TNO’s advanced AMS technology (Accelerator Mass Spectrometer) enables faster drug development. AMS is being used successfully by partner Pfizer. The pharmaceutical company has now successfully completed two studies and new studies are in the pipeline. TNO’s Steven Erpelinck and Wouter Vaes and Pfizer’s Doug Spracklin talk about the added value of the collaboration and the possibilities for the future.
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Would you like to know more about how TNO can help you accelerate drug development? Please contact Steven Erpelinck
The development of new drugs takes a very long time and the costs are enormous. At the end of 2017, the Council for Health and Society (RVS) in the Netherlands reported about the problems in the current development model, proposing that the process can be faster, better and cheaper. As for many drug candidates, it only becomes apparent late in the process that they are not safe or are less effective than expected.
AMS & microtracing
One of the ways to optimise drug research is to do more measurements during early clinical trials, in a limited number of healthy volunteers. “Thanks to increasingly sensitive measurement methods, such as AMS, we can determine the concentration and possible effects of drug candidates sooner,” says senior business developer at TNO, Steven Erpelinck. TNO is the only organisation in Europe that uses a biomedical AMS.
“We were the first organisation to carry out a micro-tracing study with biotechnological medicines”
“We were the first organisation to carry out a micro-tracing study of biotechnological drugs,” says Wouter Vaes, senior scientist and head of TNO’s AMS Lab. “Microtracing is a technique whereby very small amounts of a drug are administered to humans to investigate the feasibility of the drug at an early stage. We can then analyse this using AMS. It can help to investigate what the human body does with the drug, and vice versa.”
Vaes continues: “TNO combines microtracing with metabolite identification, which enables us to track drug candidates administered to subjects. This way we can investigate whether the human body has perhaps converted the drug into another substance, which we call a metabolite. It is essential to know what is happening in the human body, whether, for example, harmful degradation products (toxic metabolites) are released and what subsequently happens to them.”
“AMS reduces both animal testing and costs, but above all shortens the development process”
“Thanks to AMS, these pharmacokinetic data – on how an active substance is processed in the body – are available years earlier than with traditional methods. This allows a good estimate to be made much earlier about the success rate of a drug candidate. The use of micro-tracing techniques results in less animal testing, more cost savings, but perhaps more importantly, the development process is shortened. It must be said that switching to microtracers is very exciting for pharmaceutical companies, because it changes the sequence of the drug development process considerably,” Vaes says.
Collaboration with pfizer
Pfizer works successfully with TNO’s AMS technology. The collaboration started two years ago during a meeting on drug metabolism and pharmacokinetics (DMPK) at Pfizer in Groton (US). “We found TNO to be proactive and appreciated their knowledge and approach,” says Doug Spracklin, who leads the Biotransformation & Environmental Sciences group at Pfizer in Groton. “And TNO's work with AMS fitted in well with our interest to pilot this approach for our human ADME (absorption, distribution, metabolism and excretion) and mass balance studies. Furthermore, it bolsters our confidence in our partner that TNO has extensive experience in profiling and identifying metabolites. And, importantly, TNO has a unique process that allows rapid sample analysis and feedback to the clinical team.
Spracklin is very satisfied with the cooperation with TNO. “It's going very well. We exchange ideas about the approach, discuss technical aspects and logistics in detail and coordinate things well. Support for our ADME studies is fantastic. TNO moves quickly and has a lot of technological knowledge and expertise to improve methods. It is a plus that we now have our ADME dataset more quickly and that the clinical studies are conducted more efficiently. The fact that we have bioavailability data and human intravenous pharmacokinetics earlier than usual is very important to us.” Spracklin emphasises that their “cooperation brings many benefits, which puts us at the forefront.”
“Our cooperation with TNO brings many benefits, which puts Pfizer at the forefront”
TNO also has a positive view of the cooperation. “Pfizer has many good and well established and respected researchers in house, who understand the AMS applications and the technique, and see its added value on how AMS can accelerate and de-risk drug development. We exchange methods and techniques and discuss future possibilities. All in all, it is a very valuable relationship based on mutual trust. It’s good to hear that our work is appreciated,” says Erpelinck.
Implementation of AMS
It took Spracklin and his researchers some persuasion and time to convince project teams of the technology his group was so enthusiastic about. “In some cases, the fact that we could meet the team deadlines for ADME studies with AMS, but not with traditional tools, was decisive. Using AMS to support ADME studies on humans is a good technique. A future goal would be to use it at an even earlier stage and quickly stop research into drugs that do not seem to work on the basis of pharmacokinetics or disposition,” thinks Spracklin. Perhaps AMS could be used in other areas in the future, in addition to the ADME studies.
The cooperation between TNO and Pfizer is not limited to AMS. Cooperation also takes place in the field of I-screen: this platform can be used to identify how intestinal bacteria deal with and react to various substances and circumstances. And of InTESTine: investigating intestinal permeability. Besides Pfizer is also evaluating TNO’s protein binding assay Comp3.
Pfizer is also discussing the use of microtracers in drug development for children, but that is still at a very early stage. “The challenges we expect to face in the coming years, and about which there is still a lack of knowledge, include predicting the pharmacokinetics of new drugs with non-traditional clearance mechanisms and which may therefore be broken down by our bodies in other ways. There are no good tools for this yet, although we can predict the pharmacokinetics of known metabolic pathways, like cytochrome P450, very well. TNO can help with this by collaborating with us. Such challenges are not confined to Pfizer, they are issues that other companies also encounter. That TNO is responding to this adds value,” says Spracklin.