Pharmaceutical Manufacturing Handbook: Production and

106 STERILE PRODUCT MANUFACTURING
Equipment within the preparations area varies with the practices of the fi rm and
can include manual or ultrasonic wash/rinse sinks; single or double door automated
parts washers; batch or continuous glass washers; stopper washers for closure components;
CIP/SIP stations; equipment wrap areas (as described above); and staging
areas for incoming (prewash) components, dirty equipment, and cleaned components/equipment.
An adjacent classifi ed storage area(s) may be present in larger
facilities to accommodate the full variety of change parts and equipment that is not
in immediate use. Where the preparations area also supports compounding, it may
include additional equipment such as pH meters, fi lter integrity apparatus, and the
like in support of those operations. ( Note: Where compounding requires aseptic
conditions for rigorous control of bioburden, as is the case for unpreserved biologics
and other contamination - sensitive products, it is best to provide separate entry for
compounding. The moisture level and hence contamination potential in a typical
preparation area is unsuitable for entry into an aseptic compounding area).
Depending on the scale of the operation, the preparations area may include the
loading areas for both sterilizers and ovens. In high - throughput operations where
the use of tunnels for glass depyrogenation is more prevalent, glass washers and
tunnels for each fi lling line may be in separate ISO 8 rooms accessed from the
preparations area.
2.1.3.3
Compounding Area
The manufacture of parenteral solutions is ordinarily performed in ISO 7 (Class
10,000, EU Grade C) controlled environments in which localized ISO 5 unidirectional
fl ow hoods are utilized to provide greater environmental control during
material addition. These areas are designed to minimize the microbial, pyrogen, and
particle contributions to the formulation prior to sterilization. Depending upon the
scale of manufacture, this can range from small containers (up to 200 L) (disposable
containers are coming into use for these applications), to portable tanks (up to
600 L) to large fi xed vessel (10,000 L or more have been used) in which the ingredients
are formulated using mixing, heating, cooling, or other unit operations. Smaller
vessels are placed or rolled onto scales, while fi xed vessels are ordinarily mounted
on weigh cells. The vessels may be equipped for temperature and pressure measurement
instruments, as mandated by process requirements. Compounding areas often
include equipment for measuring mass and volume of liquid and solid materials
including, for example, graduated cylinders, and scales of various ranges, transfer
and metering pumps, homogenizers, prefi lters, and a variety of other liquid/powder
handling equipment. Liquid handling may be accomplished by single - use fl exible
hose, assemblies of sanitary fi ttings, or some combination thereof. A range of smaller
vessels to be used for the addition of formulation subcomponents or excipients to
the primary compounding tank may be required as well. Because parenteral formulations
can include aqueous and nonaqueous vehicles, suspensions, emulsions, and
other liquids, the capabilities of the compounding area may vary. Agitators can be
propeller, turbine, high shear, or anchor designs depending upon the requirements
of the products being manufactured, and it is not uncommon to fi nd examples of
each in larger facilities. It is preferable to perform as much of the process as possible
while the formulated liquid is nonsterile to ease sterilization requirements, although
precautions to prevent microbial and endotoxin contamination are important risk
abatement features.