In detail
Guidelines
For marketing authorisation applications for new active substances and medicinal products, ICH guideline Q1A(R2), in its version of 6 February 2003, defines the required stability data package. It refers to Q1B for photostability, Q1C for new dosage forms and Q5C for biotechnological products. In April 2025 ICH released a draft consolidated guideline, ICH Q1, for consultation; it is intended to supersede Q1A to Q1F and Q5C. Until it is finally adopted, the existing texts continue to apply.
Study types and conditions
- Stress testing: usually on a single batch of the active substance, to identify likely degradation products and pathways and to demonstrate that the analytical procedures are stability-indicating.
- Long-term study: in the general case at 25 °C ± 2 °C / 60 % RH ± 5 % or 30 °C ± 2 °C / 65 % RH ± 5 %. At submission, data covering at least 12 months on at least three primary batches should be available.
- Accelerated study: 40 °C ± 2 °C / 75 % RH ± 5 % for at least 6 months.
- Intermediate condition: 30 °C / 65 % RH, where the long-term study runs at 25 °C and a significant change occurs under accelerated conditions.
In the long-term study, testing is normally carried out every three months in the first year, every six months in the second year and annually thereafter, using validated, stability-indicating methods.
On-going stability after authorisation
Once the product is on the market, Chapter 6 of the EU GMP Guide requires an on-going stability programme. It monitors the product up to the end of its shelf life in the package in which it is sold. Unless otherwise justified, at least one batch per year of each strength and primary packaging type is included, plus additional batches after significant changes or deviations. The results must be made available to the Qualified Person, and Annex 16 explicitly lists current stability data as a basis for batch certification.
Common weaknesses
- Analytical methods whose stability-indicating power has not been demonstrated with stress data.
- Stability chambers that have not been qualified in line with Chapter 3 and Annex 15.
- OOS results and negative trends that are not investigated or, for batches on the market, not reported to the competent authority.
In practice at A&O Pharma
Stability testing is part of the analytical services offered by A&O Pharma's GMP-certified laboratory in Itzehoe. Trace analysis by triple quadrupole LC-MS/MS and microbiology are also available there. A&O Pharma can take on the validation of the analytical methods used as part of its GxP consulting.
Analytical ServicesFrequently asked questions
How long must a stability study run for a marketing authorisation application?
Under ICH Q1A(R2), long-term data covering at least 12 months on at least three primary batches should be available at submission, together with 6 months under accelerated conditions. The long-term study continues until the proposed shelf life or re-test period is covered.
What is the difference between stress testing and an accelerated study?
Stress testing reveals degradation pathways and products and shows whether the analytical methods are stability-indicating. The accelerated study at 40 °C / 75 % RH is part of the formal programme and helps, among other things, to assess short excursions from the storage conditions, for example during shipping.
Does stability testing continue after authorisation?
Yes. Chapter 6 of the EU GMP Guide requires an on-going stability programme which, unless otherwise justified, includes at least one batch per year of each strength and primary packaging type.
