Page 70 - Assurance of Sterility for Sensitive Combination Products and Materials

Aseptic processing 57

Clean rooms should have adequate air supply to maintain proper differ-
ential pressure between areas of higher cleanliness and lower cleanliness. Air
supply should be sufficient to prevent the accumulation of contamination
from material transfer, personnel activities, and other operations. Airflow
should be established according to those levels of activity. HEPA air velocity
should be sufficient to prevent contamination at working surfaces near and
around exposed products and product contact surfaces.
Clean room conditions such as temperature and humidity should be
controlled to ensure operator comfort, reduce risk of particulate contami-
nation through static charged from dry air, and reduce risk of microbiolog-
ical contamination from higher temperatures and humidity.
Clean rooms are specified by the EU as Grade A through D and by the
US FDA as ISO 5 through 7 as presented in Table 4.2. These designations
reflect expectations for total particulates and viable contamination. The
most critical aseptic operations and activities are performed in Grade A and
ISO 5 areas, with lower grade areas used for support functions.

4.16 Airflow or air profile visualization (smoke) studies

An important tool in designing and confirming proper clean room airflow
in clean room and critical aseptic processing areas are air visualization stud-
ies. These are sometimes referred to as air profile or smoke studies. These
studies involve the application of a visual medium in the form of a mist that
enables the visualization of the flow of air. Typically, gaseous liquid nitrogen
is used to visualize airflow, but other means can be used. Caution should
be exercised in the selection of visualization material and method to ensure
that the method is safe for personnel and equipment.
Air visualization enables the confirmation that
(a) filtered airflows from cleaner areas to less clean areas in a manner that
would sweep contamination from clean surfaces toward exhausts,
(b) airflows from areas of higher differential pressure to areas of lower dif-
ferential pressure, and.
(c) little or no turbulence is present at clean area surfaces.
Air visualization studies can be used to help plan and design the place-
ment of equipment and components, and it can also be used to help train
clean room operators by showing the effects of proper and improper aseptic
technique (Fig. 4.3).