See also Section 6.3 in Part A of these guidelines.

A system must be in place to ensure the continued fitness for use of the reference substances. Normally, a re-test programme is applied.

Reference substances are regularly tested for stability during their storage. A testing programme is applied which is designed to detect any sign of decomposition at an early stage using appropriate analytical techniques. The methods employed are suitable for small quantities, are both rapid and sensitive, and will have been performed during the establishment phase.

The frequency and extent of re-testing reference substances depends on a number of factors including stability, container and closure system, storage conditions, hygroscopicity, physical form and intended use. The frequency of testing and the testing methods to be employed for each reference substance must be documented.

Reference substances should preferably be subdivided and presented as single-use units. However, if the reference substance is kept in a multiuse container then re-testing will need to be more frequent because there is a greater risk of the uptake of moisture and/or decomposition of the reference substance. The testing methods should include the determination of water content and decomposition products. The maximum permitted variation from the assigned value should be predefined and if exceeded the batch should be re-established or replaced.

If the batch of primary reference substance used to calibrate the secondary reference substance is replaced, the secondary reference substance must be recalibrated against the new batch of the primary reference substance.