Optimising Biopharmaceutical Production with Pre-packed Process-Scale Chromatography Columns
The biopharmaceutical industry has made significant strides in optimising drug development and downstream production processes, with the use of chromatography columns critical for the purification of biopharmaceutical products.
However, conventional column packing can be a complex and challenging process, which can create production bottlenecks and may result in inconsistencies and errors. The quality and reproducibility of data and the product itself can also be affected, making it difficult to ensure that approved quality standards are consistently followed. In addition, the use of different resins from various suppliers further complicates the column packing process, as each supplier provides their own recommendations. This introduces an additional degree of variability that can lead to inconsistent results. If a column fails to meet the set qualifications and approval requirements, the packing process would need to be repeated, leading to delays and increased costs.
The adoption and implementation of pre-packed process-scale chromatography columns has rapidly emerged as a promising solution to overcome these challenges, improving overall processing efficiency while maintaining high levels of quality and reducing costs.
Benefits of using process-scale pre-packed columns
Pre-packed columns offer numerous operational advantages over traditional in-house column packing methods. They can be produced by specialists in state-of-the-art clean rooms, making them ready for good manufacturing practice (GMP) processing. The use of pre-packed columns reduces the risk of column-to-column variability and provides a consistent and reliable purification outcome, contributing to the quality and consistency of the final biopharmaceutical product. Moreover, a wide variety of compressible resins and incompressible media are available in standardised column sizes commonly used for preclinical, clinical, and production processes (e.g. CHT Ceramic Hydroxyapatite Media).
Addressing time-efficiency challenges, pre-packed columns provide significant time savings by eliminating the column packing step, which allows for more streamlined production timelines. This translates to increased productivity and less downtime while eliminating the need for specialised equipment. Similarly, buffer preparations are also reduced by removing packing steps. When a disposable flow path is used in conjunction with pre-packed columns, it also saves time on skid preventative maintenance (PM). Moreover, unlike traditional methods, pre-packed columns eliminate the need to account for resin lead times, column packing, and possible column packing inconsistencies in the schedule.
Operational Advantages
Offering substantial cost savings, pre-packed columns eliminate the need for manual column packing and validation, reducing the material and labour costs associated with traditional column chromatography processes. Pre-packed columns also eliminate the need for dedicated column packing areas, freeing up valuable space in the production facility. This allows for simpler suite designs and improved overall efficiency. Furthermore, by managing resin inventory in a pre-packed format, biopharmaceutical companies can reduce labour costs associated with resin handling and inventory management.
Another benefit of pre-packed columns is the increased flexibility they provide by allowing for rapid process turnover, a particularly useful feature in a facility producing multiple biotherapeutics. Process developers can choose from a wider range of resins, as expertise in packing a novel resin may not be required. Many resins can be procured in a pre-packed format, thus providing developers more flexibility in adopting new separation technologies and reducing the limitations inherent in the industry concept of "platform" resins.
Improving consistency, pre-packed columns are packed with single resin lots in standard bed heights and diameters, providing optimised, consistent slurry and packing conditions. In addition to pre-sanitisation, reduction of bioburden, and prevention of cross-contamination, each column is shipped with quality and performance documentation, and individual column release testing is performed. This can reduce QC full-time equivalent expenditures and simplify approvals. Moreover, column consistency across facilities is an added benefit when a biotherapeutic is produced at multiple sites.
By outsourcing the column packing step to a resin supplier specialising in column packing under optimal conditions, the risk of inconsistencies in the packed bed is reduced. This allows end-users to focus on more critical aspects of purifying therapeutic proteins. The use of pre-packed columns can also reduce procurement inefficiencies, such as resin inventories, elimination of resin lot matching, and maintenance of spare parts for columns and standard skids. The availability of pre-packed columns from resin manufacturers can also reduce lead times as the resin is readily available with the added benefit of a single source for technical support.
In recent years, pre-packed columns have emerged as a game-changing solution for commercial manufacturing. They have quickly become a viable approach for commercial manufacturing and are now routinely used by contract manufacturing organisations (CMOs) and innovators to produce biotherapeutics. With their ability to streamline operations, reduce costs, and improve quality, pre-packed columns represent a significant step forward for the biopharmaceutical industry. As such, they are likely to continue to play a major role in the future of biotherapeutic manufacturing.
Laura Kronbetter, Senior Global Product Manager, Process Chromatography, Bio-Rad Laboratories.