Page 67 - Assurance of Sterility for Sensitive Combination Products and Materials

54 Assurance of sterility for sensitive combination products and materials

4.13 Environmental monitoring
The environment can be a significant potential source of bioburden. The
proper design, operation, and performance of the clean room are essential
to the control contamination. Trending the environmental monitoring data
essential indication of clean room is kept in control. Risk-based approach
should be used to determine methods, locations, and frequency of moni-
toring. The FDA Aseptic Processing Guidance, the EU annex 1 GMPs, and
ISO Standard 14644–1 and 2, as well as many other global health authority
guidance and regulations, set requirements, and expectations for environ-
mental monitoring [3, 7, 13, 14].
Environmental monitoring is an indicator that the clean room is con-
trolled and remains in a qualified state. The use of environmental monitor-
ing is challenging because of the limited correlation between the condition
of the environment and the sterility of the product. Environmental moni-
toring should be used as one of the indicators if changes in the environment
have occurred since the process had been qualified. In this case, the eval-
uation of environmental monitoring trends is more useful than evaluating
excursions from prescribed limits.
Environmental monitoring sample locations and sampling frequencies
should be selected on a risk basis considering conditions that might impact
product sterility as well as predict excursions. Locations within critical fill-
ing and product contact exposure areas should be monitored to detect im-
mediate system failures or sources of contamination. Locations in adjacent
areas with lower classification can be useful indicators of systemic changes
or predictions of contamination in critical cleaner areas. Risk-based ap-
proaches that consider workflow, material and personnel traffic, equipment
operation, and critical exposure of product would be particularly useful.
Environmental monitoring for viable contamination is typically achieved
using passive settling plates, active air sampling devices—both stationary and
portable, swabs and contact plates. The environmental monitoring method
should be appropriate for the surface being monitored. Active air samplers
and settling plates can be used for air quality. Contact plates can be used for
smooth, relatively flat surfaces, such as stopper bowls, walls, and machine
bases. Swabs can be used for smaller surfaces or surfaces with crevices, such
as filling needles and stopper tracks.
Environmental monitoring, especially total (also referred to as nonvi-
able) particle monitoring where possible should be continuous and auto-
mated. There should be minimal mechanical systems located in the critical