GENENTECH, INC. 
460 POINT SAN BRUNO BOULEVARD 
SOUTH SAN FRANCISCO, CALIFORNIA 94080 
(415) 952-0123 TWX: 9103717168 
6 February 1980 
Dr. Donald S. Fredrickson 
Director, National Institutes of Health 
Room 124, Building 1 
National Institutes of Health 
Bethesda, MD 20014 
Dear Dr. Fredrickson: 
Re: Proposed Part VII - Physical containment guidelines for large 
scale uses of organisms containing recombinant DNA molecules as noted in 
44 FED. REG. 63074 (Nov. 1, 1979). 
We are pleased to submit our comments on the proposed physical Guidelines 
for the large scale fermentation of organisms containing recombinant DNA 
molecules. Genentech has made two separate requests for approval for 
large scale developmental production of such microorganisms under 
existing Guidelines. As we anticipate continually making further future 
requests for new plasmids, Genentech is concerned that the Guidelines be 
not only effective from a safety aspect but also be practical in daily 
operation. 
Our detailed comments on specific sections of the proposed Part VII 
Guidelines are attached. From a broader perspective, we offer the 
following suggestions for consideration. 
o 1. The proposed Guidelines for large scale recombinant 
fermentations are an extension of the existing Laboratory 
Guidelines and continue the misconception that larger volumes 
imply larger risks. 
Discussion: Large scale fermentations a priori present no more potential 
risk than smaller scale laboratory fermentations of recombinant 
organisms. In fact, one 400 liter fermentation in a well designed and 
operated stainless steel fermentor is much safer than using one glass 
four-liter flask on a shaker platform. 
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