Economic Analysis of Batch Vs. Continuous Processing for a Direct Compression Product

Economic Analysis of Batch vs. Continuous Processing for a Direct Compression Product

Ronnie Feng, Leslie Krone-Speck, Cat MacConnell, Robert Meyer, Scott Reynolds and Jim Velez

Cost pressures in the pharmaceutical industry continue to prompt the search for cost-reducing innovations and new ways of doing business.  Continuous processing of drug products, where goods such as tablets are manufactured without interruption for arbitrary lengths of time, has been widely cited in the general press as a significant opportunity to reduce manufacturing costs.  Upon initial examination, continuous processes do appear to provide advantages in comparison to the more common batch processes, most notably through reduction of capital and labor costs and the improvement of production yields.  The prevalence of continuous processes in lower margin industries such as foods and commodity chemicals further supports the premise that cost advantages associated with continuous processing can be realized in the pharmaceutical industry.  However, literature and lay press communications are markedly devoid of detailed descriptions of the specific characteristics that lead to quantitative reduction of cost in a pharmaceutical setting, with a notable exception being the 2011 study of S.D. Schaber et al. (Ind. Eng. Chem. Res., 2011, 50 (17), pp 10083–10092). 

In this study, we describe an assessment of a single new high volume drug product that will be produced via a simple direct compression processing route, encompassing raw material receipt and dispensing, blending, and tablet compression operations.  Unlike the study of Schaber et al., we assume that manufacture of the active pharmaceutical ingredient (API), drug product manufacture, and packaging steps occur at independent sites.  We seek to answer the question of whether continuous processing has a cost advantage over other modern, lean batch manufacturing methodologies by comparing the net present cost of manufacturing the drug product using both batch and continuous processing routes.    In the case of the batch process (BP), starting materials are received and dispensed to a single batch tumble blender and following blending, this blending tote is docked above a high speed rotary tablet press.  For the continuous process (CP), starting materials are received and dispensed to individual containers, the containers are docked above gravimetric feeders which supply a pair of continuous blenders, and the continuous blenders subsequently supply a high speed rotary tablet press.  In both cases, we assume that process analytical technologies (PAT) are used for measurement of blend and tablet uniformity, and thus both the BP and CP utilize a real time release (RTR) testing strategy. 

To perform a balanced analysis, we assume that the product would require a new facility to be built independent of whether a BP or CP is chosen. Our results indicate that although the more automated CP would require a higher upfront capital investment, the BP would require additional capital investment later in the product life cycle, to increase capacity as product sales volume grows.  Furthermore, the CP facility size would be marginally smaller than a facility utilizing BP, thus decreasing facility operating costs.  Although long-term operational data from continuous pharmaceutical processes are not available, we estimate the specific labor for CP and find that it requires less labor to operate,  and has higher uptime, relative to the BP.  Elimination of startup and shut down steps for BP results in higher yields for CP, and this yield improvement is quantitatively estimated by analysis of typical, lean BP manufacturing operations.  Even though RTR testing is employed in both cases, the cost to release each lot of material is still considered, and the larger lot sizes produced by the more automated CP are estimated to require fewer man hours to release.  Finally, shorter production cycles and less work-in-progress would result in inventory cost savings for the CP relative to the BP.

Summation of the various cost differences shows that a CP would be financially favorable over a BP, a result which is shown to be true under a variety of scenarios tested in a sensitivity analysis.  As expected, the magnitude of the savings is dependent on the production volume of the product being manufactured, with higher savings realized at higher production volumes.  However, the magnitude of the calculated cost savings is smaller than what has been reported elsewhere. This result may stem from assumptions used in other studies where the batch production models have not been “leaned out” to the maximum extent possible. Ultimately, it can be concluded that a CP can be a lower cost option for drug products which require capital investment in a new facility, but this lower cost must be balanced against the uncertainty and risk which come with new operational methods. A key finding in this study is that the benefit to risk ratio may be significantly smaller than is often noted in more informal reports on continuous processing of pharmaceuticals.