Accreditation of RM providers
The monographs contain specific instructions regarding the use of neat RM to produce reference solutions, which are used in the actual pharmacopoeia test method. These solutions are internationally referred to as working measurement standards, and are prepared by dissolving a known amount of a chemical substance (in this case the neat RM) into a known volume of solution. Analysis of these solutions on a conductivity or TOC instrument is required to meet certain criteria within the monograph, such as routine system suitability checks and calibration performance.
RM as defined by the EP can be found in section 51200 Reference Standards, which defines RM in the same manner as the International Standards Organization (ISO). ISO Guide 30;1992 Terms and Definitions used in Connection with Reference Material and ISO Guide 99:2007 International Vocabulary of Metrology Basic and General Concepts and Associated Terms both have similar definitions for measurement standards. ISO Guide 30:1992 defines RM as: "Material, sufficiently homogeneous and stable with respect to one or more specific properties, which has been established to be fit for its intended use in a measurement process." CRM is defined in EP and ISO Guide 30 as: "Reference material characterised by a metrologically valid procedure for one or more specific properties accompanied by a certificate that provides the value of the specific property, its associated uncertainty, and a statement of metrological traceability." CRM is accompanied by documentation issued by an authoritative body under an accreditation upon which the provider has been proven competent.
RM, as defined by both the EP and USP, applies only to the neat material supplied and prescribed for use in the pharmacopoeia. There are no instructions in the monographs that specify the preparation of the reference solution. Therefore, the actual performance of the preparation of the reference solution from the RM doesn't contain the traceability needed to assure the quality of the solution used in the test method. As such, the reference solutions supplied — and upon which the calibration and system suitability are performed — are not actually the RM referenced in the monographs. Reference solutions provided by third parties should be produced as CRMs, such that the user is confident of the traceability, homogeneity and stability of the solutions for their testing.7–11