“As we get smarter, we’re inventing new ideas which are straining the boundaries of what we know about science, and they don’t always fit in regulatory boxes,” the CEO of the Weinberg Group told In-Pharmatechnologist.com.
Matthew Weinberg, head of the US-based regulatory consultancy, said simulations are finding ways to repurpose or combine existing drugs “and using them in different doses and in different ways.”
“We’re dealing in a time when computer modelling, and other kinds of modelling, give us opportunities to look at the way things work that we never did before.
“And the regulatory models aren’t always applicable so the regulatory bodies have to flex to deal with new products.”
This was particularly true for “combination products and biotechnology,” he said. “Biotechnology is constantly pushing the boundaries.”
He added that the proliferation of device-drug combination products, with the help of mobile electronics, could allow the administration of some drugs for the first time outside a controlled clinical setting. This would provoke regulation on safety, extended release, and even refrigeration, he said.
‘We can’t test it on kids, but we have to use it on kids’
Another challenge in the future of regulation, said Weinberg, will be compassionate uses of pharmaceuticals in special populations before clinical trials have finished.
The UK Medicines and Healthcare Products Regulatory Agency (MHRA) will shortly launch the Early Access to Medicines Scheme (EAMS), a programme to allow doctors to prescribe certain drugs to critically ill patients before they receive marketing authorisation.
Similarly the European Medicines Agency (EMA) announced in March its Adaptive Licensing Pilot Project, a scheme to authorise some drugs early for a niche indication.
EMA spokeswoman Sophie Labbé told In-PharmaTechnologist.com the project “seeks to maximize the positive impact of new drugs on public health by balancing timely access for patients with the need to provide adequate evolving information on benefits and harms.”
Weinberg acknowledged that this “duality of pressures” – between making novel drugs available quickly and managing their risks – is not a new dilemma for regulators. During trials of HIV/AIDS antiretrovirals in the 1980s, he pointed out, activists clamoured for early access to the drugs since they considered they would die without them.
However, he said, what is growing is compassionate use in paediatric populations, which brings unique regulatory nightmares.
“Most clinical trials don’t cover kids. It’s not [as small as an] ‘orphan’ [population] but we don’t really do clinical trials on children, for very good reason.
“You really have to be intelligent about the extrapolation of adult data to children.”
Despite the challenges, Weinberg was optimistic regulatory bodies and advisors for pharmaceutical companies would work together to allow early approval of drugs in restricted populations:
“It’s challenging because we don’t know doses or the routine. There are things we don’t know because we can’t test it on kids, but we have to use it on kids.”
Reducing trials steps
Relationships between regulators and companies are changing as they negotiate trials for expensive novel drugs, Weinberg told our reporter.
“In the US there’s a big movement to go to one confirmatory Phase III trial instead of two.” Traditionally in drug development, two stand-alone Phase III studies are performed to confirm the safety and efficacy findings of Phases I and II.
“But there are some drugs where it’s too expensive or for other reasons it’s impossible to do two,” said Weinberg. For these novel products, he had begun to see sponsors contacting regulatory bodies ahead of time to warn them of the foreseen problem and present an argument for being allow to perform just one Phase III trial. But, he said, “You can’t do it all the time – it’s always the regulators’ rules.”