At the 2023 Safety Pharmacology Society (SPS) Conference in Brussels, CBSET Study Director, Dr. Donald Hodges, discussed the history, regulatory framework and other factors influencing species selection in IND-enabling studies in a partner session organized by emka TECHNOLOGIES on Maximizing Insights from Animal Studies in the Context of Rising Costs and Shortages.
Since 1937, the Food and Drug Administration (FDA) has required preclinical testing of new drugs and biologicals for pharmacologic activity and acute toxicity in animals prior to their use in clinical trials. The guidance established the use of two animal species, a rodent and a larger non-rodent mammal, for toxicological studies. However, acquiring dogs and non-human primates (NHPs) has become increasingly difficult and expensive, and their use may raise additional legal and ethical concerns.
Swine, the "other large animal" tox species
In spite of recent adaptations in the FDA modernization act, the use of animal species for IND-enabling studies remains a cornerstone of drug safety. The selection of the animal species, while flexible, must adhere to the FDA and EMA’s guidance:
- The animal, environmental and physiological attributes should simulate the clinical setting.
- Scientific information must justify the appropriateness of the chosen animal model.
- In some cases, there may not be an established or accepted animal model.
- The selected animal model should be able to address the identified objectives of the study.
- The sponsor should consider scientifically accepted animal models of disease when they exist.
In the following video, Dr. Hodges outlines how proven translational characteristics and historical data are enabling the wider adoption of swine as an alternative to dogs and NHPs in the context of shortages and rising costs.
Contact us for more information about how we can facilitate the adoption of the pig model in your lab.
With the increasing costs of preclinical studies and the intensification of ethical concerns associated with the use of companion animals for scientific research, scientists are re-discovering alternative models such as pigs, rats and rabbits to better predict human toxicity.
Göttingen, Yucatan, and Yorkshire pigs are well established in surgical and physiological research. The pig has become the model of choice for FDA approval for the testing of surgical implants intended for human use. They have also been used for years in pharmacology and toxicology.
- Pigs share many physiological and anatomical properties with humans. In the context of shortages and rising costs for research dog and primates, the pig has become an attractive option to fulfill the FDA’s “large animal species” requirement.
- Pigs are similar to humans in size and in pharmacokinetic properties. They are sensitive to a wide variety of drugs and chemicals, which can be administered using different routes (e.g. IV, oral). They constitute an excellent alternative to the use of dogs or primates for metabolic, pharmacological, life span, and ethical reasons. Indeed, their cost and acceptance for use in research are maintained by the worldwide consumption of pork meat.
- The development of research minipigs has resulted in strains of more manageable size, yielding a better use of expensive compound. Pigs can also be genetically modified to express certain targets. Indeed, genetically engineered pigs (e.g. CFTR-deficient, SCN5A-gene mutations), have led to better disease models of pulmonary and cardiovascular diseases.
- Pigs, as well as guinea pigs and rabbits, have very clean ECGs. They are effective models of cardiac electrophysiologic effects of drug candidates.
- Some of the limitations of pigs include their larger size (typically 25-45 kg in juvenile or small species, but can exceed 300 kg in adult swine), which impacts requirements for space, food, and amount of compound needed. Pigs also require some refinement in scientific and experimental protocols.
- The swine is a viable large animal alternative for tox studies, addressing a variety of ethical, legal and scientific challenges with dogs and NHPs.
- easyTEL+ implanted telemetry provides precise and continuous physiological information from traditional and non-traditional models, permitting robust and highly translational efficacy and safety outcomes early on. It has been successfully validated in pigs for GLP studies. easyTEL+’s ability to broadcast data over distances of 5m+ facilitates deployments in large animal facilities.
- CBSET scientists have extensive experience with alternative large models such as sheep and swine for safety pharmacology studies and medical device testing. They understand the specific advantages and challenges of these models and have developed unique methodologic know-how to answer complex biomedical questions.