We have come a long way from the days of blood letting, trephination, and snake oil salesmen peddling cure-all tonics. The oversight and regulation of organizations such as the European Medicines Agency and the Federal Drug Administration (FDA) have significantly improved the quality and safety of our medical and pharmaceutical products. Of course, our medical understanding has deepened dramatically, our science has become more sophisticated, and we have developed tools to perform large scale drug discovery and screening. With this deeper understanding of chemistry and drug development we have realized the importance of preserving the chemical molecules via proper storage conditions.
The ICH guidelines for stability lay out the requirements for identifying and maintaining drug efficacy by understanding the pathways of degradation. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) was founded in 1990. The European Commission, FDA from the USA, and the Ministry of Health, Labour, and Welfare (MHLW), which later became the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan are all founding members. Since that time, many other regulatory authorities from around the world have joined the ICH. The stated mission of the ICH is to “achieve greater harmonisation worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner.”
ICH guidelines for stability
The ICH guidelines for stability testing of new drug substances and products were first written in 1992 and adopted in 1993. Since that time, the document has been revised and updated a few times. The current version Q1A(R2) has been in place since 2003. The specific goal of the ICH guidelines for stability is to define the information that must be submitted with the application for the registration of each new drug molecule.
This information includes a study of how the molecule changes over time in various storage conditions. Heat, humidity, and light can all change the chemical nature of a pharmaceutical product. Some drugs are more unstable than others, and require very specific storage conditions in order to maintain efficacy. The timeline and conditions leading to the degradation of the drug molecule are throughly tested and defined via stress testing. This information is then used to define the drug’s shelf life and optimal storage conditions. The ICH guidelines for stability provide a roadmap for completing this process, and they harmonize the registration process for all drugs within the EU, USA, and Japan. Therefore, any drug that is registered in one of these regions will be accepted in either of the other two without the need for repeated stability testing.
The guidelines touch on the following topics:
- examining degradation pathways
- effects of temperature change in 10°C increments, relative humidity over 75%, susceptibility to hydrolysis, changes in pH
selection of batches
- stability testing of at least three primary batches of the drug substance
- need to be representative of the material made in production scale
container closure system
- mimimum of three time-points
- every 3 months in the first year, every 6 months in the second year, and annually thereafter for long term studies
- significant change for a drug substance means that it fails to meet its specification
statements and labeling
- in accordance with national/region requirements
- specific storage conditions on label
Regulations keep us safe, elevate the quality of our pharmaceutical products, and provide a clear path for the registration of new drugs. The ICH guidelines for stability allow for the process to be harmonized among regions so that these new drugs can be brought to market sooner.