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[Display omitted] As lyophilization continues to be a critical step in the manufacturing of sensitive biopharmaceuticals, challenges often arise during the scale up to commercial scale or the transfer from one manufacturing site to another. While data from the small-scale development of the lyophilization cycle is abundant it is typically much more difficult to extract important information from commercial scale cycles, due to the lack of process analytical technologies available on the commercial line. There is often a reluctance to include wireless temperature or pressure probes during GMP operations due to the additional contamination risk, and retrofitting equipment such as the TDLAS can be prohibitively expensive. Further, as products become more advanced, the cost of consuming the product or even the availability of material may limit the opportunities to run commercial scale trials. This paper presents two novel methods to garner critical cycle information to allow for the evaluation of cycle performance without the need for expensive analytical equipment, costly revalidation and line downtime. Critically, this can be achieved using commonly available temperature and capacitance probes on existing commercial scale equipment. The first method is a calorimetric method, based on quantifying the differences in heat transfer liquid temperature between the shelf inlet and shelf outlet. This change in temperature results from the on-going sublimation, an endo-thermic reaction occurring during lyophilization. The second method uses the differential pressure between the chamber and condenser resulting from the vapor flow from vial to condenser during primary drying. As stated by the authors both methods align well and provide valuable cycle characterization data. [ABSTRACT FROM AUTHOR]

Measurement of heat transfer coefficients (K v) is an important part of freeze-dryers characterization and as well a necessary step for executing any modelling. In most cases only an average value of K v is calculated, or an average value of center and edge vials is provided. Our aim is to go a step further and to describe the overall K v distribution various vial/ freeze drier combinations, whatever the pressure. From an experimental point of view, in this article we propose three methods to calculate the K v value for individual vials based on the ice sublimation gravimetric method. The first method we use is the most usual one, where the K v value is calculated based on the mass of sublimated ice and the product temperature measured in selected vias. In the second method, the average product temperature is estimated for each vial, based on the mass difference before and after sublimation and the K v value is calculated accordingly. In the third method, the K v is estimated by comparison to sublimation results from a simulation. Results from methods 2 and 3 are very similar results and are slightly different from those of method 1. Method 1 was shown to exhibit a systematic bias due to the fact that it is based on the temperature of recording of selected vials only, which are not representative for all positions. Once the individual values of K v have been calculated, it is possible to establish a distribution for each method. It was observed that an overlay of two normal distributions describing the center and the edge vials provides a good representation of the empirical distribution. Furthermore, we propose a holistic model aiming to calculate the K v distribution for any specified pressure. [ABSTRACT FROM AUTHOR]