Stability Testing: Why It Matters, Climatic Zones and Conditions

In short: Stability testing shows how the quality of a drug substance or drug product changes with time under temperature, humidity and light, and it supports the re-test period, shelf life and storage label. This article summarises the standard storage conditions in ICH Q1A(R2) and WHO TRS 1010 Annex 10, explains the climatic zones, and notes the new consolidated ICH Q1 guideline. It is meant for QA, QC and regulatory staff and pharmacy students.

Why stability testing is important

Stability data tell you how long a product keeps its identity, strength, quality and purity, and under which storage conditions. They are used to:

• set the re-test period (drug substance) or shelf life (drug product);
• decide the storage statement on the label, such as “Do not store above 30 °C”;
• justify the container closure system and packaging;
• support the marketing authorisation in each country, since regulators review stability data in every dossier.

ICH Q1A(R2) describes the purpose as providing evidence on how quality varies with time under the influence of temperature, humidity and light, so that a re-test period or shelf life and recommended storage conditions can be established.

Climatic zones

The world is divided into climatic zones according to long-term temperature and humidity. ICH Q1A(R2) itself addresses zones I and II (the EU, Japan and the USA). WHO guidance extends the long-term conditions to zones III and IV, which cover many tropical and sub-tropical countries.

Source for II, IVa and IVb: WHO TRS 1010 Annex 10 (2018), which notes that zone II is 25 °C/60% RH, zone IVa is 30 °C/65% RH and zone IVb is 30 °C/75% RH. A 30 °C/35% RH condition for zone III also appears in the Annex.

Tolerances are ± 2 °C and ± 5% RH in all rows.

Where does India fall?

India is a hot and humid country and is treated as a zone IV market. Many sponsors use zone IVb (30 °C / 75% RH) for products meant for India and similar markets. Note, however, that the WHO table of long-term conditions by member state (2018 version) lists 30 °C / 70% RH for India, not 30/75.

Storage conditions in ICH Q1A(R2)

For the general case, the guideline asks for data at the following conditions. The applicant may choose either long-term condition.

The intermediate study is needed only if “significant change” occurs at the accelerated condition while long-term testing is at 25 °C/60% RH. If long-term testing is at 30 °C/65% RH, there is no intermediate condition.

Refrigerated and frozen products

This table is the drug substance version of Q1A(R2); the guideline gives the same conditions for drug products intended for refrigerator or freezer storage.

The original version of this post listed frozen storage at -15 °C ± 5 °C and treated refrigerated and frozen conditions as accelerated studies. These were corrected as shown above.

WHO TRS 1010 Annex 10 (2018)

WHO’s guideline on stability testing of APIs and finished pharmaceutical products allows long-term testing at 25 °C/60% RH, 30 °C/65% RH or 30 °C/75% RH, depending on the zone in which the product will be marketed. If 30 °C/75% RH is chosen as the long-term condition, no intermediate study is required. The intermediate condition remains 30 °C/65% RH and the accelerated condition 40 °C/75% RH.

The Annex also notes the history: ICH Q1F, which set 30 °C/65% RH for zones III and IV, was withdrawn because several countries wanted a larger humidity margin, so storage conditions for these zones are now defined regionally and by WHO.

ICH Q1: the consolidated guideline

ICH has been consolidating Q1A(R2), Q1B, Q1C, Q1D, Q1E and Q5C into a single revised guideline titled “Stability Testing of Drug Substances and Drug Products” (ICH Q1). The Step 2 draft was released in April 2025 for public consultation. The US FDA published it as a draft guidance in June 2025.

Status as of 15 October 2026: the consolidated ICH Q1 was published as a Step 2 draft in April 2025, and ICH’s work plan (February 2026) targets Step 3 sign-off and Step 4 adoption in November 2026. Until then, Q1A(R2) (Step 4, February 2003) and Q1B–Q1E remain the current ICH stability guidelines. Even after Step 4, ICH guidelines apply in a region only after the regulator implements them, so continue to follow the version your regulator currently requires. The values in this article come from Q1A(R2) and WHO Annex 10 and should be re-checked against the final ICH Q1 text.

Related reading

See also: Bracketing and matrixing designs for stability study (ICH Q1D), Matrixing guidelines for stability study and SOP for recording temperature and humidity of stability chamber.

Frequently asked questions

What is the difference between long-term, intermediate and accelerated testing?

Long-term testing is done at the intended storage condition and supports the shelf life. Accelerated testing (40 °C/75% RH for 6 months) stresses the product to show likely changes. Intermediate testing (30 °C/65% RH) is added when significant change occurs at accelerated conditions.

How long must long-term data be at submission?

Q1A(R2) states a minimum of 12 months of long-term data for the general case, with 6 months at the accelerated condition.

Which condition should I use for India?

Use the zone and condition required by CDSCO and the markets you supply. Many companies choose 30 °C/75% RH to cover zone IVb. See the VERIFY note above.

Is ICH Q1 replacing Q1A(R2)?

The consolidated ICH Q1 is intended to replace the separate stability guidelines. See the status section above and check ich.org.

References

1. ICH Q1A(R2): Stability Testing of New Drug Substances and Products, Step 4, February 2003 (ich.org).
2. WHO Technical Report Series No. 1010, Annex 10: WHO guidelines on stability testing of active pharmaceutical ingredients and finished pharmaceutical products, 2018 (who.int).
3. WHO: Stability conditions for WHO Member States by region (TRS 953 Annex 2 Appendix 1, 2018 table) (who.int).
4. ICH Q1: Stability Testing of Drug Substances and Drug Products, draft (Step 2, April 2025) and EWG work plan, February 2026 — Step 4 targeted for November 2026 (ich.org).
5. US FDA: Q1 Stability Testing of Drug Substances and Drug Products, Draft Guidance for Industry, June 2025 (fda.gov).