The National Office of Animal Health, which represents over 97 per cent of the UK’s animal medicine market, states that approximately £745 million is made each year in sales of authorised veterinary medicines. As with pharmaceutical products used for humans, animal medical products are also subject to rigorous regulatory standards, with stability studies forming a crucial part of the testing process. Here, Beccy Bell, Operations Manager at analytical testing specialist Broughton explains how manufacturers can develop bespoke stability studies for veterinary medicines.
Stability testing can help determine a product’s shelf life and recommended storage conditions. These studies provide evidence of how the quality of a drug substance or medicinal product varies over time under the influence of different environmental factors, such as temperature, humidity, and light.
Stability studies are also used to establish a re-test period for a drug substance that is then applicable to future batches of that substance manufactured under similar circumstances. Usually, manufacturers will determine this by testing a minimum of three batches of the drug substance and evaluating the stability information generated (including, as appropriate, results of the physical, chemical, biological, and microbiological tests). The degree of variability of individual batches impacts the confidence that a future production batch will remain within specification throughout the assigned re-test period.
The data may show so little degradation and variability that it is apparent from looking at the data that the requested re-test period will be granted. Under these circumstances, it is normally unnecessary to go through a formal statistical analysis. If so, justifying the omission should be sufficient.
Designing a Bespoke Stability Study
Several design factors must be considered before initiating a stability study. Sometimes, stability study designs may be straightforward with a single formulation and strength, but this is rarely the case.
Firstly, for formal registration stability studies required to support the regulatory submission for a veterinary product, these studies must be performed on no fewer than three representative batches of the manufactured product. This will allow manufacturers to assess the potential batch-tobatch variability in the product’s shelf life. Those tests include biological and physiochemical stability studies carried out at regular intervals, for the finished product until three months beyond the claimed end of shelf life.
In addition, stability studies for veterinary drug products may consist of multiple strengths, packaging types, storage orientations, and container closure systems, resulting in numerous stock-keeping units (SKUs). For studies of multiple strengths and packaging types, the requirement of the study may be reduced if bracketing is applied.
When designing a stability study consideration should be given to the impact of the product’s packaging. Generally, the impact will depend on the study, and packaging assessments may not be required for all stability studies. Manufacturers may also want to consider the impact of the surface area contact ratio of the substance to the container. For veterinary drug products, shelf-life stability studies should be performed in the primary container closure system proposed for marketing. However, suppose the secondary packaging has protective properties, and the labelling states that the product is to be stored in the primary and secondary packaging. In this event, manufacturers must also assess the secondary packaging as part of the stability study.
As part of the study design, you may also want to consider an in-use stability study. In-use stability tests assess product quality after any packaging has been opened, simulating the expected use of the product.