organisms. It is important that preparation and publication for 
comment of Appendices M, N and 0, respectively, be completed 
quickly . 
Section III 
Of the two options that are presented. Option 1 is preferred 
because modification of the definition of rDNA assures that 
exemption from special rDNA regulation will be applicable 
throughout the research process and not only in the "deliberate 
release" portion of the research. 
Within Option 1, insertion of the word "foreign" in the 
first paragraph of Section 1-B of the guidelines is appropriate, 
as proposed. In the proposed footnote, the phrase "or different 
strains of an organism" should be deleted in order to avoid 
confusion with Section III-D of the guidelines. The remainder of 
the proposed footnote is appropriate as written. 
Section IV 
The proposed revisions described in this section are highly 
important clarifications of the guidelines for rDNA research and 
will provide appropriate consistency of policy and practice 
throughout the research process. Furthermore, the proposed 
revisions represent the consensus of both the primary 
pharmaceutical regulatory agency and the industries that are 
representative of pharmaceutical research using these techniques. 
Specific comments relevant to the proposed changes in Section IV 
are: 
1. Prior to proceeding to large-scale studies, an 
evaluation will already have been completed wherein the 
particular host-vector and vector-construct system has been 
demonstrated to present no significant safety issues and is 
deemed exempt at small scale. Once the safety has been 
determined for the inserted sequences the appropriate 
containment at any scale is based on the biology of the host 
organism. 
2. While existing guidelines indicate that "some latitude" 
in the application of BL1-LS requirement is permitted, of 
the five pharmaceutical products already on the market, none 
of the products’ sponsors utilized the "some latitude" 
provision, but used BL1-LS containment in large-scale 
experiments. This suggests that in actual practice local 
IBCs are reluctant to take the lead in using the "some 
latitude" provision. Hence, these IBCs require more 
specific guidance from the NIH RAC. 
3. The pharmaceutical industry has a long and distinguished 
record in fermentation techniques, and member companies will 
be submitting documentation of their individual histories in 
this field. The industrys' experience with E. Coli , B. 
subtilis and Saccharomyces cerevisiae is not as extensive as 
it is with some other host organisms, but in the time the 
Recombinant DNA Research, Volume 1 1 
[ 281 ] 
