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Cite as:Smith, G. (2020) Lyophilization Process Development. Applications for eisPAT. On-line presentation at Digital Week Biologicals Formulation Development and Drug Delivery. June 22-26th 2020Conference presentation by Geoff Smith at the on-line conference Digital Week June 22nd to 26th 2020Topics covered:- Broad band dielectric spectrometers- micro-electrode arrays incorporated within a freeze-drying microscope

Cite as:Jeeraruangrattana, Y. et al. (2016) The Application of Through Vial Impedance Spectroscopy for Optimization Freeze-Drying. Poster Presentation at the International PharmTech Conference 2016, 4th November 2016, Leicester, UK.Poster presentation at The International PharmTech Conference 2016, 4th November 2016, Leicester, UK

Cite as :Smith, G. (2015) Process Analytical Technology and the Question of Scale. Podium presentation at 7th ISLFD International Conference; 2015 July 06-10; Barcelona, SpainOutline of the presentation1. Highlight from the CDER PAT guidance document (2004)2. Brief overview of scale lengths in terms of pharmaceutical freeze-drying (from the molecular and the mesoscopic to the macroscopic)3. Features and limitations of existing PAT4. An overview of through-vial impedance spectroscopy (TVIS)5. TVIS Applications & Challenges: Ice formation Phase behaviour (TEU and TG Annealing & structural relaxation Various scales (freeze-drier heterogeneity, ice front shape)6. TVIS Future developments

Cite as :Smith, G. (2020) Z-FDM : Impedance spectroscopy enhanced freeze drying microscopy. Podium presentation at 2nd Annual Pharmaceutical Lyophilization Summit 12-13 Feb 2020, Berlin2nd Annual Pharmaceutical Lyophilization SummitFebruary 12-13, 2020 | Berlin, GermanyNH Collection Berlin FriedrichstrasseFriedrichstraße 96This presentation demonstrates the application in freeze-drying of a single analytical instrument (Z-FDM) combining impedance (Z) spectroscopy with freeze-drying microscopy (FDM). The electrical impedance spectra and visual appearance of frozen solutions were analysed with an inter-digitated micro-electrode array placed on a freeze-drying microscope stage. The critical process parameters of ice growth, sublimation drying rate and end-point were studied using Z-FDM technique in addition to observing the collapse temperature. This early study indicates that by using this combined approach it is possible to obtain further information that can be obtained currently by two separate instruments.

Cite as:Smith, G. (2018). Multi-plexing single vial proces analytical technologies. Podium presentation at "Freeze Drying of Pharmaceutical and Biologicals", Sept 18 - 21, Garmisch-Partenkirchen, Germany The presentation describes the use of a dual-electrode, through vial impedance spectroscopy (TVIS) method for the determination of drying rates and the prediction of ice interface and ice base temperatures from which the single vial heat transfer coefficient was calculated.

Cite as :Smith, G. and Jeeraruangrattana, Y. (2018). Through-vial impedance spectroscopy (TVIS): A novel process analytical technology for the development of pharmaceutical products and processes. Podium presentation at 2nd Annual Pharmaceutical Lyophilization Summit, May 24 – 25, Vienna, AustriaScope of the presentation:The first part of the talk provides a description of the TVIS measurement system followed by a brief overview of a number of applications in pharmaceutical freeze-drying.The majority of the talk then focuses on the first time reporting of the use of dual-electrode system and its application in the determination of vial heat transfer coefficient (Kv).This includes a method for predicting:(i) Ice region specific temperatures (Ti at the sublimation interface and Tb at the base of the ice mass)(ii) Ice sublimation rate (dm/dt)

This work demonstrates the application in freeze-drying of a single analytical instrument (Z-FDM) combining impedance (Z) spectroscopy with freeze-drying microscopy (FDM). The electrical impedance spectrum and visual appearance of a 5% sucrose solution was analysed with an interdigitated micro-electrode array placed on a freeze-drying microscope stage. The critical process parameters of ice growth, sublimation drying rate and end-point were studied using Z-FDM technique in addition to observing the collapse temperature. This early study indicates that by using this combined approach it is possible to obtain further information that can be obtained currently by two separate instruments.

Cite as:Jeeraruangrattana, Y. et al. (2017) Prediction of the Collapse of Freeze-Dried Lactose Solution using Through Vial Impedance Spectroscopy (TVIS). Poster Presentation at the 8th APS International PharmSci Conference, 5-7th September 2017, Hertforshire, UK.Poster presentation at The 8th APS International PharmSci Conference, 5-7th September 2017, Hertforshire, UK

Cite as:Pandya et al. (2018). Poster Presentation at Freeze Drying of Pharmaceuticals and Biologicals,18-21st September 2018, Garmisch Partenkirchen, GermanyTo demonstrate the impact of vial location on the drying rate using two parameters of non-product invasive through vial impedance spectroscopy (TVIS). These include: (i) the peak imaginary amplitude, C"PEAK, which is a direct measure of ice mass in the vial, and (ii) the peak frequency, FPEAK, which is sensitive to a change in the shape of the ice interface.

Poster title: Application of through vial impedance spectroscopy to different container

Cite as :Smith, G. (2017). Recent Advances in Through Vial Impedance Spectroscopy (TVIS) for Process Parameter Determination. Podium presentation at 9th International ISL-FD Conference April 26-28 Havana, CubaOutline of the presentation:The presentation starts with an introduction to through vial impedance spectroscopy and a description of the measurement system before going on to describe various TVIS applications in the following stages of the process:1. Freezing (Ice formation and phase separation)2. Re-heating of the frozen mass to obtain a surrogate temperature calibration based on the TVIS parameter FPEAK3. Primary drying (Drying rate based on the TVIS parameter C"PEAK from which the product dry layer resistance and evidence of micro-collapse are determined).

Cite as :Smith, G. (2017). Recent Advances in Through Vial Impedance Spectroscopy (TVIS) for Process Parameter Determination. Podium presentation at LyoTalk, May 22, Dublin, IrelandScope of the presentation:Description of TVIS Measurement SystemTVIS Application in Freezing- Ice Formation and phase separationTVIS Application in Annealing- Surrogate Temperature CalibrationTVIS Application in Primary Drying- Drying Rate- Product Resistance (Rp)- Micro-collapse

cite as : Smith G. (2016) TVIS. Through-Vial Impedance Spectroscopy. Podium presentation at SMi Lyophilization Europe; July 04-05; Kensington, London, UK. The presentation is structured as follows:1. Basic description of the measurement system hardware2. Description and Maxwell-Wagner model for the impedance spectrum of the vial containing a liquid formulation3. Illustration of how the real part impedance spectrum changes towards the end of the ice sublimation phase, and how a measurement at an excitation frequency on the high frequency side of the dielectric relaxation of ice (100 kHz) may be used to track changes in the shape of the ice mass and ultimately determine the end point of the sublimation phase4. The introduction of a re-heating and re-cooling stage (post freeing) to capture the relationship between the TVIS parameter FPEAK and the temperature of the ice mass (i.e. to calibrate the TVIS response)5. The prediction of ice mass temperature during subsequent primary drying from the calibration plot of FPEAK vs ice mass temperature. This predicted ice mass temperature is given the symbol T(FPEAK) given that it is derived from the TVIS parameter FPEAK by a process of calibration.6. The determination of drying rate from the TVIS parameter C"PEAK7. Preliminary attempts at the determination of the vial heat transfer coefficient (Kv)8. Preliminary studies on freeze-drying conductive liquids: ~4% protein solution and the determination of drying rate9. The observation of a second relaxation process (on the low frequency side of the ice relaxation peak) and the emergence/dominance of the second relaxation peak as the ice mass is reduced in primary drying. Opportunities now exist for monitoring the secondary drying process when physi-sorbed water is removed form the protein rich unfrozen fraction (i.e. dry layer).

Cite as:Jeeraruangrattana, Y., Ermolina, I., Polygalov, E., Smith, G. (2018) Application of Impedance Based Technology to Investigate the Collapse of Freeze-dried Sugar-salt Solutions. Poster presentation at Freeze Drying of Pharmaceuticals and Biologicals, Sept 18-21, Garmisch-Partenkirchen, Germany Pharmaceutical Technologies Group, Leicester School of Pharmacy, De Montfort University, UK

PURPOSE To demonstrate the impact of vial location on the drying rate using two parameters of non-product invasive through vial impedance spectroscopy (TVIS). These include: (i) the peak imaginary amplitude, C"PEAK, which is a direct measure of ice mass in the vial, and (ii) the peak frequency, FPEAK, which is sensitive to a change in the shape of the ice interface.

Cite as:Smith, G. (2015) A focus on freeze-drying. Podium presentation at APS Parenteral Focus Group meeting; January 28; Burleigh Court, Loughborough, UKPresentation Overview1. Freeze-drying – Process steps and questions?2. QbD in Freeze-Drying3. Freezing Stage – Critical process parameters : solidification end point, eutectic formation, glass formation – PAT in the freezing Stage (development & production)4. Primary Drying Stage – Critical process parameters : collapse temperature, drying rate, drying end point – PAT in the 1ry drying Stage (development & production)5. LyoDEA – A new PAT – Equivalent circuit modelling – Determination of the ice nucleation onset, the ice solidification time and the thermal equilibration time – Impact of sucrose on mannitol crystallization – Annealing times and the prediction of primary drying duration – In-vial determination of the glass transition temperature, Tg' – Strength/fragility of glass forming liquids – Primary drying rates and end point determination – Product collapse

Cite as:Jeeraruangrattana, Y. et al. (2017) Application of Impedance Based Technology (TVIS) for the Prediction of Micro-Collapse. Poster Presentation at the 5th Quality by Design Symposium, 29th March 2017, Leicester, UK.Poster presentation at The 5th Quality by Design Symposium, 29th March 2017, Leicester, UK

cite as: Smith G. (2016) The Application of Through Vial Impedance Spectroscopy (TVIS) for Process Parameter Determination in Freeze Drying Method Development. Podium presentation at PDA Europe Pharmaceutical Freeze Drying Technology; 2016 Sept 27-28, Strasbourg, FranceThe presentation starts with a description of the through vial impedance spectroscopy (TVIS) and the measurement system before going on to describe applications in the determination of various process parameters and related phenomena: Vial heat transfer coefficient (KV) Dry layer resistance (RP) Ice nucleation (onset of ice growth) Glass transition Eutectic crystallization Collapse

Cite as:Pandya et al. (2017). New Impedance Based Methodologies to Determine the Vial Heat Transfer Coefficient. Poster presentation at UK-PharmSci, 5-7th September 2017, Hatfield, UKAims: To propose a new methodology to determine the vial heat transfer coefficient (Kv) and the endpoint of primary drying. Methods: Convergence of the peak imaginary capacitance (C"PEAK) and the high frequency permittivity, C'(100 kHz) was used as a new method to calculate the drying rate and Kv and the time profile of C'(100 kHz) was used to determine the endpoint. Results: Convergence was true only within the first 5 % of ice sublimation; C'(100 kHz) plateau coincided with the visual endpoint; Conclusions: Kv should be calculated only within the first 5% of primary drying and C'(100 kHz) can be followed to detect the endpoint.

Cite as:Jeeraruangrattana, Y. et al. (2019) Through-Vial Impedance Spectroscopy (TVIS): A New Approach to Characterizing Phase Transition of Sugar-Salt Solutions. Poster Presentation for ISLFD 2019, 2-6th September 2019, Ghent, Belgium.Poster presentation.ISL-FD 9th International Conference 2-6th September, 2019, Ghent, Belgium

Cite as :Smith, G. and Jeeraruangrattana, Y. (2018). Through Vial Impedance Spectroscopy (TVIS) Dual-electrode System for Process Parameter Determination. ISL-FD Midwest Chapter Annual Meeting, April 12th 2018, Midwest Conference Centre, Northlake, IL 60164, USAThe first part of the talk provides a description of the TVIS measurement system followed by a brief overview of a number of applications in pharmaceutical freeze-drying. The majority of the talk then focusses on the first time reporting of the use of dual-electrode system and its application in the determination of vial heat transfer coefficient (Kv).This includes a method for predicting: (i) Ice region specific temperatures (Ti at the sublimation interface and Tb at the base of the ice mass) (ii) Ice sublimation rate (dm/dt)

cite as: Smith, G. (2017) Through Vial Impedance Spectroscopy (TVIS):A new method for the development of manufacturing processes for inject-able drug products. Podium presentation at 10th International Workshop on Impedance Spectroscopy; Sept 28-29; Chemnitz, Germany. Presentation Overview: - Introduction to TVIS (i) equations for the derivation of complex capacitance from the measured impedance, (ii) a simplified equivalent circuit model for the observed relaxation process; (iii) example impedance spectra and the equivalent capacitance spectra for the TVIS vial with a 5% w/v solution of lactose in the liquid and frozen states and empty- Applications for TVIS (i) calibration of TVIS parameter FPEAK for the temperature of the ice and the subsequent application of the derived parameter T(FPEAK) in the prediction of the temperature of ice during the primary drying stages; (ii) use of temperature compensated value for the height of the dielectric loss peak (CPEAK) for the determination of the ice sublimation rate.

Cite as:Jeeraruangrattana, Y. et al. (2018) Application of Impedance Based Technology to Investigate the Collapse of Freeze-dried. Poster Presentation at Freeze Drying of Pharmaceuticals and Biologicals, Sept 18-21 (2018), Garmisch-Partenkirchen, GermanyPoster presentation at Freeze Drying of Pharmaceuticals and Biologicals, Sept 18-21 (2018), Garmisch-Partenkirchen, Germany

cite as:Smith, G. (2019). Impedance Spectroscopy: Recent Developments as a Process Analytical Technology for Pharmaceutical Freeze-Drying. Podium presentation at Qepler Lyophilization Summit 13-14 Feb, PraguePodium presentation describing the application of through vial impedance spectroscopy in the determination of nucleation temperatures and solidification end points. TVIS dielectric loss parameters Fpeak and Cpeak and the dielectric storage at low frequency (e.g. 10 or 100 Hz) appear to offer the opportunity for the registration of the nucleation point for the onset of ice growth. In addition the dielectric storage at high frequency (e.g. 200 kHz) shows little temperature sensitivity and so is an ideal measurement frequency for assessing the end point of ice solidification. Post solidification, the parameter log Fpeak can then be redeployed to determine the point at which all excess latent heat has left the sample and the product temperature then equilibrates with the shelf. This work paves the way for the determination of a new critical process parameter based on the time interval between ice growth onset and ice solidification end point (alongside the ice nucleation temperature).Content of the presentation:1. Introduction2. Dielectric loss mechanisms3. TVIS Theory4. What frequency for what process?5. Observations on ice (Ice nucleation and growth; ice solidification end point)

Poster presentation.ISL-FD 9th International Conference 2-6th September, 2019, Ghent, Belgium

Cite as : Smith, G. (2020) Novel impedance-spectroscopy PAT for freeze drying process development. KTN meeting. Podium presentation at Analytical challenges & solutions for medicines manufacturing towards Industry 4.0, Centre for Process Innovation, Darlington, 2020 February 26Analytical challenges & solutions for medicines manufacturing towards Industry 4.0The Knowledge Transfer NetworkWednesday, 26 February 2020 from 09:30 to 16:30 (GMT) Darlington, United KingdomKTN and CPI will be hosting an event to consider analytical challenges & solutions for medicines manufacturing towards Industry 4.0 on 26th February.Medicines manufacturing is a key UK activity. The emerging technologies that characterise Industry 4.0 — data connectivity, advanced analytics, robotics and automation — have the potential to revolutionise every element of (bio)pharmaceutical manufacturing within the next five to ten years and are heavily reliant on reliable analytical data.The Industry 4.0 approach is expected to drive down manufacturing costs which is necessary in order to keep medicines affordable. Additionally, the increased number of therapeutic medicines being adopted such as gene therapies, cell therapies and multiple antibody derived formats provides new challenges for analytics. Thus, it is imperative to invest in innovation in analytics that will underpin the manufacture of (bio)pharmaceutical products against these developing challenges.This one-day meeting, co-organised by the Centre for Process Innovation (CPI) and KTN, will consider the challenges highlighted above in the context of the broad range of therapeutic modalities. It will take place on 26th February 2020 at the Centre for Process Innovation in Darlington. The agenda will be made up of a number of sessions covering:• development of novel sensors and analytical techniques and their regulatory adoption• real-time release and process monitoring management of analytical data for small molecules• biopharmaceuticals/vaccines and cell and gene therapies.

Cite as : Smith, G. (2016) Freeze-drying process optimization using through vial impedance spectroscopy. Podium presentation at EPSRC EHDA Network International Pharmaceutical Technology Conference, November 4, Leicester, United KingdomScope of the presentation:The talk starts with an introduction to freeze-drying and the design space for the process, then provides an introduction of Through Vial Impedance Spectroscopy (TVIS) TechnologyThe rest of the talk is then devoted to applications for TVIS in the determination of two important process parameters: ➢ Heat transfer coefficient through the vial base KV➢ Dry layer resistance which impedes the of water vapour sublimation RPThe dry layer resistance was calculated for a 2% solution of protein. This substance presents on interesting TVIS spectrum with separate contributions from the dielectric relaxation of ice and from another relaxation process associated with he unfrozen fraction.

Cite as:Smith, G. (2020) Novel electrical impedance methods in formulation and process development. Podium presentation at Freeze-Drying Technology Summit, Vienna 2020 Feb 13-14Freeze-Drying Technology SummitVienna 13-14 Feb 2020 | Vienna, AustriaHilton Garden Inn Vienna SouthHertha-Firnberg-Straße 5, 1100This presentation provides a brief introduction to electrical impedance and dielectric relaxation processes in liquid and frozen aqueous solutions, before discussing the use of micro-scale measurements in a freeze-drying microscope (highlighting potential applications for formulation screening). These microscale studies are based on a single analytical instrument (Z-FDM) which combines impedance (Z) spectroscopy with freeze-drying microscopy (FDM) with an interdigitated micro-electrode array placed on a freeze-drying microscope stage. Critical process parameters of ice growth, sublimation drying rate and end-point were demonstrated using the Z-FDM technique. A brief overview of in-vial measurements in a freeze-dryer (using through-vial impedance spectroscopy) is also given, along with the statements on potential applications for process development.

Studies of the freezing behavior of aqueous solutions of mannitol are highly relevant to lyophilization process development given the prevalent use of this excipient. Here, through-vial impedance spectroscopy (TVIS) was used to study the behaviour of an aqueous solution of 5%w/v mannitol during a freezing and re-heating cycle. Temperature calibration of the TVIS parameter FPEAK enabled the determination of the ice nucleation temperature Tn at −13 oC while the ice solidification end point was observed based on the time profile of C' (0.2MHz), i.e. the real part capacitance at 0.2 MHz. A time difference of 20 min between the onset and end point then defines the ice solidification time ti. A later step in C^' (0.2MHz) indicated that mannitol crystallized at -32 oC and 20 minutes from end of ice solidification. Upon reheating at 0.2 oC/min, a large increase in C' (0.2MHz) was seen at −32 oC indicating the onset of melting of mannitol crystals which then lasted 20 min.

This is a study of the freezing/reheating behavior of aqueous solutions of mannitol with respect to lyophilization process development given the prevalent use of the excipient. Here, through-vial impedance spectroscopy (TVIS) was used to study the thermophysical kinetics of an aqueous solution of 5%w/v mannitol during a freezing and re-heating phase of a freeze-drying cycle. Temperature calibration of the TVIS parameter FPEAK enabled the determination of the ice nucleation temperature Tn at −13 oC while the ice solidification end point was observed based on the time profile of C' (0.2MHz), i.e. the real part capacitance at 0.2 MHz. A time difference of 20 min between the onset and end point then defines the ice solidification time ti. A later step in C' (0.2MHz) indicated that mannitol crystallized at -32 oC and 20 minutes from end of ice solidification. Upon reheating at 0.2 oC/min, a large increase in C' (0.2MHz) was seen at −32 oC indicating the onset of melting of mannitol crystals which then lasted 20 min.

Studies of the freezing behavior of aqueous solutions of mannitol are highly relevant to lyophilization process development given the prevalent use of this excipient. Here, through-vial impedance spectroscopy (TVIS) was used to study the behaviour of an aqueous solution of 5%w/v mannitol during a freezing and re-heating cycle. Temperature calibration of the TVIS parameter FPEAK enabled the determination of the ice nucleation temperature Tn at −13 oC while the ice solidification end point was observed based on the time profile of C' (0.2MHz), i.e. the real part capacitance at 0.2 MHz. A time difference of 20 min between the onset and end point then defines the ice solidification time ti. A later step in C^' (0.2MHz) indicated that mannitol crystallized at -32 oC and 20 minutes from end of ice solidification. Upon reheating at 0.2 oC/min, a large increase in C' (0.2MHz) was seen at −32 oC indicating the onset of melting of mannitol crystals which then lasted 20 min.

Cite as:Smith, G. (2019) Applications for Impedance Spectroscopy in the Determination of In-Vial Phase Behaviour. Podium presentation at SMi 7th Annual Lyophilization Conference, 3-4 June, 2019, LondonPodium presentation by Geoff Smith at the 7th Annual Lyophilization Conference, London June 3rd - 4th 2019 describing the application of through-vial impedance spectroscopy in the determination of in-vial phase behaviour during freezing and annealing. Contents• Through-Vial Impedance Spectroscopy – An Introduction• Dielectric loss mechanisms in frozen solutions• Measurement frequency selection for different facets of the freezing process (ice nucleation to solidification end point)• Determination of in-vial glass transitionsTVIS dielectric storage parameter C' at low frequency (e.g. 10 or 100 Hz) allows for the registration of ice nucleation (ice growth onset) partly due to its dependence on temperature whereas C' at high frequency (e.g. 200 kHz) shows less sensitivity to temperature and so is an ideal measurement frequency for assessing the end point of ice solidification. Post solidification, the TVIS parameter log Fpeak is used determine the point at which all excess latent heat has left the sample and the product temperature then equilibrates with the shelf. This work paves the way for the determination of new critical process parameters, based on : (i) the time interval between ice growth onset and ice solidification end point (alongside the ice nucleation temperature), (ii) the time interval between ice solidification end point and thermal equilibration.

This is a study of the freezing/reheating behavior of aqueous solutions of mannitol with respect to lyophilization process development given the prevalent use of the excipient. Here, through-vial impedance spectroscopy (TVIS) was used to study the thermophysical kinetics of an aqueous solution of 5%w/v mannitol during a freezing and re-heating phase of a freeze-drying cycle. Temperature calibration of the TVIS parameter FPEAK enabled the determination of the ice nucleation temperature Tn at −13 oC while the ice solidification end point was observed based on the time profile of C' (0.2MHz), i.e. the real part capacitance at 0.2 MHz. A time difference of 20 min between the onset and end point then defines the ice solidification time ti. A later step in C' (0.2MHz) indicated that mannitol crystallized at -32 oC and 20 minutes from end of ice solidification. Upon reheating at 0.2 oC/min, a large increase in C' (0.2MHz) was seen at −32 oC indicating the onset of melting of mannitol crystals which then lasted 20 min.

Cite as:Smith, G. (2019) Electrical Impedance Methods for Developing a Lyophilization Cycle. Podium presentation at ISL-FD 9th International Conference 2-6 September, 2019, Ghent, BelgiumThe talk will describe the application of through-vial impedance spectroscopy in the determination of in-vial phase behaviour during freezing and annealing.Contents• Through-Vial Impedance Spectroscopy – An Introduction• Dielectric loss mechanisms in frozen solutions• Measurement frequency selection for different facets of the freezing process (ice nucleation to solidification end point)• Determination of in-vial glass transitionsTVIS dielectric storage parameter C' at low frequency (e.g. 10 or 100 Hz) allows for the registration of ice nucleation (ice growth onset) partly due to its dependence on temperature whereas C' at high frequency (e.g. 200 kHz) shows less sensitivity to temperature and so is an ideal measurement frequency for assessing the end point of ice solidification.Post solidification, the TVIS parameter log Fpeak is used determine the point at which all excess latent heat has left the sample and the product temperature then equilibrates with the shelf.This work paves the way for the non-invasive determination of the ice nucleation temperature, the average ice growth rate and the time interval between ice solidification end point and thermal equilibration.

Cite as:Pandya et al. (2019). Multiplexing Through Vial Impedance Spectroscopy (TVIS) with Comparative Pressure Measurement. Poster presentation at ISL-FD 9th International Conference 2-6th September, 2019, Ghent, BelgiumTwo IgG formulations, one with 5% sucrose and the other with 5% Mannitol:Sucrose (ratio 4:1) both in 20mM Histidiine 0.01% Tween 20 pH 6.5, were freeze dried in a Telstar freeze dryer equipped with Pirani and Baratron sensors and a Sciospec® five-channel through vial impedance spectroscopy (TVIS) system. The TVIS parameter C'(100kHz) (i.e. the real part electrical capacitance measured at 100 kHz) is sensitive to the amount of ice in the vial. By following the recovery of its time profile during primary drying, it was possible to determine the primary drying endpoint. The TVIS endpoint of the sucrose edge vial occurred well before the onset of the Pirani endpoint suggesting that Pirani was more sensitive to the core vials. The TVIS endpoint in the core vials also occurred somewhere close to the midpoint of the Pirani endpoint suggesting that other core vials were still in primary drying.

Poster title: Application of Impedance Based Technology to Investigate the Collapse of Freeze-dried Sugar-salt SolutionsYowwares Jeeraruangrattana, Irina Ermolina, Eugene Polygalov, Geoff Smith Pharmaceutical Technologies Group, Leicester School of Pharmacy, De Montfort University, UK

Podium presentation by Geoff Smith at the Lyophilization Summit in Prague, February 13-14th 2019, describing the application of through vial impedance spectroscopy in the determination of nucleation temperatures and solidification end points. TVIS dielectric loss parameters Fpeak and Cpeak appear to offer the opportunity for the registration of the primary nucleation whereas the dielectric storage at low frequency (eg 10 or 100 Hz) allow for the registration of secondary ice nucleation (ie ice growth). In addition the dielectric storage at high frequency (eg 200 kHz) shows little temperature sensitivity and so is an ideal measurement frequency for assessing the end point of ice solidification. Post solidification, the parameter log Fpeak can then be redeployed to determine the point at which all excess latent heat has left the sample and the product temperature then equilibrates with the shelf. This work paves the way for the determination of a new critical process parameter based on the time interval between ice growth onset and ice solidification end point (alongside the ice nucleation temperature).

Figshare field trip presentation on March 7th 2019 at the University of Leicester