Planning an ICH Q1A stability study: 36 determinations for a 24-month shelf life
Author: Dr. Oliver Kraft, Dr. rer. nat., Organische Chemie · Updated 2026-08-03
Short and direct
For a tablet, climatic zone II, target shelf life 24 months, the computed plan yields two storage conditions: 25 degrees at 60 percent relative humidity as the long-term condition and 40 degrees at 75 percent as the accelerated one. The long-term condition has seven timepoints, 0, 3, 6, 9, 12, 18 and 24 months, the accelerated one five, 0, 1, 2, 3 and 6 months. With three batches and one tested parameter that is 36 determinations.
The number 36 is the lower bound, not the effort. It applies to exactly one parameter. A real specification tests assay, related substances, appearance, water content and dissolution, and every additional parameter multiplies the number. Anyone using the plan as a quotation basis should fix the parameter list before, not after.
The computed result
| Condition | Category | Timepoints (months) | Count |
|---|---|---|---|
| 25 Grad C / 60 % rF | Langzeit | 0, 3, 6, 9, 12, 18, 24 | 7 |
| 40 Grad C / 75 % rF | beschleunigt | 0, 1, 2, 3, 6 | 5 |
| Gesamt: 3 Chargen, 1 Parameter | Aufwand | 12 Zeitpunkte gesamt | 36 |
Computed 2026-08-03 with covastab_design_study, climatic zone II, product type tablet, target shelf life 24 months. Verbatim tool output.
Why exactly these two conditions?
Climatic zone II is the subtropical and mediterranean zone that includes Europe and therefore the EU marketing authorisation area. ICH Q1A sets 25 degrees at 60 percent as its long-term condition and 40 degrees at 75 percent as the accelerated one. Zones III and IVb carry different values, which changes the plan as soon as an authorisation outside Europe is added. The climatic zone parameter is therefore the first one to set deliberately rather than leave at its default.
The computed plan includes no intermediate condition, usually 30 degrees at 65 percent. Under ICH Q1A it depends on two conditions, and both must hold. First, long-term storage must run at 25 degrees and 60 percent, because anyone already storing at 30 degrees and 65 percent has the intermediate condition as their long-term condition and needs no second one. Second, a significant change must appear under the accelerated condition. That is not an omission in the plan but the order of the guideline: the intermediate condition follows from the result and from the chosen long-term condition, not from the design.
What makes the study expensive, and what does not?
Not the number of timepoints. Three things are expensive: the number of tested parameters, the number of batches, and any repeat caused by a method that was not yet validated when the first samples went into storage. The third is what breaks schedules, and it has nothing to do with stability.
The plan assumes three batches, as ICH Q1A requires for a new application. For a change to an existing product a smaller number of batches may suffice, which roughly thirds the effort. That decision belongs before the samples go into storage, because it cannot be corrected afterwards.
Setting up the study plan in five steps
- Fix the authorisation area: The climatic zone follows from the market, not from the laboratory location. It determines both storage conditions.
- Close the parameter list: Every parameter added later creates its own time series and cannot be recovered retrospectively.
- Justify the batch count: Three batches for a new application, fewer only with a documented rationale.
- Validate methods before storage: A method validated only later devalues the earlier timepoints, and those cannot be repeated.
- Plan the Q1E evaluation: The shelf-life statement comes from the confidence bound, not from the last measured value.
Frequent questions
- Which climatic zone applies to the EU?
- Zone II. The long-term condition is 25 degrees at 60 percent relative humidity, alternatively 30 degrees at 65 percent. For a worldwide authorisation, storage is usually set against the strictest zone involved so that two studies do not run in parallel.
- What counts as a significant change?
- Under ICH Q1A this includes a five percent change in assay from the initial value, exceeding a specification limit for a degradation product, or failure in appearance, physical attributes or dissolution. If such a change occurs under the accelerated condition, the intermediate condition becomes required.
- How do I get from the data to a shelf-life statement?
- Via ICH Q1E. It sets out the extrapolation procedure, the question of poolability across batches, and the use of the one-sided 95 percent confidence bound. The shelf-life statement is the time at which that confidence bound crosses the specification limit, not the time at which the mean does.
- What is matrixing and when is it worth it?
- Matrixing means that at a given timepoint not every combination of batch, container and strength is tested, but a balanced subset. It pays off as soon as several strengths or containers are involved. With a single strength in one container there is nothing to matrix.
- Does the plan cover photostability?
- Photostability is governed separately in ICH Q1B and does not run as a timepoint inside the storage study. Whether and to what extent it is needed for a specific product is decided by the Q1B assessment, not by this study plan.
Sources
- ICH Q1A(R2): Stability testing of new drug substances and products. Source of storage conditions, timepoints and batch count.
- ICH Q1E: Evaluation of stability data. Source of the extrapolation and poolability procedure.
- ICH Q1B: Photostability testing. Governed separately, not part of the storage study plan.
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