PRINCIPLE
Equipment used
in manufacturing of pharmaceutical products should be of appropriate design and
construction, adequate size, suitably located and qualified in order that the
quality designed into each pharmaceutical product can be assured and
reproducible on a batch-to-batch production basis and to facilitate its
effective cleaning and maintenance.
DESIGN AND
CONSTRUCTION
The design
and construction of equipment should fulfill the following requirements:
equipment
should be designed and constructed to suit its intended purpose;
equipment
surfaces coming into contact with any starting material, intermediate, bulk or
finished product should not be reactive, additive, or absorptive so as to alter
its identity, quality or purity beyond the established limits;
materials
required for specific equipment operations, such as lubricants or coolants
should not come into contact with any in-process materials so as to alter the
identity, quality, or purity of starting material, intermediate, bulk or the
finished product;
equipment
should not adversely affect the product through leaking valves, lubricant drips
and the like; or through inappropriate repairs, maintenance, modifications or
adaptations;
equipment
should be designed so that it can be easily and thoroughly cleaned. It should
be cleaned according to detailed and written procedures and stored only in a
clean and dry condition;
washing and
cleaning equipment should be chosen and used in order not to be a source of
contamination;
equipment
should not present any hazard to the products. The parts of the equipment that
come into contact with the product must not be reactive, additive or absorptive
to such an extent that it will affect the quality of the product and thus
present any hazard;
all
equipment designated for use with flammable substances or chemicals or in areas
where flammable materials are used should be equipped with explosion-proof
electrical parts and should be properly grounded;
balances and
measuring equipment of an appropriate range and precision should be available
for production and control operations. Equipment employed for weighing,
measuring, testing and recording should be regularly checked for accuracy and
calibrated according to an appropriate program and procedure. The result of the
checking and calibration should be recorded. The records should be kept
properly;
filters for
liquid filtration used in the processing of products should not release fibers
into such products. An asbestos containing filter with or without subsequent
use of a specific non-fiber releasing filter should not be used; and
distilled,
de-ionized and, where appropri-ate, other water pipes should be sanitized
according to written procedures that detail the action limits for
microbiological contamination and the measures to be taken.
INSTALLATION
AND LOCATION
Equipment
should be suitably located to minimize possible cross-contamination by
substances used in the same area. Equipment should be installed in such a way
as to prevent any risk of error or of contamination.
Equipment
should be located at a sufficient distance from other equipment to avoid
congestion and to ensure that products do not become admixed or confused with
one another.
All open
mechanical belts and pulleys should be equipped with safety guards.
Water, steam
and pressure or vacuum and other lines should be installed so as to be easily
accessible during all phases of operation. Fixed pipe work should be clearly
labeled to indicate the contents and, where applicable, the direction of flow.
Each piece
of major equipment should be clearly marked with an identifying number. This
number will be used on all batch directions to designate the particular unit or
apparatus used it that specific batch. Exception is made where a piece of
equipment is solely used for one type of product.
Defective equipment
should, if possible, be removed from production and quality control areas, or
at least be clearly labeled as defective.
MAINTENANCE
Equipment
should be maintained at appropriate intervals to prevent malfunctions or
contaminations which could alter the identity, quality, or purity of the
product.
Repair and
maintenance operations should not present any hazard to the quality of the
products.
Coolants,
lubricants and other chemicals such as thermal probe solutions should be
evaluated and approved by a formal process.
Written
procedures should be established and followed for maintenance of equipment.
A written
record of major equipment maintenance and use should be included in individual
equipment logs which also identifies the date, time, product, strength and
batch or lot number of each batch processed. For equipment used solely for one
product the record can be included in the production batch records.