13 
were reviewed at the closed session of the June 1979 RftC meeting. Cn 
October 5, 1979, Eli Lilly received fron the Director, Office of Reconbinant 
Activities, NIH, a letter stating that the Director, NIH, on the recom- 
mendation of the RAC, had approved the Eli Lilly request. Meara^iile Eli Lilly 
had completed construction of a 2,000 liter vessel. A request for permission 
to operate this equipment and for approved, of a process to mamfacture insulin 
via the fermentation of organisms producing proinsulin was made in March 
1980. This request was approved by the Director, NIH, on the reconmendation 
of the RAC and the 2,000 liter vessel began operation in May, 1981. 
During 1979, Eli Lilly announced the capital expenditure of about $40 million 
for plant construction to marxjfacture biosynthetic hunan insulin. Fermentation 
plant design was patterned aifter the 2,000 liter system, with all of the contain- 
ment features employed in the pilot plant inst 2 d.lation preserved. This plant 
has been operating on a routine basis since mid-1981. Environmental monitoring 
has been an integral part of this operation since its inception. Eli Lilly 
now has over 16,000 hours of fermentation ocperienoe with the insulin producing 
E. ooli host-vector systems and various pieces of fermentation equipment greater 
than 10 liters in volune. During this time Eli Lilly has had no breaches of 
containment nor detected any environmental contamination. All systems have 
fvnctioned as designed and pjerformed reliably. 
Dr. Johnson said that nany of the safety features Eli Lilly was currently 
employing were redundant. He said Eli Lilly had instituted many of these 
features because Lilly was the first company to apply reconbinant DNA technology 
to production scale. He suggested many of these safety features could new be 
eliminated. In response Cr. McKinney invited representatives from industrial 
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