A case study on decentralized manufacturing of 3D printed medicines

Iria Seoane-Viaño; Xiaoyan Xu; Jun Jie Ong; Ahmed Teyeb; Simon Gaisford; André Campos-Álvarez; Anja Stulz; Carmen Marcuta; Lilia Kraschew; Wolfgang Mohr; Abdul W Basit; Alvaro Goyanes

doi:10.1016/j.ijpx.2023.100184

A case study on decentralized manufacturing of 3D printed medicines

Int J Pharm X. 2023 May 30:5:100184. doi: 10.1016/j.ijpx.2023.100184. eCollection 2023 Dec.

Authors

Iria Seoane-Viaño^{1

2}, Xiaoyan Xu¹, Jun Jie Ong¹, Ahmed Teyeb³, Simon Gaisford¹, André Campos-Álvarez^{4

5}, Anja Stulz⁶, Carmen Marcuta⁶, Lilia Kraschew⁶, Wolfgang Mohr⁶, Abdul W Basit^{1

4

5}, Alvaro Goyanes^{1

4

5

7}

Affiliations

¹ Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
² Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Paraquasil Group (GI-2109), Faculty of Pharmacy, iMATUS and Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), Santiago de Compostela 15782, Spain.
³ Brunel Innovation Centre, Brunel University London, Uxbridge UB8 3PH, UK.
⁴ FABRX Artificial Intelligence, Carretera de Escairón, 14, Currelos (O Saviñao), CP 27543, Spain.
⁵ FABRX Ltd., Henwood House, Henwood, Ashford TN24 8DH, UK.
⁶ Losan Pharma GmbH, Otto-Hahn-Strasse 13, 79395 Neuenburg, Germany.
⁷ Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma Group (GI-1645), Facultad de Farmacia, iMATUS and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain.

Abstract

Pharmaceutical 3D printing (3DP) is one of the emerging enabling technologies of personalised medicines as it affords the ability to fabricate highly versatile dosage forms. In the past 2 years, national medicines regulatory authorities have held consultations with external stakeholders to adapt regulatory frameworks to embrace point-of-care manufacturing. The proposed concept of decentralized manufacturing (DM) involves the provision of feedstock intermediates (pharma-inks) prepared by pharmaceutical companies to DM sites for manufacturing into the final medicine. In this study, we examine the feasibility of this model, with respect to both manufacturing and quality control. Efavirenz-loaded granulates (0-35%w/w) were produced by a manufacturing partner and shipped to a 3DP site in a different country. Direct powder extrusion (DPE) 3DP was subsequently used to prepare printlets (3D printed tablets), with mass ranging 266-371 mg. All printlets released more than 80% drug load within the first 60 min of the in vitro drug release test. An in-line near-infrared spectroscopy system was used as a process analytical technology (PAT) to quantify the printlets' drug load. Calibration models were developed using partial least squares regression, which showed excellent linearity (R² = 0.9833) and accuracy (RMSE = 1.0662). Overall, this work is the first to report the use of an in-line NIR system to perform real-time analysis of printlets prepared using pharma-inks produced by a pharmaceutical company. By demonstrating the feasibility of the proposed distribution model through this proof-of-concept study, this work paves the way for investigation of further PAT tools for quality control in 3DP point-of-care manufacturing.

Keywords: Additive manufacturing of drug products and drug delivery systems; Decentralised and distributed fabrication of formulations; Digital healthcare and industry 4.0; Direct powder extrusion of personalized pharmaceuticals; Process analytical technologies; Real-time release testing; Three-dimensional printing using M3DIMAKER.