The integration of the Yieldaliser into the open-access HPLC platform has enabled chemists to generate impurity-profile and
assay data simultaneously from a single analysis. The additional assay data obtained from the same sample preparation and
chromatographic run is therefore generated with little additional cost. Users can perform the sample preparation in ~1 minute,
thereby enabling results to be generated and emailed to their desks within 10 minutes of the sample preparation (i.e., when
the sample queue is empty). A common open-access HPLC platform also allows chemists to generate Yieldaliser data that can
support processes that have been transferred from the laboratory scale into larger production facilities regardless of where
in the world the analysis is required.
To continually improve the Yiedaliser, the software was written to enable ongoing collection of metrics, thereby monitoring
system usage. At the GSK facility in Stevenage, there has been sufficient demand during the past eight years to ensure that
four open-access systems are equipped to generate Yieldaliser data. Figure 5 displays the number and percentage of the different
types of assay analysis performed by ~50 users across the four systems in 2009.
Figure 5: Annual metrics collected using the Yieldaliser from GSK's Stevenage, Hertfordshire, United Kingdom, facility in
Figure 5 highlights the most frequent types of assay analysis performed by users at GSK's Stevenage site. More than 97% of
the analyses focused on generating yield in solution using the typical protocol or dilute protocol (see Figure 2). The data
also show that chemists that used the calibration tool throughout 2009 often did not need to determine the purity of isolated
solids (more precise data is often required on solids and therefore generated by trained analytical chemists on dedicated
The examples documented by the authors demonstrate the use of the Yieldaliser within GSK's chemical development division.
Implementation of an equivalent validated system, applicable to current good manufacturing/laboratory practice analysis, may
help standardize operating methods for determining HPLC assays. Evolving quality by design approaches for analytical methods
will potentially provide greater flexibility for changing methods that are already registered (2, 3). Improvement to the sample-preparation
protocols is also under investigation (e.g., use of liquid handling devices that can better handle 20 µl over a wide range
of solvents) to automate further sample analysis and improve accuracy and precision. Lastly, automated methodology is being
explored for automating fault detection and troubleshooting across the open-access HPLC platform (4–6).
Phil Borman* and John Roberts are managers in analytical sciences/chemical development at GlaxoSmithKline (GSK), Gunnels Wood Road, Stevenage, Hertfordshire,
SG1 2NY, United Kingdom, tel. +44 1438 763713, fax +44 1438 764414, firstname.lastname@example.org
. Barbara O'Reilly is a statistical programming analyst at Roche (Welwyn Garden City, UK). Robin Attrill is a manager in synthetic chemistry/chemical development at GSK in Stevenage. Ian Barylski is a manager and Keith Freebairn is a director, both in particle/process sciences and engineering/chemical development, at GSK in Stevenage.
1. J. Roberts et al., Amer. Pharm. Rev.
13 (2), 38–44 (2010).
2. P. Borman et al., Pharm. Technol.
31 (10), 142–152 (2007).
3. M. Schweitzer et al., Pharm. Technol.
34 (2), 52–59 (2010).
4. H. Eriksson and P. Larses, J. Chem. Inf. Comput. Sci.
32, 139–144 (1992).
5. T. Wessa et al., Organic Process R&D
4, 102–106 (2000).
6. L. Kaminski et al., J. of Pharm. and Biomedic. Anal.
51 (3), 557–564 (2010).
Editor's Note: This article is being simultaneously published in Pharmaceutical Technology Europe's October 2010 issue.