The UK medicines regulator, the MHRA (Medicines and Healthcare products Regulatory Agency) appears to be out of step with global scientific opinion that better methods are needed to improve the safety of new medicines. Although current methods include computer models and in vitro tests, they rely mainly on tests in animals.
The MHRA’s mission is “to enhance and safeguard the health of the public by ensuring that medicines and medical devices work, and are acceptably safe.” In order to fulfil their statutory duty, the onus is on them to be alert to the most predictive technologies available and – where there are clear advantages over current methods – to mandate their use. There are many exciting new technologies on offer, which promise to predict various aspects of drug safety more reliably than animal tests and some of the older in vitro tests – but unless they are included as requirements in safety testing, they will continue to be overlooked, and their enormous potential to save lives will be wasted.
In the US, several government initiatives are underway to tackle this important issue. The Predictive Safety Testing Consortium was established to address the problem that: “The tests that are used to determine drug safety today have not changed in decades.” They openly admit that “Companies have developed newer safety testing methods, but these are not generally accepted by the FDA [Food and Drug Administration, the US medicines regulator] or EMA [European Medicines Agency, the European medicines regulator] as proof of safety because the tests have not been independently validated by a third party.”
Yet the MHRA insists that animal tests are irreplaceable and is extraordinarily dismissive of two of the most exciting breakthrough technologies in drug testing: microdosing and ‘body on chip’ devices, saying that they are “not superior technologies”. This contradicts much published scientific opinion, such as this 2010 review of microdosing, which concludes: “There are some scientists who look at new methods such as microdosing with considerable suspicion, failing to recognise that their current tools are flawed. The biggest obstacle to building microdose studies routinely into the critical path of drug development is not scientific but social and economic. To incorporate microdosing into drug development requires scientists to be thinking outside the box. Once this mental hurdle is overcome, microdosing will become routine and as a result the efficiency of drug development will improve.”
and this 2012 article with video clip, which explains: “A major problem in the pharmaceutical industry right now is that the drug development model is actually broken. It just does not work. It takes many, many years to get a drug to market, it’s incredibly expensive, innumerable animal lives are lost – and then the results from animals usually don’t predict what happens in humans. So this is a huge cost to the economy and to the pharmaceutical industry. Our proposed solution is to do studies with human cells – but not just cells in a dish—cells that exhibit organ-like structures and functions.”
Of course, neither microdosing nor ‘body on chip’ devices can supply all the information necessary: each only contributes part of the jigsaw. But a combination of such powerful techniques with other advances, such as virtual organs, virtual patients and even virtual clinical trials, promises to provide more reliable information than currently used methods. Since adverse drug reactions are one of our leading – and increasing – causes of death and disability, there is clearly an urgent imperative to improve the current system.
When is the MHRA going to require that pharmaceutical companies use the best methods available to ensure the safety of medicines, both for patients and for volunteers in clinical trials – who currently bear the brunt of potentially dangerous medicines that have not always been tested for safety in humans as far as technology allows?
Please do not mention animal suffering, as this will allow them to ignore this key question.
Letters should be addressed to: Professor Sir Kent Woods, CEO MHRA, 151 Buckingham Palace Rd, London SW1W 9SZ
or emails addressed to firstname.lastname@example.org with “FAO Professor Sir Kent Woods” in the subject line.
We would be very grateful to see copies of any replies and delighted to help with further responses.