Miriam Guest

I’m an Associate Principal Scientist, working in Pharmaceutical Development. My job is ensuring the microbial safety of drug products in our development pipeline. I work to improve microbial control strategies for both sterile and non-sterile product from first time in man to authoring marketing applications and commercialisation support.

I joined AstraZeneca in 2000 as laboratory technician, after completing my degree in Microbiology at the University of Liverpool. I went on to work in early development as a formulation scientist, when I first learned about “3Rs initiatives”, which look at ‘Replacement, Reduction and Refinement’ for the use of animals in science. I then returned to microbiology in 2012.

In recent years, I have been working on a very exciting project that I feel will be instrumental in developing our approach to the use of animals in endotoxin testing. In 2016, the International Union for Conservation of Nature declared the conservation status of the North Atlantic Horseshoe Crab as “vulnerable”. I knew that this would have a direct impact on AstraZeneca, as the lysate derived from the blood of the horseshoe crab is routinely used in a test for bacterial endotoxins. Like other pharmaceutical companies, we perform this test on injectable products and their input materials to meet both regulations and patient safety requirements. However, the mortality rate in the bleeding process is low, and the majority of crabs are returned to the ocean alive.

I wanted to understand what the vulnerable status meant for this wonderful species, that had outlived dinosaurs, and how that might impact AstraZeneca and coastal biodiversity. I discovered that it is a complex issue with multiple threats to the crabs, including human development of coastlines and use as bait and in the biomedical industry. I could also see that where sub-populations were actively fished by lysate suppliers, legislation was in place, which meant the crabs had additional protection, providing population stability. As part of our focus on sustainability, I began looking at ways to address this challenge and reduce the use of horseshoe crab blood in our development portfolio.
 

In 2017 I took on the role as the lead of the AstraZeneca Global Microbiology Forum, which brings together our microbiology laboratories, driving standardisation to meet regulatory requirements, and ensuring our laboratories are ready to meet the demands of a complex and diverse development portfolio in the future. Through the Forum I was able to see what we were doing globally in endotoxin testing. I found that we were using seven variations of the assay to test our pharmaceutical waters, which used approximately 17 litres of lysate globally and could be up to 8,500 crab bleeds per year. However, one of the methods was a rapid technique using a microfluidic cartridge which reduced the use of horseshoe crab blood (lysate) by 95%.

Working with our scientific sites performing this test to understand the wider challenges they face, the volume of testing and the impact on their labs, we aimed to understand whether we could adopt a single technology throughout our network. By switching to the microfluidic cartridge for each of these tests, we could reduce our lysate consumption to less than a litre per year. Additional benefits would be increased efficiency in the labs, less hands-on time, faster time to result, increased data integrity and process robustness.

With the agreement of our sites, I approached our leadership, explained the situation and put forward the proposal to address it. With their support we received approval for improving the way we operate. We are currently working to install this technology throughout our network and take our use of horseshoe crab blood to an absolute minimum level, while still supporting the special protection of the species made possible by remaining a smaller-scale source of lysate. I am passionate about driving continuous improvement at AstraZeneca. I firmly believe that each of us can impact the sustainability agenda; all of our small activities can add together to make a big impact. If we turn our back on the horseshoe crabs, who else will save them?