-13- DRAFT
APRIL 10, 1985
D. Preclinical Toxicity Evaluation
The specific preclinical testing needs are best addressed on a
case-by-case basis with the appropriate Office. Appropriate animal tests.
which might include those for carcinogenicity, teratogenicity and effects on
fertility may be necessary for a product in which the active ingredient is
radically altered from the natural substance.
VIII. Modified Protein Products
Using recombinant DNA procedures it may be possible to modify the
structure of proteins to enhance their desired biological properties and/or
diminish undesirable ones. Any substance that is not a natural constituent of
the human body may be antigenic and also may cause unknown and possibly
adverse biological effects. The use of such a product in humans depends on a
careful assessment of its new benefits compared to the risks identifiable
during its preclinical and clinical evaluation.
IX. Clinical Trials
Clinical trials will be necessary for products derived from recombinant
DNA technology to evaluate their safety and efficacy.
1
See "Points to Consider in the Characterization of Cell Lines Used to Produce
Biologicals." Office of Biologics Research and Review, Center for Drugs and
Biologics. FDA. (Federal Register, Vol. 49, N0. 110. June 6, 1984).
2
See "Points to Consider in the Manufacture of Injectable Monoclonal Antibody
Products Intended for Human Use In Vivo," Office of Biologics Research and
Review, Center for Drug and Biologics, FDA. (Federal Register, Vol. 49, p.
1138, January 9, 1984).
3
Hochstein. H.D., Elin, R.J., Cooper, J.F., Seligmann, Jr., E.R., and Wolff,
S.M. (1973). Bull. Parenteral Drug Assoc., 27, 139-148.
4
Dinarello. C.A., (1974) "Endogenous pyrogen" in Methods for Studying
Mononuclear Phagocytes, Adams. D., Edelsan, P., and Koren, H., Eds., pp. 629-
639, Academic Press.