Drug development is a long and expensive process, but new advances employed in preclinical services may help drug pipelines become faster, cheaper, and more effective.
Developing a new drug or other medical intervention isn’t easy — or fast. In fact, it takes an average of around 12 years before a new drug actually finds its way onto the market, at a cost of an estimated $1.2 billion in R&D, testing, preclinical trials, and other expenses. That’s a lot of investment, especially when taking into account the fact that around 90% of drug trials never make it to market.
Many of those drugs which fall prey to attrition between preclinical services and the actual marketplace do so when transitioning from preclinical trials to in-human studies. This is because preclinical trials in the past have been insufficient to the task of adequately predicting efficacy and toxicity in human subjects.
Preclinical trials in animals are excellent for eliminating many drugs in early stages, but when transitioning from animal to human trials, the discrepancy between species is simply too great to generate the kind of certainty that modern drug manufacturing demands. Fortunately, new advances have helped to pave the way for better results and more efficient drug pipelines, all at a lower cost to developers.
As preclinical services take on new forms, they are better able to mimic the performance of a drug on human subjects.
The traditional method of determining toxicology during preclinical trials has been the use of 2D tissue cultures and animal studies. Unfortunately, animal tests lead to problems in transitioning to human studies as the physiological differences between species result in unpredictable outcomes. Meanwhile, 2D tissue cultures made up of cell lines typically contain genetic mutations and lack the distinctive characteristics of the tissues from which they were derived, limiting their utility as a testing model.
New advances in preclinical services have led to more robust trials that can better mimic in-human testing in a preclinical environment. This includes 3D culture and tissue models — which incorporate human cells built into three-dimensional matrices that can better mimic native tissue — and humanized rodent models.
A humanized rodent model involves testing toxicology and efficacy on mice that have been given certain human cells such as xenografts or human hepatocytes. This allows testing on human tissues in a whole-animal context, rather than limited tissue and culture models.
More recently, 3D tissue and culture models have evolved into 3D “bioprinting,” the automated production of potentially elaborate structures composed of living cells, designed to mimic the function of the tissues they represent. All of these advances allow in vivo testing that more accurately matches the results found in in vitro studies.
New advances in preclinical services help to enable needed drug development — and push it in new directions.
One example of a recent development in preclinical trials is organ-on-chip studies. Developed using technology from the Massachusetts Institute of Technology, the PhysioMimix device allows the testing of new drugs on cell cultures that mimic living human organs in the lab, without relying on animal models.
Micro-tissues are formed on open-well plates. These tissues can emulate the appearance and function of working human organs and tissues. What’s more, the devices can be linked together to analyze the interaction of drugs on different organs or organ systems at the same time.
Because PhysioMimix utilizes an open-well system for growing its tissues, it can easily accommodate primary cells, stem cells, and other tissues in order to map different organs and tissues more accurately. This modular construction also allows the removal of samples during preclinical trials, and enables technicians to change arrangements as needed for different testing scenarios. This is just one of many recent preclinical developments that are helping improve the speed and efficacy of preclinical trials.
As preclinical services evolve, new drugs can reach the market more quickly, more affordably, and with more assurance that they will work as they should.
Ultimately, the goal of all preclinical trials is to guarantee as much as possible the efficacy and safety of a new drug before it is tested in humans or reaches the larger marketplace. As advances in preclinical technology help make in vivo and in silico (animal and computer trials) more closely match the results of human testing, drug development will become faster and cheaper, while also ensuring that drugs are effective and safe before they reach human patients.