Many people can relate to the feeling of having an “a-ha!” moment over a glass of wine on a Friday evening, but few can say their revelation could potentially save the lives of 400,000 babies in the developing world.
Dr Pauline Williams, who was a senior researcher, now head of research and development for maternal and neonatal health at GlaxoSmithKline (GSK) in London, can claim exactly that.
She was reading studies in the Lancet, the UK medical journal, about an antibacterial agent, chlorhexidine, being adapted and applied to the umbilical cord stumps of newborn babies to prevent infection.
In 2000 the UN identified chlorhexidine as an overlooked “life-saving commodity” with the potential to save 422,000 lives over five years if made more widely available across parts of Africa and Asia.
“I shot upstairs to look at my mouthwash to see if chlorhexidine was the ingredient. I thought this is something we can really do, to adapt that product [to be used on newborns]. We had the in-house expertise to understand chlorhexidine and its properties and what it would take to make it into a gel [that could be applied to the umbilical cord]. It was a really magical moment in my career to be able to do that,” says Williams.
About 8.2 million children under-five die every year and about 3.3 million of those occur during the neonatal period, meaning within the first four weeks of the child's life, according to World Health Organisation (WHO) figures.
Almost three million of these babies die within one week of life, mostly in the developing world, where effective health measures can’t always be provided to the mother and baby at birth. Chlorhexidine used on umbilical cord stumps immediately after the cord is cut, could save up to 400,000 babies, according to Williams.
“A major cause [of death] is through bacteria getting through the newly-cut umbilical cord. It’s a breeding ground for bugs if it’s not cared for properly. There are lots of cultural practices to put things like cow dung and dirt onto the umbilical cord, which obviously exacerbates that risk,” she says.
Williams pitched the idea of using the chlorhexidine at a concentration much higher than in the mouthwash, but in a gel form that wouldn't run off like a liquid could. The project fit well with a partnership between GSK and Save the Children, who Williams credits with some of the innovation. The charity provided advice on the types of obstacles they encounter in the developing world that might impact the effectiveness of using a gel.
“There were some very practical aspects around how we should think about the packaging, how it needed to be very robust to get across long distances and to withstand high heat and humidity. At the same time, it needed to be easily opened because there aren’t often scissors available, and it had to have just the right amount for a single use in one sachet.
“There also had to be pictorial instructions because there’s a high degree of low literacy and illiteracy rates,” she says.
The development process took three years before it could be submitted to regulators. The formulation had to be kept simple so that local manufacturers in the developing world could pick it up. While the clinical trials had been done in previous studies, experiments had to be carried out to ensure making it in gel instead of liquid didn’t change its properties, as well as ensuring it would be stable and robust in extreme conditions, without degrading.
They then took the gel, which they have named Umbipro, through a scheme with the European Medicines Agency in association with WHO, which is specifically for medicines for the developing world. The Irish regulatory authority was the lead reviewer on behalf of the agency.
“We came out to Dublin and met with their team and they granted us accelerated review because the EMA recognised the potential public health importance of getting a medicine like this into regions with high infant death rates. That went in September of last year, and we got the positive opinion at the end of April this year,” she says.
They are currently working through the regulatory processes in the relevant countries where the gel could be used. Once approved, GSK will make the formula available to developing world manufacturers, and sell the gel at a not-for-profit price where local manufacture isn’t possible, to “maximise the access to as many babies as possible” according to Williams.
However, the gel is only helpful if it’s being used and she says this will take time and education, a process Save the Children has already begun.
“The WHO has changed its recommendation for cord care. It used to say don’t put anything on the cord, to stop the unhygienic practices and now that’s shifted to say, actually we want you to put something on the cord but only chlorhexidine. There’s been quite a lot of work Save the Children have done in the communities to make that change, for mothers, midwives and healthcare professionals to understand why there’s a new recommendation and what the benefit could be,” Williams says.
She previously worked in early drug development so this project was a learning curve for her. Following on from the project, Williams is looking to stay on a similar track.
She and her team have partnered with an academic group from Australia, to look at reducing post-partum haemorrhage (bleeding after childbirth), which is the biggest cause of maternal mortality in the developing world.
In the developed world, mothers are given an injection of oxytocin immediately after giving birth to help contract the uterus and stop bleeding. As well as being delivered by injection, the drug has to be kept refrigerated, which rules it out as a possibility in many developing world countries.
They have been developing a heat-stable inhaler to get the drug into the bloodstream in a different way, and have run initial clinical trials to test it.
“It looks very encouraging so we’re now taking that forward into further clinical studies. It’s at a much earlier stage and it’s going to take much longer because we’re starting from an earlier point but it again has the potential to save many thousands of mothers’ lives if it were made available,” says Williams.
