(465e) 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.