Abstract
Introduction
A process analytical technology (PAT) method using a near infrared (NIR) spectrometer attached to a drum blender was developed for real-time end-point detection for an extragranular blend.
Methods and theory
The method and corresponding documentation are part of the control strategy for a recently filed and approved pharmaceutical product, and the method is currently in place and in use for manufacturing of this pharmaceutical product at GlaxoSmithKline.
Results and discussion
The immediate benefits are a dramatic reduction in blend time as well as real-time verification of blend homogeneity for every batch. The development of the blending end-point method is presented and a set of fundamental requirements for developing any PAT method is proposed.
Conclusion
It is discussed how the reported PAT end-point method fits with the proposed PAT framework, and the validation aspects required to achieve a compliant method for use in drug product manufacturing are presented.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
US Department of Health and Human Services. Food and Drug Administration, Guidance: PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance, 2004.
Flåten GR, Belchamber R, Collins M, Walmsley AD. Caterpillar—an adaptive algorithm for detecting process changes from acoustic emission signals. Anal Chim Acta. 2005;544:280–91.
Sanchez FC, Toft J, van den Bogaert B, Massart DL, Dive SS, Hailey P. Monitoring powder blending by NIR spectroscopy. J Anal Chem. 1995;352:771–8.
Sekulic SS, Ward HW, Brannegan DR, Stanley ED, Evans CL, Sciavolino ST, et al. On-line monitoring of powder blend homogeneity by near-infrared spectroscopy. Anal Chem. 1996;68:509–13.
De Maesschalck R, Sanchez FC, Massart DL, Doherty P, Hailey P. On-line monitoring of powder blending with near-infrared spectroscopy. Appl Spectrosc. 1998;52:725–31.
Berntsson O, Danielsson L-G, Johansson MO, Folestad S. Quantitative in-line monitoring of powder blending by near infrared reflection spectroscopy. Powder Technol. 2002;185:185–93.
Blanco M, Gozález Bañó R, Bertran E. Monitoring powder blending in pharmaceutical processes by use of near infrared spectroscopy. Talanta. 2002;56:203–12.
Wargo DJ, Drennen JK. Near-infrared spectroscopic characterization of pharmaceutical powder blends. J Pharm Biomed Anal. 1996;14:1415–23.
Bellamy LJ, Nordon A, Littlejohn D. Real-time monitoring of powder mixing in a convective blender using non-invasive reflectance NIR spectrometry. Analyst. 2008;133:58–64.
Sulub Y, Wabuyele B, Gargiulo P, Pazdan J, Cheney J, Berry J, et al. Real-time on-line blend uniformity monitoring using near-infrared reflectance spectrometry: A non-invasive off-line calibration approach. J Pharm Biomed Anal. 2009;49:48–54.
Skibsted ETS, Boelens HFM, Westerhuis JA, Witte DT, Smilde AK. Simple assessment of homogeneity in pharmaceutical mixing processes using a near-infrared reflectance probe and control charts. J Pharm Biomed Anal. 2006;41:26–35.
Puchert T, Holzhauer CV, Menezes JC, Lochman D, Reich G. A new PAT/QbD approach for the determination of blend homogeneity: combination of on-line NIRS analysis with PC Scores Distance Analysis (PC-SDA). Eur J Pharm Biopharm. 2011;78:173–82.
Acknowledgments
This paper was presented at IFPAC10. Colleagues from the validation and automation departments in GSK are acknowledged for their support.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Flåten, G.R., Ferreira, A.P., Bellamy, L. et al. PAT within the QbD Framework: Real-Time End Point Detection for Powder Blends in a Compliant Environment. J Pharm Innov 7, 38–45 (2012). https://doi.org/10.1007/s12247-012-9119-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12247-012-9119-9