It takes a long time, many different steps, and considerable cost, before a new drug can be approved for use as a medicine. One could be forgiven for thinking that, since billions of people across the world take millions of different medications every day, the drug development pipeline is fully optimised with little need for improvement.
However, the high rate of failure (estimates suggest that over 70% of the drug development pipeline fails through the development process) and accompanying financial loss, coupled with some rather impressive technological advances in research methods mean the pipeline is ripe for, and more importantly, needs improvement.
There are several areas in the drug development pipeline that could be improved, and at Queen Mary University of London, we are working to do just that. Across the University, our researchers are finding innovative ways to refine and improve the drug development pipeline.
Improving testing models
Under current legal regulations, any new drug that is developed must be tested in animals before being tested in humans. But over the past few decades there has been increasing interest in the potential for developing and using effective alternatives to animals.
At Queen Mary, we are pioneering the development of these next generation of in vitro models, which may be better at predicting whether a new drug will work whilst also reducing the use of animals in research.
Working in collaboration with stakeholders from biopharma, charities, tech companies, funders and regulatory agencies, our Centre for Predictive in vitro Models uses human tissue and cells to recreate in the laboratory key features of human organs in organ-on-a-chip models t. The hope is that these models will allow us to study diseases and identify new therapeutic targets in systems that are closer to the human setting. These models also offer the opportunity to accelerate the delivery of safe and effective treatments by studying the activity of a new compound sooner, in a human-relevant system that better replicates where the drug will be used.
Our new organ-on-a-chip centre, one of the largest in Europe, is also leading the way in education and training through its Centre for Doctoral Training and the world's first organ-on-a-chip Master's Degree Programme. In this way we are ensuring that the next generation of biomedical researchers are equipped with the skills and experience required to incorporate these state-of-the-art in vitro models into the research programmes of the future.
An example of how we have used these methods to good effect is the work Queen Mary colleagues have done to build 3D-multi-cellular models of cancerous tumour microenvironments. These models – called organoids – contain cancer cells, healthy cells, immune cells and structural molecules that support the tumour. They provide us with a system that enables closer assessment of the influence of the tumour microenvironment on cancer development, offering novel opportunities for identifying new, potentially non-toxic, approaches to treatment.
Queen Mary is leading the way in collaborating with pharmaceutical companies and other end users to maximise the adoption of alternative methods such as these, with a view to driving human-relevant science and accelerating successful development of drugs. These technologies will also play an important role in supporting the Government's ambition to identify alternatives to animals in research, which they recently announced and which our researchers provided their expert views on.
Making manufacturing more sustainable
Another stage of the drug delivery pipeline where improvement is needed is in manufacturing. The manufacturing of drugs is a lengthy process that is associated with high volumes of carbon emissions. Chemical separations alone, a key part of pharmaceutical manufacturing, accounts for between 10-15% of global energy use.
Researchers at Queen Mary are working to change this; to reduce the negative impact of drug manufacturing on the environment without impacting on the quality of the product.
Take our academics who have developed ultra‑thin polymer "nano‑sieve" membranes. This innovative 'smart' membrane separates and purifies liquid drugs without boiling. Using these membranes in the place of traditional chemical separation techniques reduces the carbon emissions and decreases the solvent waste levels, making drug manufacturing more sustainable. Working with industry partners, Queen Mary researchers aim to integrate these membranes into pharmaceutical production lines to recycle solvents, maintain high product purity and cut the overall negative environmental footprint associated with medicine manufacturing.
Another example of our innovation in this area is, Exactmer, a Queen Mary Innovation spinout company. With strategic support from GSK, they have established a new UK industry‑academic consortium developing renewable bio‑based solvents to cut the pharmaceutical sector's solvent‑related carbon emissions by 60%. By creating advanced membrane purification technologies and validating these greener solvents in real manufacturing settings, this work aims to enable affordable, pharma‑grade, bio‑based solvents that can replace fossil‑derived ones without major infrastructure changes.
Putting it to the test – equally
Once the drug has been made and tested in animal models, then comes the time to test it in human clinical trials. Any new drug has to pass successfully through a series of phased human testing to confirm that the drug is safe and that it works on the human body the way it should. A drug successfully demonstrating efficay in a phase three clinical trial in the target patient group is the gold standard required before it can be made available as a medicine.
Whilst the trials testing process is universally accepted as a validated and effective approach to determine the safety and effectiveness of a drug, there has been growing appreciation that many trials lack generalisability – that is, they are not inclusive of the global population. Many involve only or predominantly people of White / European ancestry, are limited in the age range they include and have fewer women participating. What this means is that many drugs that have been approved for use in the general population have been approved based upon demonstration of safety and effectiveness in only a subsection of society.
Queen Mary researchers, many of whom are clinical academics, are making huge progress in changing this. They are carrying out more inclusive clinical trials by working not just with colleagues in the NHS or industry, but by working directly with the patients, particularly those in communities often excluded from trials.
Take our SHARE Research Collaborative. The team is comprised of researchers from racially-minoritised backgrounds, members of the LGBTQ+, neurodivergent and disabled communities. . They are challenging and changing how clinical trials are conducted by putting equity and inclusivity at the core of their research. They are designing studies and protocols in collaboration with people with lived experience, involving them at every stage of their research and in doing so, are making sure that new treatments developed will benefit – and be available – to all those that need them.
As well as carrying out inclusive, equitable clinical trials, Queen Mary is working to ensure genomic research – which can reveal insights into how conditions develop, can lead to the development of new treatments and can support with testing new treatments – is more diverse. We are doing this through Genes and Health, the world's largest community-based study of genetics and health in British Bangladeshi and British Pakistani people, and through the Black Health Legacy research project, which aims to become the UK's largest community-based health research programme for Black, Black African and Black Caribbean people.
Our clinical researchers also tackle notoriously hard to treat disease. For example, clinical trials led by researchers at Queen Mary have proven the efficacy of the first new treatment for people with advanced bladder cancer in 40 years. This, and other, research has led to changes in NHS treatment guidelines and offers new hope for patients with historically few options.
There is always room for improvement
Queen Mary University of London academics are working to improve the drug development pipeline: from discovery and pre‑clinical modelling, through to sustainable manufacturing and equitable clinical trials.
Our researchers are pioneering human-relevant in vitro systems that seek to improve prediction and reduce reliance on animal models, advancing greener and more efficient manufacturing technologies that significantly cut carbon emissions and solvent waste, and reshaping clinical research to ensure that new treatments are developed with and for the diverse communities they are intended to serve.
Through these innovations, and by asking where meaningful improvements can be made, Queen Mary is helping modernise and strengthen the drug development pathway so that future medicines are safer, more effective, more sustainable and available for all who need them.
