000 L) storage biocontainers. These biocontainers are suitable for holding and processing bulk product, as well as for managing and supplying peripheral fluids around unit operations, such as cell culture media, buffer and cleaning solutions.
Allegro biocontainers and their accompanying hardware – including totes and trolleys for transport, storage and handling – are designed to integrate with other systems in the range.
Available in standard configurations that expedite faster qualification following customer evaluation, Allegro biocontainers are designed for ease of installation and use, have enhanced robustness, and are subjected to an extensive validation program. They are also 100 percent leak-tested.

Simple, efficient mixing
The Allegro line features a range of efficient mixing solutions in standard and jacketed (thermal control) stainless steel tote formats – which are both simple and reliable. The line of single-use mixers can incorporate sensors (e.g., pH, conductivity and temperature) and load cells for on-line monitoring and control. Efficient process monitoring and control solutions for mixing steps are easily achieved because the units are designed to be integrated with the Allegro MVP automated single-use system.
The Allegro portfolio also features two magnetic-based mixing technologies:

1. The Pall Magnetic Mixer is a flexible, single-use mixing system with the drive unit located on a portable cart. It is best for solid to liquid applications that require robust mixing steps, such as buffer and media preparation.

2. The LevMixer® system is based on superconductive levitation technology, which causes no mechanical shear or particle generation. It can be used to mix volumes from 10 L to 1000 L across a range of operations, from buffer preparation to final formulation. The unit is capable of directly measuring the impeller speed to ensure process consistency.

For smaller scale mixing, the Allegro line includes the Wand mixer system for product development and cGMP applications. It is capable of mixing from 1 L to 200 L across the five available sizes (5, 10, 20, 50 and 200 L), and is best for applications where portability, high mixing efficiency, reliability, ease of use and a small footprint are required.

Making sterile connections
Connecting units in the Allegro range is also straightforward. All Kleenpak® Presto sterile connectors can be either Gamma irradiated or autoclaved, and because the Kleenpak Presto sterile connectors are made from bisphenol-A (BPA) free polyethersulfone (PES), they are compatible with a wide range of process fluids and solvents.
Kleenpak sterile connectors enable the connection of disposable systems and manifolds – even in an uncontrolled environment – while maintaining the sterile integrity of the systems. Kleenpak II sterile connectors are best suited for high volume sterile fluid transfer in single-use or hybrid systems. For an enhanced level of security, the Kleenpak Presto sterile connector offers intuitive operation that allows sterile connections to be carried out in a simple three-step operation.

System approach to automated processing
Today’s drug manufacturers are looking to operate in single-use mode with the same level of reliability and robustness expected from traditional, fully automated process solutions. With the Allegro MVP platform, media and buffer preparation, pH adjustment, membrane chromatography, sterile, depth and virus filtration, viral inactivation and bioburden reduction can all be automated. The platform is designed to enhance flexibility, productivity and product consistency, while simultaneously reducing labor costs and operator errors in upstream and downstream processing.
Users can optimize conditions via configurable, fully disposable flow paths, incorporating single-use sensors for the control of key parameters. The system can also be customized with a large selection of pre-designed manifolds and sensors, connectors, tubing types, filters and pre-filters.
Allegro single-use TFF systems enable fully automated ultrafiltration/diafiltration (UF/DF) processes from 20 L to 2000 L. The compact systems are easy to optimize, ensuring low feed/retentate volumes with the flexibility to run cassette surface areas from 0.5 to 10 m2. Users have a choice of single-use sensors for feed/retentate and permeate manifolds and 2D and 3D biocontainers for retentate product recovery and buffer/WFI.

Total solutions, total support
Single-use technologies are ideally suited to support the scale up of both batch and continuous bioprocesses from clinical to commercial scale. Single-use technology eliminates the need for cleaning and significantly reduces setup and switch-over times, providing flexibility. Single-use equipment also enables rapid changes in production configurations, schedules and product volumes in response to changing market needs. Furthermore, single-use systems can be readily replicated in multiple locations, ensuring consistent production. Single-use technologies, therefore, mesh well with FDA quality initiatives, including quality-by-design (QbD), process analytical technology (PAT) and continuous processing.
Recognizing the need in the biotech industry for more flexible and efficient manufacturing strategies, as well as the growing interest in continuous manufacturing as a promising solution, Pall Life Sciences has committed to developing single-use technologies that will enable integrated bioprocessing. Because it is essential for new bioprocessing technologies to be scalable, Pall is taking the process development/GMP architecture approach, with the introduction of development-scale solutions that are designed to be further developed at the commercial scale for operation under GMP conditions. The full product offering is backed by onsite custom service support for process development and optimization at any scale or phase of development and production.

Pall Life Sciences has worked to create the AllegroTM portfolio as a broad solution for users, leveraging single-use technology and automation to provide users with enhanced control, flexibility and higher quality end products. To learn more about the AllegroTM portfolio, please visit:
www.pall.com/allegro

For a video that highlights Pall Life Sciences total single-use solutions, please visit:
https://vimeo.com/205384850

References
1. KJ Kinsella, SS Dewan, “Single use market – Rise of single-use technologies & systems in biopharmaceuticals,” Drug Development & Delivery (2015).
2. Platas Barradas et al., “Criteria for bioreactor comparison and operation standardisation during process development for mammalian cell culture,” BMC Proceedings, 5(suppl 8) (2011).

The original version of this article was published as supplement form of The Medicine Maker sponsored by Pall Life Sciences.



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