Historically, new medicines have been sought from natural compounds found in plants, fungi or marine organisms, and this still happens today. When biological activity is discovered in this way, the important molecule is extracted from its natural source, identified and synthesised – usually chemically. Chemists then make many close variations (called analogues), to try and maximise the desired effects and minimise unwanted effects. However, researchers have also developed many sophisticated ways of creating new active substances. Increasingly, medicines can be designed using computer-aided design, based on knowledge gained from the study of genes (genomics), a deeper understanding of disease processes, and the study of the numerous protein products from specific genes (proteomics).
The development of completely new classes of medicines typically depends on research into the fundamental mechanisms of disease, and often involves collaboration between industry and universities or other research institutes.
We work with our member companies to enhance understanding of preclinical safety and provide a forum to share experiences in what is known as a ‘pre-competitive space’, where information is not commercially sensitive. ABPI member companies also work together in a number of non-competitive research collaborations. For example, they fund a collaboration with the Centre for Drug Safety Science at the University of Liverpool, with the aim of better understanding the fundamental science behind adverse drug reactions, and increasing the safety of new medicines.
A vital part of medicines development, particularly preclinical safety research, involves the use of animals. Indeed, UK and European regulations currently require that all new medicines are tested on animals before being used in humans, to ensure patient safety.
The skill of transferring research effectively from preclinical models to early clinical research in man is known as translational medicine. It also works two ways, by applying what is learnt in clinical practice to refer to clinical models. We have worked closely with NIHR in the establishment of the first Translational Research Partnerships (TRPs). These unique partnerships, run by the NIHR Office for Clinical Research Infrastructure, facilitate collaborations between industry and academia to drive translational research. There are currently two TRPs in operation: one focussing on inflammatory respiratory disease, the other on joint and related inflammatory diseases. We and our member companies continue to work closely with the TRPs to ensure they are aligned with industry, helping to translate early research to safe and effective medicines as quickly as possible.
Before a new medicine can be given to humans in the UK, a clinical trial application (CTA) must be approved by an agency of the Department of Health known as the Medicines and Healthcare products Regulatory Agency (MHRA). The application is reviewed by independent medical and scientific experts, who recommend whether trials can begin in humans or whether more research is required first.
If a CTA is granted, a new medicine will pass through a long and complex process of early and later stage clinical studies before the company can seek authorisation to make the medicine available for doctors to prescribe for widespread use.
The time, costs, and resources associated with clinical trials are very high. Clinical trial simulation is one innovative way that can improve the efficiency of clinical development. Simulation can be used across the drug development process, from informing study design, to modelling drug-drug interactions, and specific patient populations (e.g. paediatrics). We are working with our members and regulators to develop guidance on these innovative tools, such as physiologically based pharmacokinetic (PBPK) modelling.
The UK scored a world first in the AZ-MRC initiative that provided unprecedented access to proprietary pharmaceutical compounds for academia to use in preclinical or clinical research as tool compounds, for example to gain understanding of mechanisms of disease. In some cases, access to compounds that may have been terminated in the development process for a particular disease indication, may be explored for repurposing in another disease indication (where there is a scientific rationale) - this would save considerable time and effort in development, and open up potential avenues for new treatments.