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Homogenizing Perfected: Solutions for Pharma Industry

Solutions for Optimal Lyophilization

Biopharma Group, UK is committed to providing a world-class service to their customers. With over decades of experience in the application of all aspects of freeze drying technology and having successfully processed over 1000 substances on behalf of clients, the R&D Consultancy division of Biopharma Group provides contract research and development services, training and advanced instrumentation to the global biopharmaceutical and related industries.

Together with their knowledge of pilot-scale and industrial freeze-dryers, they offer a uniquely comprehensive service covering all aspects of freeze-drying from pre-formulation through to full-scale production and dried product analysis. Additionally, Biopharma Group remains at the forefront of analytical instrumentation development, having designed and developed a range of advanced analytical instruments i.e. the Lyostat5 freeze drying microscope (FDM), Lyotherm3 DTA & impedance analyser & most recently, the MicroPress for quantifying lyo-cake robustness.

LyoStat 5 Freeze Drying Microscope

Lyostat 5 from Biopharma Technology Ltd (BTL) is an advanced freeze drying microscope, with PC control for image and data capture and analysis functions.Freeze drying microscopy (FDM) was established in the 1960s as a technique for identifying critical formulation parameters and is the only method for reliably determining collapse temperatures. Historically FDM was used only for collapse / eutectic temperatures but the latest generation FDM can also enables identification of crystallization phenomena, the potential for skin/crust formation, and the effects of annealing on ice crystal growth and solute structure.

lyostat-freeze

Lyostat 5 analysis uses just 2µl and is typically complete in under an hour. Lyostat 5 is supplied fully validated as a complete working system against a series of standard solutions . Lyostat 5 is PC controlled to provide sophisticated image and data capture and analysis functions, which also allows the user to make a video of their sample under analysis. The software is also available in a 21CFR11 compliant version.

BTL has expertise in the formulation of products, accounting for the lyophilisation(freeze drying) steps involved in the development and/or production process. To date BTL has worked with over 1800 products, from small molecules to proteins, organisms, whole cells , collagen products, blood and archaeological samples.

  • Real-time image, sample temperature and chamber pressure displayed on screen
  • Data archiving and profile plotting capability
  • Uses just 1 to 2µL sample
  • LED light source for 60,000 hours of illumination
  • Enables rapid observation of collapse, melting and eutectic event temperatures
  • ‘Image Gallery’ enabling comparisons of stored image sequences
  • High resolution camera provides sharp, clear visualization
  • Motorized vacuum control option, to enable specification of exact pressure
  • Pre-delivery testing includes validation of complete working system against a published series of standard solutions
  • IQ/OQ, service, maintenance and requalification packages
  • Over 1800 different formulations studied so far!
What the Technique / Instrument Is:

Thermal Analysis by Surface Characterisation (TASC) is a software addition to the Lyostat 5 that is used to analyse data files generated by the LINK software post-analysis. It is suited to the high resolution (2.3MP) of the PointGrey colour camera and to the fixed and reproducible focus on the Lyostat 5 imaging station.

How It Works:

TASC analyses incremental changes to successive images in the focus area by the brightness and colour of each pixel, to produce a normalised TASC trace overlay to the data graph. It then looks at changes in the selected area and shows a change in the line based on the degree of collapse. If the collapse temperature is roughly known (by visual inspection of the data file) TASC can then pinpoint the start of this collapse in this region.

Benefits:
  • Accurate and quantitative analysis
  • Reduces operator error in the analysis of the precise collapse temperature
  • Can retrofit to previous results to check validity
  • Flexible analysis useful for many other application outside of freeze drying using the Lyostat 5 – online resources available for more information
Lyotherm 3 Freeze Drying Impedometer

The Lyotherm 3 is a unique combination of an emerging analytical technique, impedance analysis, combined with traditional differential thermal analysis (DTA). These techniques use two different perspectives to enhance the analysis data providing an extra dimension to the information allowing for greater detail and more informed decision making.The new Lyotherm 3 has been developed specifically to meet the analysis challenges that those working with analytical data for frozen state solutions encounter including the need for a higher impedance ceiling for early transitions in particular

ElectricalImpedance: Impedance combines capacitance, inductance and resistance into one metric that relates to molecular mobility within the sample. This identifies softening, stabilization, crystallization, glass transitions, melting and other phase changes.

DTA: Identifies the thermal signature of events by comparing the temperature of the sample to a reference. Identification of exo/endotherms, glass transitions and melting events gathers more information on the events seen with impedance.

One of the major advantages of the Lyotherm 3 is the increased sensitivity to minor reorientations and thus glass transitions.The Lyotherm 3 often finds the same, or more, events in complex solutions, and often identifies more information to give a better profile of those events than can be seen in mDSC due to the collaboration of electrical and thermal techniques.

Features & Benefits of using the Lyotherm 3:
  • Determines critical parameters of samples within the frozen state (Tg’, Crystal Transitions, Teu, Softening)
  • Identifies viscosity changes within the frozen structure
  • Optimised for frozen state analysis
  • Typical analysis time: 1 hour
  • Alarms and liquid nitrogen precision allow greater control over analysis
  • Updated control unit and wiring design reducing benchtop footprint
  • Simplified operation to increase reliability of results
  • Most accurate analysis data available on the market
  • Clear graph data and flexibility during post-analysis
  • Simple data processing – exporting to Excel tailors the graph to the analysis
  • On-site installation includes full training into operation and interpretation of results
Micropress – Lyo cake Analyzer

Traditional methods of assessment of the physical and structural properties of a freeze-dried cake are limited to subjective, qualitative tests that do not necessarily provide evidence of robustness to transport and handling.

Our solution

Biopharma has developed a quantitative method for determining the robustness (Young’s Modulus) and strength (max stress at failure) of lyophilized cakes. The MicroPress uses a linear actuator to gently compress the cake while a load cell accurately measures the force applied. The resulting stress-strain profile captured by the integrated software is then exportable to Microsoft Excel for further interpretation and analysis.

By performing this analysis, the user can determine how the cake will behave during storage and shipment.

Cake strength can be affected by:
micropress-cake-strength
Key benefits of using MicroPress
  • Determine key parameters for cake quality
  • Easily measure physical properties
  • In situ analysis – no sample prep required
  • Shelf mapping
  • Ensure product quality during storage
  • Batch QA/QC
  • Quick analysis time (less than 1 minute)
  • Identify vials with microcollapse
  • Quickly compare multiple vials
  • Determine cakes with a weaker structure which may not stand up to shipping
  • Ensure product quality to the point of delivery
  • Batch reproducibility
A graph of Dextran showing elastic properties, compression and decompression.
micropress-graph
Differential Scanning Calorimetry (DSC)

DSC Stage – Modular Add-On offers a new compact alternative for conducting thermal analysis on both liquid and dry state samples, especially since the DSC stage shares the same control module and peripherals with our Lyostat5 Freeze Drying Microscope where it can be purchased as an optional add-on expanding the Lyostat5 capabilities. Furthermore, the dual pan system allows for comparison against a reference sample and maximises the thermal signal from solute-related events over the ‘noise’ resulting from the solvent and pan.

One of the most important benefits of the DSC stage is that, unlike other DSC systems, it includes the ability to be mounted on an imaging station for visual degradation analysis and TASC (Thermal Analysis by Surface Characterisation) during DSC experiments through a sapphire window. Visually observing the physical changes that the DSC trace is quantitatively reporting can be of great benefit, especially for troubleshooting. These images can be made into videos and easily, exported with a data ribbon and annotated.

Freeze Drying Sample Analysis Services

BTL together with Spinco Biotech offer our customer the lyo sample analysis services towards FDM Lyostat analysis, Lyotherm Analysis & DSC Analysis as combined or as an individual need. Helping our customers with the faster turn-around-time for the sample analysis, non hazards a non-toxic samples can now be analysed within India at Spinco Towers, Chennai location.

For additional details, please write to info@spincotech.com

Lyo Consultancy & Training from experts

Biopharma offers end-to-end consultancy for freeze drying right from formulation development through scaleup process. Beisdes, Biopharma also offer bespoke training courses with custom topics.

Please reach out to info@spincotech.com for additional details