Innovative approach for identifying root causes of glass defects in sterile drug product manufacturing.
In sterile drug product manufacturing, scratched and broken glass containers (i.e., vials) cause product losses, glass particles, equipment contamination and additional cleaning efforts. However, mechanical resistance and exposure of vials to mechanical stress are not sufficiently understood, and no systematic approach for reducing glass-related losses is established. Manufacturers may tackle glass-related losses more rationally if (i) frequencies for inflicting disqualifying damages to drug product containers are known for given forces, (ii) actual exposure in industrial filling lines is quantified and (iii) process enhancements are derived based on collected information. In this work, an innovative approach for exploiting these opportunities, identifying glass defect root causes and reducing glass defects is provided. Devices for quantifying (i) damaging frequencies and (ii) actual exposure are presented and then applied in an industrial case study on sterile drug product manufacturing; finally, (iii) process enhancements are derived and implemented. In the case study, frequencies for scratching vials at given forces as well as breaking forces have been determined. Peak exposure in the investigated filling line was detected at 6 N. As a result of the case study, key machine parts were identified and adjusted.
ETH Zuerich, Vladimir-Prelog-Weg 1, Zuerich 8093, Switzerland; F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel 4070, Switzerland. Electronic address: lukas.g.eberle@gmail.com.
Lukas
L
Eberle
F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel 4070, Switzerland.
Alexander
A
Svensson
F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel 4070, Switzerland.
Andreas
A
Graser
F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel 4070, Switzerland.
Joerg
J
Luemkemann
The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Hirokazu
H
Sugiyama
F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel 4070, Switzerland.
Rainer
R
Schmidt
ETH Zuerich, Vladimir-Prelog-Weg 1, Zuerich 8093, Switzerland.
Konrad
K
Hungerbuehler
D004345:Drug Industry; D005898:Glass; D011786:Quality Control
Parenterals; Pharmaceutical manufacturing; Process Analytical Technology (PAT); Process intensification; Production efficiency; Quality by Design (QbD); Tribology