title: Correlation of laboratory and production freeze drying cycles.
abstract: The purpose of this study was to develop the correlation of cycle parameters between a laboratory and a production freeze-dryer. With the established correlation, key cycle parameters obtained using a laboratory dryer may be converted to those for a production dryer with minimal experimental efforts. In order to develop the correlation, it was important to consider the contributions from the following freeze-drying components: (1) the dryer, (2) the vial, and (3) the formulation. The critical parameters for the dryer are the shelf heat transfer coefficient and shelf surface radiation emissivity. The critical parameters for the vial are the vial bottom heat transfer coefficients (the contact parameter Kcs and separation distance lv), and vial top heat transfer coefficient. The critical parameter of the formulation is the dry layer mass transfer coefficient. The above heat and mass transfer coefficients were determined by freeze-drying experiments in conjunction with mathematical modeling. With the obtained heat and mass transfer coefficients, the maximum product temperature, Tbmax, during primary drying was simulated using a primary drying subroutine as a function of the shelf temperature and chamber pressure. The required shelf temperature and chamber pressure, in order to perform a successful cycle run without product collapse, were then simulated based on the resulting values of Tbmax. The established correlation approach was demonstrated by the primary drying of the model formulation 5% mannitol solution. The cycle runs were performed using a LyoStar dryer as the laboratory dryer and a BOC Edwards dryer as the production dryer. The determined normalized dried layer mass transfer resistance for 5% mannitol is expressed as RpN=0.7313+17.19l, where l is the receding dry layer thickness. After demonstrating the correlation approach using the model formulation 5% mannitol, a practical comparison study was performed for the actual product, the lactate dehydrogenase (LDH) formulation. The determined normalized dried layer mass transfer resistance for the LDH formulation is expressed as RpN=4.344+10.85l. The operational templates Tbmax and primary drying time were also generated by simulation. The cycle run for the LDH formulation using the Edwards production dryer verified that the cycle developed in a laboratory freeze-dryer was transferable at the production scale.
authors.affiliation: BioPharma Solutions, Baxter Healthcare Corporation, Round Lake, IL 60073, USA. wei_kuu@baxter.com
authors.forename: Wei Y
authors.initials: WY
authors.lastname: Kuu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hardwick
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Akers
mesh_terms: D000465:Algorithms; D004349:Drug Packaging / Q000379:methods / Q000592:standards; D005612:Freeze Drying / Q000379:methods* / Q000592:standards; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008353:Mannitol / Q000032:analysis; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013696:Temperature; D014835:Volatilization
chemical_list: D008353:Mannitol; D007770:L-Lactate Dehydrogenase