Attachment IV - Page 28 
— 6 — 
DRAFT 
NOVEMBER 7, 1983 
V. Production 
The cell* used In each production run should be characterized by analysis 
of relevant phenotypic or genotypic markers, and tested for adventitious agents 
In samples taken Just prior to termination of culture. 
The procedures and materials used for cell grovth and Induction of 
product expression should be described In detail. 
Data on the consistency of yield of the product from full-scale culture 
should be maintained, and criteria for the rejection of culture lots should be 
established . 
Penicillin and other beta-lactam containing antibiotics should not be 
used In production runs. 
VI. Purlf lcatlon 
The methodology of harvesting, extraction, and purification should be 
described In detail, and the removal of any toxic chemicals Introduced by these 
procedures should be demonstrated. 
The extent of purification of recombinant DNA products should be 
consistent with the Intended use of the product. Blologlcals which are to be 
administered repeatedly or at high concentrations should be adequately pure to 
prevent the development of undeslred Immune or toxic reactions to contaminants. 
Although recombinant DNA products may be demonstrated to be 99Z pure by 
physicochemical characterization, special attention should be directed toward the 
removal of certain contaminants which may be present In small amounts. The 
purification process should specifically eliminate undesirable antigenic 
materials and detectable viruses, microbial contamination and nucleic acids. 
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