Microscopic dose means microscopic risk
New technology makes it possible to conduct initial clinical trials with microscopically small doses of new pharmaceutical substances. The method is called microdosing and provides rapid information on the pharmacokinetics of compounds in humans, that is, how it is absorbed and eliminated by the body. This is achieved in a manner that can practically be described as risk free.
"Microdosing represents a breakthrough in the pre-study phase of clinical trials and means that healthy volunteers can be administered a literally microscopic dose of the substance – as little as a thousandth of the amount thought necessary in treatment. This has become possible thanks to the development of instruments in recent years. With "High Performance Liquid Chromatography Tandem Mass Spectrometry" (HPLC-MS/MS) it is now possible to measure minuscule quantities of compounds in the blood," explains Leif Svensson, the head of Active Biotech's chemistry section, which analyses and quantifies small molecules in, for example, human blood.
"The microdosing concept has developed primarily through user needs, that is, needs expressed by human pharmacokineticists and clinicians, although participating in the development on the analysis methodology side has also been exciting," he continues.
Major benefits
The Swedish Medical Products Agency appreciated at an early stage that microdosing represented an opportunity to minimize risks for the first test subjects to be administered a hitherto unknown substance. The method eliminates the need for large-scale toxicology studies and consequently also reduces the need for animal testing.
"Microdosing is ideal for initial pharmacokinetic studies on humans," says Leif Svensson. The method straightforwardly provides information on how the compound is absorbed and eliminated by the human body, without the test subjects being exposed to any medical risks. The benefits are therefore significant, both for animals and human test subjects, as well as for the company, which saves time.
At the forefront Active Biotech was early to adopt the philosophy behind microdosing and has already conducted two studies – one on an immunomodulating substance and one on a potential cancer drug. This has been possible because the company is small, un-bureaucratic and innovative, and is able to rapidly adjust its strategy.
To date, the method has required individual permits from the authorities in each country concerned. However, official guidelines for use are now being prepared by the central European authority.
Own production
"When microdose becomes standard, Active Biotech will already have two experiences of its possibilities and we must ensure that we maintain our position as one of the foremost companies in this area. Above all, we must adapt the production of active drug substance so that it is suited to the microdose format. We already have the production of small quantities for human use in place in accordance with international quality regulations. When this experience has been adapted and refined, Active Biotech will be able to produce its own drug substance for use in humans. Combined, this will facilitate the development of substances with suitable pharmacokinetic properties.
Perfect size
"We are thus able to take a substance all the way from early research to the first clinical study," Leif Svensson underscores. "We are small enough to change course quickly and large enough to be able to house the technology and expertise necessary for the flexible handling of drug research".
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