INCREASING PRODUCTIVITY IN BIOLOGICS MANUFACTURING
As discussed above, single-use technologies offer higher productivity in terms of process time (cleaning is not required)
as well as floor space (no cleaning equipment). However, to maximize the benefit, the technology should provide the whole
unit operation. For example, in the case of chromatography step, using a single-use column alone yields only partial benefit
as the chromatography skid still requires cleaning post-use. The ReadyToProcess program at GE Healthcare Bio-Sciences AB (Uppsala,
Sweden) aims to provide a more integrated solution that includes the prepacked, presanitized, and prequalified columns and
a chromatography system with a disposable flow path. The flow path is also presanitized and contains an air-trap, UV and conductivity
meters, and a flow meter. The flow path can be assembled on the system in less than 10 minutes. As seen in Figure 8, implementation
of this technology could lead to reduction in changeover time by up to three days, from seven to four days. This reduction
would give a 20% to 30% increase in the number of batches produced per year for a 49-week production schedule based on seven
or 14-day production campaigns, respectively. Furthermore, if changeover time is reduced to no more than one day per production
line, without disrupting any of the operation ongoing in the production suite (the parallel production line concept), then
the increase in the number of extra batches made per year could be between 40 to 160%. The exact efficiency depends on the
changeover time and the length of a single campaign. While a similar increase in number of batches could be achieved by using
duplicate columns and skids such that the cleaning is performed when the column and skid are offline, this will require a
significantly higher capital expenditure and floor space for the duplicate columns and skids. Another possibility is to use
a single system for all chromatography steps during manufacturing of a single batch. This will result in reduction of the
cost of equipment by 66% as well as lower floor space requirement.
Figure 9 presents a comparison of break-even plot for conventional and ReadyToProcess based operations. The analysis assumes
that: 1) each batch produced generates the same level of revenues, either current or future; 2) the fixed cost for the conventional
operation is three times higher than for the ReadyToProcess one; and, 3) the operating cost per batch for the conventional
technology is 50% lower. The two arrows in the figure show the level of net income after tax for the reference (conventional)
case and the case when 40% more batches can be produced per year, respectively. The increase in the number of batches is related
to the decrease in changeover time. It is seen that the higher operating cost associated with the use of single-use technologies
is outweighed by significantly lower capital cost contribution. Thus, an introduction of such technologies results in a higher
net income as long as number of batches produced using these ready-to-use technologies is larger than the number of batches
that could be produced using conventional techniques. A real revenue curve for an average biologic is expected to be steeper
than the revenue curve shown in Figure 9.
Technologies enabling quick changeover times, and at the same time providing high manufacturing flexibility allowing quick
responses to market demands, will become more popular because they offer higher productivity as well as better economics.
Xuemin Liu is marketing manager and Mike Collins is senior R&D engineer, applications, both at Pall Life Sciences, East Hills, NY; Nathalie Fraud is senior scientist, purification process development at Sartorius Stedim North America, Edgewood, NY; Jennifer Campbell is field marketing manager and Inese Lowenstein is director, virus safety solutions, both at Millipore Corporation, Billerica, MA; Karol M. Lacki is R&D staff scientist at GE Healthcare Bio-Sciences AB, Uppsala, Sweden; and Anurag S. Rathore is the director of process development at Amgen, Inc.,
Thousand Oaks, CA, 805.447.4491, firstname.lastname@example.org
. Rathore is also a member of BioPharm International's
editorial advisory board.
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