It depends on the disease that you want to research. Different animal models work better for different diseases
Hello Priyansha Singh
Preclinical testing or assessment is the interlink between drug discovery (i.e., bench—in vitro, in silico, in vivo—research and development, drug candidate selection) and clinical testing and ultimate availability of the drug product to the patient.
Animals are biologically similar to humans and susceptible to many of the same health problems. Also, they have short life cycles so they can easily be studied throughout their whole lifespan or across several generations.
For selection of animal for preclinical study, please refer to the attached article.
Article Requirements and selection of an animal model
.Best.
Gabriel Silva Marques Borges sir i am working on Portal Hypertension and for the preclinical models i have studied that there are C57BL6 mice, SD rats and Wistar rats being used.
My question is why only these strains we are using
thank you
Hi,
As you said in the question, the goal determines the type of model (pre-clinical). The type of clinical trial determines our choice. The key to the selection is whether the model is relevant. For example, another model we need when you aim to assess absorption by skin tissue only to show the difference between two SC formulations at the absorption phase of the drug which is approved and from 30 years on the market. Another model you need is when your drug candidate will go to First in Human study. Consequently, model/species selection depends on different contexts and could be different depending on future needs:
Which phase of clinical trials should support the model
- Generics bioequivalence trials support
- Biosimilarity assessment support
- FIH only
- phase I only or later phases
- Structure of the study (Time of patients/healthy volunteers exposition on the drug)
- If patients’ - specificity of the disease
The structure of the drug or drug candidate determines the model as well
- Differences between synthetics and biotechnological drugs (immune response)
- Work with transgenic animals
- Work with homologues drug / affinity to target in specific animals
- Specific translational goals related to the mechanism or mode of action
Specific regulatory expectations or development process needs
- For example panel of tox studies, batch comparison etc.
Pre-clinical means before clinical development. In the case of one drug development sometimes numerous models are used in one project across the whole development process good example is a therapeutic monoclonal antibody (Tysabri) where numerous studies were performed across the drug development process:
Single & repeated dose tox studies
(CD-1 mice; guinea pig; juvenile and adult cynomolgus)
Pharmacokinetics after a single dose and repeated dose
(repeated dose tox studies with cyno model)
Toxicokinetics
(Beagle dogs)
Cardiovascular profile after a single dose
(Beagle dogs)
Reproductive toxicity
(guinea pigs; cynomolgus monkeys)
Carcinogenicity
(mice)
PK linearity
(guinea pigs; cynomolgus)
Single dose PK/PD comparability study (different processes),
(cynomolgus)
Single dose bioequivalence study (formulation buffers),
(cynomolgus)
PK comparability between two different stages of drug development
(cynomolgus; guinea pigs)
Interactions with interferon PK/PD study
(Rhesus monkey)
Reference for this example Pharmacology reviews package 1-6:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/125104s000_natalizumab.cfm
And the final conclusion:
“All models are wrong, but some are useful” as said George Box
and my :-)
The answers you want to know are the best factors that describe the model you need.
Best regards
Tomasz
I have just seen this article in Nature:
'US agency seeks to phase out animal testing'
https://www.nature.com/articles/d41586-022-03569-9?&utm_source=hybris_campaign&utm_medium=email_&utm_campaign=animaltesting-index&utm_content=newsletter&sap-outbound-id=A2BCBBDEAA88C66E6264E5C2CB822BCD1DC398AF
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