For certain kinds of bacteria, we have reached the end of the line. No new antibiotics have been developed for decades, and some superbugs are now resistant to all those we have. There is no one solution to the problem of antibiotic resistance, but we desperately need new antibiotics.
Far from helping, though, drug regulatory agencies are discouraging the development of new antibiotics, say those who met in London last week to discuss solutions to the problem of antibiotic resistance, at a conference organised by the British Society for Antimicrobial Chemotherapy. New Scientist finds out what is going on.
Why are regulators coming under fire?
They are making it ever harder and more costly to get new antibiotics approved. The US Food and Drug Administration (FDA) came in for the most criticism.
Advertisement
I don’t live in the US, why should I care about what the FDA does?
The US has the biggest drugs market. If companies don’t think they can get an antibiotic approved there, they often won’t try to get it approved anywhere, meaning the whole world loses out.
How are regulators making it harder to get drugs approved?
The FDA keeps on changing the criteria needed to get new antibiotics approved. In particular, it is making it harder to get some kinds of antibiotics approved on a “non-inferiority basis” (see below). Some of the changes are “arbitrary and unfounded”, according to George Talbot, a biopharma consultant and member of the Antimicrobial Availability Task Force set up by the Infectious Diseases Society of America.
What does non-inferiority mean?
Normally, a drug’s efficacy is established by showing it works better than a placebo. But it is unethical to give patients placebos when they might be killed by superbugs. Instead, companies have been allowed to do so-called non-inferiority trials where the new antibiotic is compared with an existing one, and if it works roughly as well it can get approval. Now the FDA is pushing companies to show new antibiotics are superior to existing ones.
Surely we only need new antibiotics if they work better?
Not necessarily. We don’t know what evolution is going to throw at us next. An antibiotic that does not perform better than another according to one narrow set of criteria established by regulators might still turn out to be very useful in some other way. For instance, resistance can sometimes be overcome by combining antibiotics with other drugs, but only some combinations work. So the more approved antibiotics there are, the better our chances of finding ways of dealing with new superbugs.
Isn’t lowering standards a little risky?
The issue is effectiveness, not safety. Talbot says there is no evidence that ineffective antibiotics are being approved, so by demanding ever higher proof of efficacy, regulators are tackling a problem that does not exist. “The balance has been lost between ensuring the availability of antibiotics to protect public health and ensuring possibly ineffective antibiotics do not reach the market,” he claims.
What else are regulators doing wrong?
Regulators approve drugs for diseases or conditions, and they are increasingly approving drugs only for very specific indications or symptoms. For instance, an antibiotic might be approved only for treating certain kinds of skin infections. But antibiotics are designed to target organisms that cause diseases, not diseases themselves, so some flexibility is needed.
Is there an easy way to help the situation?
Approval processes are becoming ever lengthier and more protracted, but new superbugs don’t hang around waiting for regulators. To keep up, we have to be able to move fast as well, says David Livermore, head of antibiotic resistance testing at the UK’s Health Protection Agency. One idea is to allow provisional approval of new antibiotics once their safety is established, testing their effectiveness as you go along.
Topics:
