TY - JOUR
T1 - The need for new control strategies for particulate matter in parenterals
AU - Poms, Johannes
AU - Sacher, Stephan
AU - Nixdorf, Matthias
AU - Dekner, Michael
AU - Wallner-Mang, Sabine
AU - Janssen, Ines
AU - Khinast, Johannes G.
AU - Schennach, Robert
PY - 2019/7/3
Y1 - 2019/7/3
N2 - An undesirable characteristic in lyophilized parenteral products is the potential presence of particulate matter in the final product, which may affect patient safety. In this study, quality risk management tools described in the International Conference on Harmonization Guideline Q9 were used to estimate the risks for a pharmaceutical manufacturing line, based on three critical quality attributes: (1) visible particulate matter; (2) lyo-cake collapse traces; and (3) lyo-cake melt-back traces. Together with a Process Failure Mode Effect Analysis (PFMEA), an input-output analysis of the individual unit operations identified seven major material classes of extrinsic particulate matter. In addition to the process assessment, an experimental investigation of the location of impurities in lyophilized products was performed. To that end, intentionally contaminated vials were examined to locate the particulate matter and its possible migration. The results emphasize the importance of a full transmission mode release testing since the particles may enter the interior of the lyo-cake. A theoretical explanation of the observed impurity locations is provided.
AB - An undesirable characteristic in lyophilized parenteral products is the potential presence of particulate matter in the final product, which may affect patient safety. In this study, quality risk management tools described in the International Conference on Harmonization Guideline Q9 were used to estimate the risks for a pharmaceutical manufacturing line, based on three critical quality attributes: (1) visible particulate matter; (2) lyo-cake collapse traces; and (3) lyo-cake melt-back traces. Together with a Process Failure Mode Effect Analysis (PFMEA), an input-output analysis of the individual unit operations identified seven major material classes of extrinsic particulate matter. In addition to the process assessment, an experimental investigation of the location of impurities in lyophilized products was performed. To that end, intentionally contaminated vials were examined to locate the particulate matter and its possible migration. The results emphasize the importance of a full transmission mode release testing since the particles may enter the interior of the lyo-cake. A theoretical explanation of the observed impurity locations is provided.
KW - lyophilization
KW - particulate matter
KW - quality by design
KW - quality control strategy
KW - Quality risk management
KW - visual inspection
UR - http://www.scopus.com/inward/record.url?scp=85063912276&partnerID=8YFLogxK
U2 - 10.1080/10837450.2019.1585449
DO - 10.1080/10837450.2019.1585449
M3 - Article
C2 - 30821571
AN - SCOPUS:85063912276
SN - 1083-7450
VL - 24
SP - 739
EP - 750
JO - Pharmaceutical Development and Technology
JF - Pharmaceutical Development and Technology
IS - 6
ER -