Genetic Engineering & Biotechnology News

NOV1 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Page 45 of 57

8 | SEPTEMBER 1, 2018 | Single-Use Technologies for Bioprocessing switching to intensified fed-batch/perfusion processes, it is also possible to commercially produce high quantities of multiple biologi- cal drugs in state-of-the-art single-use/hybrid flexible and modular facilities at an accept- able cost of goods sold (COGS). And this would represent a very attractive model for the biomanufacturing facility of the future. This approach would present the best option for companies to initially design and build the facility at a lower cost, realizing a high- throughput, low-cost-per-gram process plat- form that can bring product to market faster and, eventually, "scale out" in a flexible and modular way as the market diversifies and demand increases over time. Conceptual Design For biopharmaceutical companies, advan- tageous manufacturing strategies may be de- termined during conceptual design (CD) if a process-centric approach is adopted. Such an approach is supported by the Sartorius P4S ® (Process 4 Success ® ) platform, a detailed CD offering that helps companies optimize vari- ables such as throughputs, process strategies (fed-batch, intensified), and technologies (sin- gle-use, hybrid). By using a process-centric approach, com- panies may build facilities that incorporate suitable technologies, follow effective manu- facturing and automation strategies, and manifest risk-based classifications (closed, functionally closed, etc.). The companies may arrive at the best layouts (Figure 1) for meet- ing their throughput goals. In addition, a company could carry out process modeling using the BioPharm Services BioSolve ® tool, for example. Doing so would allow the company to estimate the operational expenditures and COGS for the entire facility. Executing a CD project prior to making an investment decision would be extremely beneficial to a biopharmaceutical company. It would reduce uncertainties related to pro- cess, manufacturing, and automation strate- gies, as well as those related to market de- mand. It would also heighten a company's confidence in its business case, including its product pricing strategy. At the start of a CD project, the Sartorius P4S tool may be used to define mass balance for a specific process or even a generic pro- cess. In a multiproduct scenario, mass balance helps companies select technologies and size equipment. It includes the relevant processing parameters for all process steps and defines the required volumes and processing times. During this exercise, the individual pro- cess steps are defined within all related unit operations and can be drawn directly into a process flow diagram. For the GMP room layout, the process and related requirements such as scheduling, media/buffer preparation, and distribution strategy are of central impor- tance. The manufacturing suites will be de- signed around the process and not vice versa. Insights from a Case Study An instructive case study concerns a 6 × 2 kL plant that employed different manufactur- ing scenarios, namely fed-batch (3 g/L), N-1 perfusion (6 g/L), and concentrated fed-batch (10 g/L). It was found that the maximum ca- pacity was between 500 and 1800 kg/year depending on the scenario used. The related capital investment cost needed for the facil- ity was in the region of €100 million ($115 million), and the annual costs were a fraction of those of a traditional stainless-steel facility, which were dominated by depreciation. The detailed design and realization of this kind of intensified facility requires adoption of certain processing units and technologies as there are existing limitations in single-use products and technologies in the market. These limitations, however, are minor and will no doubt be overcome by near-term ad- vances that will enable full-scale intensified processing with single-use technologies. The design of such a facility can be highly flexible, enabling multiple products to be pro- duced with short changeover times. In such a facility, it would be possible to implement 1) closed single-use technologies in upstream processes, and 2) single-use/hybrid technolo- gies in downstream processes that are closed or can be made functionally closed. It could also prevent contamination of processes in cleanroom surroundings and processes further downstream, and even allow for ballroom/ dance-floor operation for entire processes up to formulation. Designing unit operations in a modular way in these layouts further enhances process flexibility and minimizes changeover times by enabling easy exchange of unit op- Single-Use Modules Expedite Total Solutions Continued from page 6 Figure 2. ISA S95 structure: four-level automation concept. Abbreviations: BMS/EMS: building monitoring system/environmental monitoring system; DCS: distributed control system; ERP: enterprise resource planning; OEE: overall equipment effectiveness; PAT: process analytical technology; PI: process intelligence; PLC: programmable logic controller; SCADA: supervisory control and data acquisition.

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