A New Method Based on the Regression of Step Response Data for Monitoring a Freeze-Drying Cycle

Pisano, Roberto; Fissore, Davide; Barresi, Antonello

doi:10.1002/jps.23976

Cited by 16 publications

(7 citation statements)

References 24 publications

(48 reference statements)

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“…While much attention has been dedicated to the advancement of continuous manufacturing, the freeze-drying community is making extensive efforts to improve process robustness and achieve the stringent requirements of quality, safety, and efficiency set by regulatory authorities. In this perspective, research on freeze-drying has mainly focused on process control, monitoring, − optimization, and scaling-up . Many efforts have been made to improve the quality and uniformity of the product, , as well as on the development of cycles that guarantee the stability of APIs .…”

Section: Introductionmentioning

confidence: 99%

From Batch to Continuous: Freeze-Drying of Suspended Vials for Pharmaceuticals in Unit-Doses

Capozzi

Trout

Pisano

2019

Ind. Eng. Chem. Res.

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In response to the current trend in the pharmaceutical industry, a new concept for the freeze-drying of pharmaceuticals in unit-doses is presented: the continuous freeze-drying/lyophilization of suspended vials. This configuration makes it possible to set up a continuous freeze-drying process that produces a final product with similar characteristics to those traditionally obtained by means of the batch process but which avoids the drawbacks of conventional, batch freeze-drying. The feasibility and advantages of this new concept are presented in this work. Continuous freeze-drying has been found to improve heat transfer uniformity and reduce the primary drying duration by 2–4 times. As far as the structure of lyophilized products is concerned, SEM micrographs of the lyophilized samples showed that this technology improves vial-to-vial and intravial homogeneity.

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Section: Introductionmentioning

confidence: 99%

From Batch to Continuous: Freeze-Drying of Suspended Vials for Pharmaceuticals in Unit-Doses

Capozzi

Trout

Pisano

2019

Ind. Eng. Chem. Res.

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“…A similar result was previously obtained for the freeze-drying from pure water. 30 Even if this task has been done for the pressure decrease test, the results obtained are still valid for the VMS because they refer to those relationships that describe the fluid dynamics through the duct and that are common for both methods.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, a noninvasive method has been proposed by Pisano et al 30 to monitor in-line a freeze-drying cycle using the pressure decrease test. Similar to the pressure rise test, chamber pressure is modified for a short time, but in this case, chamber pressure decreases.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Monitoring of a Freeze-Drying Process for tert-Butanol/Water Cosolvent-Based Formulations

Pisano

Fissore

2016

Ind. Eng. Chem. Res.

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Freeze-drying from mixtures of water and organic solvents has been demonstrated to be beneficial to both product quality and process duration. The aim of this study was to develop a new model-based technology (referred to as valveless monitoring system) that makes it possible to monitor noninvasively the sublimation step in the case of lyophilization from both aqueous solutions and organic/water cosolvent systems. This technology can directly measure the rate of sublimation and infer key quality variables, which cannot be measured online, from process variables (i.e., pressure inside the drying chamber and condenser) that are commonly measured during a freeze-drying cycle. These estimations are useful not only to monitor the process but also to design the cycle. In fact, the proposed monitoring system can also estimate either the heat transfer coefficient or the mass transfer resistance through two separate experiments. This study also shows how these two parameters (coupled with a mathematical model of the process) can be used to identify the values of the process conditions that allow maintenance of key quality variables within specified limits. Examples of application of this system to a tert-butanol/water cosolvent-based formulation are presented and discussed to demonstrate the effectiveness of the proposed approach.

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“…With the goal of overcoming the problem of the product temperature rise during the pressure rise test, Pisano et al ( 2014 ) proposed to carry out a different test, called pressure decrease test, to monitor the state of the system. In this case, the drying chamber is no longer isolated from the condenser, but the pressure variation in the chamber is induced by closing the controlled leakage valve and, thus, chamber pressure decrease.…”

Section: Model-based Pats Based On the Measurement Of Chamber Pressurmentioning

confidence: 99%

Model-Based PAT for Quality Management in Pharmaceuticals Freeze-Drying: State of the Art

Fissore

2017

Front. Bioeng. Biotechnol.

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Model-based process analytical technologies can be used for the in-line control and optimization of a pharmaceuticals freeze-drying process, as well as for the off-line design of the process, i.e., the identification of the optimal operating conditions. This paper aims at presenting the state of the art in this field, focusing, particularly, on three groups of systems, namely, those based on the temperature measurement (i.e., the soft sensor), on the chamber pressure measurement (i.e., the systems based on the test of pressure rise and of pressure decrease), and on the sublimation flux estimate (i.e., the tunable diode laser absorption spectroscopy and the valveless monitoring system). The application of these systems for in-line process optimization (e.g., using a model predictive control algorithm) and to get a true quality by design (e.g., through the off-line calculation of the design space of the process) is presented and discussed.

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A New Method Based on the Regression of Step Response Data for Monitoring a Freeze-Drying Cycle

Cited by 16 publications

References 24 publications

From Batch to Continuous: Freeze-Drying of Suspended Vials for Pharmaceuticals in Unit-Doses

From Batch to Continuous: Freeze-Drying of Suspended Vials for Pharmaceuticals in Unit-Doses

Noninvasive Monitoring of a Freeze-Drying Process for tert-Butanol/Water Cosolvent-Based Formulations

Model-Based PAT for Quality Management in Pharmaceuticals Freeze-Drying: State of the Art

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