Reference standards serve to test production lots. In the context of food safety, the control of hazards potentially associated with foods typically involves the application of control measures in the food chain, from primary production, through processing, to consumption. The Guidelines for the validation of food safety control measures of the Codex Alimentarius Commission present information on the concept and nature of validation, tasks prior to validation, the validation process and the need for re-validation (more 3.3.6.).

EMEA (1) requires manufacturers to provide a reference standard at the time of submission. This should either be an already established international or national standard, or in the case of new molecules, an in-house primary reference material with known characteristics used for calibration purposes. Typically, the same reference material is used in different types of tests (e.g. biological activity, physicochemical characteristics, purity), although if necessary, it is possible to use separate reference materials (e.g. for impurities of different origin). The application procedure also requires the manufacturer to provide a description of the manufacture and/or purification of reference materials (if applicable), along with documentation of the characterization, storage conditions and stability of reference material(s).

Another key step is the validation of the analytical procedures in the specifications. According to EMEA's guidelines (1), it needs to be done prior to submission of the application to the regulatory authorities and must follow the applicable guidelines. These are the ICH Harmonised Tripartite Guidelines "Validation of Analytical Procedures: Definitions and Terminology" and "Validation of Analytical Procedures: Methodology". Exceptions are possible in cases when the analysis of certain biotechnological and biological products requires unique tests. Regarding food derived from modern biotechnology, food authentication, food speciation etc., the Codex Alimentarius Commission places an emphasis on the acceptance of methods of analysis which have been validated through a collaborative trial conforming to an internationally accepted protocol according to ISO 5725:1994 or the AOAC/IUPAC Harmonized Protocol.