White Papers – Posters – Presentations
White Papers, Posters & Presentations for Freeze Drying Scientists. Click on the title for more information.
Considerations When Freeze Drying Tissue
White Paper by T.N. Thompson, President – Millrock Technology Inc
Click here to download the white paper: Hybrid Pharmaceutical Vials for Lyophilized Biological Drugs and Vaccines
Full article can be found on The Journal of Pharmaceutical Sciences website. Access requires a journal subscription.
Johnathan M. Goldman, Xiaodong Chen, Jeffrey T. Register, Vishwas Nesarikar, Lavanya Iyer, Yongmei Wu, Naila Mugheirbi, Jasmine Rowe
Abstract:
We have implemented the use of a small-scale, 7-vial Micro Freeze Dryer (MicroFD®; Millrock Technology, Inc.) that has the capability to accurately control heat transfer during lyophilization. We demonstrate the ability to fine-tune the MicroFD® vial heat transfer coefficient (Kv) to match the Kv of vials in a LyoStar III laboratory-scale unit. When the MicroFD® is run under conditions that match the Kv of the LyoStar III, the resulting lyophilization performance between scales results in equivalent product temperature profiles and critical quality attributes for the same drying process. The proposed workflow demonstrates how exploitation of Kv control in the MicroFD® enables cycle development of at-scale lyophilization processes using only 7 product vials. By changing the MicroFD® Kv, laboratory and, potentially, manufacturing cycles may be simulated using only 7 product vials for tremendous active pharmaceutical ingredient savings, as long as at-scale heat transfer coefficients are well characterized.
Full article can be found on The Journal of Pharmaceutical Sciences website. Access requires a journal subscription.
David Fissore, Giuseppe Gallo, Angelo Emiliano Ruggiero, Taylor N. Thompson
Abstract:
This paper deals with the use of a small-scale freeze-dryer, where very few vials are loaded (e.g. 19, each 10 mL, or 7, each 20 mL), for freeze-drying cycle investigation. The system has a metallic ring surrounding the batch of vials, in contact with the external ones, and its temperature is manipulated independently from that of the shelf on the basis of the temperature of the product measured by thermocouples in some vials of the batch. The experimental study was carried out using two sucrose solutions (5% and 10% w/w), aiming to verify the homogeneity of the batch. Both product temperature and the weight loss after 6 h from the onset of the primary drying stage were selected as key parameters. Experiments were carried out according to a 2 N design of experiments, with two values of chamber pressure (60 and 90 mTorr) and two values of shelf temperature (−20 and 0 °C). Satisfactory results may be obtained by selecting a ring temperature 5 °C lower than that of the monitored samples in case of both products investigated. Besides, the system appears to be useful for the estimation of the coefficient of heat transfer to the product (Kv) and of the resistance of the dried cake to vapour flux (Rp), thus enabling the use of mathematical modelling for process design and optimization.
Recommended Best Practices for Process Monitoring Instrumentation in Pharmaceutical Freeze Drying
Full article can be found on The Journal of Pharmaceutical Sciences website. Access requires a journal subscription.
Steven Nail, Serguei Tchessalov, Evgenyi Shalaev, Arnab Ganguly, Ernesto Renzi, Frank Dimarco, Lindsay Wegiel Steven Ferris, William Kessler, Michael Pikal, Greg Sacha, Alina Alexeenko, T. N. Thompson, Cindy Reiter, James Searles, and Paul Coiteux
Abstract:
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.
Effect of Ice Fog Controlled Nucleation on Variation of Ice Weight
PowerPoint by Tatsuhiro Kodama, Senior Researcher – Daiichi Sankyo Co. Ltd.
J. Goldman1, J. Register2 X. Chen, V. Nesarikar1, J. Rowe, Bristol-Myers Squibb Company, Princeton University
Developing Transferable Freeze Drying Protocols Using AccuFlux® and a MicroFD®
YouTube Presentation: Millrock Technology - Scaling Up Your Protocol - The Innovative MicroFD
Integrated heat flux measurements as a noninvasive monitoring technique for freeze drying
Ilona Konrad, Victoria Pauli1, Wolfgang Friess, Andrea Hawe, Gerhard Winter, Angelika Freitag
Qiming Wang (Millrock Technology Inc.), Michael Sztucki, T Narayanan (European Synchrotron Radiation Facility), Brian Ivin, Adrian Marley, Kieran Joyce, Prem Mohanty, Evgenyi Shalaev (Allergan)
Abstract: Crystallization of excipients during freeze-drying could have a major impact on both the manufacturing process (e.g., rate of drying) and quality of the finished product. In this investigation, binary solutions of water+NaCl and water+surfactant (poloxamer) were studied by DSC, low-temperature synchrotron small- and wide-angle X-ray diffraction (XRD), and heat-flux transducers (HFT) which are incorporated into the shelf of a Millrock Technology, Inc. MicroFD freeze-dryer with LyoPAT II. In the HFT experiments, the heat flux between the shelf and vials was measured during cooling/warming cycles.
For NaCl-water solutions, primary ice nucleation and secondary solute+water crystallization (equivalent to eutectic crystallization for a binary system) during cooling, and secondary (eutectic) solute+ice and ice melting during warming were detected by HFT. Behavior of poloxamer-water system was more complex, with at least three consecutive transitions taking place during cooling, i.e., primary water crystallization, formation of a liquid crystalline (tentatively, cubic) phase, and finally appearance of a crystalline poloxamer phase with 3-dimensional translational order. The study confirms that crystallization behavior as observed by laboratory-based tests (DSC and XRD)
could be different from the behavior of a formulation during real freeze-drying runs, and also presents HFT as a useful non-invasive tool to monitor excipients crystallization in vials.
Heat Flux Measurement as a Process Analytical Technology for Freeze Drying
YouTube: Millrock Technology - T.N. Thompson Explains Heat Flux
Innovative approaches for lyophilization process, equipment and drug product characterization
Ahmad M. Abdul-Fattah, Coriolis Pharma Research GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany
