Or. Donald S. Fredrickson 
Page 2 
November 29, 1979 
because of laboratory scale convenience and not risk. The RAC 
recognizes experiments at the PI level and is considering host 
vector systems at the HVO, EKO level. At the September 6-7, 
1979, meeting the RAC recommended exclusion of all E. coli K12 
experiments (excluding over 10L) from the 'Guidelines. In view 
of these considerations and in view of the physical reliability 
and stability of large-scale fermentation equipment .it is 
inconsistent to recognize only two levels of physical contain- 
ment (P2-LS and P3-LS). This clearly fails to recognize the 
containment of the vessel itself which may be superior to the 
containment features added by the laboratory environment of 
either of those categories. We believe there should be at 
least three containment levels, i_.e. , Pl-LS, P2-LS, and P3-LS. 
Since a number of criteria put forth by the Working Group 
on physical containment Guidelines clearly reflect some lack of 
experience, knowledge and perception of operation and 
reliability of modem large-scale fermentation equipment, we 
strongly urge and recommend the appointment of an industrial 
advisory group reflecting the appropriate experience. A model 
and precedent for such a group can be found in the GMAG organi- 
zation in the U.K. The availability of such a group as a tech- 
nical advisory resource should be available to or represented 
on the RAC as we move towards large-scale experiment, develop- 
ment, and production utilizing recombinant organisms. 
In addition, we would make the following specific comments 
on the draft: 
p. 3 — VII-B-l-g — We feel’ laboratory coats should meet 
this requirement at the P2-LS level. Operators 
have to leave the area for meals, visit restrooms, 
etc. 
VII-B-1-1 — Validation of procedures should be 
adequate for demonstration of the inactivation of 
the organisms. Delete that part of the last 
sentence beginning with the word ’’inactivation" 
and replace it with "validated procedures for 
inactivation of the organisms have been employeo". 
P* A — VII-B-2-a — HEPA filters need not be designated; 
We recommend insertion of "filters capable of 
sterilizing or equivalent procedure". In some 
cases incineration should be considered. HEPA 
filters are fragile, will not hold up to steam 
sterilization, etc. The RAC has already approved 
units with equivalent- filters. 
[ 244 ] 
