MEMORANDUM 
DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE 
PUBLIC HEALTH SERVICE 
FOOD AND DRUG ADMINISTRATION 
TO : Dr. Tim Henry, HFY-31 
Office of Health Affairs 
DATE: January 14, 1980 
FROM : Supervisory Chemist 
HFD-140 
SUBJECT: Comments: Containment Guidelines for Large-Scale Uses of Organisms 
Containing Recombinant DNA Molecules 
In answer to your questions as asked on the Transmittal Slip, it appears 
that the Guidelines are compatible with large scale pharmaceutical fer- 
mentation procedures. As to completeness, the comments which follow will 
address this query. The Guidelines are not naive but appear to be ser- 
iously considered and well organized. 
I recommend the following additions and modifications for your considera- 
tion: 
1. All entrances to the production area should be equipped with 
flashing red warning lights which direct attention to the 
universal biohazard sign. This applies to P2-LS Level, page 
2 item VII-B-l-b and P3-LS Level, page 7 item VII-C-1-e. 
2. A statement regarding the use of face masks to protect 
against inhalation of viable organisms is needed. 
3. Additional precautions may be needed under VII-B-l-n and 
VII-C-1-q in the transportation of the durable leak-proof 
container. Although it is sealed, should it not be de- 
contaminated on the outer surfaces prior to transportation 
from the production area? 
4. Under VII-B-3-c and VII-C-3-i the floor drain system should 
be equipped with a removable, leak-proof holding tank in-line 
as an added precaution against contamination of the environ- 
ment. 
5. Under VII-B-2-a and VII-C-2-a the HEPA filter should be autoclave- 
sterilized or incinerated if to be discarded. If not discarded, 
the filter should be autoclave-sterilized before re-use. 
6. There should be a slightly negative air pressure in the operations 
area so that air from outside is drawn in and air inside the 
operations area does not escape when doors or other ports are 
opened. 
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