The Value of Primary Working Standards in Pharmaceutical Quality Control

The use of primary API quantitation standards as working standards has clear advantages over the widely established use of secondary standards. According to United States Pharmacopeia in 2021, secondary standards carry a higher measurement uncertainty than the primary standard upon which they depend. This may lead to out-of-specification (OOS) results, which are not realized by the user. It is argued that orthogonal quantitative methods, as recommended by FDA for API standards, can be used to establish primary working standards, which can then be used in multiple analytical methods. An example is provided in this article, which details how to calculate the expanded measurement uncertainty (U) for the certified assay value by considering two orthogonal assay methods. Key concepts used include the root sum of squares of the uncertainties to reflect uncorrected method bias in the expanded measurement uncertainty U of a reference standard, rules for treating measurement uncertainty as described by Eurachem’s guide on quantifying uncertainty in analytical measurement, and the introduction of guard bands to protect acceptance zones. It is argued that commercially well-available reference materials produced under the scope of an ISO 17034 accreditation can be used as assay standards for frequent testing within compendial and non-compendial analytical methods.

Peer-reviewed research

Submitted: June 3, 2022
Accepted: July 20, 2022

About the Author

Moritz Perscheid is a pharmaceutical chemist at LGC.

Article details

Pharmaceutical Technology
Volume 46, Number 9
September 2022
Pages: 34-39

Citation

When referring to this article, please cite it as M. Perscheid, "The Value of Primary Working Standards in Pharmaceutical Quality Control," Pharmaceutical Technology 46 (9) (2022).