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type of soil include fermenters or bioreactors that have been thermally inactivated
prior to cleaning; especially challenging is the air–liquid interface where media
and cell mass agglomerates and dries during the cell growth phase. Spray dryers
and evaporators also present acleaning challenge as the equipment surfaces are
coated with ahighly concentrated soil, often comprised primarily of denatured
protein and mineral content.
Protein denaturation in these examples can result in acarbohydrate-proteinfat-mineral
matrix, which can be very difficult to attack with an alkaline cleaner
alone. The acid override program is amore extensive treatment than any of the
previously described programs, and can be effective in removing the soils noted
above. The program uses a strong, hot acid solution in recirculation for an
extended wash period to attack the tenacious protein and mineral soils. The
concentrated alkaline is introduced after the acid wash duration to “override” the
acid solution and continue recirculation, without discharge of solution. The alkaline
wash phase to attack the fat and carbohydrate components of the soil. This
approach conserves water usage, and minimizes discharge of concentrated acids
to waste.
The CIP program begins with atraditional rinse operation to send all freerinsing
soil to drain prior to establishing a recirculated chemical wash phase
using ahot acid solution. The CIP circuit is next subjected to ahot acid wash to
attack the protein component of the matrix, breaking down peptide bonds and
minerals, exposing the fat and carbohydrates trapped within the denatured
protein matrix. The acid solution may be recirculated for a period of 25 to
30 minutes prior to introducing concentrated alkaline cleaner to override the acid
solution, the alkaline solution then working to remove the remaining exposed
soils. The alkaline solution may be recirculated for aperiod 30 to 45 minutes
prior to being flushed out with asubsequent rinse phase. The remainder of the
program concludes in the same manner as the traditional alkaline-based
wash program.
Solvent-Based Cleaning Programs
The application of a solvent-based cleaning program is primarily to bulk
pharmaceutical chemical or API facilities, with organic and inorganic solvents
employed for both process operations and cleaning the equipment. As noted in
chapter 16, the process equipment and piping may not be hygienic in design or
fully susceptible to CIP technology. The process cleaning is often performed in a
contained manner to protect personnel from potent compounds and solvent
exposure, as well as solvent release to atmosphere. The application of CIP cleaning
can improve cleaning reliability while minimizing the operator exposure to potent
compounds and reduce manual cleaning required to restore this equipment for
process use.
These CIP operations typically occur between process campaigns, and
cleaning frequency may vary as acampaign may be one week or one year in
duration. However, between process lots, aprocess solvent flush may be used to
prevent build up of process soil. The soils noted may not be susceptible to
dissolution, suspension and removal by aqueous cleaning solutions. Organic
process solvents rely primarily on solubility for the removal of the soil residue,
and can perform their cleaning duty without introducing an external contaminant