Attachment IV - Page 34 
-12- DRAFT 
NOVEMBER 7, 1983 
dose. Theoretical concerns regarding transforming DNA derived from the cell substrate 
will be minimized by the general reduction of contaminating nucleic acid. 
4 . Antigen Contamination 
Products which are administered repeatedly and/or in large doses 
should be assayed for trace antigenic constituents likely to contaminate the final 
product. Tests such as Western blots, radioimmunoassays and enzyme-linked 
immunosorbent assays using high affinity antibodies raised against ho6t cell 
lysates, appropriate subcellular fractions or culture medium constituents, should be 
used to detect contaminating antigens. Such methods can provide sensitivity in the 
range of 1 to 100 parts per million. Because the detection of antigens will be 
limited by the specificity and sensitivity of the antisera used, these Immunoassays 
will complement but not replace silver stain analysis of SDS-PAGE gels. Patients 
given large or repeated doses of a product should be monitored for the production of 
antibodies to potentially contaminating antigens. 
5 . Microbial Contamination 
Tests for microbial contamination should be conducted using 
prescribed sterility testing procedures. Absence of bacteria (aerobes and anaerobes), 
fungi, yea6t and mycoplasma in the final product should be demonstrated. 
D. Toxicity tests in animals 
A recombinant DNA product that is demonstrated to be identical to a 
natural substance for which the pharmacology and toxicology data are already developed 
will generally not be required to undergo all the animal toxicity tests normally 
carried out in the evaluation of a new product. Any recombinant DNA product 
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