12 
that heat distribution within such ccnplex systans is not as straight- 
forward as it might appear. Ihese studies led to changes in fermentor or 
piping designs. In addition to temperature measurements, validation was also 
concerned with the cverall reproducibility of the inactivation processes. 
Ihe interacticMi between the fermentor operator, the equipment, the corputer, 
and the procedural protocol was observed to determine if these ccmponents 
ccnplemented each other and insured inactivation reproducibility. 
ar. Mith said standard medical surveillance is available to all Eli Lilly 
employees, but is nandatory for all employees involved in any phase of reccm- 
binant ENA projects. It includes an annual physical examination, blood analysis, 
urinalysis, chest x-r^, height, weight, blood pressure measurenents, general 
health questionnaire, an audiogram and an E3^G. In addition, a baseline serum 
sarple is prepared from each recombinant ENA worker and frozen in liquid nitro- 
gen. Additional tests are required if an individual is exposed to a significant 
breach of containment, but a containment breach has never occurred. Operators 
must r^»rt all illnesses and are not allowed to work with viable organisms 
v^ile c*i ary type of antimicrobial therapy. 
E)r. Muth then described Eli Lilly's first sitmission requesting exception 
to the 10 liter prohibiticxi. He said the sutmission contained; (1) a descrip- 
tion of the E. coli host and plasmid, (2) the design, test data, and validation 
results for 150 liter fermentors, (3) detailed operator protocols, and 
(4) risk assessment studies involving the feeding of reconbinant organisrvs to 
genm-free animals. Also described was the method of chemical inactivation 
of the microbial population at the end of each fermentation run. The data 
[498] 
