Stability testing is an essential part of drug development as it ensures the efficacy and safety of the medicinal product throughout its shelf life. It allows the evaluation of APIs and drug product stability under the influence of various environmental factors that will enable us to determine their behavior and changes over time.
Being such vital studies, they are subject to regulatory submission as there is a need for evidence of a product’s efficacy and safety over its lifetime. The guidelines established by the International Council for Harmonization (ICH) serve as the globally accepted standard, and specifically Q1A-Q1F have been the go-to standard for standardizing stability testing and ensuring compliance with regulatory requirements and patient needs.
This article focuses on the industry changes ahead during this current year as these guidelines were last updated in 2003, and drug products and substances have experienced significant changes with the rise of more complex molecules such as biologics, biosimilars, oligonucleotides, or even advanced therapies.
ICH Guidelines for Stability Testing
Current guidelines for stability studies are divided into six parts from ICH Q1A to Q1F, and each one of them focuses on different areas of stability testing. Together, their goal is to serve as a reference, dividing stability testing into three different types of studies: long-term stability studies (real-time), intermediate studies, and accelerated studies.
Given these three types of studies, we can evaluate APIs and drug products in different circumstances such as different moments of their shelf life, or during transport, etc.
In addition to this, ICH guidelines also determine distinct climatic zones based on temperature and humidity, serving as a guide to studies that simulate various climatic environments around the world. This testing is essential as drugs will be eventually tested and stored in different zones across the globe and each one of them presents diverse climatic requirements that can affect quality and efficacy.
Adapting to Changing Trends in Stability Studies
Even though the ICH guidelines for stability testing provide a robust framework for the industry, they were last updated in 2003. During these past years, we have witnessed a significant increase in the presence of biologics and more recently advanced therapies. These innovative and more complex medicinal products present unique challenges in stability testing and typically require additional parameters to measure and the need for more customized testing conditions.
The current guidelines’ approach presents some difficulties around this particular topic. While there is a specific guideline for biological products (ICH Q5C), this requires interpreting the guidelines on an individual basis, and it is unclear how they are intended to work together. It is unclear which other guidelines from the ICH Q1 family apply to biologics besides the specific chapter that is focused on them. This problem is especially significant when dealing with newer and emerging products such as advanced therapies because they are not addressed specifically in the current guidelines and there is more uncertainty around their stability testing.
What’s to Come in 2024 and Ahead
Due to all these changes in the industry and according to the ICH business plan, Q4 of 2024 is the tentative date for the first public version of the revised Q1 guidelines.
It is expected that the current divided guidelines for stability studies will be harmonized into one core document with all of them condensed, and then specific topics will be addressed in the attached appendixes. This would align with the most recent guidelines developed by ICH that rely more in this type of structure and would provide scientists with a more consistent approach improving harmonization and facilitating application to the different product types tested.
The other important changes that will come are related specifically to risk management principles and will be aligned with the most recent guidelines from ICH. They will include new technologies and modern tools not included in the current guidelines that would help with modeling and stability strategies.
Finally, one of the other topics to be addressed would be the inclusion of more novel molecules and products such as advanced therapies into a more harmonized document which would facilitate the work of scientists and drug developers.
Partnering for Success
In this market of increasing complexity of products, strict timeframes, and demanding regulatory requirements, the assistance of a trusted partner and the outsourcing of stability testing have become vital for pharmaceutical companies. Specifically, CROs provide comprehensive stability services, from long-term studies to accelerated testing. With state-of-the-art equipment and facilities, and adherence to regulatory standards and guidelines, Kymos Group stands as a reliable partner throughout the entire drug development lifecycle.
With EMA and FDA-inspected EU sites equipped with walk-in climatic chambers combined with a storage capacity of 100m3, Kymos Group specializes in ICH-compliant stability studies for small and large molecules. From initial method development to ongoing stability programs, we provide end-to-end support to accelerate time-to-market and ensure regulatory compliance.
Additionally, we bring extensive experience in a wide variety of products and different types of formulations (tablets, capsules, liquids, creams, gels, etc.).
Find here our detailed list of services:
- ICH stability testing (long-term, intermediate, accelerated)
- Ongoing stability programs
- Preliminary stability and compatibility studies
- Development & Validation of stability-indicating methods
- Stress testing (light, pH, humidity, temperature, oxidation)
- Photostability of drug substances and drug products
- In-use stability: multidose containers, parenteral solutions
- Holding time studies for bulk products
- Thermal cycling, freeze-thaw, transportation
- Full study management
If you require assistance with your stability studies or any of your CMC or bioanalytical studies, please contact us or send us an email to commercial@kymos.com
