Operational Qualification of a 3D Printer for Drug Manufacturing

Contexte
The qualification of pharmaceutical equipment is a requirement of Bonnes pratiques de préparation (BPP) 3D printing, widely used in various fields, has been studied for medicine manufacturing over the past decade. However, when the S600D 3D printer with LIQ11 head, initially designed for other applications was purchased, the manufacturer Lynxter did not provide an operational qualification (OQ) protocol.

Objective
Achieve an OQ of the 3D printer in semi-solid extrusion (SSE) and compare the results between two formulations.

Material and method
The compositions of the tested formulations are: sodium starch glycolate, carboxymethylcellulose, water for formulation 1 (F1) and lactose, sodium starch glycolate, Kollicoat^®, water for formulation 2 (F2). Based on printing speed, layer height, and printlet size, 3 level pairs (minimum, medium, maximum) were defined, resulting in 9 printing series. The maximum speed (Vmax) determined is 2000mm.min-1, the speed for which a minimal printing time is observed. The minimum speed (Vmin) is 600mm.min-1, the speed for which the printing time of one unit is less than 20 minutes. The average speed is 1100 mm.min-1 (Vmoy). Layer heights are set at 25% (Hmin), 60% (Hmoy), and 85% (Hmax) of the nozzle diameter (0.58 mm). The object size is doubled (Tmax) or halved (Tmin) from the initial size (Tmoy). The criteria evaluated are extrusion quality, mass uniformity, and size uniformity (diameter and height). Batches of 20 tablets were made for Tmin and Tmoy, and 8 tablets for Tmax, representing the quantity that can be produced with a single syringe of gel.

Results
Out of the 9 series, 78% (n=7) achieved correct extrusion with F1 and 89% (n=8) with F2. Extrusion defects were observed for the Vmin/Hmin series at size Tmoy and Tmax with F1, and for the Vmin/Hmin series at size Tmax with F2. Mass uniformity was non-compliant for the Tmin sized printlets at Vmin/Hmin for F2 and Vmax/Hmax for F1. The dispersion of the measured diameter and/or height values was higher than 5% for F1 and F2 with the Vmoy/Hmoy and Vmax/Hmax series at size Tmin, and for Vmin/Hmin at size Tmoy.

Conclusion
This OQ protocol highlights a limitation of the 3D printer for gel extrusion at Vmin speed. Additionally, the resolution seems poorer for smaller objects, with greater dispersion in their mass and size. These results also reveal variability between the two formulations, explained by the fact that the same printing parameters were applied to F1 and F2. This demonstrates the correlation between the rheological properties of the gel and the quality of extrusion for the 3D printer in SSE drug manufacturing.

¹ Bonnes pratiques de préparation, ANSM 2023