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Do chronic studies in two species provide significant value in drug development?

Chronic studies in rodent (6 months) and non rodent (9 months) are required for approval of a new drug. Results of these studies are not required until the NDA is submitted, i.e. all the clinical trials are complete. The results of these studies are rarely included in the drug label. Since we generally have subchronic data in two species and long-term exposures in carcinogenicity studies, are the required chronic studies adding to patient safety?
Regulatory and Safety Evaluation
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1
Jesús Rafael Rodriguez Amado
Chronic studies like subchronic toxicity at 14, 28, and 90 days, must be conducted in two or more species or biomodels to provide significant value in the final step of drug development. These are preclinical testing that offer several advantages in drug development:

  1. Predictive Value: Testing a drug in two different species, typically one rodent species (e.g., rats and rabbits) and one non-rodent species (e.g., pork, dogs or horse), allows for a better assessment of its safety profile, select dosage for future studies, and consider possible genetic variation. If adverse effects are consistently observed across both species, it increases the confidence that these effects are likely to occur in humans as well.
  2. Identification of Species-Specific Effects: Some drugs may exhibit species-specific responses due to differences in metabolism, physiology, or genetics. Chronic studies in two species can help identify these variations and distinguish between effects that are unique to one species and those that are more likely to be relevant to humans.
  3. Safety Margin Assessment: Comparing the dose levels at which adverse effects occur in both species to the anticipated therapeutic dose in humans helps in establishing an appropriate safety margin. A wider safety margin indicates a safer drug candidate.
  4. Compliancy of Regulatory Requirement: Regulatory agencies such as the FDA (U.S. Food and Drug Administration) often require chronic studies in two species to assess the long-term safety of a new drug before it can progress to clinical trials.
  5. Identification of Safety Concerns: Chronic studies can reveal potential safety concerns, including chronic toxicity, carcinogenicity, and reproductive effects, which might not be apparent in shorter-term studies.
1
Rajat Sandhir
Many drugs respond differently to different drugs. We have shown that in case of few molecules
1
Jordana Andrade
Yes! Chronic animal studies aim to observe the cumulative effects of repeated daily exposure and carcinogenicity. These are different endpoints than those observed in sub-chronic tests. And the use of different species is important since different species may respond in different ways, and the use of more than one species aims to minimize the failure rate of observing toxic effects. 

0
Mouse Doctor
Yes.  No model system is perfect, thus appropriate testing in two species lends confidence to the results.
0
Mary Ellen Cosenza
The premise is incorrect. Chronic tox studies in two species are required to also support clinical trials of 3-months or longer duration. Carcinogenicity studies are not generally required until the NDA. The data over many years and collected by several expert working groups continues to support the use of two species (one rodent and one non-rodent) for investigation of small molecule drugs. In most cases 6-months is two species is probably sufficient. 
Biologics and other modalities are a different question. 
0
SOUTERRA
Yes, chronic studies in two species provide significant value in drug development by providing a better understanding of long-term effects and safety profiles.
0
Archana
The toxicity of a drug can depend on several factors such as dosage, chemical activity, route of exposure, rate of absorption, detoxification mechanisms adopted by the body, etc. Chronic toxicity studies enable the assessment of the long-term effects of the drug and the use of multiple species can help predict the cumulative toxicity in humans. Since long-term toxicity can arise from the deleterious effects of the drug ultimately causing neurological, or reproductive defects, autoimmune disorders, or other side effects (which may take some time to develop) It is important to study these effects in chronic toxicity in multiple species. 

0
Saira siddique
Yes, it provides because chronic exposure means repeated doses for a specific duration..which not only tells about the protective effects but also the any other side effects of that novel drug. And different species have their own physiology and they behave differently to different drugs ..this species difference experiment also be more  helpful in drug development 
0
Pam Marone
yes, usually, particularly in an appropriate species.

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Created
03/15/2023
Answer Count
9
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7
Creator
David Jacobson-Kram