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Abstract A holistic approach was taken to characterise lyophilisers at both laboratory and commercial scale to design a focused validation strategy for commercialising parenteral drug products. Vial heat transfer coefficients (Kv) and equipment mass transfer boundaries were generated for a Lyostar II and three commercial scale IMA Lyomax lyophilisers. K v studies were performed using gravimetric methodologies. K v calculated for the Lyostar II was equivalent to the commercial equipment at 133 µBar however trended higher below 133 µBar and lower above 133 µBar potentially impacting primary drying product temperature during scale-up depending on the chamber pressure recipe set point. Kv profiles were consistent within and across the commercial equipment. Edge effect was most prominent at commercial scale with minimal shielding of the edge vials in contrast to the presence of a metal ring around the vial pack in the Lyostar II. Equipment capability studies for mass transfer showed commercial scale equipment could achieve lower chamber pressure and greater sublimation rates when compared to the Lyostar II. Furthermore, differences were also measured between large-scale lyophilisers based on condenser orientation (horizontal vs vertical). The results demonstrate greater equipment capability of the two-storey vertical configuration with respect to choked flow regime. Worst-case locations within a commercial lyophiliser were identified providing rationale for reduced sampling for product shelf-mapping locations. This work provides guidance on execution of commercial scale characterisation studies and application of the data to enhance scale-up, technical transfer and focused process validation strategies.

A holistic approach was taken to characterise lyophilisers at both laboratory and commercial scale to design a focused validation strategy for commercialising parenteral drug products. Vial heat transfer coefficients (Kv) and equipment mass transfer boundaries were generated for a Lyostar II and three commercial scale IMA Lyomax lyophilisers. Kv studies were performed using gravimetric methodologies. Kv calculated for the Lyostar II was equivalent to the commercial equipment at 133 µBar however trended higher below 133 µBar and lower above 133 µBar potentially impacting primary drying product temperature during scale-up depending on the chamber pressure recipe set point. Kv profiles were consistent within and across the commercial equipment. Edge effect was most prominent at commercial scale with minimal shielding of the edge vials in contrast to the presence of a metal ring around the vial pack in the Lyostar II. Equipment capability studies for mass transfer showed commercial scale equipment could achieve lower chamber pressure and greater sublimation rates when compared to the Lyostar II. Furthermore, differences were also measured between large-scale lyophilisers based on condenser orientation (horizontal vs vertical). The results demonstrate greater equipment capability of the two-storey vertical configuration with respect to choked flow regime. Worst-case locations within a commercial lyophiliser were identified providing rationale for reduced sampling for product shelf-mapping locations. This work provides guidance on execution of commercial scale characterisation studies and application of the data to enhance scale-up, technical transfer and focused process validation strategies. [ABSTRACT FROM AUTHOR]