The Challenges
Preparation, movement and storage of process fluids is critical to maintaining the smooth operation of complex bioprocesses. These challenges have historically been met with a series of stainless steel, reusable vessels, each requiring maintenance, cleaning, cleaning validation and sterilization or sanitization before use. However, the logistics of ensuring vessels and connecting pipework are available for use when the process needs them, can be complex and can consume significant resources and facility footprint.
Moving to a suite of related single-use solutions can significantly reduce your capital investment, simplify production and reduce non-value adding operations to increase the economy, flexibility and agility of manufacturing facilities. These solutions can be further enhanced through automation, which provides additional control, monitoring and reporting for tasks that are otherwise performed manually.
Fluid Handling and Management
From the preparation and movement of simple buffers and cleaning fluids to the filling of the final drug product, the need to safely process, collect, transfer, and transport fluids is present throughout every pharmaceutical process. These challenges can be met by a series of components or integrated into automated single-use systems.
Allegro™ Single-Use Systems
Combining multiple single-use components into a defined system to meet a specific user requirement requires a detailed knowledge of process requirement and regulatory context. Functional designs need to be supported by high quality components with close control of specifications and performance with assembly and quality release processes in place to safeguard that any system received meets the quality standards demanded by the application.
Storage
Flexible vessels, often referred to as bioprocessing bags or biocontainers can be designed to meet specific requirements as part of an Allegro™ single-use system, or used as standard systems for common sampling and storage applications.
Allegro™ 2D Standard Systems for low volumes of 50 mL to 50 L.
Allegro™ 3D Standard Systems for larger volumes of 50 L to 3,000 L.
Totes
Storing, protecting and moving 3D biocontainers to maximize operational flexibility and process practicality.
Plastic, collapsible and stackable Allegro™ Plastic Totes for up to 500 L.
Stainless steel stackable Allegro 3D Stainless Steel Totes for the storage for up to 3,000 L.
Allegro™ Jacketed Totes for temperature- controlled storage of up to 500 L.
Allegro™ 3D Transportation Totes for the safe shipment of 100 L to 200 L.
Bioprocessing Workstations
Compact, multipurpose workstations ensure the safe retention of multiple biocontainers and provide a convenient portable platform for related equipment wherever required within the process.
Allegro™ Bioprocessing Workstations to accommodate multiple bioprocessing bags from 10 L to 100 L.
Fluid Preparation
The preparation of simple solutions and buffers or the addition of excipients to final formulation may have different requirements but all have a direct impact upon the smooth operation of the process. Single-use solutions can reduce capital investment and increase process flexibility when compared to traditional stainless-steel mixing vessels. They can readily be adopted on their own, or as part of a wider single-use processing philosophy.
Mixing
Preparing process buffers and maintaining homogenous process fluids requires a mixing solution that can range from simple fluid recirculation through a single-use system or high shear mixing systems depending upon the process needs. A range of mixing technology ensures the optimal technology is available to meet every mixing challenge.
Allegro™ Single-Use Mixers – efficient, low shear, general purpose mixing over a wide range of applications including shear sensitive solutions from 50 L – 1,000 L
LevMixer® System - for buffer preparation and product contact mixing with a levitating impeller to remove the shaft, seals and bearings from inside the single-use mixer system. A separate external drive unit can drive multiple tank sizes to mix from 6 L to 1,000 L.
Magnetic Mixer – ideal for media and buffer preparation. A portable universal drive can provide robust mixing for even the most challenging powder applications from 6 L to 2,000 L.
Powder Handling
The addition of solids to formulate simple solutions and process buffers in a controlled environment requires careful control. When used with appropriate mixing solutions, granules and powders can be prepared separately and added in a controlled and contained manner at the point of mixing.
Pall® PD2 Powder Handling Bags – for safe and easy powder containment and transfer.
Integration and Automation
Combining mixing technology with filtration and fluid management permits the automated preparation of fluids using standard recipes to mix, adjust pH and filter process buffers.
Allegro™ MVP Single-Use System - to provide local control of both the mixer and pumped volume additions to automate pH targeting with standardized recipes.
Aseptic Processing
Maintaining a low bioburden throughout a typical process is an essential element of current good manufacturing practice (cGMP). This control increases towards the later stages of drug substance production where sterility is necessary to maintain the safety of the final drug product. The use of pre-sterilized, single-use systems to help with this challenge is now commonplace.
Bioburden Filtration/Sterile Filtration
The use of filtration to control process bioburden or, when validated, to achieve sterility is common throughout biopharmaceutical processes. A wide range of membranes, sizes and styles ensure the perfect match at all points within the process.
Supor® EAV Membrane Filter Cartridges - for bioburden control of process buffers and additions.
Supor® EX Grade ECV Membrane Filter Cartridges - for versatile sterile filtration of all process fluids, intermediates and drug substance.
Fluorodyne® EX EDT Membrane Filter Cartridges - 0.1 micron filtration for enhanced sterility control and the retention of mycoplasma.
Sterile Connections and Disconnections
From maintaining bioburden control to validated aseptic transfer, the simple and reliable connection or disconnection of process components while maintaining the validated state builds flexibility into any critical process.
Kleenpak® Presto Sterile Connectors - (1/4 in. to ¾ in. hosebarb; ½ in mini sanitary clamp;)
Kleenpak™ Sterile Connectors - the disposable Kleenpak sterile connector allows for the dry connection of two separate fluid pathways, while maintaining the sterile integrity of both.
Kleenpak™ II Sterile Connectors - for wide bore tubing with hosebarb connections up to 25 mm (1 in.) and 25-38 mm (1-1.5 in) sanitary
Kleenpak™ Sterile Disconnectors - for convenient and secure sterile disconnection of flexible tubing
Buffer Management
In a variety of bioprocessing steps, ranging across multiple product recovery, purification
and formulation processes such as diafiltration and chromatography, the use of buffers within downstream processing is particularly important as they are used to protect proteins from variations in pH and to ensure that proteins interact correctly with various media to maximize performance of the specified purification process.
Thousands of liters of buffers are produced each year for use in the manufacturing of biopharmaceutical products in clinical or commercial-scale processes, which requires a large resource input from the operator’s time producing the buffer solutions, to the facility space for storing the vast amount of buffers created, and the logistics of using them across the unit operations.
However, the increasing demands of buffer management and preparation can be addressed using in-line dilution, saving floorspace and costs and improving efficiency.