The development of lyophilised products helps reduce the impact of cold chain management from refrigerated warehouses to point use. These products, typically, benefit from lower shipping costs, simplify product use, and provide a longer shelf life within the diagnostics, biologics, pharmaceuticals and nutraceutical industries.
Recently, we have seen a trend shift from traditional lyophilised cakes to lyophilised reagent beads, also known as ‘lyobeads’, which are spheres of customisable, lyophilised material. Unlike traditional lyophilised formats, each individual bead contains a single, accurately measured dose of a precise formulation. These single-dose beads – like all lyophilised material – retain long-term stability at ambient temperature and therefore do not need expensive cold chain shipping or refrigeration during storage.
Lyophilised beads also present further performance and efficiency opportunities,1 particularly in terms of assay accuracy, speed and ease of process:
- Accuracy – lyophilised beads contain a single, precisely measured dose, minimising the potential for variance.
- Cost savings through improved efficiency – with less risk of user errors, a longer shelf life, and less exposure to moisture, wastage is significantly reduced, saving time and money.
- Quick and simple – lyobeads reconstitute quickly due to their volume-to-surface area ratio and come pre-packaged, ready for immediate use.
The process of manufacturing lyobeads requires a high level of expertise as it starts with the creation of a custom lyophilised bead which is stable and suitable for large-scale manufacture. This is usually achieved by the use of a Freeze Drying Microscope (FDM)2 to understand the critical temperatures for the primary drying phase of the freeze drying cycle. In conjunction with the FDM, the use of a Differential Scanning Calorimetry (DSC) or Lyotherm (DTA & impedance analyser)3 will provide thermal analysis to ensure product stability throughout the lyophilisation process and future storage conditions. The final process for scale-up and manufacturing, is the quality control assessment of lyobeads to meet the required standards for appearance, size and successful drying.
Primary quality control processes for lyobeads include residual moisture content measurement, visual appearance, dissolution rate, assay sensitivity and physical properties. Of these processes, lyobead properties – ultimate tensile strength (maximum strength a bead can withstand before breaking) and friability (how easily the beads can break into smaller parts under duress) – can be best assessed by the MicroPress, a mechanical properties analyser, in a simple non-destructive manner where analysis and quality of the data are independent of the subjective experience of the operator. The precise dosage measurements within the lyobeads were mentioned earlier as a key differentiator between lyobeads and lyocakes, therefore in the lyophilised format, it is paramount to ensure the full product is intact for final use. The lyobeads, during storage, will typically be held within a secondary container and by their nature move within the receptacle, it is therefore imperative that it is manufactured to sustain these movements particularly during shipments.
The MicroPress is an innovative instrument designed and developed by Biopharma Group’s instrumentation specialists to quantify in-situ microscopic defects within low-density materials and, specifically, in all freeze-dried products to provide pivotal data as to whether or not the products produced have the proper physical characteristics. The MicroPress can quantitively determine the strength and physical robustness of lyobeads and lyocakes in situ. With set parameters and analysis methods, MicroPress will be able to analyse the freeze-dried product structure. This allows for fast and effective batch screening to be applied to your products, especially when time and resource costs are at a premium; with a standard method, the analysis can be completed in less than one minute per freeze-dried product.