5 
Dr. Barkley thought use of the word "prevents" in Appendix K-II-D was inappro- 
priate. Appendix K-II-D specifies that exhaust gases must be passed through a 
HEPA filter, and a HEPA filter is 99.97 per cent efficient for particles three- 
tenths of a micron or larger. 
Dr. Barkley thought the efficiency limits for processing viable materials under 
.P1-I5 should be of the order of those obtained with laminar flow biologic safety 
cabinets and HEPA filters. Dr. Marsh said particular emphasis was placed in 
early RAC discussions on the reguirement to inactivate the fermentation before 
transfer fran primary containment. The term "primary containment" was inter- 
preted bo mean hard pipe connections between the fermentor and subsequent 
process ina units, and centrifuges had to be contained. 
Dr. McGarrity asked an Eli Lilly representative to describe the facilities 
meetinq the Pl-LS specification as ccmpared to facilities used in conventional 
fermentations. Dr. Marsh replied that under Pl-LS containment the entire 
fermentor system must be closed. The agitator seals must all be double sealed 
and operated under steam pressure. The lines must be welded or a validated 
pressure fitting sealing process must be used. Exhaust gases must be trapped, 
condensed and burned or passed through redundant filters. 
Dr. Mahaffey asked if Eb_ coli had been used in conventional fermentation 
processes. Dr. Marsh replied that several years ago Eli Lilly produced 
I /-asparaginase through FL_ ooli fermentation. At that time Eli Lilly used the 
employee protection procedures utilized in antibiotic production. 
Dr. Mahaffey asked Dr. Marsh to describe the operator protection procedures 
designed by Eli Lilly for use under conventional operation conditions. 
Dr. Marsh replied that Eli Lilly and Ocmpany have operator training programs 
for every process. Training is dependent on (1) the particular process with 
which the operator is involved, and (2) the requirements of the process. 
Dr. William Muth of Eli Lilly and Company said aerosols will be generated at 
two points inside the plant in conventional production facilities: (1) at 
the agitator seal, and (2) in the sampling process. A well-ventilated workplace 
appears to protect the worker as these aerosols are quickly diluted . 
In the case of contained Pl-LS fermentors , the agitator seal is very carefully 
constructed . The seal is a double mechanical seal wdth steam under pressure 
between the two seams. Samples are taken in a closed fashion at Eli Lilly 
facilities. Dr. Muth said aerosols also form out of the vent stack. If a 
thousand cubic feet of air passes into a fermentor, a thousand feet of air 
canes out; this exhaust air is vented cut of the stack. At Eli Lilly air 
vented out of the fermentor passes through a series of four air treatments; 
the lf)12 calculated reduction in organisms is cumulative across the four units. 
Each exhaust filter has a non-sterile side where condensate accumulates. 
Condensate also accumulates during the sample-taking procedure. These conden- 
sates are taken by hard pipe to a condensate collection tank. The condensate 
is sterilized before disposal. 
[ 341 ] 
