Stability Studies

Stability Testing provides evidence on the quality of a drug substance or drug product varies over a given time period and under the influence of various environmental factors including temperature, humidity and light. This enables a re-test period, or a shelf life, to be established with recommended or specified storage conditions.

Stability studies are designed to include testing of those attributes that are susceptible to change during storage and are likely to influence quality, safety, and/or efficacy.

The testing primarily covers the following attributes: physical, chemical and microbiological, as appropriate.

- Physical: Appearance, melting point, water content, clarity and colour of solution, pH , dissolution and disintegration characteristics, viscosity, crystal modification or particle size.

- Chemical: Assay, Degradation products, Related Substances, Residual Solvents.

- Microbial: Growth in microorganisms. Efficiency of preservative contents such as antioxidants and/or antimicrobial preservatives

The frequency of test points for long-term studies should be sufficient to establish the stability profile for a given period. For drug substances with a proposed re-test period of at least 12 months, the frequency of testing at the long term storage condition is usually every 3 months over the first year, then every 6 months over the second year and annually thereafter through the proposed re-test period.

The recommended test frequency for the intermediate storage condition is a minimum of four time points, including the initial and final time points (e.g., 0, 6, 9, 12 months), for a 12-month study.

For accelerated storage conditions the test frequency is recommended to be a minimum of three time points, including the initial and final time points (e.g., 0, 3, and 6 months), for a 6-month study.

Generally a drug substance should be evaluated under storage conditions that test its thermal stability and its sensitivity to moisture. The long term testing normally covers a minimum of 12 months’ duration on at least three primary batches.

Standard conditions recommended in the ICH Guidelines and available at Butterworth are:

- 25°C ± 2°C/60% RH ± 5% RH

- 30°C ± 2°C/65% RH ± 5% RH

- 40°C ± 2°C/75% RH ± 5% RH

These cover the climatic zones I and II to cover the three regions of the EC, Japan and the United States.

If long-term studies are conducted at 25°C ± 2°C/60% RH ± 5% RH and “significant change” occurs at any time during 6 months’ testing at the accelerated storage condition, additional testing at the intermediate storage condition should be conducted and evaluated against significant change criteria.

A 5% change in the Assay content would be seen as a “significant change”, but a fuller definition can be found in the ICH Guidelines Q 1 A (R2) - Stability Testing of new Drug Substances and Products.

Photostability testing should be conducted on at least one primary batch of the drug product if it is suspected that the product or any of its components are susceptible to light and is available at Butterworth Laboratories Ltd, see BLP07 – Forced Degradation.


For more information please contact  David Bell, Head of Projects

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