(624c) Supply Chain Management Challenges In Continuous Pharmaceutical Manufacturing (CPM)

Continuous Pharmaceutical Manufacturing (CPM) is a concept with a demonstrated potential to revolutionize the pharmaceutical industry and achieve Quality by Design (QbD) via implementation of knowledge-driven process modeling and online Process Analytical Technology (PAT) data acquisition. The main advantages of CPM over batch pharmaceutical processes include process intensification via continuous flow reactions and separations, lean manufacturing and elimination of long (idle) batch times. Nevertheless, product quality and uniformity must strictly adhere to regulatory specifications and may well be affected by feedstock quality disturbances, which are currently addressed by offline lot analyses. Considering that full-scale CPM production lines are already under construction and may streamline and facilitate high-volume manufacturing of some blockbuster drugs which enjoy ample patent protection, it is useful to investigate the potential impact of CPM practices on traditional pharmaceutical supply chains.

The pharmaceutical supply chain is characterized by the incessant quest for more efficacious formulations: the latter relies on a highly regulated R&D pipeline for novel API screening and new product development, and on the elaborate standardization of manufacturing, prescription marketing and distribution operations. Rapid licensing and patent longevity is a sine qua non prerequisite towards ensuring economic success. Launching “first to market” often relies on technically robust (rather than optimal) manufacturing recipes, which have a clear potential to be licensed quickly and replicated worldwide without any reconfiguration.

Batch pharmaceutical manufacturing processes are the overwhelming majority in modern pharmacopoieia: Multinational pharmaceutical firms possess several strategically located production facilities worldwide and many major distribution centers in order to effectively meet the demand within each country or region. The vast variability of legal, technical and economic regulations in the host countries further perplexes importing, storage, exporting and disposal constraints on feedstock, key intermediate and API compounds. Concurrently, the past proliferation and current prevalence of batch pharma production plants (tank farms) is a consequence of the century-long established paradigm of iterative pharmaceutical chemistry research, reinforced by the wide versatility of these facilities, where myriads of synthetic chemical routes have been conceived, explored, documented and scaled up, resulting in generations of structurally similar compounds. Most importantly, batch processing times, lot manufacturing and product changeovers have been studied exhaustively, thus enabling systematic production planning which efficiently address demand fluctuations.

Continuous manufacturing lines, in contrast to batch-oriented tank farms, eliminate idle times between processing units by definition; however, a deeper understanding of the process is required (Plumb, 2005). Demand variability is harder to tackle, but an entire CPM line can fit in a lab room (Roberge et al., 2008). Multiproduct CPM plants can thus be constructed, provided that the combination of target products and the geographic location are judiciously selected, so as to achieve high demand and close proximity to markets.

The present paper focuses on a comparative quantitative analysis of several key technical and economic performance indicators for two different (batch vs. CPM) strategic pharmaceutical manufacturing scenaria. The geographic region, production/distribution basis, drug portfolio, patent protection and market share data are assumed given and constant, with reasonable technical assumptions made with respect to the comparative technical efficiency and economic viability of process alternatives (Gerogiorgis et al., 2010). The focus of this investigation is to explore the conditions under which a rapid CPM transition is advisable.

Keywords: Continuous Pharmaceutical Manufacturing (CPM), Supply Chain Management (SCM).

REFERENCES

Gerogiorgis, D.I., Barton, P.I., et al. (2010). Comparative economic analysis of continuous and batch pharmaceutical manufacturing: A case study (submitted).

Gerogiorgis, D.I., Barton, P.I., et al. (2009). Steady state optimization of a continuous pharmaceutical process. Computer-Aided Chemical Engineering (Proceedings of PSE 2009) 27(1): 927-932, Elsevier, Amsterdam.

Plumb, K. (2005). Continuous processing in the pharmaceutical industry – Changing the mind set. Chem. Eng. Res. Des. 83(A6): 730-738.

Roberge, D.M., Zimmermann, B., Rainone, F., Gottsponer, M., Eyholzer, M., Kockmann, N. (2008). Microreactor technology and continuous processes in the fine chemical and pharmaceutical industry: Is the revolution underway? Org. Proc. Res. Dev. 12(5): 905-910.