Ensuring that pharmaceutical products reach the consumer without degradation during shipping and storage has led to the creation of stability testing guidelines. All pharmaceutical products must undergo rigorous and standardized stability tests before they are approved for sale around the world. This has not always been the case for components of In-Vitro Diagnostic (IVD) kits used in clinical and research laboratories worldwide.
These kits contained expiration dates and optimal storage conditions, but they didn’t undergo rigorous testing of stability with temperature change, oxygen exposure, light exposure, and other potential drivers of degradation over time. However, the importance of ensuring the stability of IVD kits eventually led to the creation of guidelines for stability testing of in-vitro diagnostics by the Clinical Laboratory Standards Institute (CLSI) in 2009. The updated IVD stability testing guidelines are titled EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents.
Pharmaceutical stability testing served as the model for IVD stability testing. Pharmaceutical stability tests check for short term and long term stability of the drug compounds and identify necessary packaging and storage conditions. The guidelines were first written in 1990 by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human use (ICH), and they are updated regularly. The Q1A(R2) document for pharmaceutical stability testing details every test that must be completed for every drug compound that is registered for sale.
Pharmaceutical stability tests
The first step of stability testing of drug compounds is to understand the pathways of degradation and the timeline of degradation. This means that the drug is exposed to extremes in temperature, humidity, light, and oxygen. Any changes in consistency, color, or composition are recorded, and the drug is then checked to see if any chemical changes occurred and how that affected efficacy. Sometimes the products of degradation can actually be harmful and dangerous for human consumption, and that information is important to know. After these initial stress tests the next step is to develop packaging that will prevent degradation during storage and will preserve the drug in its most effective state. Then the packaged drug will be stored for a minimum of one year and will be tested again to see if any breakdown occurred during that time.
IVD stability tests
IVD kits contain many reagents that react differently to storage over time. Kits may contain proteins, enzymes, fluorescent dyes, buffers, positive and negative controls, and other sensitive materials. If any one of these reagents change over time, then the entire diagnostic may fail in a clinical setting and produce a false negative or positive result which would affect treatment plans and could compromise patient health in a similar way that degraded drugs could. The IVD stability guidelines give requirements for defining shelf life, transport conditions, and storage conditions for all reagents in the kit. The guidelines also address the process for understanding and defining stability once the reagents are opened. These guidelines apply to newly designed IVDs as well as those already on the market, and stress the importance of long term monitoring.
For more information on how to perform stability testing for a newly designed IVD, please consult the CLIA IVD stability guidelines and read chapter 8 in Sepmag’s ebook “The basic guide for the use of magnetic beads in chemiluminiscent immunoassays.