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PHARMACEUTICAL ENGINEERING
The Official Technical Magazine of ISPE
T
Introduction erators will occasionally make an error. As new production
his following discussion provides an processes were introduced over the years, the incremental
overview of a representative project expansions to the cleaning program were accommodated
entailing renovation of a substantial until its performance began to suffer both in terms of rework
equipment cleaning program from and schedule impacts.
manual to automated methods. The Similarly the handling of parts in strong caustic solutions
project was in a biopharmaceutical and manual HWFI rinses eventually produced safety inci-
facility that produced several differ-
ent bulk drug substances in separated
process trains. Cross contamination was
a major concern in all phases of the project development and
implementation.
Existing Situation
The facility was a first-generation biopharmaceutical facility
which had evolved to house close-quarter manufacture of
multiple products. In the original plant design, CIP and SIP
were employed for large vessels and lines, but the major-
ity of cell culture, harvest, and purification equipment was
broken down after each use and the parts treated through a
Clean-Out-of-Place (COP) program of manual parts cleaning
using soak tanks.
Manual cleaning carries risk to the process because it is
so dependent on rigorous and consistent performance of
sometimes arduous physical tasks while wearing elaborate
PPE by a variety of individuals. Even the most dedicated op- Figure 1. Manual washing utilizing soak tanks.
Figure 10. Example of customized wash racks developed for the project.
the URS with an allowance for a few more if needed. Having document produced the load document that describes the
a three-fold increase in wash racks was a challenge for the complete relationship between the required kit, the rack(s)
project team. Wash racks are in a range of $20 to 30,000 needed to reliably clean all the items in the kit, the specific
each, depending on complexity. load patterns to be processed and the quantity of each wash
The final resolution of the rack designs to the kitting item in a load - Figure 9.
The load document and the 3-D mod-
els became the basis for the Preparation
and loading SOPs. Document specialists
used the 3-D models to create a sequence
of visual aids that illustrate the loading
process stepwise, from the perspective of
the person performing the loading activ-
ity - Figure 10.
Another challenge with the wash racks
on the project was, as stated earlier,
a disproportionate focus on the box
rather than how it would be used. The
development of the kitting process was
not initiated until after bid award, which
then drove the design and quantities. It
took many months longer than antici-
pated to finalize the design and manufac-
ture of all the wash racks. The design and
manufacturing capacity requirements
were severely underestimated as well as
Figure 11. FAT of a wash rack for portable vessels and components. the costs to the end users.