Intelligent ADME Outsourcing

In vitro absorption, distribution, metabolism and excretion (ADME) tests are used to characterise a compound’s properties at an early stage in drug discovery. The aim is to reduce the risk of candidate compound failure due to poor pharmacokinetic behaviour before reaching clinical trials. Over the last 10 to 15 years, the industry has been performing ADME screening ever earlier in the stages of drug discovery. The drive for this testing remains as strong as ever. It is estimated that an improvement in predicting the failures by 10 per cent prior to clinical trials could save a company $100 million in development costs per drug (1). ADME is now an established and essential part of integrated drug discovery and development programmes, providing indispensible information to enable iterative chemistry, target discovery and biology processes on which pipelines depend.

PHARMACEUTICAL INDUSTRY STRATEGY

The pharmaceutical industry has long been reviewing and reshuffling its available resources. With cost issues driving a lot of research overseas into China and India, those groups remaining in Europe need to ensure that business remains profitable. The current global economic downturn has prompted a renewed drive to maximise the efficiency of the drug discovery pipeline and reduce associated costs. Since the drug discovery process is lengthy as well as costly, the twin goals of researchers have, for some time, been to identify potential drug candidates earlier and terminate less promising projects sooner in order to improve efficiency and productivity. With competitive pressures to maintain their efficiency, minimise costs and stay abreast of current technologies, contract research organisations (CROs) offer that extra productivity and represent a resource which can be switched on and off as the project or financial needs of the client dictate. Most outsourcing companies have been built to adapt and tailor their services to the requirements of different clients, whereas change within a large research organisation can be a slow and difficult process. Hence, outsourcing in research is increasingly being seen as a way to control costs and focus spending as well as tap into areas of additional expertise and experience, both technical and scientific, which can augment that available in-house.

The availability of relatively high-throughput ADME assays has led to vast amounts of data being generated in large pharma companies, but has not greatly improved their success rate. In some cases, tests will have been conducted on compounds which were never likely to make the grade, and those numbers have been inflated by the output of combinatorial chemistry approaches. Therefore, there is a need for rational and intelligent testing. For many projects, the number of compounds being submitted for ADME testing has fallen again in recent years. Smaller, focused libraries are being made and, rather than a blanket screening approach, rational ADME screening cascades are designed to address those issues which are expected, based on calculated properties of the molecules and the location of the target in the body, or those problems revealed by preliminary in vivo pharmacokinetic studies.