Page 8 of Attachment B 
DESCRIPTION OF PAST EXPOSURES 
Data on exposure of employees during fermentation processes with organisms 
containing recombinant DNA are limited to the results of the environmental 
monitoring previously mentioned and the medical surveillance program Eli 
Lilly has implemented. No quantitive data are available to document 
range or incidence of exposure. The company voiced concern about the 
practicability of the methods currently used for environmental monitoring, 
yet recognized the need for such monitoring. 
EVALUATION OF THE PLANT AND PROGRAMS 
Laboratory and Production Facility Design 
Physical containment laboratories at the P-2 and P-3 level of containment 
used for research and development of recombinant DNA techniques were toured. 
These were well designed and were basically operated within the NIH Guide- 
lines for Recombinant DNA research. A P-3 level laboratory utilized for 
research and shake flask fermentation was toured; no apparent problem 
areas were noted. A P-2 laboratory with 10-1 iter fermentors and bench- 
top continuous culture apparatus (being readied for operation) housed 
work concerning 1 aboratory-to-product ion development. 
The equipment specially designed for large scale growth of recombinant DNA 
organisms was housed in two locations. A room, separated by a partition 
from a conventional pilot fermentation area, housed modified 150-liter 
fermentors. A Pl-LS (large scale) area with a 2000-liter fermentor, modi- 
fied to contain recombinant DNA organisms will be used for production 
development and production of clinical trial material. This fermentation 
system was still in the developmental phase, and undergoing sterilization 
validation procedures, at the time of this survey; fermentation with recom- 
binant DNA work is not housed in a distinctly confined room, but is in 
a pilot production area in immediate proximity to conventional fermentors 
of the same size. Access to the tops of the fermentors is by a single 
stairway and catwalk. Descriptions of fermentor modifications may be 
found in the following section and appendix 1 of this report. 
Engineering Controls 
As with other fermentation processes the concept of containment is not 
only to prohibit escape of organisms from, but also to exclude entry 
into the system. Thus, the engineering design and measures implemented 
by Eli Lilly to achieve the dual aspect of containment are quite sophis- 
ticated. This attention to process integrity and thus, effective control 
for personnel exposure demonstrates the level of containment that Eli Lilly 
attempts to maintain with recombinant DNA fermentation processes. Because 
of the design of this large scale operation, it is possible that more 
risk for worker exposure to recombinant DNA organisms (e.g. from acciden- 
tal spillage or aerosol production) would occur in the shake flask labora- 
tory than on the production floor. 
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