Page 69 - Assurance of Sterility for Sensitive Combination Products and Materials

56 Assurance of sterility for sensitive combination products and materials

prior to changing of gloves and upon exit from the cleanroom, and after
certain more extensive or critical interventions. Ample time from sanitiza-
tion of gloves to the monitoring of gloves should be considered, that is, the
monitoring of gloves should not be performed on gloves that have been
recently sanitized. Gown monitoring locations should be selected based on
potential risk posed to the sterile product. Typically, higher risk areas on the
gown such as seams, openings or connections are present as well as sleeves,
front, and neck area should be monitored.
Personnel monitoring may be performed by quality, microbiology, or
operations personnel providing they have the proper training and supervi-
sion. Personnel monitoring should be performed in an area where it does
not pose a risk to aseptic process operations.

4.15 Clean room design

The use of clean rooms represents a significant contamination control
method. Clean rooms should be designed to be cleaned and sanitized using
commercial disinfectants. Seams, cracks, crevices, and openings where dirt
and contamination can collect but cannot be adequately cleaned or sani-
tized should either be eliminated or sealed. Walls, floors, ceilings, doors, and
other surfaces should be smooth and cleanable. Drains should not be present
in areas where critical aseptic operations are taking place. Access to clean
rooms should be limited to clean personnel and materials. The use of in-
terlocking doors and active air pass-throughs that limit cross contamination
between clean materials and personnel with soiled or compromised materi-
als and personnel should be used. Access to clean rooms should be through
controlled areas using proper technique to decontaminate materials, transfer
carts, equipment, and other items.
Clean rooms should be supplied with HEPA filters with the filter(s) po-
sitioned to adequately cover and protect critical operations. Initially, clean
rooms should be classified and HEPA filters certified to meet certain air
cleanliness and performance standards such as ISO Standard 14644 [13, 14].
Clean rooms should be qualified at rest and in operation to confirm that
they maintain classification during operation. HEPA filters should be cer-
tified to confirm they are integral and perform properly. HEPA filters and
clean rooms should be recertified and re-qualified on a periodic basis to
ensure that they perform at a qualified state and level.