Buffers are critical inputs into all downstream processing steps associated with the manufacture of therapeutic proteins. The large volumes of buffer required present ongoing logistical challenges and account for a significant portion of a facility’s footprint, labor requirements and equipment costs.
The first edition Biomanufacturing Technology Roadmap identified the improvement of buffer management as a key strategic need for the industry. A BioPhorum collaboration of leading biopharmaceutical companies, engineering firms and suppliers has therefore been working together for 18 months to meet this need.
It developed a design for a Buffer Stock Blending (BSB) System to support the preparation of buffers in-line and on demand from concentrated single-component stock solutions. The collaboration on a user requirements specification fueled a desire to prototype the design and the team obtained funding from NIIMBL1 to build the skid with vendors IPEC and Pieper Automation.
The functional specification has been signed off and the vendors are moving into the build phase. The team is now preparing for factory acceptance testing, delivery of the Buffer Stock Blending (BSB) System to NIIMBL’s laboratory at the University of Delaware, performance testing and the subsequent release of the design and dataset.
The team has also recently published two white papers. The first, NIIMBL-BioPhorum Buffer Stock Blending System: A More Advanced Concept for Buffer Manufacturing, describes the project and activities up to the award of the contract to IPEC, and explains the industry drivers for change and the team’s approach to buffer preparation. The second paper, An Economic Evaluation of Buffer Preparation Philosophies for the Biopharmaceuticals Industry, is a deep-dive into some of the modeling work done to support the project.
The team is now writing a realization protocol that it will execute. This will establish that the Buffer Stock Blending (BSB) System is capable of supplying the buffers required by typical purification processes, at a quality that is acceptable and equivalent to traditional batch buffer preparation.
The dataset will then be evaluated alongside further modeling data to demonstrate that the design has achieved the expected benefits, and an addendum to the first white paper will be published in the first half of 2020.
To ensure the supply of buffers needed for the manufacture of biotherapeutic products, particularly with an expected increase in upstream productivity, Nathalie Frau (Head Biologics Technology Innovation & Strategy – Downstream Processing at Sanofi) said the industry needs to address the exponential challenges it will face regarding facility footprints, labor requirements, capital costs and logistics.
“The implementation of an automated in-line buffer manufacturing system can significantly reduce capital and operating costs, and minimize the volume of buffers to be prepared per batch, the number of buffers to be prepared and the associated labor,” said Frau. “This technology also offers the possibility to purchase standardized, ready-to-use, concentrated and single-component stock solutions to connect them directly to the buffer manufacturing system.”
For example, the move to single-use bags of less than 2,000L instead of large stainless steel tanks (often more than 12,000L), could create potential savings of more than $20m per facility built. Labor requirements will also be significantly reduced and buffer preparation can be cut from a 3×7-day operation to a 1×5-day operation in each facility.
The technology also has the potential to enable the transition from a predominately stainless steel facility, common today, to a predominately single-use facility of the future, with the potential to deliver a capital reduction of more than $100m for each new facility.
BioPhorum has blazed a trail on this project with some key initiatives:
- Industry collaboration on requirements (BioPhorum)
- Using an open architecture – anyone can build and improve it
- Successful consortium (including NIIMBL) to build and test the prototype.
By mid-2020, the project will deliver a fully tested and documented approach to buffer preparation while driving industry adoption through an open-source approach to the publication of the design and dataset.
For more information on the Buffer Preparation project and the NIIMBL-BioPhorum Buffer Stock Blending (BSB) System, please contact Danièle Wiseman on [email protected]
 This work was performed under financial assistance award 70NANB17H002 from the US Department of Commerce, National Institute of Standards and Technology.