Since 2002, the National Institute of Standards and Technology (NIST) and the National Institutes of Health’s (NIH) Office of Dietary Supplements (ODS) have collaborated to develop multiple tools to help laboratories perform ingredient identification and chemical quantification analyses. The major tools offered by NIST are reference materials and quality assurance programs (QAPs), both of which provide supplement brands and labs the means to objectively determine and demonstrate the quality of their measurements.

NIST reference materials for quantitation are intended to be used in method development and method validation, and as a quality control (QC) tool. These quantitative reference materials are well characterized matrix-based materials that are designed to represent the range of analytical challenges experienced by quality control and testing labs. NIST reference materials designed to meet the needs of dietary supplement analyses are often produced in suites including raw materials, ingredients and finished products. The supplement reference materials have been packaged and evaluated for homogeneity/stability and have been value assigned for specific botanical marker compounds, contaminants, and nutritional and toxic elements as appropriate. Through regular use of a reference material and control charts, laboratories can be assured that the entire measurement process is valid, from calibration, through sample preparation, instrumental analysis and data processing.

NIST and NIH ODS also administer a laboratory QAP focused on the measurement of nutrients, phytochemicals and potential contaminants in dietary supplements and foods. QAPs are used by individual laboratories to ascertain their performance compared with the rest of the community and compared with the “correct” answers when the data has been accurately assessed, and they can be used to troubleshoot analytical methods. These programs are structured similarly to proficiency testing or round robin testing, except pass/fail scores are not assigned.

The NIST/NIH Health Assessment Quality Assurance Program (HAMQAP) focuses on eight measurement categories, including nutritional elements, toxic elements, water-soluble vitamins, fat-soluble vitamins, fatty acids, botanical marker compounds and contaminants. Participants determine in which individual studies they will participate during a given exercise and the samples to be measured are provided by NIST. Laboratories are encouraged to use in-house methods for analyses and are asked to answer detailed questions about sample preparation, analytical separations (if used), methods of detection and approaches to calibration. These questions allow NIST and participating labs to analyze the results and find systematic sources of bias that may explain conflicting or inconsistent results. For example, in one QAP exercise, participants were able to perform measurements with a higher degree of concurrence when they used a common calibrant material. In another exercise, NIST was able to identify sources of measurement bias in a sample preparation process that involved extraction, hydrolysis, derivatization and instrumental analysis.

When contract laboratories or manufacturers can provide relevant data, including control charts, reference material results, method validation data and certificates of performance from QAPs and proficiency test data, it is possible to evaluate the scientific validity of the methods used as well as the performance of the laboratory. To accomplish this, it is important for manufacturers and testing labs to use both reference materials and QAPs. While QAPs serve as means to establish the capabilities of a lab, they only apply to specific analytes in certain matrices. HAMQAP studies are not designed to include the same specific analytes in every effort; therefore, it would be difficult for laboratories to track proficiency based on QAP participation alone.

To establish a record of performance from day to day, instrument to instrument, and analyst to analyst, it is important to consistently run control materials. When available, the best control materials are externally developed reference materials with quantitative values (either certified or non-certified) for the analytes of interest and associated uncertainties indicating that sources of measurement bias have been evaluated. Often there are materials available with the analyte of interest, but in a dissimilar matrix (e.g., powdered leaf instead of an aqueous extract from leaf) or at a prohibitive cost. In these cases, it is essential for labs to develop in-house reference materials that can be value assigned and used in QC approaches that can be compared to results with an external reference material.

NIST and NIH ODS are working to help dietary supplement labs and researchers tackle longstanding and emerging analytical challenges. Establishing identity and authenticity in dietary supplements is essential for ensuring the quality and safety of the products. This issue has long been an area of consideration for NIST and NIH ODS, and efforts to develop reference materials specifically designed to be fit-for-purpose for botanical identity testing have recently increased. Currently NIST botanical reference materials are available that are guaranteed to be representative of the article(s) in commerce, to use them in comparison to a manufacturer’s materials in production. Most of the focus has been on plant materials; however, industry needs processed ingredients and finished product reference materials as well. The appropriate design of reference materials fit for a wide range of tests, including DNA analyses, thin-layer chromatography (TLC), and non-targeted spectroscopic and spectrometric methods, can be challenging and is currently being explored. Furthermore, a known challenge in demonstrating authenticity through quantitative analyses is that it can be difficult to obtain enough authentic samples to create a statistically significant model of “positives” that represents the biological and chemical diversity found within a plant species, and NIST and NIH ODS are actively engaging with stakeholders to find solutions to this barrier.

If specific needs are not available, NIST staff are happy to work with the industry to develop reference materials (if there is enough need) and to provide guidance on developing in-house reference materials. NIST and NIH are interested in discussing new QAP studies to meet the needs of the community.

Learn more about the implementation and adhering to testing methods from Catherine A. Rimmer during the “Trust in Testing: Contract Labs for Safe, Compliant Supplements” session on Thursday, Oct. 17, 2019 at 2:00 p.m. at SupplySide West in Las Vegas. This session is underwritten Venable.

Catherine A. Rimmer is natural products program coordinator at the National Institute of Standards and Technology (NIST), and Adam J. Kuszak is director of the analytical methods and reference materials program (AMRM) at the National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Laboratories can learn more about HAMQAP, by signing up for an account at qa.nist.gov//hamqap and more about NIH efforts in analytical resources for dietary supplement labs, by visiting the ODS Analytical Methods and Reference Materials Program website.