What are Certified Reference Materials?
The use of reference materials in the laboratory is widespread. These materials are most often used as control samples for control charting, drift correction, second-source verification of calibration, method validation, evaluation of method bias and measurement uncertainty, instrument conditioning, and demonstration of analyst or laboratory proficiency. Many ASTM International standards provide guidance for use of reference materials and certified reference materials, or instructions for their preparation.
The following definitions are provided in general requirements for the competence of reference material producers (ISO 17034):
- Reference material (RM) – 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 (CRM) – Reference material characterized by a metrologically valid procedure for one or more specified properties, accompanied by a reference material certificate that provides the value of the specified property, its associated uncertainty, and a statement of metrological traceability.
- Reference material producer (RMP) – Body (organization or company, public or private) that is fully responsible for project planning and management; assignment of, and decision on property values and relevant uncertainties; authorization of property values; and issuance of a reference material certificate or other statements for the reference materials it produces.
Reference material is a generic term for material, with or without an assigned accepted reference value (ARV), that is used in a laboratory for a specific purpose. These materials can be produced in-house or in a designated laboratory. They can be used internally, distributed for free, or commercially available. The highest quality reference materials are produced by RMPs that maintain an ISO 17034-compliant quality system and demonstrate their technical competence through a formal, independent verification by an accreditation body (AB) of their choice.
Reference materials listed on an RMP’s scope of accreditation issued by their AB are commonly referred to as accredited reference materials. These materials are produced by highly-skilled personnel, follow high-quality standards with well-planned and documented production processes, and are backed up by objective evidence in the form of quality and technical records. Therefore, use of accredited RMs provides laboratories with confidence in the quality, consistency, and fitness for purpose of the RM.
ASTM-published standards provide instructions for production of reference materials, including the standard guide for production, testing, and value assignment of in-house reference materials for metals, ores, and other related materials (E2972) and the standard practice for rubber–preparation, testing, acceptance, documentation, and use of reference materials (D4678). However, ASTM is not an accreditation body, and, therefore, does not grant formal recognition of technical competence and accreditation for these materials.
A subset of accredited RMs are CRMs with a statement of uncertainty and metrological traceability of the certified property values. Preferably, the certified property value should be traceable to the International System of Units (SI). When this is technically not possible, demonstration of metrological traceability to an appropriate reference is acceptable. The assigned property value uncertainty is associated with the production of a CRM and needs to at minimum include the following components: property value characterization, homogeneity, long-term stability (shelf life), transportation stability, and repeated-use stability, when applicable.
Per ISO 17034, statistical methods used for characterization of a CRM, property value assignment, and its uncertainty, need to be appropriate for the application. In addition, RMPs are not allowed to outsource the assignment or the authorization (approval) of property values and their uncertainties.
Guidance for characterization and assessment of homogeneity and stability is provided in ISO Guide 35. The committee on quality and statistics (E11) maintains several standards describing statistical methods that are applicable to evaluation of CRMs, such as:
- Standard practice for calculating sample size to estimate, with specified precision, the average for a characteristic of a lot or process (E122)
- Standard guide for sampling design (E1402)
- Standard practice for dealing with outlying observations (E178)
- Standard practice for calculating and using basic statistics (E2586)
- Standard practice for evaluating equivalence of two testing processes (E2935)
- Standard practice for regression analysis with a single predictor variable (E3080)
- Standard guide for homogeneity of samples and reference materials used for inter- and intra-laboratory studies (E3264)
Although the RMP can seek the advice of a contracted statistician, they must have competent personnel on staff who can defend the implemented statistical methodology and authorize the assigned property value and uncertainty. When a contracted statistical consultant is engaged, the RMP needs to assure that the consultant has knowledge in all elements of ISO Guide 35, as well as an understanding of laboratory and production processes used by the RMP. In addition to providing advice on the use of statistical methodology for assignment of property value and its uncertainty, a statistician must also train the RMP’s staff so they can competently describe and defend the implemented statistical practice and review and authorize the assigned property value and its uncertainty.
When distributed to users, accredited RMs are accompanied by documentation endorsed using an accreditation symbol (seal) with the RMP’s accreditation scope certificate number. Table 1 provides a comparison of information on a product information sheet, a document distributed with an accredited RM, and information on a CRM certificate.
Although expensive, CRMs are becoming indispensable in assuring the validity of laboratory results, especially when metrological traceability of results is important for users of measurement data. For example, calibration of analytical instruments with CRMs will establish metrological traceability of measurements. Known ARVs and uncertainties will increase confidence in the accuracy and precision of calibration. Using RMs for initial (second-source) confirmation of calibration or for quality-control materials will provide confidence in the validity of measurement results.
Polona Carson, Ph.D., is quality management specialist at Neptune and Company, Inc. Carson is also an active member of the committee on quality and statistics (E11) and member at large of the executive subcommittee (E11.90).
John Carson, Ph.D., is senior statistician for Neptune and Co. and the Data Points column coordinator. Carson is a member of the committees on quality and statistics (E11), petroleum products, liquid fuels, and lubricants (D02), air quality (D22), environmental assessment, risk management, and corrective action (E50), and personal protective clothing and equipment (F23).