Implementation of a fully integrated continuous manufacturing line for direct compression and coating at a commercial pharmaceutical facility - Part 1: Operational considerations and control strategy.

Autor: Conway SL; Pharmaceutical Technical Operations, MSD, Cramlington, UK. Electronic address: stephen_conway@merck.com., Rosas JG; Pharmaceutical Technical Operations, MSD, Cramlington, UK., Overton P; Pharmaceutical Technical Operations, MSD, Cramlington, UK., Tugby N; Pharmaceutical Technical Operations, MSD, Cramlington, UK., Cryan P; Quality Operations, MSD, Cramlington, UK., Witulski F; Global Pharmaceutical Commercialization, MMD, Merck & Co., Inc., Rahway, NJ, USA., Hurley S; Global Pharmaceutical Commercialization, MMD, Merck & Co., Inc., Rahway, NJ, USA., Wareham L; Global Pharmaceutical Commercialization, MMD, Merck & Co., Inc., Rahway, NJ, USA., Tantuccio A; Global Pharmaceutical Commercialization, MMD, Merck & Co., Inc., Rahway, NJ, USA., Ramasamy M; Analytical Chemistry in Development and Supply, MMD, Merck & Co. Inc, Rahway, NJ, USA., Lalloo A; Regulatory-CMC, MRL, Merck & Co., Inc., Rahway NJ, USA., Gibbs M; Global Engineering Solutions, MMD, Merck & Co., Inc Rahway, NJ, USA., Meyer RF; Global Pharmaceutical Commercialization, MMD, Merck & Co., Inc., Rahway, NJ, USA.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Jul 25; Vol. 642, pp. 122820. Date of Electronic Publication: 2023 Apr 05.
DOI: 10.1016/j.ijpharm.2023.122820
Abstrakt: We implement a fully integrated continuous manufacturing (CM) line for direct compression and coating of a pharmaceutical oral solid dosage form in a commercial production facility. In this first paper of a two-part series, we describe process design and operational choices made to introduce CM using infrastructure originally intended for batch operations. Consistent with lean manufacturing principles, we select equipment, facilities, and novel process analytical technologies that meet production agility goals alongside an existing batch process. Choices address process risks, are aligned with existing quality systems, yet allow exploration of CM agility benefits in commercial operations. We outline how operating procedures, control schemes, and release criteria from the historical batch process are adapted for CM with modified lot and yield definitions based on patient demand. We devise a hierarchy of complementary controls including real-time process interrogation, predictive residence time distribution models of tablet concentration, real-time product release testing using automated tablet NIR spectroscopy, active rejection and diversion, and throughput-based sampling. Results from lots produced under normal operational conditions confirm our CM process provides assurance of product quality. Qualification strategies to achieve lot size flexibility aims are also described. Finally, we consider CM extensions to formulations with differing risk profiles. Further analysis of results for lots produced under normal operational conditions is provided in part 2 (Rosas et al., 2023).
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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