11 
Dr. Muth then showed slides of some of the equipment employed in the fe menta- 
tion process: closed stainless steel vessels, designed, built and tested to 
canply with pressure codes, modem corfxjting instrumentation monitors, etc. 
Dr. Hjth said antibiotic fermenters are designed prinarily to exclude cont 2 ni- 
nating organisms. In ccmpliance with the NIH Guidelines, these fe men tors 
were adapted to contain the fermentation organ isns as well as to exclude 
con tamina tors. Fermentor containment could be attained by altering standard 
antibiotic fermentors by (1) filtering or incinerating all exhaust gases, 
(2) installing pre^r agitator seals at the junction in the agitator shaft, 
(3) instituting proper sampling and inoculating procedures, and (4) chemiccQly 
or thermally inactivating the fermentor contents prior to processing. Other 
aspects of the procedure requiring greater scrutiny were: (1) ervironmental 
containment monitoring, (2) development of detailed written procedural 
protocols, (3) training of fermentation personnel, and (4) validation of 
the canplete system. 
Dr. Mjth said e^vi^onment^d contaionent monitoring is performed contiruously 
and consists of microbiological sampling of the exhaust air systems after 
filtration, sampling of the operator envirorment, and integrity testing of 
the exhaust filter system. More than 5,000 enviromental seirples have been 
taken through May, 1982. No reconbinant IKA containing organises have been 
detected. Cr. MJth said the fermentation broth is tested after each chemical 
and thermal inactivation procedure. In addition the entire system was validated 
to show that the fermentation microbes had been inactivated. For example, 
%*ien thermal sterilization was anployed, the tanperature at multiple points 
was measured throughout the fermentor and its processing lines. It was fotnd 
(497] 
