Storage conditions in stability guidance

Which conditions does ICH Q1A(R2) define for formal studies?

For the general case of a drug substance, ICH Q1A(R2) lists a long-term condition of 25 °C ± 2 °C at 60% relative humidity (RH) ± 5% RH, or 30 °C ± 2 °C at 65% RH ± 5% RH, with at least 12 months of data at submission. It lists an intermediate condition of 30 °C ± 2 °C at 65% RH ± 5% RH and an accelerated condition of 40 °C ± 2 °C at 75% RH ± 5% RH, each with at least 6 months of data.^[1]

For drug substances intended for a refrigerator, the guidance lists long-term testing at 5 °C ± 3 °C and accelerated testing at 25 °C ± 2 °C and 60% RH ± 5% RH. For a freezer it lists a long-term condition of -20 °C ± 5 °C with the retest period based on real-time data, and it considers storage below -20 °C case by case.^[1]

The guidance states that the storage conditions and study lengths chosen should be sufficient to cover storage, shipment and subsequent use, and that alternative storage conditions can be used if justified.^[1]

What separates long-term, accelerated and stress testing?

The Q1A(R2) glossary defines long-term testing as stability studies under the recommended storage condition for the retest period or shelf life proposed for labeling, and accelerated testing as studies that increase the rate of chemical degradation or physical change by using exaggerated storage conditions. It adds that results from accelerated testing are not always predictive of physical changes.^[1]

Stress testing, in the same guidance, helps identify likely degradation products, establish degradation pathways and the intrinsic stability of the molecule, and validate the stability-indicating power of the analytical procedures. It covers temperatures in 10 °C steps above the accelerated condition, humidity of 75 percent RH or greater where appropriate, oxidation and photolysis, and the guidance refers to ICH Q1B for the standard photostability conditions.^[1]

How does ICH Q5C approach proteins and polypeptides?

ICH Q5C states that for products whose active components are typically proteins or polypeptides, molecular conformation and biological activity depend on noncovalent as well as covalent forces. It describes these products as particularly sensitive to temperature changes, oxidation, light, ionic content and shear, and states that stringent storage conditions are usually necessary.^[2]

Q5C states that primary data supporting a requested storage period should come from long-term, real-time, real-condition studies, and that because most finished products of this kind need precisely defined storage temperatures, those studies may be confined to the proposed storage temperature.^[2]

On humidity, Q5C states that such products are generally distributed in containers that protect against humidity, so testing at different relative humidities can usually be omitted where the containers are shown to protect sufficiently. On light, it refers applicants to the regulatory authorities case by case, and it cautions that the accelerated and stress conditions of the general stability guideline may not be appropriate for these products.^[2]

Among the characteristics Q5C lists for monitoring in the final container is the moisture level of powders and lyophilized products.^[2]

What are a retest period and a shelf life?

ICH Q1A(R2) defines the retest period as the time during which a drug substance is expected to remain within its specification, provided it has been stored under the defined conditions, after which a batch should be retested. It defines shelf life as the period during which a drug product is expected to remain within its approved shelf life specification when stored under the conditions on the container label.^[1]

The same glossary states that for most biotechnological or biological substances known to be labile, it is more appropriate to establish a shelf life than a retest period.^[1]

Q1A(R2) also states that a storage statement for labeling should be based on the stability evaluation, that terms such as ambient conditions or room temperature should be avoided, and that a retest date should be displayed on the container label where appropriate.^[1]

How are temperature excursions and average temperatures described?

According to ICH Q1A(R2), data from the accelerated condition and, where appropriate, the intermediate condition can be used to evaluate short-term excursions outside the label storage conditions, such as might occur during shipping.^[1]

The guidance defines mean kinetic temperature as a single derived temperature that, if maintained over a defined period, gives the same thermal challenge as a range of higher and lower temperatures over an equivalent period. It notes that mean kinetic temperature is higher than the arithmetic mean temperature and takes the Arrhenius equation into account.^[1]

Is the stability guidance being revised?

In June 2025 FDA published a draft guidance, ICH Q1 Stability Testing of Drug Substances and Drug Products, which describes itself as a consolidated revision that supersedes ICH Q1A-F and Q5C. Its stated scope includes chemically synthesised drug substances, among them polypeptides, and proteins and polypeptides produced using recombinant DNA technology.^[3]

The FDA guidance page marks the ICH Q1 document as a draft that is not for implementation.^[3]

Limitations

The conditions in ICH Q1A(R2) are those of formal studies supporting registration applications in the European Union, Japan and the United States, and the guidance permits justified alternatives. ICH Q5C states that accelerated and stress conditions for biotechnological products should be selected case by case.^[1],[2]

A storage condition in a guidance document describes a study design, not the stability of a given material; ICH Q5C ties a storage period to real-time data on the product itself.^[2]

This page describes what the cited guidance documents say. It gives no storage, handling or preparation instructions.

This page describes what the cited documents say. It is not a statement that any PepGenex material has been manufactured, tested or released under any of them.

Compound profiles

Research peptide profiles in this library. What this page describes applies to peptide lots in general; none of these profiles reports a result of it for any lot.

• Semaglutide research profile
• Tirzepatide research profile
• Retatrutide research profile

References

1. ICH Q1A(R2) Stability Testing of New Drug Substances and Products. U.S. FDA guidance for industry, November 2003. FDA docket FDA-2002-D-0222
2. ICH Q5C Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products. U.S. FDA guidance for industry, July 1996. FDA guidance, July 1996 · 61 FR 36466
3. ICH Q1 Stability Testing of Drug Substances and Drug Products. U.S. FDA draft guidance for industry, June 2025. FDA docket FDA-2025-D-1106