GENENTECH, INC. 
COMMENTS ON PROPOSED PART VII GUIDELINES — LARGE SCALE USES OF 
ORGANISMS CONTAINING RECOMBINANT DNA MOLECULES 
LARGE SCALE -P2 LEVEL 
Page 3-VII-B-l-g: We believe that this requirement is too extreme for 
the P2-LS level. Laboratory coats should be adequate. 
Operating staff most frequently leave the area. We 
recommend use of the Laboratory Guidelines II-B-2-a-( 12) 
specification. 
Page 3-VII-B-l-h: The phrase "except as necessary for access" should be 
inserted following the word "closed." 
Page 3-VII-B-l-m: The phrase "or disinfected by validated procedures" 
should be inserted following the word "autoclaved." 
Page 4-VII-B-2-a: The phrase "HEPA filter" should be replaced by 
"filter(s) capable of sterilizing or equivalent 
procedure." This is a case of specifying a means rather 
than a desired objective. HEPA filters may not be the most 
practical means of accomplishing the objective in a 
particular installation. 
Page 5-VII-B-2-b-(4) : The word "disassembly" should be deleted as it 
does not apply to large-scale industrial fermentors, but 
only to small table-top fermentors. Large industrial or 
pilot plant stainless steel fermentors are cleaned and 
steam sterilized in place with no disassembly. 
Page 6-VII-B-3-b : The requirement for "curb or similar architectural 
feature" is highly impractical and unnecessary. Steel 
fermentors do not rupture, explode, or develop huge leaks. 
The probability of such a massive spill is so low that it 
holds exceedingly low risk. To require such a curbing 
would require extensive renovation of existing facilities, 
would be impractical to work around and add almost nothing 
to the physical containment features. In the event of a 
highly unlikely failure of two valves in series, the 
contents of a fermentor can be rapidly disinfected by 
in-place chemical sterilization as needed. To safeguard 
against the spreading of a small leak such as during 
sampling or harvesting of the batch, we recommend adding 
the phrase "or 500 liters of broth, whichever is smaller" 
after the words "total liquid volume." 
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