The changing face of the biopharmaceutical industry has brought about an increased need for flexibility and adaptability, with developments in upstream processing resulting in higher product yields, and with multi-product facilities becoming commonplace. In addition to this there is always the ever-present call for manufacturers to reduce costs without compromising the essential facets of quality and safety.
Process intensification, specifically higher cell culture titers, has increased the volume of buffer required and magnified the challenges posed by traditional buffer preparation. The extensive and varied range of biotherapeutics currently being developed has led to significantly different process demands, and the necessity for biomanufacturing facilities to cope with processes that may be vastly different in scale. This has a direct impact on the number of process buffers required.
It is also apparent that the market for existing products has seen an upward trend, with the industry responding through expansion and improvement to existing manufacturing facilities to meet the demand. Additional changes to the demand for buffers comes from the drive for continuous bioprocessing, as the progressive nature of business pushes facilities to become increasingly efficient and productive. This development has seen a rise in the usage of multi-column chromatography, single-pass TFF and the different buffer demands that the continuous operating mode requires.
The result of these industry developments is a continued increase in the volume and diverse range of buffers required to satisfy process needs - challenges that The BioPhorum Technology Roadmap for the Biopharmaceutical Manufacturing Industry, clearly recognized in its identification of buffer preparation as an area that requires improved solutions and technological advancement.
Preparation of buffers is an essential support function of all bioprocessing facilities developing monoclonal antibodies, gene therapies, and vaccines. The buffers used in these processes are utilized in purification stages such as chromatography, viral inactivation and filtration, and in the final formulation steps – typically tangential flow filtration and bulk filling.
The individual buffers have unique chemical attributes that utilise the parameters of pH and conductivity to positively impact process performance, providing a stable environment for target proteins. A well-chosen buffer that has been accurately prepared is key to ensuring the level of activity within the target protein remains intact.
The Buffer Preparation Problems and Challenges
Traditional buffer preparation, however, can be a challenge - it is labor-intensive, requires large quantities of chemical reagents and takes up a significant footprint within a manufacturing plant (both during production and when stored). The everyday reality is that buffer preparation drives biopharma plant schedules and dictates plant capacity, and it is the forward-thinking production team that is looking for effective ways to manage the buffer process as a whole, and not be slowed down by traditional time-consuming bottlenecks.
|PAIN POINTS CAUSED BY TRADITIONAL BUFFER PREPARATION|
These pain points can be sufficiently addressed by the utilization of in-line dilution of buffer concentrates, supported by single-use fluid handling and mixing solutions. Effectively, this is a process whereby multi-component buffer solutions are prepared in fixed vessels or single-use mixers at high concentrations and are subsequently diluted for process use.
As a process, in-line dilution offers less risk than in-line conditioning, which blends concentrated stock solutions. In-line dilution prepares the same number of buffer formulations as traditional preparation - however the buffer solutions are five to twenty times more concentrated and subsequently diluted with Water For Injection at the point of use.
Automation of this process can facilitate just-in-time delivery allowing for a significant reduction in the volumes of buffer required and removes the need for lengthy buffer hold stages, previously caused by the traditional route of preparing large quantities of multiple buffers in advance.
Buffer preparation is a largely manual process, falling behind upstream and downstream processes that commonly run on fully automated systems. The manual process is burdened by labor-intensive processes such as weighing and dispensing of powders and transfer of solids to buffer mixing and buffer hold tanks. There is a clear argument that a higher level of automation is key to the future of effective buffer management.
|THE VALUE OF IN-LINE DILUTION|
Allowing buffer concentrate to be diluted in a timely fashion through an easy-to-use automated buffer workstation, reduces risk posed by potential operator error and seamlessly joins up process steps. A buffer workstation has the added advantage of simplifying both regulatory oversight and quality management, with process documentation and batch-specific detail residing in one place.
The good news is that the pain points associated with buffer preparation can now be addressed efficiently through the advancement of well-designed automated technologies. Our understanding of the bottlenecks in buffer management that hinder production, enables us to partner with you to attain a robust buffer management strategy that encompasses preparation, mixing, storage, and a just-in-time solution at the point of use.