The right chromatography systems are the backbone to a reproducible, well-optimized and efficient purification process
Chromatography performance can be significantly increased, and associated costs reduced with the right systems: chromatography columns, packing skids and control hardware. Well executed column-packing will provide efficient, reproducible and performant packed beds, important to ensure robustness and safety for the final product.
The right chromatography control system allows to automate the delivery of cleaning, sanitizing and conditioning buffers to the chromatography column, and can enable to cycle the chromatography column several times during the batch, requiring smaller columns and subsequent lower capital investment. Ultimately, this opens the door to continuous chromatography.
Any hardware is traditionally dedicated to an individual process operation. However, flexible hardware can be configured to accommodate multiple chromatography stages and support both packed column and membrane-based purification technologies. Such chromatography systems minimize capital investment and may contribute to greater process agility for multipurpose and multiproduct facilities. Maximal flexibility can be achieved when the control hardware can be equipped with a variety of single-use flow paths, with increasing tubing size depending on the associated column and flow rates.
Traditional chromatography systems
Cleanable and sanitizable chromatography columns, at all scales, supported by process control and packing systems, are used by the majority of approved manufacturing processes. The strength of prior knowledge and the track record of regulatory acceptance makes this the default approach and is an easy choice for those with a strong track record of process development, technology transfer and facility expansion. Despite high levels of capital investment for the largest systems and the required cleaning and cleaning validation, this can still be seen as the best fit for large-scale manufacturing and for facilities that may be dedicated to the production of a single product.
Traditional manual and semi-automated packing methods for chromatography columns depend heavily on the capabilities and attention levels of a few skilled operators. During packing, valve adjustment, pump flow rates and piston movement must be manually controlled by the operators and recorded in a batch record. These are lengthy, complex, and error-prone processes. In addition, manual and semi-automated packing methods can waste substantial amounts of media, the costs of which can run as high as $15,000 per liter; typically, 5% to 10% of the total column volume of media is left in the slurry tank after packing. Expiry issues with blending this excess into the next pack often mean that the excess media is thrown out. Automated packing systems have successfully enabled users to reduce the ‘waste’ on expensive chromatography resins during column packing. In addition, as with any good automation, it saves on labor time and enables agility in the work environment.
The Resolute range of columns, process control and AutoPak packing systems support all process scales from large-scale pilot and full-scale production, and offer a unique combination of active multi-axis piston control, precision linear actuation and fully automated unit operations that deliver:
- Fully scalable technology
- Quiet, clean operation
- Reduced operator involvement and error
- Predictable, time efficient packing
The single-use alternative
The adoption of a single-use manufacturing philosophy is rapidly developing as the go-to strategy to increase the productivity of existing facilities and to allow greater flexibility to meet changing demands of these facilities. The most visible process benefits associated with the adoption of single-use technology in general include faster turnaround times and increased productivity due to the elimination of cleaning.
The AllegroTM single-use chromatography system extends these benefits to chromatographic operations, allowing greater adoption of the single-use philosophy throughout downstream processing. The disposable product contact flow path also means that a single system can manage multiple chromatography stages in the purification process to minimize capital investment and maximize productivity. Working with traditional packed columns, prepacked columns or membrane-based chromatography products, the flexible process options make the use of single-use chromatography systems the ideal choice for multi-product facilities and for the manufacture of small volumes of clinical material. Using a single-use chromatography system can reduce long term processing costs by up to 18% and deliver flexibility to support all scales of clinical manufacture.
The potential of continuous processing has been discussed for several decades. However, the technology necessary to realize these benefits in bioprocessing has, until recently, been slow to match the expectation. Whether you plan for a fully continuous process, or choose to extract the value from individual technologies by including a hybrid solution, Pall’s range of continuous ready technologies gives you access to these benefits to reduce cost and maximize process agility and facility utilization.
Cadence™ BioSMB systems support multicolumn and multi-stage chromatography steps to maximize sorbent utilization and integrate multiple operations to support both batch and continuous purification. When coupled with other continuous ready technology, the Cadence BioSMB system becomes the heart of continuous downstream purification to deliver purified, virus free drug substance ready for final formulation. When benchmarked against traditional chromatography methods, using the Cadence BioSMB system for downstream purification can save 34% through significant reductions in capital and labor costs. These savings can be multiplied when integrated into a fully continuous downstream process, significantly reducing footprint and maximizing facility utilization.