Reducing Animal Testing in Veterinary Drug Development
Developing a veterinary drug is a long and complex process. Before a therapy ever reaches an animal study or veterinary clinical trial, formulation scientists must understand how the drug behaves, whether it’s stable, how it releases after administration, and whether it’s likely to perform consistently in the target species.
For subcutaneous (SC) therapies in particular, this process becomes especially challenging. Unlike oral dosage forms, SC formulations interact directly with a highly complex tissue environment where diffusion, depot formation, precipitation, viscosity, and local fluid exchange can dramatically influence drug absorption and bioavailability.
The difficulty is that many of these behaviors are difficult to predict using traditional benchtop tests alone. As a result, veterinary development teams often face an uncomfortable decision early in development: either move straight into target animal studies with limited confidence, or perform additional exploratory studies that increase cost, timelines, and animal use.
What Testing Is Typically Involved in Veterinary Drug Development?
Developing a veterinary medicine involves multiple stages of testing designed to answer different scientific questions before a product reaches the target species. For subcutaneous formulations, the workflow often progresses through several phases.
- Early Physicochemical Characterization
At the earliest stage, scientists evaluate the basic properties of a formulation, including: Solubility, Stability, Viscosity, Syringeability /injectability, pH, Osmolality, Particle size and compatibility with excipients, and these studies are typically performed in simple benchtop assays. While these tests are essential, they provide limited insight into what happens after injection into subcutaneous tissue.
- In Vitro Release and Screening Studies
Once a formulation appears viable, researchers often perform early release testing or screening assays to compare candidates. These studies may involve: Dissolution systems, Dialysis methods, Static release chambers, Simple diffusion assays and Gelation or precipitation observations. These tools can help identify obvious formulation issues, but they often lack physiological relevance. This creates a major knowledge gap between early in vitro screening and real in vivo behavior.
- Species-of-Interest Animal Studies
Eventually, formulations progress into animal studies using the intended veterinary species or relevant preclinical models. Depending on the indication, this may involve Dogs, Cats, Horses, Cattle, Swine, Poultry etc. At this stage, researchers begin evaluating Pharmacokinetics (PK), Relative bioavailability, Injection site behavior, Depot persistence, Tolerability, Dose and Safety. These studies are resource-intensive and often represent a major development bottleneck.
Whilst veterinary products often benefit of getting to their target species earlier and skipping smaller animal studies, there are still ethical as well as time and financial considerations with going straight to the species of interest. Once testing in vivo, there is limited opportunity for rapid formulation iteration meaning changing formulation strategy becomes substantially more difficult. This means less innovation but still with the risk of late-stage failure.
The Translation Problem in SC Development
One of the greatest challenges in veterinary subcutaneous drug development is understanding how a formulation will translate from simple laboratory testing into real biological tissue. Many formulations can appear highly promising during early benchtop assessment, yet behave very differently following injection, particularly in the case of complex long-acting or depot-based systems where local tissue interactions strongly influence release and absorption. These scenarios are often difficult to predict using conventional in vitro methods alone and, in many cases, are only identified once animal studies are already underway, increasing both development risk and resource burden.
Why Earlier Prediction Matters
Veterinary pharmaceutical teams are increasingly focused on improving the quality of decision-making much earlier in the development process. The objective is no longer simply to generate larger volumes of data, but instead to produce data that is more representative before committing to costly in vivo studies. By improving early confidence, teams are better positioned to rank-order formulations sooner in development, remove weaker candidates prior to animal testing, and concentrate experimental effort on those with the highest probability of success.
Introducing SCISSOR N3TM: A Physiologically Relevant Intermediate Step
The Pion SCISSOR N3 platform was developed specifically to help address this translational gap. Rather than moving directly from simplified in vitro assays into animal models, SCISSOR introduces an intermediate stage that is designed to better reflect physiological conditions in a controlled and reproducible way. In a typical workflow, formulations progress from benchtop screening into SCISSOR-based physiological assessment before advancing to targeted in vivo studies. Within this framework, SCISSOR is used to simulate key aspects of the subcutaneous environment, allowing scientists to observe formulation behavior under constraints that more closely resemble those encountered after injection.
What SCISSOR Enables Veterinary Scientists to Assess
Within the SCISSOR system, researchers are able to evaluate a range of formulation behaviors that are difficult to capture using standard in vitro approaches. This includes drug release profiles, diffusion characteristics, depot formation, and formulation integrity over time. It also allows direct comparison of how different formulations perform under consistent SC-like conditions providing earlier insight into how compositional changes influence performance before progressing into species-based studies.
Applications Where SCISSOR Is Especially Valuable
In long-acting veterinary injectables, where sustained exposure over extended periods is essential, SCISSOR can provide valuable early information on release rank order, depot robustness, and how formulation differences influence overall release behavior. This type of insight can help de-risk lengthy in vivo studies by identifying promising candidates earlier in the workflow.
In situ forming gel systems present a particular challenge in development because their behavior is strongly influenced by solvent exchange, local diffusion conditions, phase transition kinetics, and the confined nature of tissue-like environments. SCISSOR provides a more representative setting in which these systems can be studied, enabling scientists to observe gel formation dynamics, structural stability, release behavior, and differences in depot formation. This can be particularly useful for visualizing and understanding how formulation composition drives in situ performance.
For biologics and monoclonal antibodies, where even small formulation changes can significantly affect subcutaneous absorption, SCISSOR offers a means of earlier differentiation between candidates. It supports formulation comparison and helps build confidence prior to in vivo studies, particularly for highly concentrated or viscosity-sensitive systems where traditional screening methods may not fully capture performance differences.
Supporting More Efficient and Ethical Development
Animal studies remain an essential part of veterinary drug development, but there is a growing emphasis on ensuring that they are as targeted, efficient, and informative as possible. By improving the quality of information available earlier in development, SCISSOR can help reduce unnecessary exploratory studies, strengthen the rationale behind study design, and ensure that resources are focused on the most promising candidates. This aligns with broader efforts to support reduction principles within development workflows.
Importantly, SCISSOR is not positioned as a replacement for in vivo testing. Instead, it serves as a decision-enabling bridge between traditional benchtop assays and animal studies, helping to ensure that the studies that do take place are better informed from the outset.
