Page 41 of Attachment H 
FOR THE RECORD 
3. 
seal. The fermenters are designed Co permit withdrawal of samples through 
a closed system. A variety of sensors attached to each fermenter permit 
remote monitoring of operating conditions at a central station. Both 
visual and printout records are available. 
The establishment of the integrity of the containment features of the 
fermenters and the development of certain basic production processes are 
accomplished with a non-debillitated strain of the host organism to be 
utilized in production. 
Other Facilities 
In addition to the foregoing we were provided a tour of large scale 
facilities that are utilized for the production of antibiotics. In 
relation to the production of recombinant DNA materials these facilities 
would probably be suitable for the production of organisms requiring PI 
level containment at the laboratory level. 
The use of the facilities for P2 level work would probably require some 
modification to the equipment to accomplish control of aerosols which 
could be released to the environment through penetrations, e.g., shaft 
seals, exhaust vents and etc. in the fermentation equipment. For pro- 
cesses which would require manipulation of the viable organism outside 
the fermenter, a closed system would be required. However, neither the 
need for modification nor development of closed systems would appear to 
present a significant problem. 
Discussion 
Subsequent to the tour of the facilities there was a discussion of the 
draft (November 14, 1979) guidelines for large scale production of 
organisms containing recombinant DNA molecules. 
In addition to the comments previously provided, Eli Lilly urged. that 
guidelines governing conditions for production of organisms requiring 
PI level containment be included. They felt it reasonable to project 
that production efforts would be accomplished at the lowest permissible 
level of containment and that modifications to existing equipment, C&, g- , 
elimination of bottom penetrations, control of exhaust gases, sealing of 
shaft penetrations) would not present a significant problem. 
It was also noted that conduct of production at the lowest permissible 
level of containment would contribute to the development of large scale 
recombinant DNA production technology by minimizing the need for exten- 
sive redesign of existing equipment. 
[477] 
