Pharmaceutical companies are looking to predict the behaviour of drugs earlier and earlier in the development phase, making subsequent human trials more efficient and saving time and money. TNO, an independent research organisation, is offering innovative solutions.
The most reliable method of predicting the performance of a drug is through a human study, but countless human trials take their toll on pharmaceutical companies both in terms of time spent and money paid out. TNO, a research organisation offering innovative solutions for the pharmaceutical industry, is now using a combination of methods to make reliable predictions about drugs at an early stage of development.
"We will test, say, five formulations of a drug using our in vitro and in silico methods," explains Miriam Verwei, project leader of Pharmacokinetics at TNO. "The pharmaceutical company will then know which formulation is the most promising and which formulation they need to test in a human study. If you do not have to perform a human trial with each compound and each formulation, it saves a lot of money."
Newly developed drugs tend to demonstrate low solubility and low permeability, resulting in low bioavailability. Consequentially, more sophisticated formulations are required to keep the bioavailability of drugs at an acceptable level.
Before reaching the stage of human trials, Verwei and her colleagues will investigate various individual processes to work out exactly which process is responsible for the low bioavailability of a particular drug. This then provides the pharmaceutical company with reliable information about which process they need to focus on to ensure that bioavailability is at a suitably high level.
"We have an in vitro gastrointestinal model (TIM), which reliably simulates human conditions and looks at whether the drug can be absorbed after being released from the formulation," Verwei, an expert on both in vitro and in silico studies, begins. "The next step is focussing on intestinal absorption - that is whether the compound will go through the intestinal wall. If you combine these two processes, you can get a good idea of which process is responsible for low bioavailability. Companies then get more information at an earlier stage of development, making the whole process more efficient."
TNO's main priority, according to Johan TeKoppele, science manager of the Biosciences Business Unit, is the most accurate possible translation of information.
"The translation of testing is the key issue in our whole portfolio ranging from pre-clinical to clinical trials," he expands. "We are constantly focussed on how our pre-clinical research predicts what will happen in humans."
During and following the economic downturn, pharmaceutical companies have been focused on saving as much money as possible, yet TeKoppele refuses to compromise on the standard of information TNO provides. "We are really working from the angle of how we can get the best value - the most relevant information, that is - for the lowest cost," he says. "But sometimes you want to pay a bit more and have far superior information; it pays off in the longer run. Quality, standards and innovation levels are key for us. We want to take fundamental knowledge and turn it into applications or, to put it another way, we want to turn science into value."
Nowhere is this philosophy more clearly illustrated than in the areas of research TNO plans to undertake in the coming months and years, particularly in the arena of systems biology.
"Systems biology is a different way of thinking about biology," TeKoppele explains. "It's a very new field and, because of this, new issues and questions keep popping up. So it is our aim to connect systems biology to the existing methods of drug development. If we can add this to our pre-clinical testing facilities, there is no doubt that we can add value to our clients' research."
Other areas TNO will be investigating include personalised medicine or subgroup treatment and microdosing, which allows companies to perform studies on humans at a very early stage of drug development. The pharmaceutical industry can certainly rest assured that TNO is fully committed to predicting - in pre-clinical settings - how drugs will behave when administered to humans.