4 
Dr. Max Marsh of Eli Lilly arri Company told the working group Eli Lilly was 
proposing this modification as the organisms listed in Appendix C do not pre- 
sent significant risks to the operators or to the environment. Dr. Marsh 
said the cost of the equipment required to achieve ccmplete containment, as 
currently required by Appendix K, is significantly higher than the cost of 
equipment normally used in fermentation. Thus, there is a processing and an 
economic advantage in not requiring absolute aerosol containment in large-scale 
operations using these organisms. He emphasized that each manufacturer would 
be liable for any effects associated with its product. 
Dr. Marsh said the Eli Lilly and Company would use discretion in determining 
containment conditions . If a gene product were highly toxic, tight containment 
would be employed to protect the operators . 
Dr. Marsh suggested that a fourth containment category, Pi-Exempt Large-Scale 
(Pl-ELS ) might be introduced to apply to organisms listed in Appendix C. 
Alternatively language permitting seme flexibility in the interpretation of 
Pl-LS might be added to the Guidelines. 
Dr. Marsh said the data Eli Lilly and Company had supplied in support of their 
proposal show that aerosolization of EL_ coli K-12 in a production atmosphere 
is minimal under deliberate spill conditions; e.g., there is no major contami- 
nation of the environment or the atmosphere in the vicinity of the production 
process . 
Dr . Gerard McGarrity pointed out that these data were generated using an E. 
coli K-12 host-vector system. The proposal, however, requests modification 
of Pl-LS conditions as applied to cerevisiae and asporogenic EL_ subtilis 
host- vector systems as well as to E. coli. 
In addition. Dr. McGarrity thought the language of the proposal was vague. He 
preferred that the proposal specify the procedures to be modified. 
Dr. Emmett Barkley of the NTH Division of Safety, vho had helped to draft 
Appendix K, said Pl-LS conditions were not intended to require absolute contain- 
ment. Indeed, it was envisioned that under Pl-LS viable materials would in 
seme cases have to be processed outside of the primary fermentation vessel. 
For this reason, Appendix K-II-A states that the material shall be handled in 
a closed system or other primary containment equipment and the word ''minimized'' 
indicates that absolute containment is not required at that step. He felt 
the language describing Pl-LS is flexible with the exception of the word 
"prevents" in Section K-II-D. Appendix K-II-D specifies that: 
"Exhaust gases removed from a closed system or other primary containment 
equipment shall be treated by filters vhich have efficiencies equivalent 
to HEPA Filters or by other equivalent procedures (e.g., incineration) to 
prevent the release of viable organisms containing reccmbinant ENA mole- 
cules to the environment." 
[ 340 ] 
