Laboratory Products
Solving Freeze Drying Bottlenecks For Diagnostics and Vaccines Production In The ‘New Normal’
Author: Tim Lewis, Biopharma Group
The Covid-19 pandemic has largely been characterised by speed; the speed at which the virus spread, the exponential increase in affected patients, the overload of healthcare systems and even the speed at which our adaptations to the virus became the ‘new normal’.
From the onset of the outbreak, things were moving very quickly. The Chinese authorities announced a new cluster of pneumonia cases in a live food market in Wuhan on the 31st December 2019 and closed the market on the 1st January 2020. The Chinese CDC then confi rmed the virus as Sars-CoV-2 on the 9th of January and the 1st genome sequence was published the next day in the GenBank database.
Almost overnight, an industry that relies on methodical processes to produce safe and effective products, threw everything into trying to research, manufacture and distribute these products, encouraged by both government subsidy and a desire to do the right thing, but also the prospect of being fi rst to market and the commercial gains that would ensue. ‘Time to market’, quite often measured in years, became a metric measured in weeks with pressures that were felt throughout the parent organisations along with their R&D and production partners.
What quickly became apparent was that one area, freeze drying, would be a signifi cant bottleneck in terms of both research and manufacture.
Freeze drying is used to remove water from a liquid, leaving a dry product or a ‘cake’ as it is known. Everyone is familiar with freeze dried coffee, which starts as a liquid product, has the water removed to leave a dried residue and can then be restored by the simple process of adding water back to the product. Diagnostic reagents and vaccines that have a short shelf life window of days or hours can have that shelf life extended to years by using freeze drying, whilst also increasing the ability to transport and store in ambient conditions, vital if vaccines and diagnostics are going to reach populations that are isolated or have less well developed infrastructures.
Addressing the Bottlenecks
The speed at which the characterisation of the virus occurred prompted a massive work shift in the diagnostics and vaccine industries, who turned their not inconsiderable resources to producing one of the following:
1. An antigen test to diagnose patients with symptoms
2. An antibody test to understand which patients have had the disease and may be immune 3. A vaccine that would protect from the virus itself
Freeze drying capacity is a limited resource that would normally be expanded by adding additional machines, but in a time of crisis when many manufacturing units are closed and their reopening uncertain, the lead times for new freeze dryers can run into months or even years in some cases. It is a timescale that doesn’t really work for the immediacy of a pandemic.
With an increasing demand for R&D work to fi nalise diagnostic kits and a consequential increase in production volumes of those kits, we were faced with just this scenario at Biopharma Group.
The 3 key areas identifi ed that would allow us to fulfi l the demand that COVID had generated were:
1. Cycle Development and product formulation
Freeze Drying cycles can range from hours to days and are a complicated interaction of chemistry and volume. Generally, the more water that a product contains the longer it will take to freeze dry but freeze-drying time is also affected by the chemical constituents of the products and excipients that are added to it. By changing the freeze-drying cycle and the product formulation, it is possible to increase activity of an active ingredient whilst reducing the cycle length considerably. An example was a diagnostic reagent with a 5-day drying cycle and a visibly poor fi nished product. Using Biopharma Group’s own specialist pre-lyophilisation analytical instruments, the Lyostat & Lyotherm, the R&D team were able to understand the critical temperatures of the product and identify the weaknesses in the formulation. A range of excipients were identifi ed that would:
• aid the bulking of the lyophilisate and improve the visible quality of the fi nished product • thermally stabilise the solution, increasing its critical temperatures
• provide protection to the active ingredient during lyophilisation, increasing product activity considerably
INTERNATIONAL LABMATE - SEPTEMBER 2020
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