Application of Single-Use Equipment for Buffer Storage and Distribution in Medium Size mAb Production Facility

B iopharmaceutical processes are operated in aqueous systems using large quantities of WFI or Purified Water (PW). In the upstream process (USP), WFI is required for media preparation and feed solutions. In the downstream process (DSP), large quantities of PW or WFI are required for buffers, with buffer preparation, buffer storage, and distribution systems representing a significant portion of the process equipment used for the downstream purification in monoclonal antibody (mAb) production facilities. However, the overall required volumes for buffer storage as well as the complexity for buffer distribution are often underestimated. This is especially the case for multi product facilities, which need a high degree of flexibility and short time intervals for product changeover. In large scale production facilities of 10,000 L and more working volume, stainless steel systems have been installed traditionally using large buffer tank farms for buffer storage and complex transfer line configurations for buffer distribution. In small scale production facilities, single-use systems with bags for buffer storage and flexible hoses for buffer distribution are widely used; however, size limitations and a higher degree of manual operations in regulated cGMP production environments must be taken into consideration. This article describes an intelligent hybrid system approach in which both technologies – stainless steel systems and single-use systems – have been combined in the best possible manner in consideration of the pros and cons of each individual technology. The system described for buffer storage and buffer distribution has been realized for a 2,000 L mammalian cell culture production facility at Kemwell Biopharma Pvt. Ltd., India (a Contract Manufacturing Organization (CMO)). The article will discuss the basic concepts and the selection criteria for utilizing single-use or stainless steel systems. Furthermore, practical examples will be provided for novel process designs as well as for novel equipment design details, such as interfacing flexible hoses with stainless steel piping that need SIP/CIP capabilities. Finally, the level of flexibility achieved by still keeping the systems simple and safe will be highlighted.