What are DART studies?
DART, or Developmental and Reproductive Toxicology, studies assess critical information about drug exposure effects before and during mating, and evaluate maternal and fetal changes during gestation, identifying any alterations in the development of the progeny following birth. In essence, these studies elucidate the toxicity effects of the compound in question.
Why are the challenges of assessing risks by toxicity?
Depending on when the exposure takes place, different organs or aspects of development may be affected and these periods of time are the critical periods of susceptibility. Toxicants can be made up of various agents initiating a wide variety of mechanisms in the body. They may also affect only certain populations, based on genetic differences or varying health histories. The potential mechanism of action of the toxicant must be understood at many levels of the biological organization (pathways, cells, etc.) to truly understand the overall processes of developmental toxicity.
How are DART studies different from general toxicology studies?
DART studies are not separate from different from standard toxicology in that they have the same application of toxicological principles such as toxicokinetics (TK), pharmacokinetics (PK), ADME, and other such parameters. There is however special emphasis on the timing and duration of exposure, dose level, and the consequence on the mother and fetus both.
Why are DART studies essential?
DART studies assess information about how exposure to a drug effect different developmental stages. Such altered development may be manifested as death, malformation, growth retardation, or functional deficits. FDA guidance recommends certain international standards for the harmonization of the assessment of nonclinical developmental and reproductive toxicity testing and deems that these studies are required before human clinical trials and marketing authorization. In order to initiate clinical trials for women of child-bearing potential (WOCBP), the FDA requires the initiation of preclinical developmental and reproductive toxicology (DART) studies using mammalian research models.
What is the typical DART program?
The typical species for DART studies include rats and rabbits via multiple routes of administration but other research models are also available for DART, such as mouse, hamster, dog, minipig, and monkey. There are a few types of DART studies and each focus on studying a different phase of the developmental process:
- Fertility and Early Embryonic Development (FEED) study (Segment I) evaluates the effects on mating, estrous cyclicity, spermatogenesis, and ability to produce a viable implant. At Frontage, we assess sperm count, motility, and morphology are assessed using a Hamilton-Thorne Analyzer.
- Embryofetal Development (EFD) study (Segment II) demonstrates the effects of gestational exposure on the pregnant female and the developing fetus during the organogenesis period. This study evaluates fetal development and survival.
- Pre- and Post-natal (PPND) study (Segment III) quantifies the effect of gestational and lactational maternal exposure on embryonic development, the process of parturition, and the development of the offspring.
For more information on the dosing parameters, definitive study details, and study timelines, watch our webinar: Guidelines for Developmental and Reproductive Toxicity (DART).
When should we conduct DART studies?
The EFD and FEED designs can be run in parallel and are generally required for Phase 2 Clinical Trials. PPND studies are usually required for Phase 3 Clinical Trials but can be done earlier if needed.
A Partner for DART Studies
Choosing a CRO like Frontage offers you access to highly trained expert scientists with a long history of successfully performing specialized toxicology studies, including regulated DART studies. At Frontage, we offer single and multi-generation studies and have the capability to conduct DART studies following the ICH S5 (R3) Guideline. Request a quote for a DART study.
- Developmental and Reproductive Toxicology: A Practical Approach (Third Edition) by Ronald Hood