Page 6 of Attachment C 
the 600-liter (metal) and 10-liter (glass) fermentors. Single pass 
ventilation, negative air pressure in the room, floors sloped to 
drains in order to contain large spills, and controlled entry are 
additional features not required by N1H for Pl-LS. Non-porous and 
readily cleanable walls, floor, and ceiling are also planned. However, 
several problems exist in the production area that may possibly be 
corrected when the program requirements are achieved. 
The production' room is immediately adjacent to high traffic areas and 
the public reception area of the facility. This problem is compounded 
by a "fire door" (opens into the room) that accesses into the hall- 
way from the public reception area. The door was locked and only 
openable from inside the production room. Sloped floors have been 
installed in the room, yet none of the access doors had thresholds. 
Feasibly a large spill could flow under the door. 
The integrity of the containment design may be compromised by the 
10-liter fermentors being glass, the shake flask method of innocula- 
ting the large fermentor, and the agitator drive and seals of the 
600-liter fermentor being bottom-mounted. 
Engineering Controls 
The ventilation systems, fermentor exhaust gas filtration, waste pro- 
ducts control, biological safety cabinets, access barriers, and all 
interior room surfaces in the P-3 and P-1 laboratories with the NIH 
guidelines. 
The NIH guidelines for the Pl-LS containment level do not require 
specific ventilation measures or distinct room confinement. Genentech 
has added these features to their production area. Exhaust gases pass 
through a ceramic filter and then an incinerator. Air entering the 
system also passes through a ceramic filter. 
Sterilized liquid wastes from the fermentation system are drained to 
the public sewer. None of the process materials are recycled or 
treated (other than sterilization by live steam or addition of the 
chemical killing agent) prior to disposal. Solvent and radiation 
wastes are handled separately and are not disposed of in the public 
sewer. 
Validation Procedures 
The sterilization process is validated for thorough activity an- 
ually. Steam sterilization effectiveness is checked during each batch 
with indicator crayons or strips. These indicator methods only de- 
pict, at best, if the required sterilization temperature was reached 
at a given location. They do nof identify areas of the system that 
may not have been thoroughly sterilized. 
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