In our view the P3-LS provisions are probably unnecessary. Any process being 
scaled up in large fermenters or being put into actual production should be 
engineered into safe hosts and sufficiently characterized to allow derating 
to P2-LS or Pl-LS containment conditions. 
A number of the proposed laboratory practices advocated by the Working Group 
on large scale physical containment guicOines clearly illustrate the lack 
of experience , perception and knowledge of large scale fermentations. We 
feel that a meaningful understanding of the operation, design and reliability 
of modern large scale equipment is necessary and strongly recommend that 
an industrial advisory group with the appropriate experience be appointed to 
assist in this task. 
In addition, we would specifically recommend the following changes in the 
proposed laboratory practices for P2-LS. 
p. 3 -- VII-B-l-g. We feel appropriate laboratory coats should meet con- 
tainment needs as long as they are not worn out of the production 
facility. 
VII-B-1-1. We feel that material from fermenters should be trans- 
ferable to other facilities if validated procedures are followed 
for inactivation of organisms. 
VII-B-l-m. We are unclear as to the meaning of the phrase "...prior 
to processing for reuse." If a fermenter is to be reused immediately 
is it necessary to sterilize the tank empty before a fresh fermentation, 
medium is added and sterilized? 
p. 4 -- VII-B-2-a. We recommend inserting "viable" in the phrase "...proce- 
dures involving viable organisms containing recombinant DNA molecules." 
Also, HEPA filters should not be specified, as other filters with 
more desirable properties are available which accomplish the desired 
objective. 
p. 5 -- V I I- B-2-b- ( 2 ) . We feel that the "integrity of containment" can be 
recognized and monitored by a number of sensing and monitoring 
devices and that use of the term "observation" may be too narrow and 
restrictive. 
V I I-B-2- (4 ) . To talk about disassembly of large scale fermentation 
equipment does not convey an understanding of the design, construction 
and operation of such equipment. We recommend deletion of "disassembly," 
i_.e _. — facilitates cleaning and maintenance to assure integrity 
of — . 
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