Page 6 of Attachment B 
Since recombinant DNA fermentation is in the research/production develop- 
ment stage, very few employees are currently involved. The anticipated 
number of workers involved with recombinant DNA fermentation processes 
is expected to be minimal due to the nature of the process and the man- 
power requirements dictated by the system technology. 
DESCRIPTION OF THE PROCESS 
Fermentation processes, including those involving recombinant DNA, start 
in a P-2 or P-3 lab setting as ampoules of culture stored in N 2 which are 
then used to inoculate a shake flask containing the appropriate nutrients. 
After an incubation period the inoculum (the contents of a shake flask) is 
transferred, in a specially designed metal container, to the production 
floor. This container is designed to preclude escape or entry of viable 
organisms during inoculation of the fermentation vessel. Metal fermentation 
vessels used by Lilly for recombinant DNA range in sizes from 10-liters, 
150-liters, or 2000-liters, depending upon the process, stage of develop- 
ment, or stage of culture growth. Culture is introduced into the 150-liter 
vessel or the 2000-liter vessel, by a stainless steel vessel that is steri- 
lizable after transfer of the contents and before the vessel is detached 
from the fermentator, the vessels are charged with nutrients, water, and 
inoculum by closed system design to maintain physical containment. 
The fermentation process is monitored and is terminated by chemical or 
physical means when the harvest stage is attained. Eli Lilly is currently 
using thermal techniques to terminate the process. The batch is then re- 
moved from the fermentor by pressure, and extraction of the desired product 
takes place. The mechanism of extraction may be by centrifugation or lyso- 
genesis, depending upon the nature of the process and the desired product. 
Product extraction operations were not viewed during this visit. 
The fermentor, inoculating device, shake flask and all exposed equipment 
are sterilized with steam after use to prevent contamination of succeeding 
operations and work environment. 
DESCRIPTION OF INDUSTRIAL HYGIENE, SAFETY, AND MEDICAL PROGRAMS 
Safety and Heal th 
The company has a well organized safety and health program that is steered 
by the Corporate Safety and Health Committee and the Department of Industrial 
Health and Safety. Safety representatives are located at each site to mon- 
itor the work practices of employees. Periodic safety and housekeeping 
inspections are made in each plant by the plant safety representatives and 
a member of line supervision. Departmental and divisional safety committees, 
with rotating memberships, meet monthly for review of safety and/or health 
issues and to make recommendations. 
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