Pharmaceutical Manufacturing Handbook: Production and

122 STERILE PRODUCT MANUFACTURING
active air sampling, and there are also reports that active air sampling may have
advantages in terms of sensitivity. Passive sampling using settle plates can be a useful
adjunct in critical areas with limited access and where an active sampler might
interfere with airfl ow or entail a worrisome intervention risk. It must be recognized
that attempts to support the “ sterility ” of the cleanest aseptic environments (those
in ISO 5) by aggressive sampling may have exactly the opposite effect. Sampling
too frequently will increase process contamination risk by causing critical interventions
that are best avoided within these very clean environments. As personnel are
the greatest single source of microbial contamination and conduct the sampling,
sampling intensity should be carefully considered. There is no value to taking air
samples beyond those required to assess the relative cleanliness level within the
environment.
Surface Sampling Surfaces in the classifi ed environments are monitored using a
variety of methods but most commonly with contact plates (on smooth surfaces) or
swabs (for irregular surfaces). Surface sampling in aseptic environments (ISO 5/6)
is typically performed after the completion of the process to avoid the potential for
adventitious contamination of the production materials as a consequence of sampling
activities during the process. Fortunately, studies indicate that contamination
does not build up during typical processing operations in modern clean rooms.
Sampling with these materials may leave a trace of media or water on the sampled
surface, and cleaning of the surface immediately after sampling is commonplace.
Sampling of product contact surfaces (i.e., fi ll needles, feeder bowls, etc.) should only
be performed after completion of the process, and the results of this testing should
not be considered as an additional sterility test on the products. As in any form of
manual environmental sampling, the risk of contamination by samplers during the
processing of a sample makes the data less than completely reliable. Sampling of
surfaces such as walls and fl oors should not be overdone because with good attention
to aseptic technique they should be of little concern relative to actual process
risk. Sampling on these surfaces is probably most useful in assessing ongoing changes
in microfl ora and to confi rm the adequacy of the disinfection program.
Personnel Sampling The monitoring of personnel gown surfaces is an adaptation
of surface sampling in which samples are taken from surfaces on the operator. In
ISO 5 environments, this ordinarily entails the gloved hands and perhaps forearms.
As with any other sampling of a critical surface (the gloved hand is often in closest
proximity to sterile product contact surfaces and sterilized components), the sampling
should be performed at the conclusion of the aseptic activity. Sampling during
the midst of the process risks contamination of the product and should be avoided.
Sampling of other aseptic gown surfaces is ordinarily restricted to gowning certifi cation
or postmedia fi ll testing, where more aggressive sampling can sometimes be
informative. Whenever a gowned individual is sampled, the sample should be taken
in the background environment (not ISO 5), and the individual should immediately
exit and regown before continuing any further activity in the aseptic core area.
Sampling of personnel in less critical environments can be useful; however, meeting
regulatory expectations in these areas is ordinarily straightforward. Recommended
contamination levels often distinguish among the different room classifi cation levels
found within clean rooms. While this may seem reasonable, it is not completely