Thermo Scientific™ Watson LIMS™ software version 7.7 introduces a dedicated Internal Standard (IS) response review workflow. IS response review aims to reduce the risk of over- or under-reporting final concentration data based on anomalous internal standard peak area. The new capabilities align with the U.S. Food and Drug Administration (FDA) guidance “Evaluation of Internal Standard Responses during Chromatographic Bioanalysis.” Here, we examine IS response review and how Watson LIMS supports IS review best practices.
What is IS Response?
The FDA guidance document defines IS response as a measurement of the signal from the IS, which is typically generated during liquid chromatography-mass spectrometry bioanalysis. In analytical chemistry, ISs are usually a structural analog or stable isotope of an analyte of interest and are commonly used in chromatographic analytical methods to correct for variability in sample processing and analysis.
A known IS quantity is added to all samples, including quality controls (QCs), calibration standards (Cals), and study samples prior to sample prep. The specific IS selected for a method should have similar properties to the analyte of interest so that it tracks to any changes within the analyte measurement that may occur during sample processing and data acquisition.
The FDA guidance document provides recommendations to sponsors, applicants, and contract research organizations regarding IS response variability in chromatographic analytical data submitted in investigational new drug applications, new drug applications, abbreviated new drug applications, biologics license applications, and supplements. The document provides the Agency’s current thinking on IS response variability and its potential impact on the accuracy of analyte concentration measurements.
Using Watson for IS Response Review
The IS review capabilities in Watson LIMS version 7.7 are aligned with industry best practices. The new capabilities are designed with feedback from customers performing IS review using chromatography software.
In defining the new workflow, the team observed that users will often define criteria a priori such that users can review and identify individual outliers or systemic trends – thereby reducing the risk of reporting inaccurate concentration data impacted by anomalous IS response. To meet this requirement, Watson LIMS enables users to define criteria upfront. Users can select from three different methods, with different sample types to select that will comprise the reference point. Each IS within the assay can store its own criteria, in case there is a mix of stable-labeled and analog ISs. Since not all labs employ an SOP governing IS review, Watson LIMS also enables users to bypass the IS definition and move directly into the visualization tools.
New visualization tools are provided to review IS response. Highlights include:
- Zoom in on specific data points
- Show limits visually across the data points
- Group by dilution factor (could indicate a matrix effect at lower dilutions)
- View sample name
- View IS response trends
After reviewing IS response data, users can make informed decisions and act on results that do not meet the defined criteria. For subjects that are over/under the criteria set within the assay, users can apply a result comment, tag for reassay, deactivate, or toggle not reportable.
Watson LIMS version 7.7 records a history of the IS review. The record captures who performed the review, when it was performed, the IS criteria, Run ID, Watson assay ID, and the %CV. The %CV is useful to view across runs for a given assay ID, providing a view on variability across routine analysis runs.
Supporting your bioanalytical laboratory
Watson LIMS software provides bioanalytical laboratories with the ability to track their data through each step in the scientific workflow. New and enhanced functionality available in Watson LIMS version 7.7 provides greater value for the principal investigator, the analyst, and the study coordinator.
While optimizing processes throughout the bioanalytical workflow, Watson LIMS software also ensures complete traceability and sample chain of custody. Whether your laboratory is focused on only biologics or has a mixed portfolio supporting pharmaceutical drugs and biologics, Watson LIMS software provides a complete solution for bioanalytical laboratories.
Visit the Watson LIMS website to learn how Watson LIMS software can support your laboratory.