Dr. William J. Gartland, Jr. 
January 22, 1987 
The host microorganisms, E^_ col i K-12, Bacillus subtilis and 
Saccharomyces cerves iae have been safely used at both laboratory 
and production-scale levels for many years. Recombinant 
derivatives of these organisms have been demonstrated to be safe, 
resulting in the exemption from the Guidelines for certain 
laboratory uses. The safety consideration of recombinant 
microorganisms are the same regardless of whether they are being 
used under laboratory conditions or for the large-scale production 
of cloned gene products. Biological containment is already 
inherent in these host-vector constructs. 
Under the provisions of Appendices C-II, C-11I, and C-IV; 
IBC's are required to set containment conditions when culture 
volumes greater then 10 liters are being employed. The NIH 
Guidelines suggest that where appropriate conditions outlined in 
Appendix K should be followed. However, a certain flexibility is 
given to the 1BC in the three Appendices under consideration in 
this proposal. Unfortunately, the present wording is ambiguous and 
IBC's have been reluctant to interpret the term "some latitude" in 
a meaningful way. This has complicated strategic planning at those 
companies where facilities to scale-up production are being 
designed. As a result, all of the pharmaceuticals approved by FDA 
are produced at BLl-LS, the most restrictive containment option for 
the two organisms used as hosts. 
Dr. Young's proposal would establish criteria for facility 
design which IBA believes is entirely appropriate. This would give 
to the IBC's a continuum of containment options to consider. It is 
important to remember that those products that are produced by the 
commercial sector are all regulated by an appropriate federal 
agency such as EPA or FDA. The product review requires a thorough 
assessment of the manufacturing process and the regulatory agency 
must be satisfied that the containment conditions for production 
are safe and environmentally sound. Historically, these regulatory 
agencies have looked to the NIH-RAC to provide expert advice on 
scientific questions about recombinant DNA research. IBA believes 
that NIH-RAC approval of this specific proposal would be in keeping 
with that advisorial role. 
IBA hopes that these comments are useful to NIH-RAC as they 
deliberate on these issues. 
Sincerely , 
Recombinant DNA Research, Volume 1 1 
[285] 
