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Introduction and Historical Development 15
CIP and SIP Again Defined
As described above and practiced today, the CIP process is essentially chemical in
nature, and generally requires recirculation to minimize water and chemical costs.
Flushing, washing, rinsing, and (optional) sanitizing solutions are brought into
immediate contact with all product contact surfaces under controlled conditions of
time, temperature, and concentration, and continuously replenished. Vessels and
filter housings are sprayed and piping is pressure washed. Steam-in-place (SIP) is
the next logical step following CIP. The objective is to reduce the microbiological
content in the equipment. Depending on the process requirements, SIP means to
“sanitize” or “sterilize” the equipment. Both CIP and SIP can be applied to fixed or
portable process vessels and holding vessels and process piping systems
consisting of pumps, interconnecting piping, and valves. In addition to the basic
tanks and piping, CIP circuits may include filter housings, membrane filters,
homogenizers, centrifugal machines, heat exchangers, evaporators, dryers,
congealing towers, screw and belt conveyors, process ductwork, and avariety
of packaging machines.
The successful application of CIP requires that the technology be understood
and accepted by all disciplines involved in design, fabrication, installation,
commissioning, and validation of aproject. DeLucia (4) suggested that “cleaning
is (too often) an afterthought in the design of pharmaceutical facilities.” Process
development groups, design firms, and equipment vendors focus on their own
process expertise and everyone assumes that “cleanability belongs to the CIP
system and the validation department.” The above-described equipment can be
cleaned thoroughly and efficiently only if the cleaning requirements are integrated
into the complete design process.
3-A Practice Revision
As this is being written, the 3-A Standards Committee is in the process of
developing new definitions to be included in the next revision of the 3-A Practice.
B1.1 CIP cleaning. The removal of soil from product contact surfaces in their
process position by circulating, spraying, or flowing chemical detergent
solutions and water rinses onto and over the surfaces to be cleaned.
Components of the equipment which were not designed to be cleaned in
place are removed from the equipment to be manually cleaned. (CIP was
previously referred to as mechanical cleaning.)
B1.2 Manual (COP) cleaning. Removal of soil when the equipment is partially or
totally disassembled. Soil removal is effected with chemical solutions and
water rinses with the assistance of one or a combination of brushes,
nonmetallic scouring pads and scrapers, and high- or low-pressure hoses,
with cleaning aids manipulated by hand, or wash tank(s) which may be fitted
with recirculating pump(s).
The design principles on which the CIP and SIP procedures for the generic twotank
train have been described above constitute a “template” that has been
successfully applied in many of this nation’s newest biopharmaceutical facilities
during the past 15 years. The projects have varied in size from asfew as five fixed
vessels, to as many as 65 vessels ranging in capacity from 30Lto 15,000 L(15 m 3 ).
The process facilities have included pilot plant R&D and clinical trials production,
blood fractionation, respiratory care products, the production of multiple biological