Holding Data to a Higher Standard, Part I: A Guide to Standard Production, Use, and Data Validation

June 20, 2018
Abstract / Synopsis: 

Testing, manufacturing, and research laboratories face more challenges and regulations than ever before. Many accreditation bodies issue increasing numbers of guidelines. Regulatory agencies increase the number of compounds and elements that need to be reported while the levels of detection required are being decreased. There is often a lot of time, effort, and money invested in deciphering the data and determining its validity and accuracy. Here, we explore the accreditation, regulation, and guidelines around the manufacture and use of standards and certified reference materials (CRMs) and discuss the variables from accreditation to uncertainty involved in producing and using standards and reference materials. We also discuss the changing field of chemical analysis and the challenges that arise from the pursuit of increasingly smaller levels of detection and quantitation, including clean laboratory techniques to reduce analytical error and contamination in standards use and data collection.

The complex question of whether or not data or results are valid involves both the testing process and the actual calculated results. The question of whether or not the results reflect the true answer becomes a function of the accuracy of your standards.

Standards in the laboratory industry can be either procedural standards or metrological standards. A procedural or method standard is an authoritative quality system, procedure, or methodology considered by general consensus as the approved model or method. These types of standards are created by organizations such as the International Organization for Standardization (ISO), Association of Official Agricultural Chemists (AOAC), and American Section of the International Association for Testing Materials (ASTM), to name just a few. In some instances, laboratories seek accreditation to validate their procedures and methods to ensure some benchmark of accuracy and quality.

The second important type of standard used to determine data validity are metrological standards. A metrological standard is the fundamental example or reference for a unit of measure. Simply stated, a standard is the “known” to which an “unknown” can be measured. Metrological standards fall into different hierarchical levels. The highest levels of metrological standards are primary standards. A primary standard is the definitive example of its measurement unit to which all other standards are compared and whose property value is accepted without reference to other standards of the same property or quantity (1,2). Primary standards of measure, such as weight, are created and maintained by metrological agencies and bureaus around the world.

Secondary standards are the next level down within the hierarchy of standards. Secondary standards are close representations of primary standards that are measured against primary standards. Chemical standards companies often create secondary standards by comparing their material to a primary standard, making that standard traceable to a primary standard source. The third level of standards are working standards, which are often used to calibrate equipment and are created by comparison to a secondary standard.

There are also many standards designated as reference materials, reference standards, or certified reference materials. These materials are manufactured or characterized for a set of properties and are traceable to a primary or secondary standard. If the material is a certified reference material (CRM), then it must be accompanied by a certificate that includes information on the material’s stability, homogeneity, traceability, and uncertainty (2,3). 

Stability, Homogeneity, Traceability, and Uncertainty

Stability is when a chemical substance is nonreactive in its environment during normal use. A stable material or standard will retain its chemical properties within the designated “shelf life” or within its expiration date if it is maintained under the expected and outlined stability conditions. A material is considered to be unstable if it can decompose, volatilize (burn or explode), or oxidize (corrode) under normal stated conditions.

Homogeneity is the state of being of uniform composition or character. Reference materials can have two types of homogeneity: within-unit homogeneity or between-unit (or lot) homogeneity. Within-unit homogeneity means there is no precipitation or stratification of the material that cannot be rectified by following instructions for use. Some reference materials can settle out of solution, but are still considered homogeneous if they can be redissolved into the solution by following the instructions for use (that is, sonicate, heat, shake). Between-unit or lot homogeneity is found between separate packaging units.

Traceability is the ability to trace a product or service from the point of origin through the manufacturing or service process through to final analysis, delivery, and receipt. Reference materials producers must ensure that the material can be traced back to a primary or secondary standard.

Uncertainty is the estimate attached to a certified value that characterizes the range of values where the “true value” lies within a stated confidence level. Uncertainty can encompass random effects such as changes in temperature, humidity, drift accounted for by corrections, and variability in performance of an instrument or analyst. Uncertainty also includes the contributions from within-unit and between-unit homogeneity, changes because of storage and transportation conditions, and any uncertainties arising from the manufacture or testing of the reference material.

Types of Uncertainty

There are two basic classifications for types of uncertainty: Type A and Type B uncertainty. Type A uncertainty is associated with repeated measurements and the statistical analysis of the series of observations. Type A uncertainty is calculated from the measurement’s standard deviation divided by the square root of the number of replicates.

  1.  International Vocabulary of Metrology – Basic and General Concepts and Associated Terms (VIM), 3rd Edition (JCGM member organizations [BIPM, IEC, IFCC, ILAC, ISO, IUPAC, IUPAP and OIML] 200, 2012). Available at: http://www.bipm.org/vim.
  2. International Organization for Standardization (ISO) Guide 30, "Terms and Definitions Used in Connection with Reference Materials."
  3. International Organization for Standardization (ISO) ISO Guide 17034, "General Requirements for the Competence of Reference Material Producers."
  4. Standard Format and Guidance for AOAC Standard Method Performance Requirement (SMPR) Documents (Version 12.1; 31-Jan-11).

Patricia Atkins is a Senior Applications Scientist with SPEX CertiPrep in Metuchen, New Jersey. Direct correspondence to: [email protected]

How to Cite This Article

P. Atkins, Cannabis Science and Technology 1(2), 44-48 (2018).