THE UPJOHN COMPANY 
KALAMAZOO. MICHIGAN 49001. USA 
TELEPHONE (616) 323-4000 
January 25, 1980 
Dr. D. 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 submit herewith the views of The Upjohn Company on the proposed physical 
containment guidelines for large scale uses of organisms containing Recombinant 
DNA molecules. 
We believe the Large Scale Working Group has made a sincere attempt to develop 
physical guidelines for large scale cultures but feel that the proposed 
guidelines do not adequately reflect the reality of present day large scale 
production processes. 
The working group has only recognized two physical containment levels i.e. 
P2-LS and P3-LS. The proposals for P2-LS containment are in a large measure 
desirable and applicable for the scale-up or production of Recombinant 
DNA organism and products which pose a perceived biohazard. There are, 
however, recombinant organisms and products which do not present any perceivable 
biohazard, for example recombinant organisms produced through self-cloning 
or through- cloning DNA from closely related saprophytic organism Ue. 
a streptomycete containing DNA on an indigenous plasmid from another saprophytic 
streptomycete. Thus, the proposed guidelines should provide a category, 
e.£. Pl-LS, which would cover recombinant organism with no perceived 
hazard. One could visualize that the RAC could derate organisms to Pl-LS 
by procedures similar to those used currently to derate the physical and 
biological containment level of recombinant organims. We would further 
propose that Pl-LS be equated to the containment practices of current 
standard large scale fermentations. These would essentially be equivalent 
to the requirements given in the guidelines for PI physical containment levels 
(II-B-l-a through IIB-l-C). 
[ 264 ] 
