Pre/Nonclinical Study

Duration

Time

Clinical Study Supported

Safety pharmacology

Toxicokinetic, pharmacokinetic   studies

Single dose acute toxicity or dose escalation study in two species

Local tolerance studies using relevant route of administration

1-3 weeks, depending on kinetic data

14 days

A few hours to several weeks depending on sample and test type

Prior to Phase I.  Information should be available by the time early Phase I trials are completed.

Phase I/II

Repeated dose toxicity studies in one rodent and one non-rodent model

Should equal or exceed the duration of Phase I/II studies: (minimum 2 weeks, maximum 12 months; generally 1-3 months for biotech-derived products )

To support Phase III:
1 month
3 months
6 months

Prior to Phase I

Prior to Phase III

Phase I/II:
2 weeks to
12 months

Phase III:
 < 2 weeks
 < 1 month
 > 1 month

Genotoxicity studies

Variable

Complete prior to start of Phase II and all pediatric clinical trials

Phase I/II
Pediatric clinical trials

Reproductive toxicity studies

(> 1 month-long repeated dose toxicity studies required prior to tests).

Pre-mating treatment interval of 4 weeks for males and 2 weeks for females. 
Continue treatment throughout mating for males and at least through implantation for females.

Collect and evaluate data through two or more generations.

Not required if repeated dose toxicity studies including evaluation of male and female reproductive organs have been done.

Complete all female reproductive toxicity and genotoxicity studies prior to Phase I/II studies.  Pre- and postnatal development study prior to marketing approval.

Complete prior to pediatric studies

Phase I/II (males, and females
not of child-bearing potential)

Phase I/II (pregnant females and females of childbearing potential)

Pediatric clinical trials

Carcinogenicity studies

Variable

Prior to long-term pediatric trials.  Not usually needed unless there is cause for concern. 

Pediatric clinical trials

Juvenile animal safety studies

Variable

When previous safety data are insufficient

Pediatric clinical trials

Supplementary toxicity studies

Variable; dependent on previous toxicity studies

Required if previous findings indicate special concerns