What are the ICH stability storage conditions for long-term, intermediate and accelerated studies?

1The conditions in ICH Q1A(R2).

ICH Q1A(R2), Stability Testing of New Drug Substances and Products, reached Step 4 on 6 February 2003. It defines the stability data package for registering a new drug substance or product in the EU, Japan and the US, and says alternative approaches can be used when there are scientifically justifiable reasons.¹ The FDA, the European Commission and MHRA are among the regulators ICH lists as having implemented it.²

The guideline sets the same conditions for drug substances and drug products in the general case, with separate cases for cold storage and for products in semi-permeable containers.¹

The minimum data at submission is 12 months at the long-term condition and 6 months at the accelerated and intermediate conditions, on at least three primary batches.¹ It is up to the applicant to choose 25 °C/60% RH or 30 °C/65% RH for long term, and if the long-term condition is 30 °C/65% RH, “there is no intermediate condition”.¹

The conditions and study lengths “should be sufficient to cover storage, shipment, and subsequent use”, and accelerated and intermediate data can be used to judge short excursions such as those during shipping.¹ For biotechnological and biological products, Q1A(R2) points to ICH Q5C.¹

2When the intermediate condition is needed.

Intermediate testing is triggered by results, not planned in every study. If long-term studies run at 25 °C/60% RH and “significant change” occurs at any time during 6 months at the accelerated condition, the product is also tested at 30 °C/65% RH and evaluated against the same criteria. The application then includes at least 6 months’ data from a 12-month intermediate study.¹

For a drug substance, significant change means failure to meet its specification. For a drug product, it generally means:¹

1. a 5% change in assay from its initial value, or failure to meet potency criteria for biological or immunological procedures;
2. any degradation product exceeding its acceptance criterion;
3. failure to meet criteria for appearance, physical attributes or functionality, such as colour, phase separation, hardness or dose delivery, although some physical changes such as softening of suppositories may be expected under accelerated conditions;
4. where relevant, failure to meet the pH criterion; or
5. where relevant, failure to meet dissolution criteria for 12 dosage units.

For refrigerated products, a significant change between 3 and 6 months at the accelerated condition means the shelf life is based on real-time long-term data. A significant change in the first 3 months needs a discussion of short excursions, for example during shipping.¹

3Conditions for hot and humid markets.

ICH withdrew Q1F, its guideline for climatic zones III and IV, in June 2006, and left the storage conditions for those zones “to the respective regions and WHO”.² ICH’s explanatory note on the withdrawal, which WHO reproduces in its 2018 guideline, kept 30 °C/65% RH as the Q1A(R2) intermediate condition. It said regulators in the ICH regions accept “more stringent humidity conditions such as 30 °C/75% RH” should an applicant decide to use them.³

WHO’s guideline, Stability testing of active pharmaceutical ingredients and finished pharmaceutical products (Technical Report Series No. 1010, Annex 10, 2018), lists three long-term conditions for the general case: 25 °C/60% RH, 30 °C/65% RH or 30 °C/75% RH, each ± 2 °C and ± 5% RH. Which one applies “is determined by the climatic zone in which the FPP is intended to be marketed”, and if the long-term condition is one of the 30 °C conditions there is no intermediate condition. Accelerated testing stays at 40 °C/75% RH.³ WHO warns that testing only at zone I/II conditions for products supplied to zones III and IV “could potentially lead to substandard products”.³

WHO’s Expert Committee on Specifications for Pharmaceutical Preparations split zone IV into IVa, hot and humid, at 30 °C/65% RH, and IVb, hot and very humid, at 30 °C/75% RH. WHO’s prequalification team assumes prequalified medicines will be used in every sub-zone of zones III and IV unless the applicant justifies otherwise, so it expects shelf life to be based on complete long-term data at 30 °C ± 2 °C/75% RH ± 5% RH.⁴

4Pull points and study design.

For a proposed shelf life or re-test period of at least 12 months, Q1A(R2) recommends long-term testing every 3 months in the first year, every 6 months in the second and annually after that. Accelerated studies need at least three time points over 6 months, such as 0, 3 and 6 months, and intermediate studies at least four over 12 months, such as 0, 6, 9 and 12 months.¹ Bracketing and matrixing can reduce testing if justified.¹

Drug product studies use at least three primary batches of the marketed formulation in the proposed container closure system, two of them at least pilot scale, and cover each strength and container size unless bracketing or matrixing is applied.¹

WHO adds that time points are dated from the start of storage, that testing should be completed as soon as possible, and that excursions beyond the chamber tolerances “for more than 24 hours should be described in the study report and their effects assessed”.³

5What GMP requires of a stability programme.

In the US, 21 CFR 211.166 requires a written stability testing programme with sample sizes and test intervals based on statistical criteria, storage conditions for the samples retained for testing, “reliable, meaningful, and specific test methods” and testing in the marketed container closure system. Its results set storage conditions and expiration dates.⁵

In the EU, Chapter 6 of the GMP guide requires an on-going stability programme over the shelf life, run to a written protocol that uses “standardised ICH/VICH conditions for long term testing, consistent with the product labelling”. Unless justified, at least one batch per year of each strength and primary packaging type goes into it, and stability chambers are qualified and maintained under Chapter 3 and Annex 15.⁶

6Where the guideline is going.

ICH is replacing Q1A to Q1F and Q5C with a single guideline, ICH Q1. Its draft reached Step 2b on 11 April 2025, the regulators’ public consultations ICH lists closed in July and August 2025, and on 6 November 2026 ICH lists its status as Step 3. Until it is final and adopted, Q1A(R2), which ICH lists at Step 5, is the implemented guideline.²

7How it runs in Seal.

In Seal, a stability study runs from its protocol version: the population, package, conditions, timepoints and sample quantities. Protocols can start from templates for ICH long-term, intermediate and accelerated studies, photostability and an annual commercial programme, which your team confirms for each product before use. Each pull records which units left which chamber position, when, who moved them and when the laboratory received them, and a missing result stays visible as owned work rather than a blank cell.

Neil can plan the next stability pulls from protocol windows, chamber inventory and laboratory capacity, for the study planner to confirm, and can review a stability trend by comparing time points against the approved limits. The study owner assesses the trend; a summary does not establish shelf life.