An international reference reagent is a WHO reference standard whose activity is defined by WHO in terms of a unit. This category of reference standard is intended to be interim and is not envisaged to be replaced.
Enough information should have been gathered in the period following a material’s establishment as a reference reagent to allow it to be considered as an international standard. Once a material is established as an international standard, the potency is expressed in international units (IUs).
Following evaluation in an international collaborative study, it is expected that the formally assigned potency in IU will be identical to the original assigned unitage. Assignation of a different value would only be done on the basis of sound scientific reasons.
The class of reference reagent was established in response to the speed of development of some new biological products. The need for reference standards with an official WHO status is often identified as a result of both regulatory and scientific activities
In order to shorten the time between the preparation of a candidate material and its distribution, it is enough for a limited number of laboratories to examine a characterised product and agree to the assignment of potency as expressed in units. As a minimum, the bulk material used in the preparation should be shown to retain biological activity consistent with the assigned unitage by a competent laboratory, for example the manufacturer, and this biological activity should be confirmed by an independent laboratory, preferably a WHO collaborating laboratory.
The candidate preparation should be shown to meet the specifications for filling and stability as defined in WHO guidelines.
The WHO collaborating centre provides WHO with the necessary information on the source and characteristics of the preparation. Physico-chemical characterisation should be included if at all possible. Such reference reagents should not be product-specific.
An international reference panel is a group of reference materials established to collectively aid the evaluation of assays or diagnostic tests. International reference panels comply with the general requirements for WHO reference standards, except that in some cases it might not be necessary to assign unitages to each individual member of a panel.