3D printing personalized medications in a hospital: Rapid and non-destructive dose verification of printed medicines enabled by miniaturised spectroscopy

Three-dimensional printing (3DP) of pharmaceuticals is as an enabling technology for personalised medicine and is a versatile production technology for compounding automation and decentralised manufacture. However, non-destructive quality control (QC) methods are needed for the small batch medicines production. This study investigated for the first time two miniaturised and handheld near-infrared (NIR) and Raman spectrometers as QC measures for accurately quantifying tamoxifen in medicines manufactured in Gustave Roussy Cancer Campus Hospital Pharmacy during preparation for a clinical trial. A 'hub-and-spoke' model approach was applied with manufacture of calibration samples in a research environment (i.e. hub or control site) for spectral data acquisition in the hospital pharmacy (i.e. spoke, point-of-care or manufacturing site) for calibration and validation (hospital pharmacy produce) samples containing 30 % w/w tamoxifen citrate, utilising the same suppliers of materials for production. Both NIR and Raman devices yielded highly accurate and predictive models from spectra acquisition into the open capsule bodies and through closed capsule shells and were deemed suitable as QC methods for rapidly determining the tamoxifen content in the medicines produced via pharmaceutical 3DP in the hospital for the clinical trial. This study proved that both miniaturised analysers may be used as non-destructive QC methods for the 3DP medicines production in the hospital pharmacy, and that a 'hub-and-spoke' approach for development of non-destructive chemometric models may accelerate the decentralised or modular manufacturing paradigm of 3DP medications. Future application and implementation of either technology as QC measure at decentralised manufacturing facilities may come down to other factors such as connectivity to in-line, integrated systems, costs, and safety.