Implementation of a fully integrated CM direct compression and coating process at a commercial pharmaceutical facility - Part 2: PAT and RTD results for normal operational conditions batches.

Autor: Rosas JG; MSD, Pharmaceutical Technical Operations PAT, UK. Electronic address: juan.rosas@organon.com., Brush P; Merck & Co. Inc, Analytical Chemistry in Development and Supply PAT, United States., Thompson B; Merck & Co. Inc, Analytical Chemistry in Development and Supply PAT, United States., Miller C; Merck & Co. Inc, Analytical Chemistry in Development and Supply PAT, United States., Overton P; MSD, Pharmaceutical Technical Operations, UK., Tugby N; MSD, Pharmaceutical Technical Operations, UK., Stoliarskaia D; MSD, Pharmaceutical Technical Operations PAT, UK., Hurley S; Merck & Co. Inc, Pharmaceutical Commercialization Technology, United States., Ramasamy M; Merck & Co. Inc, Analytical Chemistry in Development and Supply PAT, United States., Conway SL; MSD, Pharmaceutical Technical Operations, UK.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Apr 05; Vol. 636, pp. 122814. Date of Electronic Publication: 2023 Mar 12.
DOI: 10.1016/j.ijpharm.2023.122814
Abstrakt: This is the second of two articles detailing the continuous manufacturing (CM) development and implementation activities for an marketed product which have been realized in novel, qualified equipment, using validated control strategy elements to enable manufacture of batches under current good manufacturing practices (cGMP) and compliant with data integrity principles. Here, the application of process analytical technologies (PAT) and automation tools on batches produced under normal operational conditions is reviewed. The results from residence time distribution (RTD) models for predicting API concentration, in-line near infrared (NIR) testing of blend uniformity (BU) and at-line NIR spectroscopy analysis of core tablet concentration and tablet identity for real-time release testing (RTRT) are discussed. The influences of process equipment and design choices on NIR and RTD model variability, as well as the use of the PAT tools for monitoring the evolving properties understanding of CM process development, such as overcoming flow instabilities, is described. Results demonstrate that the RTD and NIR models developed and validated are robust to operating conditions and are critical for assuring steady state control of the continuous manufacturing process. Finally, the NIR and RTD model lifecycle, including procedures for necessary and normal model upgrades in a cGMP production environment, are presented.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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