Residence time distribution as a traceability method for lot changes in a pharmaceutical continuous manufacturing system

• Published in: International journal of pharmaceutics Vol. 611; p. 121313
• Main Authors: Sánchez-Paternina, Adriluz, Martínez-Cartagena, Pedro, Li, Jingzhe, Scicolone, James, Singh, Ravendra, Lugo, Yleana C., Romañach, Rodolfo J, Muzzio, Fernando J., Román-Ospino, Andrés D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.01.2022
• Subjects: Continuous manufacturing (CM); Near-infrared spectroscopy (NIRS); Pharmaceutical Preparations; Residence time distribution (RTD); Step-change experiments; Surrogate materials; Traceability; Traceability; Near-infrared spectroscopy (NIRS); Step-change experiments; Continuous manufacturing (CM); Residence time distribution (RTD); Surrogate materials
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.121313

[Display omitted] Residence time distribution (RTD) models were developed to track raw material lots and investigate batch transitions in a continuous manufacturing system. Two raw materials with similar physical properties (granular metformin and lactose) were identified via Principal Component Analysis (PCA) from a library of bulk material properties and used to simulate the switching of lots during production. In-line near-infrared (NIR) spectra were collected with the powder flowing through a chute in a continuous manufacturing system to monitor metformin and lactose concentration in step-change experiments with Partial Least Squares (PLS) models. RTD provided an understanding of raw material propagation through the continuous manufacturing system. Transition times between raw material changes were identified using the results of two multivariate approaches PLS and PCA. The methodology was implemented to discriminate the transition zone in a raw material change, contributing to design control strategies for acceptance and diverting mechanisms.