The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Michael J. Pikal - One of the best experts on this subject based on the ideXlab platform.
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Recommended Best Practices for Process Monitoring Instrumentation in Pharmaceutical Freeze Drying—2017
AAPS PharmSciTech, 2017Co-Authors: Steven L. Nail, Serguei Tchessalov, Evgenyi Shalaev, Arnab Ganguly, Ernesto Renzi, Frank Dimarco, Lindsay A Wegiel, Steven Ferris, William Kessler, Michael J. PikalAbstract:Recommended best practices in monitoring of product status during pharmaceutical Freeze drying are presented, focusing on methods that apply to both laboratory and production scale. With respect to product temperature measurement, sources of uncertainty associated with any type of measurement probe are discussed, as well as important differences between the two most common types of temperature-measuring instruments—thermocouples and resistance temperature detectors (RTD). Two types of pressure transducers are discussed—thermal conductivity-type gauges and capacitance manometers, with the Pirani gauge being the thermal conductivity-type gauge of choice. It is recommended that both types of pressure gauge be used on both the product chamber and the condenser for Freeze Dryers with an external condenser, and the reasoning for this recommendation is discussed. Developing technology for process monitoring worthy of further investigation is also briefly reviewed, including wireless product temperature monitoring, tunable diode laser absorption spectroscopy at manufacturing scale, heat flux measurement, and mass spectrometry as process monitoring tools.
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recommended best practices for process monitoring instrumentation in pharmaceutical Freeze drying 2017
Aaps Pharmscitech, 2017Co-Authors: Steven L. Nail, Serguei Tchessalov, Evgenyi Shalaev, Arnab Ganguly, Ernesto Renzi, Frank Dimarco, Lindsay A Wegiel, Steven J Ferris, William J Kessler, Michael J. PikalAbstract:Recommended best practices in monitoring of product status during pharmaceutical Freeze drying are presented, focusing on methods that apply to both laboratory and production scale. With respect to product temperature measurement, sources of uncertainty associated with any type of measurement probe are discussed, as well as important differences between the two most common types of temperature-measuring instruments—thermocouples and resistance temperature detectors (RTD). Two types of pressure transducers are discussed—thermal conductivity-type gauges and capacitance manometers, with the Pirani gauge being the thermal conductivity-type gauge of choice. It is recommended that both types of pressure gauge be used on both the product chamber and the condenser for Freeze Dryers with an external condenser, and the reasoning for this recommendation is discussed. Developing technology for process monitoring worthy of further investigation is also briefly reviewed, including wireless product temperature monitoring, tunable diode laser absorption spectroscopy at manufacturing scale, heat flux measurement, and mass spectrometry as process monitoring tools.
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The effect of dryer load on Freeze drying process design
Journal of Pharmaceutical Sciences, 2010Co-Authors: Sajal M. Patel, Feroz Jameel, Michael J. PikalAbstract:ABSTRACT Freeze-drying using a partial load is a common occurrence during the early manufacturing stages when insufficient amounts of active pharmaceutical ingredient (API) are available. In such cases, the immediate production needs are met by performing lyophiliza-tion with less than a full Freeze dryer load. However, it is not obvious at what fractional load significant deviations from full load behavior begin. The objective of this research was to systematically study the effects of variation in product load on Freeze drying behavior in laboratory, pilot and clinical scale Freeze-Dryers. Experiments were conducted with 5% mannitol (high heat and mass flux) and 5% sucrose (low heat and mass flux) at different product loads (100%, 50%, 10%, and 2%). Product temperature was measured in edge as well as center vials with thermocouples. Specific surface area (SSA) was measured by BET gas adsorption analysis and residual moisture was measured by Karl Fischer. In the lab scale Freeze-dryer, the molar flux of inert gas was determined by direct flow measurement using a flowmeter and the molar flux of water vapor was determined by manometric temperature measurement (MTM) and tunable diode laser absorption spectroscopy (TDLAS) techniques. Comparative pressure measurement (capacitance manometer vs. Pirani) was used to determine primary drying time. For both 5% mannitol and 5% sucrose, primary drying time decreases and product temperature increases as the load on the shelves decreases. No systematic variation was observed in residual moisture and vapor composition as load decreased. Further, SSA data suggests that there are no significant freezing differences under different load conditions. Independent of dryer scale, among all the effects, variation in radiation heat transfer from the chamber walls to the product seems to be the dominant effect resulting in shorter primary drying time as the load on the shelf decreases (i.e., the fraction of edge vials increases).
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evaluation of tunable diode laser absorption spectroscopy for in process water vapor mass flux measurements during Freeze drying
Journal of Pharmaceutical Sciences, 2007Co-Authors: Henning Gieseler, William J Kessler, Michael Finson, Steven J Davis, Phillip A Mulhall, Vincent Bons, David J Debo, Michael J. PikalAbstract:The goal of this work was to demonstrate the use of Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure the water vapor concentration and the vapor flow velocity in the spool connecting a Freeze-dryer chamber and condenser. The instantaneous measurements were used to determine the water vapor mass flow rate (g/s). The mass flow determinations provided a continuous measurement of the total amount of water removed. Full load runs of pure water at different pressure and shelf temperature settings and a 5% (w/w) mannitol product run were performed in both laboratory and pilot scale Freeze Dryers. The ratio of "gravimetric/TDLAS" measurements of water removed was 1.02 +/- 0.06. A theoretical heat transfer model was used to predict the mass flow rate and the model results were compared to both the gravimetric and TDLAS data. Good agreement was also observed in the "gravimetric/TDLAS" ratio for the 5% mannitol runs dried in both Freeze Dryers. The endpoints of primary and secondary drying for the product runs were clearly identified. Comparison of the velocity and mass flux profiles between the laboratory and pilot Dryers indicated a higher restriction to mass flow for the lab scale Freeze dryer.
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evaluation of tunable diode laser absorption spectroscopy for in process water vapor mass flux measurements during Freeze drying
Journal of Pharmaceutical Sciences, 2007Co-Authors: Henning Gieseler, William J Kessler, Michael Finson, Steven J Davis, Phillip A Mulhall, Vincent Bons, David J Debo, Michael J. PikalAbstract:ABSTRACT The goal of this work was to demonstrate the use of Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure the water vapor concentration and the vapor flow velocity in the spool connecting a Freeze‐dryer chamber and condenser. The instantaneous measurements were used to determine the water vapor mass flow rate (g/s). The mass flow determinations provided a continuous measurement of the total amount of water removed. Full load runs of pure water at different pressure and shelf temperature settings and a 5% (w/w) mannitol product run were performed in both laboratory and pilot scale Freeze Dryers. The ratio of “gravimetric/TDLAS” measurements of water removed was 1.02 ± 0.06. A theoretical heat transfer model was used to predict the mass flow rate and the model results were compared to both the gravimetric and TDLAS data. Good agreement was also observed in the “gravimetric/TDLAS” ratio for the 5% mannitol runs dried in both Freeze Dryers. The endpoints of primary and secondary drying for the product runs were clearly identified. Comparison of the velocity and mass flux profiles between the laboratory and pilot Dryers indicated a higher restriction to mass flow for the lab scale Freeze dryer. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1776–1793, 2007
Antonello Barresi - One of the best experts on this subject based on the ideXlab platform.
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Use of computational fluid dynamics for improving Freeze-Dryers design and process understanding. Part 1: Modelling the lyophilisation chamber
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2018Co-Authors: Antonello Barresi, Valeria Rasetto, Daniele L. MarchisioAbstract:Abstract This manuscript shows how computational models, mainly based on Computational Fluid Dynamics (CFD), can be used to simulate different parts of an industrial Freeze-drying equipment and to properly design them; in particular, the Freeze-dryer chamber and the duct connecting the chamber with the condenser, with the valves and vanes eventually present are analysed in this work. In Part 1, it will be shown how CFD can be employed to improve specific designs, to perform geometry optimization, to evaluate different design choices and how it is useful to evaluate the effect on product drying and batch variance. Such an approach allows an in-depth process understanding and assessment of the critical aspects of lyophilisation. This can be done by running either steady-state or transient simulations with imposed sublimation rates or with multi-scale approaches. This methodology will be demonstrated on Freeze-drying equipment of different sizes, investigating the influence of the equipment geometry and shelf inter-distance. The effect of valve type (butterfly and mushroom) and shape on duct conductance and critical flow conditions will be instead investigated in Part 2.
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sputtered thermocouple array for vial temperature mapping
The Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Marco Parvis, Sabrina Grassini, Daniele Fulginiti, Roberto Pisano, Antonello BarresiAbstract:This paper describes the development and characterization of a thin film thermocouple array to be used as a non-invasive solution to map the temperature distribution inside small vials used for Freeze-drying pharmaceutical chemicals. Pharmaceutical chemicals are often produced by means of Freeze-Dryers with very good results, even though the slowness of drying process may increase the product cost. Increasing the shelf temperature accelerates the drying process, but can increase the risk of melting and damaging the product. This risk could be minimized by following the product temperature evolution during the drying step, by means of a noninvasive measuring system able to perform an in situ continuous monitoring. Actual sensors are too invasive to permit a reliable measurement and in addition their dimension does not allow to employ many sensors in a small volume. This paper describes the development of a new multi-sensor structure based on an array of thermocouples having nanometric thickness. The thermocouple array can be embedded into the glass wall of a test vial having all the other characteristics equal to the remaining batch thus providing meaningful and reliable results. Prototypes of the proposed thermocouple array have already been realized and tested making it possible to map the temperature at intervals of few millimeters, following the ice edge during lyophilization.
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Scale-up and Process Transfer of Freeze-Drying Recipes
Drying Technology, 2011Co-Authors: Davide Fissore, Antonello BarresiAbstract:This paper proposes a simple and effective methodology for the scale-up and process transfer of Freeze-drying recipes. Process modeling allows the study of the silico product evolution in a given Freeze-dryer, and calculation of the operating conditions that result in the same product dynamics in different equipment. Few experiments are necessary to determine model parameters and to characterize the two Freeze-Dryers. The problem of the batch non-uniformity and the effect of the parameters' uncertainty are also addressed. The effectiveness of this approach is demonstrated by means of various examples.
Henning Gieseler - One of the best experts on this subject based on the ideXlab platform.
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Effect of Freeze-Dryer Design on Drying Rate of an Amorphous Protein-Formulation Determined with a Gravimetric Technique
Pharmaceutical development and technology, 2008Co-Authors: Henning Gieseler, Geoffrey LeeAbstract:A Freeze-drying balance was used to determine momentary drying-rate, , of a sucrose/BSA formulation contained in a vial with varying shelf packing density, O2. A comparison between two different laboratory-scale Freeze-Dryers was made. The effects of O2 on differed between the two units, attributed to drying chamber design and its effects on heat transfer. At high O2 the differences are annulled because of the shielding effects of surrounding vials. Parallel effects of O2 were also found on product temperature, Tb, measured in the balance vial. Tb was used to calculate vial heat transfer coefficient, Kv. Kv was strongly reduced with increasing O2, but reached a plateau value at high O2.
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Evaluation of a New Wireless Temperature Remote Interrogation System (TEMPRIS) to Measure Product Temperature During Freeze Drying
AAPS PharmSciTech, 2008Co-Authors: Stefan Schneid, Henning GieselerAbstract:The purpose of this research was to evaluate a new wireless and battery-free sensor technology for invasive product temperature measurement during Freeze-drying. Product temperature is the most critical process parameter in a Freeze-drying process, in particular during primary drying. The product temperature over time profile and a precise detection of the endpoint of ice sublimation is crucial for comparison of Freeze-drying cycles. Traditionally, thermocouples are used in laboratory scale units whereas resistance thermal detectors are applied in production scale Freeze-Dryers to evaluate temperature profiles. However, both techniques show demerits with regard to temperature comparability and biased measurements relative to vials without sensors. A new generation of wireless temperature sensors (Temperature Remote Interrogation System, TEMPRIS) were used in this study to investigate for the first time their value when applied to Freeze-drying processes. Measurement accuracy, capability of accurate endpoint detection and effect of positioning were delineated by using product runs with sucrose, mannitol and trehalose. Data were compared to measurements with 36-gauge thermocouples as well as to non-invasive temperature measurement from Manometric Temperature Measurements. The results show that the TEMPRIS temperature profiles were in excellent agreement to thermocouple data when sensors were placed center bottom in a vial. In addition, TEMPRIS sensors revealed more reliable temperature profiles and endpoint indications relative to thermocouple data when vials in edge position were monitored. The results of this study suggest that TEMPRIS may become a valuable tool for cycle development, scale-up and routine manufacturing in the future.
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evaluation of tunable diode laser absorption spectroscopy for in process water vapor mass flux measurements during Freeze drying
Journal of Pharmaceutical Sciences, 2007Co-Authors: Henning Gieseler, William J Kessler, Michael Finson, Steven J Davis, Phillip A Mulhall, Vincent Bons, David J Debo, Michael J. PikalAbstract:The goal of this work was to demonstrate the use of Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure the water vapor concentration and the vapor flow velocity in the spool connecting a Freeze-dryer chamber and condenser. The instantaneous measurements were used to determine the water vapor mass flow rate (g/s). The mass flow determinations provided a continuous measurement of the total amount of water removed. Full load runs of pure water at different pressure and shelf temperature settings and a 5% (w/w) mannitol product run were performed in both laboratory and pilot scale Freeze Dryers. The ratio of "gravimetric/TDLAS" measurements of water removed was 1.02 +/- 0.06. A theoretical heat transfer model was used to predict the mass flow rate and the model results were compared to both the gravimetric and TDLAS data. Good agreement was also observed in the "gravimetric/TDLAS" ratio for the 5% mannitol runs dried in both Freeze Dryers. The endpoints of primary and secondary drying for the product runs were clearly identified. Comparison of the velocity and mass flux profiles between the laboratory and pilot Dryers indicated a higher restriction to mass flow for the lab scale Freeze dryer.
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evaluation of tunable diode laser absorption spectroscopy for in process water vapor mass flux measurements during Freeze drying
Journal of Pharmaceutical Sciences, 2007Co-Authors: Henning Gieseler, William J Kessler, Michael Finson, Steven J Davis, Phillip A Mulhall, Vincent Bons, David J Debo, Michael J. PikalAbstract:ABSTRACT The goal of this work was to demonstrate the use of Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure the water vapor concentration and the vapor flow velocity in the spool connecting a Freeze‐dryer chamber and condenser. The instantaneous measurements were used to determine the water vapor mass flow rate (g/s). The mass flow determinations provided a continuous measurement of the total amount of water removed. Full load runs of pure water at different pressure and shelf temperature settings and a 5% (w/w) mannitol product run were performed in both laboratory and pilot scale Freeze Dryers. The ratio of “gravimetric/TDLAS” measurements of water removed was 1.02 ± 0.06. A theoretical heat transfer model was used to predict the mass flow rate and the model results were compared to both the gravimetric and TDLAS data. Good agreement was also observed in the “gravimetric/TDLAS” ratio for the 5% mannitol runs dried in both Freeze Dryers. The endpoints of primary and secondary drying for the product runs were clearly identified. Comparison of the velocity and mass flux profiles between the laboratory and pilot Dryers indicated a higher restriction to mass flow for the lab scale Freeze dryer. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1776–1793, 2007
William J Kessler - One of the best experts on this subject based on the ideXlab platform.
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recommended best practices for process monitoring instrumentation in pharmaceutical Freeze drying 2017
Aaps Pharmscitech, 2017Co-Authors: Steven L. Nail, Serguei Tchessalov, Evgenyi Shalaev, Arnab Ganguly, Ernesto Renzi, Frank Dimarco, Lindsay A Wegiel, Steven J Ferris, William J Kessler, Michael J. PikalAbstract:Recommended best practices in monitoring of product status during pharmaceutical Freeze drying are presented, focusing on methods that apply to both laboratory and production scale. With respect to product temperature measurement, sources of uncertainty associated with any type of measurement probe are discussed, as well as important differences between the two most common types of temperature-measuring instruments—thermocouples and resistance temperature detectors (RTD). Two types of pressure transducers are discussed—thermal conductivity-type gauges and capacitance manometers, with the Pirani gauge being the thermal conductivity-type gauge of choice. It is recommended that both types of pressure gauge be used on both the product chamber and the condenser for Freeze Dryers with an external condenser, and the reasoning for this recommendation is discussed. Developing technology for process monitoring worthy of further investigation is also briefly reviewed, including wireless product temperature monitoring, tunable diode laser absorption spectroscopy at manufacturing scale, heat flux measurement, and mass spectrometry as process monitoring tools.
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evaluation of tunable diode laser absorption spectroscopy for in process water vapor mass flux measurements during Freeze drying
Journal of Pharmaceutical Sciences, 2007Co-Authors: Henning Gieseler, William J Kessler, Michael Finson, Steven J Davis, Phillip A Mulhall, Vincent Bons, David J Debo, Michael J. PikalAbstract:The goal of this work was to demonstrate the use of Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure the water vapor concentration and the vapor flow velocity in the spool connecting a Freeze-dryer chamber and condenser. The instantaneous measurements were used to determine the water vapor mass flow rate (g/s). The mass flow determinations provided a continuous measurement of the total amount of water removed. Full load runs of pure water at different pressure and shelf temperature settings and a 5% (w/w) mannitol product run were performed in both laboratory and pilot scale Freeze Dryers. The ratio of "gravimetric/TDLAS" measurements of water removed was 1.02 +/- 0.06. A theoretical heat transfer model was used to predict the mass flow rate and the model results were compared to both the gravimetric and TDLAS data. Good agreement was also observed in the "gravimetric/TDLAS" ratio for the 5% mannitol runs dried in both Freeze Dryers. The endpoints of primary and secondary drying for the product runs were clearly identified. Comparison of the velocity and mass flux profiles between the laboratory and pilot Dryers indicated a higher restriction to mass flow for the lab scale Freeze dryer.
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evaluation of tunable diode laser absorption spectroscopy for in process water vapor mass flux measurements during Freeze drying
Journal of Pharmaceutical Sciences, 2007Co-Authors: Henning Gieseler, William J Kessler, Michael Finson, Steven J Davis, Phillip A Mulhall, Vincent Bons, David J Debo, Michael J. PikalAbstract:ABSTRACT The goal of this work was to demonstrate the use of Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure the water vapor concentration and the vapor flow velocity in the spool connecting a Freeze‐dryer chamber and condenser. The instantaneous measurements were used to determine the water vapor mass flow rate (g/s). The mass flow determinations provided a continuous measurement of the total amount of water removed. Full load runs of pure water at different pressure and shelf temperature settings and a 5% (w/w) mannitol product run were performed in both laboratory and pilot scale Freeze Dryers. The ratio of “gravimetric/TDLAS” measurements of water removed was 1.02 ± 0.06. A theoretical heat transfer model was used to predict the mass flow rate and the model results were compared to both the gravimetric and TDLAS data. Good agreement was also observed in the “gravimetric/TDLAS” ratio for the 5% mannitol runs dried in both Freeze Dryers. The endpoints of primary and secondary drying for the product runs were clearly identified. Comparison of the velocity and mass flux profiles between the laboratory and pilot Dryers indicated a higher restriction to mass flow for the lab scale Freeze dryer. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1776–1793, 2007
Berit Reinmüller - One of the best experts on this subject based on the ideXlab platform.
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Design of HEPA-filter units in order to prevent airborne contamination of autoclaves and Freeze Dryers when doors are open
2010Co-Authors: Catinka Ullman, Bengt Ljungqvist, Berit ReinmüllerAbstract:Design of HEPA-filter units in order to prevent airborne contamination of autoclaves and Freeze Dryers when doors are open
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Airborne contamination risks for aseptic manufactured sterile drug products during loading and unloading of Freeze-Dryers
2007Co-Authors: Bengt Ljungqvist, Berit ReinmüllerAbstract:Airborne contamination risks for aseptic manufactured sterile drug products during loading and unloading of Freeze-Dryers
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Loading and unloading of Freeze-Dryers: airborne contamination risks for aseptically manufactured sterile drug products.
PDA journal of pharmaceutical science and technology, 2007Co-Authors: Bengt Ljungqvist, Berit ReinmüllerAbstract:In pharmaceutical manufacturing, Freeze-drying processes can be adversely affected by temperature differences relative to the surrounding air. Loading and unloading of Freeze-Dryers are performed either without or with temperature differences between the cleanroom and the chamber of the Freeze-dryer. This operation can cause a flow of room air through the opening, creating a contamination risk, especially when manual handling of material is performed in this area. To minimize this risk, a high-efficiency particulate air (HEPA) filter unit should be installed above the opening to provide clean air and protect the opening. Here the theoretical relationships are discussed and design criteria are presented.
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Design of HEPA-filters above autoclaves and Freeze-Dryers.
PDA journal of pharmaceutical science and technology, 1998Co-Authors: Bengt Ljungqvist, Berit ReinmüllerAbstract:In pharmaceutical manufacturing some processes and process equipment cause temperature differences relative to the surrounding air, e.g. sterilisation and Freeze-drying processes. Generally there is a temperature difference when a door to such equipment is opened. This can cause a flow of room air through the opening, creating a contamination risk, especially when manual handling of material is performed in this area. To minimize this risk, a HEPA-filter unit should be installed above the opening to provide clean air and protect the opening. The airflow needed through the HEPA-filters depends mainly on the temperature difference between the chamber and the room and the size of the opening. The flow of clean air should be greater than that of the theoretically calculated flow in order to minimize contamination hazards. In this paper the theoretical relations are discussed and design criteria are presented in a simplified form with graphical representations. Results from a case study are described and the experimentally estimated air-flow values are compared with the theoretically calculated values.
