Please cite this article in press as: Walthe, J., et al., The business impact of an integrated continuous biomanufacturing platform for recombinant protein production. J. Biotechnol. (2015), http://dx.doi.org/10.1016/j.jbiotec.2015.05.010 ARTICLE IN PRESS G Model BIOTEC 7112 1–10 Journal of Biotechnology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Journal of Biotechnology j ourna l ho me page: www.elsevier.com/locate/jbiotec The business impact of an integrated continuous biomanufacturing platform for recombinant protein production Jason Walthe a,1 Q2 , Rahul Godawat a,∗,1 , Chris Hwang a , Yuki Abe b , Andrew Sinclair b , Konstantin Konstantinov a a Late Stage Process Development, Biologics R&D, Sanofi, Framingham, MA 01701, USA b Biopharm Services, Chesham, HP51SD, UK a r t i c l e i n f o Article history: Received 6 March 2015 Received in revised form 11 May 2015 Accepted 12 May 2015 Available online xxx Keywords: Continuous bioprocessing Perfusion cell culture Continuous capture Biosolve Cost of goods Net present value a b s t r a c t The biotechnology industry primarily uses batch technologies to manufacture recombinant proteins. The natural evolution of other industries has shown that transitioning from batch to continuous processing can yield significant benefits. A quantitative understanding of these benefits is critical to guide the imple- mentation of continuous processing. In this manuscript, we use process economic modeling and Monte Carlo simulations to evaluate an integrated continuous biomanufacturing (ICB) platform and conduct risk-based valuation to generate a probabilistic range of net-present values (NPVs). For a specific ten- year product portfolio, the ICB platform reduces average cost by 55% compared to conventional batch processing, considering both capital and operating expenses. The model predicts that these savings can further increase by an additional 25% in situations with higher than expected product demand showing the upward potential of the ICB platform. The ICB platform achieves these savings and corresponding flexibility mainly due to process intensification in both upstream and downstream unit operations. This study demonstrates the promise of continuous bioprocessing while also establishing a novel framework to quantify financial benefits of other platform process technologies. © 2015 Published by Elsevier B.V. 1. Introduction The biotechnology industry is relatively young, beginning with the commercial launch of recombinant insulin and monoclonal antibodies in the 1980s. Over the next twenty years, the industry grew rapidly and focused on bringing innovative products to the market. This era of product innovation led to high revenues and large profit margins, resulting in the establishment of a manufac- turing technology base with little regard for cost and effectiveness of manufacturing assets. As the industry has matured, it has increasingly recognized that there are major issues with the structure and cost of these manufac- turing approaches (Farid, 2007). Extensive research has improved understanding around the costs of goods (COGs) for recombi- nant protein production, leading to large reductions (as much as 100-fold) in operating expenses via process improvements and operational efficiencies (Sinclair and Monge, 2002; Rathore et al., 2004; Werner, 2004; Rajapakse et al., 2005; Farid, 2013). Key exam- ∗ Corresponding author. E-mail address: rahul.godawat@sanofi.com (R. Godawat). 1 Contributed equally to the work in this manuscript. ples of process improvements include cell culture titer increases (Croughan, 2008) and improved downstream yields (Gronemeyer et al., 2014). Examples of operational efficiencies include template platform processes (Kelley, 2007; Shukla and Thömmes, 2010) and operational improvement programs (Han et al., 2010) allowing bet- ter utilization of existing infrastructure. Collectively, this work has been a celebrated success for cost engineers, development scien- tists and operations groups in the industry. However, biotechnology companies are now facing a new set of business realities and uncertainties that include adapting to potential competition after patent expiry, supplying complex and rapidly evolving biologics portfolios and driving growth through patient access beyond current mature markets (Gottschalk et al., 2013; Love et al., 2013; Ernst and Young, 2014). (For clarity, in this manuscript, we focus only on bioprocess development and specifi- cally omit challenges in discovery and clinical research.) In the face of this changing landscape, two common needs for future bioman- ufacturing are emerging: increased flexibility and reduced cost of goods. Manufacturing flexibility allows companies to manage a complex and evolving portfolio where product numbers, volumes and types are always in flux due to scientific and market uncertain- ties, and mergers and acquisitions. Although operating expenses for http://dx.doi.org/10.1016/j.jbiotec.2015.05.010 0168-1656/© 2015 Published by Elsevier B.V. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62