MANUFACTURING
INTEGRATED CONTINUOUS BIOMANUFACTURING Continuous manufacturing provides a new paradigm for biotherapeutics manufacturing. It has been shown to deliver high productivity (10-15X), lower cost of goods (by 50-75 per cent), and a more consistent product quality. This article highlights the key benefits of continuous processing for production of biotherapeutic products as well as the challenges that a practitioner is likely to face and solutions that are available today. It is emphasised that a centralised control platform for an integrated bioprocess is essential for real time data acquisition and on-line process control. Anurag S Rathore, Professor, Department of Chemical Engineering, Indian Institute of Technology Nikita Saxena, Research Associate, Indian Institute of Technology
B
atch manufacturing is the technology platform that is currently used for production of biopharmaceutical products. It involves step-by-step processing wherein one-unit operation must finish before commencement of the next operation. The mobility between the unit operations is slow as a result, affecting the overall productivity. In addition, the biopharmaceutical industry suffers from complexities related to scale-up, technology transfers, and batch to batch variability in product quality. This has prompted interest amongst the manufacturers to migrate from batch to continuous processing. Perhaps the biggest motivator is the significant difference in productivity. While the automation for the shift requires investment in the initial stage however the long-term profitability aspects are compelling. Studies have demonstrated a reduction of 50-75 per cent in the cost of manufacturing due to 10-15X increase in productivity which
44
P H A RM A F O C U S A S I A
ISSUE 40 - 2020
results in significantly reduced footprint of the manufacturing facility along with reduced capital cost as well as improved use of consumables. In addition, the cost involved with the transportation of batches to lab for analysis is also reduced (Jungbauer & Hammerschmidt, 2017). In the pharmaceutical industry, shifting to continuous manufacturing saved operating cost by 9 per cent to 44 per cent, capital expenditures by 20 per cent to 76 per cent and foot print reduction by 40 per cent to 90 per cent (Spencer et al. 2011). Improved capacity utilisation of the production chain in achieving demand and supply requirements, improved implementation of complex recipes, elimination of transition times anda more consistent upkeep of the schedules are some of the advantages that continuous processing offers over batch manufacturing (Rathore et al. 2015) (Figure 1). In addition, the development of soft sensors (Figure 2) and process analytical tools
(PAT) are likely to further enhance control and consistency of product quality (Thakur et al. 2019, Zobel et al. 2017, Hebbi et al. 2019). Further, process automation reduces the need for manual interventions, thereby resulting in fewer human errors and minimum system disturbance. While the benefits of continuous processing are quite significant, the transition from batch to continuous is technically quite complex. The concept of Quality by design (QbD) is quite aligned to what continuous manufacturing offers with respect to modernisation of production and improvement of consistency in product quality (Rathore & Winkle 2009). The systematic, science and risk-based methodology that is adopted towards experimentation and knowledge generation ensures that the manufacturer utilizes robust control strategies. For a manufacturer to successfully run a continuous process, this knowledge base is essential
