When it comes to designing a GLP safety study for a medical device or process, selecting the appropriate animal model is one of the most critical elements.
The challenge is that no animal matches the human anatomy. Dogs, pigs and sheep are quadrupeds, while humans are bipeds. Our shapes and sizes differ, as do our cardiac and vascular systems, along with our other anatomy. So the choice of animal model often must come down to some key considerations:
- precedents from previous research
- size of animal model, and the ability to implant the device in the correct location
- whether the animal model shares characteristics in their anatomy that are representative of the target human population.
Occasionally, a client or scientist’s personal preference can influence the decision. But the GLP safety study is always designed with the end in mind: present the data for regulatory review that shows the device or procedure development is ready to proceed to a well-designed human trial.
Here’s a look at some of the considerations for animal models in preclinical testing.
Precedent can be a useful guide not only in designing a study, but can also aid in the regulatory review process, because it lets the FDA perform a direct comparison to previous research results. During the design and selection process, the team will conduct a comprehensive literature search of PubMed, NCBI, Toxline and DTIC, so they can review previous research and learn whether a non-animal alternative exists.
Size of the animal model relative to device
Size matters in choosing the right animal model. The animal-to-human relationship, the size of the medical device, and the ability to use the device as intended in the correct implant location all are considerations in animal model selection.
As an example, a rabbit or mouse are not suitable animal models in a preclinical safety evaluation of, say, a transcatheter aortic valve replacement. Based on size alone, how would you implant, let alone use, a device that’s sized and intended for human use in a much smaller animal model?
Sheep and swine are animal models large enough to accommodate such devices. Their size allows for the intended delivery and implantation location of the device, making these the more appropriate choice.
Using expertise of the animal model species
The selection process requires thorough knowledge of each species’ anatomy and physiology. It is equally as important to understand how each species is similar and/or different to your target patient population. How does the anatomy, physiology and disease state compare to the target patient population?
With these considerations, animal models can sometimes fall into predictable patterns:
- A sheep’s valve structure makes them ideal for studies that involve an aortic valve, tricuspid valve or mitral valve.
- Stent and structural heart studies usually involve swine animal models.
- A canine’s left atrial appendage structure has similarities to a human’s, so they’re an appropriate model for evaluating and testing new treatments of atrial fibrillation.
[Read about the animal models at American Preclinical Services]
Translatability of medical device testing
After the regulatory review process, the next step is human clinical trials. One thing regulators are evaluating is the probability that the device would translate to safe and effective human use, after a successful animal trial. However, no device is ever 100% translatable, and a successful outcome in an animal model doesn’t always replicate in a human trial. During the design of the safety studies, the team is looking to maximize the probability of translatability by opting for animal models that have a suitable size, anatomy and characteristics.
For more detailed information about the scientific capabilities of APS in helping you design and execute your preclinical safety study, visit AmericanPreclinical.com.