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Calibration, Qualification & Validation

Reference materials are substances or materials with well-established and consistent values of one or more properties. They are essential in ensuring measurement accuracy through method calibration, validation, uncertainty estimation, and value assignment.

 

Reference materials are crucial in analytical testing workflows and quality assurance schemes. They are produced under strict conditions and differ from standard laboratory reagents due to their certified and traceable data. The world of reference materials encompasses various concepts, including Certified Reference Materials (CRMs), different quality grades, metrological traceability, and certificates of analysis, making it a diverse and sometimes confusing field.

 

Reference materials are categorized into five main groups based on their quality grades, ranging from national metrology and primary standards to Certified Reference Materials (CRMs), Reference Materials (RMs), Analytical Standards, and research grade or research chemicals. The certification and traceability requirements become more stringent as we move from lower to higher quality grades. While national governments provide top-level standardization, CRMs and RMs adhere to specific ISO guidelines such as ISO 17034, ISO/IEC 17025, and ISO Guide 31.

 

Producers of reference materials must meet these ISO requirements to manufacture CRMs or RMs. For Certified Reference Materials, a Certificate of Analysis must be provided, with information defined by the aforementioned ISO guidelines. Quality specifications for the last two categories are established by independent producers rather than by a national government or ISO accreditations specific to CRMs and RMs.

National Metrology Standard (e.g. NIST, JRC, NMI Australia)

Compendial Standard (e.g. USP, EP, BP, JP, IP)

  • Issued by an authorized body
  • Considered to provide the highest level of accuracy and traceability

 

Certified Reference Material (CRM) (ISO 17034, 17025)

  • Considered to provide the highest level of accuracy, uncertainty, and traceability to an SI unit of measurement
  • Manufactured by an accredited Reference Material Producer

 

Reference Material (RM) (ISO 17034)

  • Fulfilling ISO requirements which are less demanding than for CRMs
  • Manufactured by an accredited Reference Material Producer

 

Analytical Standard (ISO 9001)

  • Certificate of Analysis available
  • Level of certification varies

 

Reagent Grade / Research Chemical

  • May come with a Certificate of Analysis
  • Are not characterized for use as reference materials

Reference materials are utilized in three distinct formats ‒ powder, solution, or matrix ‒ based on the method’s demands or product availability. The correct choice of reference material is vital for a laboratory’s testing application, as the accuracy of the results relies on the quality of the reference used.

 

SELECTION OF REFERENCE MATERIALS BASED ON TESTING PURPOSE

The qualification and calibration of instruments necessitate establishing and maintaining their traceability, which can be achieved through the use of selected reference materials. In routine system suitability applications, it is essential to choose practical, easy-to-use, reliable, and cost-effective reference materials suitable for daily use. During method validation, highly accurate and precise reference materials are crucial to demonstrate the accuracy and precision of the laboratory method.

For identity and screening purposes, reference materials must possess proven authenticity and identity as significant attributes. In applications involving quantitation, assays, or stability assessments, stable and accurate reference materials are indispensable.