Standard substances are stored in accordance with the instructions in the certificate or accompanying documentation. They must be stored in climatically controlled rooms or storage areas.
The substances should generally be stored in tightly sealed containers in a dry environment that is protected against humidity and heat.
Under dry conditions is normally defined as storage at a relative humidity below 40% (higher values up to 45% are permitted) or in tightly sealed containers that are water vapour proof.
Controlled room temperature refers to a 20°C to 25°C range. Temperatures as low as 15°C and up to 30°C are permitted if the mean kinetic temperature remains ≤25°C. Temperatures up to 40°C for <24 h are also permitted (source: Storage conditions in accordance with the chapter "Preservation, Packaging, Storage and Labelling" in the USP). Other USP storage conditions are outlined in Figure 1.
Figure 1: USP storage conditions
Storage under stricter conditions than required is normally permitted if appropriate for the substance. However, not every standard substance or reagent is suitable for cool or cold storage (e.g. hygroscopic substances and some liquids). In order to minimise the impact of environmental conditions or freezing and thawing on the quality of a substance, the smallest possible containers or portions should be stored. Strongly hygroscopic substances must be stored in a desiccator and light-sensitive substances in darkness. Certain highly sensitive chemicals must be stored under a protective gas, e.g. argon. Narcotic standards must be stored with a view to the increased security restrictions that apply to the substances (in accordance with the requirements of the Federal Opium Agency).
The expiry date must be indicated on every standard substance and reagent and – where necessary – the shelf life after opening. The shelf life after opening should not exceed the expiry date of the unopened container. When this date has been reached, the substances must be disposed of or their quality must be retested. If the result of the retest is positive, a new expiry date must be specified.
Shelf lives are normally defined based on the information in the certificate or accompanying supplier documentation. The shelf life of prepared solutions is taken from the relative test instructions or validation documents and must be observed during their use.
Research results from literature can also be used for a specific substance or substance family, if there are no supplier or manufacturer instructions.
If information about the shelf life is not available, it must be determined using suitable tests and stability storage for a defined range (cf. guidelines on stability testing, e.g. ICH Q1A). Validated stability indicating methods must be used for this purpose. All relevant tests should be carried out. Based on this stability data, the expiry date and time frame for re-evaluation and/or retesting are set.
The storage requirements for reagents are similar to the requirements for standard substances. Less complex methods can be used to determine the shelf life. As in the case for standard substances, the accompanying supplier documentation is the main point of reference. Information on the shelf life can also be found in the literature!
Figure 2 lists some sample references from the literature.
Figure 2: List of shelf lives of reagents and solutions taken from the literature
The impact of fresh or older reagents on the results can be determined when the analytical method is validated during the robustness evaluations. In accordance with ICH Q2B, the stability of solutions influences the analytical method and must be examined as part of the robustness. The shelf live can be assigned based on the result. Critical results from these tests can also be checked during the system suitability test.
Another option is the use of a risk analysis to prove that ageing of the reagent does not affect the result. This can be scientifically argued, or proven using quotations from the literature or experimentation.
Formal stability testing can be mandatory for solutions (FDA) that are used for the quantitative determination of content and impurities.
Reagents play an even more important role during bioanalytical testing (cell assays, immunochemical tests, etc.). The problem is mostly dealt with during the validation of the analytical methods and the qualification of reagents.
The text is an excerpt from the GMP MANUAL.
Dr. Markus Limberger
PHAST GmbH, Homburg