Page 9 of Attachment C 
A registry of all workers employed with recombinant DNA process 
should be established and maintained for reference to determine 
any abnormal medical problems or unusual occurances that someday 
may be attributed to recombinant DNA processes. NIOSH has had 
considerable experience in designing and maintaining such worker 
registries and can thus provide assistance in design, imple- 
mentation, and logistical requirements. The comparability of 
individual company registries is desirable for optimum and 
successful surveillance on an industry wide basis. 
Biological monitoring of worker body fluids for specific organ- 
isms carrying recombinant DNA molecules is costly and technically 
.demanding. Quantitative and qualitative sampling of air and sur- 
faces in the production and laboratory areas can be an effective 
measure of sanitation, environmental conditions, and efficacy 
of control measures. Environmental sampling programs have been 
utilized in hospitals, the food industry, and containment labor- 
atories for years and the principles of these programs are ap- 
plicable to the operations at Genentech. The efficacy, sensi- 
tivity, and accuracy of environmental sampling and analytical 
techniques should, however, be considered and their validity must 
be established prior to utilization. The procedures analysis, 
sampling points and sampling schedules, thus established, should 
be formalized in writing. 
Containment controls could be enhanced by designing an unbreakable 
inoculating device for large fermentors. It should be capable of 
being sterilized after inoculating but prior to detachment from the 
fermentor. The presently used shake flask method of inoculating large 
fermentors is unwieldy and provides potential for exposure by acci- 
dental breakage, spillage, or aerosol production during detachment 
from the fermentor. Replacement of the glass 10-liter fermentors with 
metal cased ones would also preclude' accidental exposure due to 
breakage of the glass. Repositioning of the agitator drive and seals 
from the bottom of the fermentor to the top should be evaluated. This 
may facilitate better engineering design and ease of maintenance. A 
leaking seal, in the bottom of the fermentor, could allow drainage 
of culture liquid resulting in a substantial exposure. 
Physical containment of the fermentation process, up to and including 
inactivation of the culture is mandatory. Physical containment of the 
biological material within a closed system should, preferrably, also 
extend through the cell lysis and product extraction phases. Capital 
investment for this now would not only enhance production aspects but 
also would minimize potential for worker exposure to products. 
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