While perusing the current USP <11>, USP Reference Standards, which became effective on December 1, 2025, it was noted that the USP Reference Standard description was amended to state “highly characterized physical materials or digital data demonstrated to have the appropriate qualities to support their intended use as references for comparison in compendial tests.”  The General Chapter further states that “USP Reference Standards may be presented either as physical materials or as datasets in the form of USP digital Reference Standards (dRS) representing the identity and/or a quantity of a substance” (emphasis added).  Traditionally, USP has provided reference standards in the form of physical materials, either in vials or ampoules.  However, the concept of a digital reference standard is not entirely new.

In the previous version of USP <11> (effective November 1, 2020), digital reference standards were mentioned once, in the Qualitative Determinations section, where it was stated that “Digital and Visual USP RS: Unlike chemical reference materials, these USP RS are not physical materials used in chemical analysis.  Instead, these visual images are used by analysts to compare test articles to ensure that they meet compendial requirements.”  This text has since been revised in the current version of USP <11>, which states that “Visual USP RS may be provided as USP dRS encoded as digital data files suitable for direct analysis via software or conversion to visual images in the form of photographs, spectra, or other patterns.”

The current USP <11> also states, “Criteria for proper use of USP dRS in compendial procedures are detailed in the applicable USP–NF monographs and/or general chapters.  USP dRS may require utilization of specialized software, appropriate USP digital Certificates, or permits.”  So, which compendial procedures are using USP dRS?  The results of a query of the USP, using the search terms “dRS” and “digital,” suggests that digital reference standards have not yet been implemented in the monographs as none were identified.  When the USP reference standard catalogue was queried for “dRS,” no standards with the dRS designation were found.  Thus, it seems that the USP has introduced the concept of compendial digital reference standards, but it has not yet implemented any dRS or updated USP monographs for digital reference standards.  This appears to be further supported by a USP press release from January 22, 2026 titled “USP to Lead Development of Digital Quality Standards to Support Adoption and Regulatory Confidence,” which announced that the USP was developing dRS and digitally structured compendial methods (digital Documentary Standards (dDS)) for digital workflows to be integrated into the USP-NF.  The press release did not identify whether any dRS and dDS were implemented or pending implementation.

After thinking about the digital standard concept, which includes digital reference standards and digital documentary standards, you may have questions, as did I, such as:

Is a digital reference standard a new concept?  Would the FT-IR library that I compare my sample spectrum to (with a % match) be considered a dRS or a dDS?

Digital reference standards are not an entirely new concept as FT-IR libraries have been used for identification testing for several decades.  For USP monograph testing, it is acceptable to compare the spectrum of the material under test against a spectrum of the current USP reference standard saved in the instrument’s library.  However, it is a new concept from the USP standpoint as the USP has previously only offered physical reference standards and not digital reference standards.  The digital FT-IR scan saved in the instrument’s library would be considered a dRS.

What are USP digital Reference Standards (dRS)?

As per the USP website (here), USP dRS are “digital data demonstrated to have the appropriate qualities to support their intended use as references for comparison in compendial tests.”

What are USP digital Documentary Standards (dDS)?

As per the USP website, USP dDS are “machine-readable in a validated, digital-first format, designed to power advanced laboratory workflows and enable the adoption of new technologies into quality systems.”  An example of a dDS would be a digital version of a USP monograph test method that could be integrated into an electronic laboratory notebook.

How are USP digital Reference Standards (dRS) established?

As per USP <11>, the datasets obtained from a physical reference standard/material or from a set of authentic samples may be used to establish a dRS.  A multidimensional measurement dataset from a set of reference substances may also be used to establish a dRS.  In addition, theoretical calculations may also be used to optimize the USP dRS with experimental data from reference materials.

What are the benefits of digital standards (dRS and dDS)?

As per the USP website, manufacturers can advance digitization without compromising quality, if dRS and dDS are embedded into connected systems, as there would be an audit trail of every step taken, including version-controlled reference materials and simplified data reviews.  In addition, there would be less variability across laboratories as the digital workflows and reference materials would be standardized.  Furthermore, the implementation of digital standards (dRS and dDS) should reduce delays, streamline operations, free resources, drive continuous improvement, and support innovation.

Are there any concerns with digital standards (dRS and dDS)?

The biggest hurdle to overcome would be acceptance by manufacturers and regulatory agencies.  As with all new technologies, such as Artificial Intelligence (AI) and new analytical instrument techniques and approaches, there is a hesitance for acceptance without an adequate and supported justification, as is anticipated to be a regulatory expectation.

Do the Japanese Pharmacopoeia (JP) and European Pharmacopoeia (EP) have dRS available?

Currently the JP only offers physical reference standards.  However, the EP, in a sense, does offer digital reference standards.  Since at least July 2021, reference spectra have been available in a pdf format from the EP; these are authenticated IR spectra to be used for identifying pharmaceutical substances.  The EP does not have digital reference standards, as defined by the USP, consisting of digital data files that may be used for direct analysis via software or converted to visual images in the form of photographs, spectra, or other patterns.

Digital standards are in their infancy and it will be interesting to see how this concept is further implemented and accepted by manufacturers and regulatory agencies.  If you have any questions concerning USP reference standards or the use of their digital analogs by your firm, please reach out to us at LCS@LachmanConsultants.com for a consultation.