SECTION I 
The revisions proposed in this section are appropriately consistant 
with the regulatory process presented in the published "Coordinated 
Framework for Regulation of Biotechnology". The proposal makes it 
clear that duplicative review by Federal agencies is unnecessary. 
SECTION II 
The proposed revisions provide a useful clarification of what 
constitutes deliberate release into the environment. However, it is 
crucial that Appendices M, N and 0 be prepared by those with 
appropriate scientific expertise, published for comment, and 
incorporated into the guidelines in a timely manner. 
SECTION III 
We agree with the conclusions of the RAC working group that certain 
types of experiments in which no foreign DNA is introduced into an 
organism are appropriately not subject to special regulation as 
"recombinant DNA". 
Option 1, to revise the definition of recombinant DNA molecules in 
Section I-B, is preferred; however, to be consistent with section 
III-D-3, the phrase "or different strains of an organism" should be 
deleted . 
SECTION IV 
Commissioner Young of FDA has proposed changes to the guidelines which 
we agree are consistent with production-scale practices utilizing safe 
microorganisms in the pharmaceutical industry. 
We have experience utilizing recombinant B. subtilis , S. cerevisiae and 
E. coli host-vector systems which are exempt from the guidelines for 
small-scale laboratory uses. Once safety has been determined for the 
inserted sequences, the appropriate containment at any scale should be 
based on the biology of the host organism. 
In our experience at production scale (e.g. utilizing the recombinant 
E. coli strain used to produce Protropin), safety characteristics of 
the host-vector system such as infectivity or pathogenicity have not 
been changed in the transition from laboratory to manufacturing. We 
have established a safe record of proceeding from small to large-scale 
production with a variety of microbial host-vector systems and believe 
that the proposed change to the guideline reflects this safety-in-use 
experience . 
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