Certified reference materials

ISO REMCO definitions ISO REMCO, the ISO committee responsible for guidance on reference materials within ISO, defines the following classes of reference material: ; Reference Material: Material, sufficiently homogeneous and stable with respect to one or more specified properties, which has been established to be fit for its intended use in a measurement process. ; Certified Reference Material: Reference material characterized by a metrologically valid procedure for one or more specified properties, accompanied by a certificate that provides the value of the specified property, its associated uncertainty, and a statement of metrological traceability. Alternative terminology Other bodies may define classes of reference material differently. WHO guidelines for biological reference materials use the WHO terms • Primary chemical reference substance: a chemical reference substance ... whose value is accepted without requiring comparison to another chemical substance. • Secondary chemical reference substance: substance whose characteristics are assigned and/or calibrated by comparison with a primary chemical reference substance. The United States National Institute of Standards and Technology (NIST) uses the trade marked term Standard Reference Material (SRM) to denote a certified reference material that satisfies additional NIST-specific criteria. In addition, commercial producers adhering to criteria and protocols defined by NIST may use the trademark "NIST traceable reference material" to designate certified reference materials with a well-defined traceability linkage to existing NIST standards for chemical measurements. == Types of reference material ==

ILAC describes the following five types of reference material: • Pure substances; essentially pure chemicals, characterised for chemical purity and/or trace impurities. • Standard solutions and gas mixtures, often prepared gravimetrically from pure substances. • Matrix reference materials, characterised for the composition of specified major, minor or trace chemical constituents. Such materials may be prepared from matrices containing the components of interest, or by preparing synthetic mixtures. • Physico-chemical reference materials, characterised for properties such as melting point, viscosity, or optical density. • Reference objects or artifacts, characterised for functional properties such as taste, odour, octane number, flash point and hardness. This type also includes microscopy specimens characterised for properties ranging from fibre type to microbiological specimens. == Production ==

Principal steps in producing certified reference materials The preparation of certified reference materials is described in general in ISO Guide 17034 and in more detail in ISO Guide 35. Preparation of biological reference standards is described in WHO Guidance. In addition it may be important to assess the commutability of a reference material; this is especially important for biological materials. natural materials are rarely homogeneous on the scale of grams so production of a solid natural matrix reference material typically involves processing to a fine powder or paste. Homogenization can have adverse effects, for example on proteins, so producers must take care not to over-process materials. For example, stabilizing agents such as antioxidants or antimicrobial agents may be added to prevent degradation, liquids containing certified concentrations of trace metals may have pH adjusted to keep metals in solution, and clinical reference materials may be freeze-dried for long term storage if they can be reconstituted successfully. An equal number of subsamples (usually two or three) is then taken from each CRM unit and measured. Subsamples are measured in random order. Stability assessment Stability assessment and testing strategies Stability is among the essential properties of a CRM (see definitions above), and stability assessment is accordingly required for certified reference materials. Other reference materials will usually undergo experimental tests of stability at some point prior to the material being distributed for sale. Where reference materials are certified for more than one property, stability is expected to be demonstrated for every certified property. CRMs are typically monitored at a range of temperatures and the results are used to predict the rate of change at a proposed, usually low, storage temperature. Often, the prediction uses a well known degradation model such as an Arrhenius model. The principal disadvantage of accelerated studies is that reference materials, like any other material, can degrade for unexpected reasons over time, or can degrade following different kinetic models; predictions can then become unreliable. Isochronous studies In most stability studies, real-time or accelerated, a few units of the reference material are tested at intervals. If the measurement system used for testing the materials is not perfectly stable, this can generate imprecise data or can be mistaken for instability of the material. To overcome these difficulties, it is often possible to move RM units, at intervals, to some reference temperature where they remain stable, and then test all the accumulated units - which have undergone different exposure times - at the same time. This is referred to as an isochronous study. This strategy has the advantage of improving the precision of data used in assessing stability at the cost of delaying results until the end of the stability study period. == See also ==