Ch. 7— The Use of Animals in Testing • 159 
The safety of an additive is established by evalu- 
ating data from combinations of tests. The amount 
of testing that must be performed is determined 
by the amount of information already available 
and the degree of toxicological concern. Guidelines 
have been developed {Toxicological Principles for 
the Safety Assessment of Direct Food Additives 
and Color Additives Used in Food (56), known as 
the Red Book) that contain detailed procedures ade- 
quate to meet minimum requirements. However, 
manufacturers are permitted to modify the test- 
ing as they deem necessary as long as the data are 
equal to or better than what would be derived by 
using the guidelines. 
Food safety has been important to FDA since the 
early 1900s. However, the use of animals to test 
food additives was not begun until the passage of 
the 1954 Pesticide Chemical Amendments and the 
1958 Food Additive Amendments. The most fa- 
mous amendment, sponsored by Delaney, required 
that any additive that induces cancer in animals 
or in humans be banned. 
Drugs for Humans 
FDA regulates all human drugs, including bio- 
logical ones. The 1938 amendments of the Federal 
Food, Drug, and Cosmetic Act require drug man- 
ufacturers to submit evidence to FDA that a new 
drug is safe prior to commercialization. Safety 
evaluations are primarily based on preclinical ani- 
mal testing and subsequent clinical testing in hu- 
mans. In 1962, amendments to the act required 
that the effectiveness of a new drug also be dem- 
onstrated, and this is accomplished through clini- 
cal testing. 
The requirements to use animals to test new hu- 
man drugs depend on the proposed scope of clini- 
cal investigation and on the drug’s anticipated use. 
Determining the best procedures for testing is com- 
plex because of the variation that exists in the use 
and activity of drugs. Testing must be tailored to 
each drug and specific requirements are deter- 
mined by considering the route of administration, 
the target population, the length of treatment, and 
the relationship of the drug to others already in 
use. In addition to the formal procedures required 
under the Good Laboratory Practices regulations 
(see ch. 13), guidelines are available to aid manu- 
facturers in designing test protocols. Manufac- 
turers commonly discuss their programs with FDA 
before and during testing, as well as afterward. 
Guidelines are available for tests required for 
drugs intended for oral, parenteral, dermal, inhala- 
tion, ophthalmic, vaginal, and rectal uses, and those 
used in combination. Duration of proposed human 
administration is a major factor for determining 
the particular animal test species, the number of 
animals, and the duration of the test. 
Biological products— any virus, therapeutic se- 
rum, toxin, antitoxin, vaccine, blood, blood com- 
ponent or derivative, or allergenic product used 
to prevent, treat, or cure human diseases or in- 
juries— are regulated under the Public Health Serv- 
ice Act and the Federal Food, Drug, and Cosmetic 
Act. As with drugs, before a new vaccine or aller- 
genic can be marketed, the manufacturer must 
provide test data to show that the product is safe 
and effective. FDA’s Center for Drugs and Biologies 
licenses the product and the manufacturing facil- 
ity . For some products, tests are performed on each 
batch to assure that standards of potency and 
safety are met prior to release. For most of these, 
requirements are specified in the Code of Federal 
Regulations . 
Food and Drugs for Animals 
Food for pets, food -producing animals, and any 
other animal is subject to the same basic regula- 
tory requirements as food for humans, with the 
addition of testing in the target species. 
The Federal regulation of animal drugs, medi- 
cated feeds, and feed additives began under the 
1938 act. The 1968 Animal Drug Amendments con- 
solidated animal food and drug laws, keeping the 
1962 standard for safety and effectiveness. The 
basic intent of these statutes and their resultant 
regulations is to avoid using substances that may 
leave harmful residues in animal products intended 
for human consumption, and to avoid harm to 
food-producing and other animals. 
FDA regulates all animal drugs except those 
derived from living matter (biologies), which are 
regulated by USDA. Animal drugs may not be mis- 
branded or adulterated. Testing is done to sub- 
stantiate labeling claims and to prove safety. A "new 
